update of carcinogenicity studies in animals and humans of 535 marketed pharmaceuticals

Mutation Research 750 (2012) 1–51

Review

Update of carcinogenicity studies in animals and humans of535 marketed pharmaceuticals

Giovanni Brambilla *, Francesca Mattioli, Luigi Robbiano, Antonietta Martelli

Department of Internal Medicine, Division of Clinical Pharmacology and Toxicology, University of Genoa, Viale Benedetto XV, 2, I-16132 Genoa, Italy

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

2. Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46

3. Results and discussion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47

A R T I C L E I N F O

Article history:

Received 28 April 2011

Received in revised form 12 September 2011

Accepted 17 September 2011

Available online 23 September 2011

Keywords:

Carcinogenicity of 535 marketed

pharmaceuticals

Carcinogenicity studies in animals

Carcinogenicity studies in humans

A B S T R A C T

This survey is a compendium of information retrieved on carcinogenicity in animals and humans of 535

marketed pharmaceuticals whose expected clinical use is continuous for at least 6 months or

intermittent over an extended period of time. Of the 535 drugs, 530 have the result of at least one

carcinogenicity assay in animals, and 279 (52.1%) of them gave a positive response in at least one assay.

Only 186 drugs (34.8%) have retrievable information on carcinogenicity in humans, and 104 of them gave

to a variable extent evidence of a potential carcinogenic activity. Concerning the correlation between

results obtained in animals and epidemiological findings, 58 drugs gave at least one positive result in

carcinogenicity assays performed in animals and to a variable extent displayed evidence of

carcinogenicity in humans, but 97 drugs tested positive in animals and were noncarcinogenic in

humans or vice versa. Our findings, which are in agreement with previous studies, indicate that the

evaluation of the benefit/carcinogenic risk ratio should be always made in prescribing a drug.

� 2011 Elsevier B.V. All rights reserved.

Contents lists available at SciVerse ScienceDirect

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jo u rn al h om epag e: ww w.els evier .c o m/lo cat e/ rev iew sm rCo mm un i ty ad dr es s : w ww.els evier . co m/lo c ate /mu t r es

1. Introduction

Among the various adverse reactions that drugs may cause, theoccurrence of carcinogenic effects cannot be excluded. In order toassess the potential risk to humans of carcinogenic effects, theregulatory authorities of Europe, USA and Japan recommend thatgenotoxicity and carcinogenicity studies are performed before theapplication for marketing approval of pharmaceuticals. Presentguidelines for genotoxicity testing of pharmaceutical [1–3]indicate a standard test battery that consists of: (i) a test for genemutation in bacteria; (ii) an in vitro test with cytogeneticevaluation of chromosomal damage with mammalian cells or anin vitro mouse lymphoma tk assay that can detect both genemutation and chromosomal damage; (iii) an in vivo test forchromosomal damage using rodent hematopoietic cells. For a

* Corresponding author. Fax: +39 010 353 8232.

E-mail addresses: [email protected], [email protected]

(G. Brambilla).

1383-5742/$ – see front matter � 2011 Elsevier B.V. All rights reserved.

doi:10.1016/j.mrrev.2011.09.002

compound that induces a biologically relevant positive result inone or more in vitro tests, a further in vivo test using a tissue otherthan the bone marrow/peripheral blood should be done. Guide-lines for carcinogenicity testing of pharmaceuticals [4,5] indicatethat a long-term carcinogenicity study plus a short- or medium-term in vivo system should be performed for all pharmaceuticalswhose expected clinical use is continuous for at least 6 months aswell as for pharmaceuticals used frequently in an intermittentmanner in the treatment of chronic recurrent conditions. In theabsence of clear evidence favouring one species, the rat should beselected. In long-term carcinogenicity assays the highest doseshould be at least 25-fold higher, on a mg/m2 basis, than themaximum recommended human daily dose or represent a 25-foldratio of rodent to human AUC. The Maximum Tolerated Dose(MTD) or a limit dose of 2000 mg/kg can be used as alternatives.

The International Agency for Research on Cancer [6] in the 99volumes of IARC Monographs on the Evaluation of CarcinogenicRisks to Humans published in the years from 1972 to 2010examined 203 drugs or groups of drugs. Carcinogenicity studieswere considered sufficient for 72 drugs, limited for 58, and

http://dx.doi.org/10.1016/j.mrrev.2011.09.002

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http://dx.doi.org/10.1016/j.mrrev.2011.09.002

Table 1Carcinogenicity in animals and carcinogenicity in humans of 535 marketed pharmaceuticals.

Test compound Test system Resulta Doseb Reference

1. Abacavir(13670-78-5)

Long-term carcinogenesis assay, mice

(clitoral and preputial gland tumours)

+ 55–330 mg/kg/day [9]

Long-term carcinogenesis assay, rats (liver,

thyroid, clitoral and preputial gland

tumours)

+ 30–600 mg/kg/day [9]

2. Abarelix(183552-38-7)

Long-term carcinogenesis assay, mice � 300 mg/kg sc every 4 weeks [9]

Long-term carcinogenesis assay, rats � 100 mg/kg sc every 4 weeks [9]

3. Acamprosate(77337-76-9)

Long-term carcinogenesis assay, Sprague-

Dawley rats

�(x2.5) 400 mg/kg/day [9]

4. Acarbose(56180-94-0)


Dawley rats (kidney and Leyding cell

tumours)

+ 500 mg/kg/day [9]


Dawley rats

� NR [9]

Long-term carcinogenesis assay, Wistar

rats

� NR [9]

5. Acebutolol(53164-05-9)

Long-term carcinogenesis assay, mice �(x1.4) 300 mg/kg/day [10]

Long-term carcinogenesis assay, rats �(x2.8) 300 mg/kg/day [10]

6. Acetohexamide(968-81-0)

Long-term carcinogenesis assay, B6C3F1

mice

�(x1.3) 12,718 ppm in diet [10,11]

Long-term carcinogenesis assay, F344 rats �(x2.0) 20,000 ppm in diet [10,11]

7. Acetylmethadol(1477-40-3)

Long-term carcinogenesis assay, mice � 30.1 mg/kg/day [12]

Long-term carcinogenesis assay, rats (liver

tumours)

+ 3.1–16.6 mg/kg/day [12]

8. Aciclovir(59277-89-3)

(Group 3)

Long-term carcinogenesis assay, CD-1

Swiss mice

�(x2.7) 450 mg/kg/day [13]


Dawley rats

�(x5.5) 450 mg/kg/day [13]

Humans: cancer at any site ? [13]

9. Acitretin(55079-83-9)

(*tested as etretinate)

Long-term carcinogenesis assay, male

mice* (vessel tumours)

+ 0.5 MRHD/kg/day [9]

Long-term carcinogenesis assay, female

mice*

�(x2.8) 0.5 MRHD/kg/day [9]


rats

�(x0.2) 2 mg/kg/day [9]

10. Acrivastine(87848-99-5)

Long-term carcinogenesis assay, mice � 250 mg/kg/day [9]


Human: cancer at any site � [14]

11. Actarit(18699-02-0)

Long-term carcinogenesis assay, mice � 3 g/kg in diet [10,15]

Long-term carcinogenesis assay, rats � 3 g/kg in diet [10,15]

12. Adapalene(106685-40-9)

Long-term carcinogenesis assay, mice � 2.6 mg/kg/day on skin [9]

Long-term carcinogenesis assay, male rats

(pheochromocytomas)

+ 0.15–1.5 mg/kg/day [9]


rats (thyroid tumours)

+ 0.15–1.5 mg/kg/day [9]

13. Adefovir(10694125-7)


Long-term carcinogenesis assay, rats � 5 mg/kg/day [9]

14. Adriamycin(23214-92-8)

Long-term carcinogenesis assay, rats

(mammary tumours)

+ 8 mg/kg iv [16]

(Group 2A) Human: cancer at any site ? [17]

15. Albendazole(54965-21-8)



16. Albuterol(18559-94-9)



rats (ovary leiomyomas)

+ 2–50 mg/kg/day [9]

17. Alendronate(66376-36-1)

Long-term carcinogenesis assay, male mice �(x1.2) 10 mg/kg/day [9]


mice (harderian gland tumours)

+ 5 mg/kg/day [9]


(thyroid adenomas)

+ 3.75 mg/kg/day [9]

18. Alfuzosin(81403-80-7)

Long-term carcinogenesis assay, mice � 100 mg/kg/day [9,18]

Long-term carcinogenesis assay, rats � 100 mg/kg/day [9,18]

G. Brambilla et al. / Mutation Research 750 (2012) 1–512

Table 1 (Continued )


19. Allopurinol(315-30-0)



20. Almotriptan(154323-57-6)



21. Alosetron(122852-42-0)



22. Alprazolam(28981-97-7)

Long-term carcinogenesis assay, mice �(x4.8) 10 mg/kg/day [9,18]


Humans: ovarian cancer �, (+) [19,20]

23. Alprenolol(13655-52-2)

Long-term carcinogenesis assay, rodents + NR [21]

24. Aluminium hydroxide(21645-51-2)

Long-term carcinogenesis assay, mice � 200 mg/kg/day ip [10,22]

25. Amiloride(2609-46-3)


Long-term carcinogenesis assay, male rats � 6 mg/kg/day [9,18]


rats

� 8 mg/kg/day [9,18]

Humans: kidney cancer (+) [23]

26. Aminophenazone(58-15-1)


mice

� 0.08% in dr. wt. [10,24,25]

27. Amiodarone(1951-25-3)


(thyroid tumours)

+ 5 mg/kg/day [9,10]

28. Amlexanox(68302-57-8)

Long-term carcinogenesis assay, mice � NR [18]

Long-term carcinogenesis assay, rats � NR [18]

29. Amlodipine(88150-42-9)

Long-term carcinogenesis assay, mice �(x1.2) 2.5 mg/kg/day [10,18]

Long-term carcinogenesis assay, rats �(x2.4) 2.5 mg/kg/day [10,18]

Human: cancer at any site �, � [23,26]

30. Amobarbital(57-43-2)


31. Amoxapine(14028-44-5)


(pancreas tumours)

(+) 5 HD/kg/day [18]

Humans: breast cancer �, �, �, ?, ? [27–31]

Ovarian cancer �, ?, (+), ? [19,20,32]

Colorectal cancer ? [33]

Cancer at any site ? [34]

32. Amphetamine(300-62-9)

Long-term carcinogenesis assay, mice �(x2.4) 19–30 mg/kg/day [9]


Humans: Hodgkin’s disease ? [35]

33. Ampicillin(69-53-4)

(Group 3)


male mice

� 3 g/kg/day [36]


female mice (lung tumours)

(+) 3 g/kg/day [36]

Long-term carcinogenesis assay, F344N

male rats (leukaemias and

phechromocitomas)

+ 750 mg/kg/day [36]

Long-term carcinogenesis assay, F344N

female rats (mammary tumours)

(+) 750 mg/kg/day [36]

Humans: lung and skin tumours ? [36]

34. Amprenavir(161814-49-9)

Long-term carcinogenesis assay, male mice

(liver tumours)

+ 600 mg/kg/day [9]


mice

�(x2.0) 600 mg/kg/day [9]


(liver tumours)

+ 750 mg/kg/day [9]


rats

�(x4.0) 750 mg/kg/day [9]

35. Amsacrine(51264-14-3)

(Group 2B)

Long-term carcinogenesis assay, A/J mice � 10 mg/kg/week ip � 7 weeks [13]


rats (intestine and skin tumours)

+ 3 mg/kg/day iv � 6 times [13]

36. Anastrozole(120511-73-1)


(lymphosarcomas and ovary tumours)

+ 50 mg/kg/day [9]


uterus and thyroid tumours)

+ 25 mg/kg/day [9]

37. Aprepitant(170729-80-3)


(skin fibrosarcomas)

+ 125 mg/kg/day [9]

G. Brambilla et al. / Mutation Research 750 (2012) 1–51 3




mice

� 500 mg/kg/day [9]


Dawley rats (liver and thyroid tumours)

+ 50 mg/kg/day [9]

38. Aripiprazole(129722-12-9)

Long-term carcinogenesis assay, male ICR

mice

�(x5.6) 30 mg/kg/day [18]


ICR mice (pituitary and mammary

tumours)

+ 3 mg/kg/day [18]

Long-term carcinogenesis assay, F344

male rats

�(x3.8) 10 mg/kg/day [18]


female rats (mammary fibroadenomas)

+ 10 mg/kg/day [18]


Dawley male rats

�(x22.8) 60 mg/kg/day [18]


Dawley female rats (adrenal gland

tumours)

+ 60 mg/kg/day [18]

39. Arsenic trioxide(1327-53-3)

Carcinogenesis assay, in animals no data [9]

Humans: cancer at any site + [17]

40. Asparaginase(9015-68-3)

Long-term carcinogenesis assay, newborn

mice (lung adenomas)

(+) 2500 IU/kg � 4 days ip [9]

41. Aspirin(50-778-2)

Long-term carcinogenesis assay, CB6 mice �(x0.5) 382 mg/kg/day [25]

Long-term carcinogenesis assay, rats �(x1.2) 0.5% in diet [9]

Long-term carcinogenesis assay, rats �(x0.07) 26.9 mg/kg/day [25]

Long-term carcinogenesis assay, F344 rats �(x0.5) 200 mg/kg/day [25]



rats

�(x1.0) 400 mg/kg/day [25]

Humans: lung cancer �, (+) [37,38]

Breast cancer �, �, (+) [39–41]

Urinary tract cancer �, �, (+) [42–44]

Esophageal cancer � [45]

Endometrial cancer � [46]

Ovarian cancer (+) [47]

Gallbladder cancer � [48]

Colorectal cancer � [49]

Melanoma (+) [50]

Cancer at any site � [50]

42. Astemizole(68844-77-9)

Long-term carcinogenesis assay, Swiss

mice

�(x19.2) 400 ppm in diet [51]




rats

� 800 ppm in diet [51]

Humans: cancer at any site � [14]

43. Atenolol(29122-68-7)

Long-term carcinogenesis assay, C57BL/

10J mice

� 300 mg/kg/day [18,52]

Long-term carcinogenesis assay, Alderly

Park strain 1 rats

� 300 mg/kg/day [18,25,52]


(adrenal, pituitary and thyroid tumours)

(+) 500 mg/kg/day [18]


rats (adrenal and mammary tumours)

(+) 500 mg/kg/day [18]

Humans: cancer at any site ?, ? [23,26]

44. Atomoxetine Long-term carcinogenesis assay, mice �(x5.3) 458 mg/kg/day [9]



Ovarian cancer �, �, (+) [19,20,32]



45. Atorvastatin(134523-00-5)


(liver tumours)

+ 400 mg/kg/day [9]

Long-term carcinogenesis assay, male rats �(x14.2) 100 mg/kg/day [9]


rats (muscle tumours)

(+) 100 mg/kg/day [9]

Humans: breast cancer �, � [53,54]

Cancer at any site �, ? [55,56]

Lymphoid malignancies + [57]

46. Atovaquone(95233-18-4)


(liver tumours)

+ human AUC � 5 [9]


47. Atropine(51-55-8)


Dawley female rats

� 50 mg/kg/day � 5 days/

week � 28 months

[10,25]




48. Auranofin(34031-32-8)



mice

�(x4.6) 7.45 mg/kg/day [25]


(kidney tumours)

+ 23 mg/kg/day [10]


(kidney tumours)

+ 1 mg/kg/day [10]

49. Aurothioglucose(12192-57-3)

Long-term carcinogenesis assay, C3H

female mice (mammary tumours)

(+) 10 mg/mouse ip [58]

Long-term carcinogenesis assay, CBA


(+) 400 mg/kg ip [58]

Long-term carcinogenesis assay, AKR mice

(osteomas)

(+) 750 mg/kg ip [58]

Long-term carcinogenesis assay, CBA male

mice (hepatomas)

(+) 400 mg/kg ip [58]

50. Azacitidine(320-67-2)

(Group 2A)

Long-term carcinogenesis assay, AK female

mice (leukaemias)

+ 1.5–0.8 mg/kg/day ip � 50

days

[36]

Long-term carcinogenesis assay, A/He

mice (lung tumours)

+ 90 mg/kg � 3/week ip � 8

weeks

[36]


male mice

� 4.4 mg/kg � 3/week ip � 52

weeks

[36]


female mice (hematopoietic tumours)

+ 2.2 mg/kg � 3/week ip � 52

weeks

[36]

Long-term carcinogenesis assay, BALB/c

mice (lung, skin and lymphoreticular

tumours)

+ 2 mg/kg/week ip � 50 weeks [36]


Dawley rats

+ 5.2 mg/kg � 3/week [10]

Long-term carcinogenesis assay, Fisher

male rats (testes tumours)

+ 2.5 mg/kg � 2/week ip � 9

months

[36]


male rats (testes tumours)

+ 2.5 mg/kg � 3/week � 1 year [36]

51. Azapropazone(13539-59-8)


mice

� 1.25 mg sc [59]

52. Azathioprine(446-86-6)

(Group 1)


newborn mice (leukaemias)

+ 40 mg/kg � 4 days [60]

Long-term carcinogenesis assay, C57BC

mice (hematopoietic tumours)

+ 100 mg/kg sc/week [60]

Long-term carcinogenesis assay, NZB/NZW

hybrid mice (various types of tumours)

+ 0.2 mg/mouse � 5/week [60]

Long-term carcinogenesis assay, NZB mice

(thymic lymphomas)

+ 100 mg/kg 1–3/week [60]


mice (various types of tumours)

+ 7.5–30 mg/kg � 3/week [60]


male mice

�(x0.03) 20 ppm in diet [60]


female mice (various types of tumours)

+ 20 ppm in diet [60]

Long-term carcinogenesis assay, F344 rats

(earduct carcinomas)

+ 150 mg/kg in diet [60]


Dawley rats

?(x0.51) 37 mg/kg ip � 3/week [60]


Dawley female rats (lymphomas and

squamous cell carcinomas)

+ 1.2–2 g/rat po (total dose) [60]

Long-term carcinogenesis assay, monkeys � 3 mg/kg/day [25]

Humans: non-Hodgkin’s lymphomas + [17,60]

Cancer at any site (+) [17,60]

53. Azelastine(58581-89-8)




54. Baclofen(1134-47-0)


mice

? NR [18]

55. Balsalazide(80573-04-2)


Dawley rats

�(x2.4) 2 g/kg/day [18]

56. Barbital(57-44-3)


male rats (kidney tumours)

+ 160 mg/kg/day [25]


female rats

�(x2.6) 160 mg/kg/day [25]

57. BCNU(154-93-8)

(Group 2A)

Long-term carcinogenesis assay, Swiss-

Webster male mice

? 2.5 mg/kg � 3/week ip � 6

months

[60]





Webster female mice (lung tumours and

fibrosarcomas)

(+) 2.5 mg/kg � 3/week ip � 6

months

[60]


Dawley rats

� 4 mg/rat po [60]


Dawley rats (tumours at various sites)

+ 1.5 mg/kg � 3/week ip � 6

months

[60]


Dawley rats (peritoneal cavity tumours)

+ 1 mg/kg/week ip � 1 year [60]


male rats (lung tumours)

+ 75 mg/m2 iv every 6 weeks [60]

Humans: acute nonlymphocytic leukaemia ? [17,60,61]

58. Beclometasone(4419-39-0)

Long-term carcinogenesis assay, rats � 2.4 mg/kg/day po

and � inhalation

[9]

59. Benazepril(86541-75-5)

Long-term carcinogenesis assay, mice �(x9.0) 150 mg/kg/day [9,10,18]

Long-term carcinogenesis assay, rats �(x18.3) 150 mg/kg/day [9,10,18]


60. Bepridil(64706-54-3)

Long-term carcinogenesis assay, mice �(x4.8) 6.67 mg/kg/day [18]


(thyroid adenomas)

(+) 100 mg/kg/day [18]

61. Betaxolo(63659-18-7)

Long-term carcinogenesis assay, mice �(x7.2) 60 mg/kg/da [9,18]

Long-term carcinogenesis assay, rats �(x11.7) 48 mg/kg/da [9,18]

62. Bezitramide(15301-48-1)

Long-term carcinogenesis assay, dogs �(x1.7) 0.63 mg/kg/day po [62]

63. Bicalutamide(90357-06-5)


(liver tumours)

(+) 75 mg/kg/day [9]


(thyroid tumours)

+ 5 mg/kg/day [9]


(Leydig cell tumours)

+ 5 mg/kg/day [9]


rats (uterus tumours)

+ 75 mg/kg/day [9]

64. Bisacodil(603-50-9)

Long-term carcinogenesis assay, p53(+/�)

mice

� 8 g/kg/day po [63]

Long-term carcinogenesis assay, F344 rats (+) 0.3% in diet [10]

Long-term carcinogenesis assay, F344 rats (+) 0.3% in diet [10]

65. Bisoprolol(66722-44-9)



66. Bleomycins(11056-06-7)

(Group 2B)

Long-term carcinogenesis assay, mice ? NR sc, im [17,60]


(fibrosarcomas and kidney tumours)

+ NR sc [17,60]

Humans: acute nonlymphocytic leukaemia ? [17,60]

67. Bosentan(147536-27-8)


(liver tumours)

+ 450 mg/kg/day [9]


(astrocytomas)

+ 500 mg/kg/day [9]

68. Brimonidine(59803-98-4)



69. Bromocryptine(25614-03-3)

Long-term carcinogenesis assay, OF1 mice �(x .4) 50 mg/kg/day [20]


Dawley male rats

�(x4.3) 44.5 mg/kg/day [20]


Dawley female rats (uterine tumours)

+ 44.5 mg/kg/day [20]

70. Brotizolam(57801-81-7)


Long-term carcinogenesis assay, rats ? 200 mg/kg/day [64]

71. Budenoside(51333-22-3)



Dawley male rats (gliomas and liver

tumours)

+ 50 mg/kg/day [9]


Dawley female rats

� 50 mg/kg/day [9]

72. Bumetanide(28395-03-1)

Long-term carcinogenesis assay, CD male

rats

� 60 mg/kg/day [18,65]

Long-term carcinogenesis assay, CD female

rats (mammary adenomas)

? 60 mg/kg/day [18,65]





73. Buprenorphine(52485-79-7)



(Leydig’s cell tumours)

+ 56 mg/kg/day [9]

74. Bupropion(34911-55-2)


Long-term carcinogenesis assay, rats ? (x6.5) 300 mg/kg/day [9]


Ovarian cancer �, �, (+) [19,20,40]



75. Buspirone(36505-84-7)

Long-term carcinogenesis assay, mice �(x13.4) MRHD � 167 [18]

Long-term carcinogenesis assay, rats �(x21.6) MRHD � 133 [18]

76. Busulfan(55-98-1)

Carcinogenesis in animals no data [9]

Humans: secondary malignancies + [9]

77. Butorfanol(42408-88-2)

Long-term carcinogenesis assay, mice �(x18) 60 mg/kg/day [9,16]


78. Cabergoline(81409-90-7)

Long-term carcinogenesis assay, male mice �(x3.9) 0.98 mg/kg/day [9]


mice (uterus tumours)

+ 0.98 mg/kg/day [9]

Long-term carcinogenesis assay, male rats �(x2.6) 0.32 mg/kg/day [9]



+ 0.32 mg/kg/day [9]

79. Caffeine(58-08-2)

(Group 3)



+ 500 ppm in dr.wt. [66]

Long-term carcinogenesis assay, C57BL6

mice

�(x0.4) 55 mg/kg/day [25]


rats

�(x6.5) 2000 ppm in dr.wt. [10,66,67]


Dawley rats

� (x6.5) 2000 ppm in dr.wt [10,66,68]


Wistar rats (pituitary adenomas)

+ 2000 ppm in dr.wt. [10,66]


Dawley male rats

�(x1.6) 1020 ppm in diet [66]


Dawley rats

�(x1.6) 100 mg/kg/day [66]

Humans: bladder tumours (+) [66]

Breast cancer ? [66]


Non-Hodgkin’s lymphoma � [70]

80. Calcitonin(47931-85-1)

Long-term carcinogenesis assay, F344 and

Sprague-Dawley rats (pituitary adenomas)

+ 80 IU/kg/day sc [9]

81. Candesartan cilexetil(145040-37-5)


Long-term carcinogenesis assay, rats � 1 g/kg/day [9,18]

82. Captopril(62571-86-2)

Long-term carcinogenesis assay, mice � 1.35 g/kg/day [9,18]

Long-term carcinogenesis assay, rats � 1.35 g/kg/day [9,18]


83. Carazolol(57775-29-8)


Dawley rats

� 900 ppm in diet [22]

84. Carbamazepine(298-46-4)

Long-term carcinogenesis assay Sprague-

Dawley rats (liver and testes tumours)

+ 25 mg/kg/day [9]

85. Carbidopa(28860-95-9)

Long-term carcinogenesis assay, male rats �(x0.3) MRHD � 2 [9]

86. Carbromal(77-65-6)


mice

� 2500 ppm in diet [71]

Long-term carcinogenesis assay, F344 rats � 2500 ppm in diet [71]

87. Carteolol(51781-06-7)


mice

� 230 mg/kg/day [72]



mice

� 0.15% in diet [73]

Long-term carcinogenesis assay, offspring

mice

? 150 mg/kg [74]


88. Carvedilol(72956-09-3)


Long-term carcinogenesis assay, rats �(x12) 75 mg/kg/day [9,18]




89. CCNU(13010-47-4)


Webster mice (lymphomas and lung

tumours

+ 1.25–5 mg/kg � 3/week ip � 6

months

[17,60]


Dawley rats (lung tumours)

+ 5 mg/rat po [17,60]

Humans: acute nonlymphocytic leukaemia ? [17,60,61]

90.Celecoxib(169590-42-5)

Long-term carcinogenesis assay, male mice � 25 mg/kg/day [9,10]


mice

� 50 mg/kg/day [9,10]

Long-term carcinogenesis assay, mice �(x0.6) 25–50 mg/kg/day [9,10]

Long-term carcinogenesis assay, male rats � 10 mg/kg/day [9,10]


rats

� 50 mg/kg/day [9,10]

Long-term carcinogenesis assay, rats �(x4.9) 10–200 mg/kg/day [9,10]

Humans: breast cancer �, �, (+) [39,41,75]

Lung cancer � [37]

Esophageal cancer �, � [45,76]

Gastric cancer � [76]


Kidney cancer (+) [44]

91. Celiprolol(56980-93-9)


mice

�(x10.8) 900 mg/kg in diet [25,77]


Dawley rats

�(x19.5) 8000 ppm in diet [25,78]


Dawley rats

�(x21.9) 900 mg/kg in diet [25,79]

Long-term carcinogenesis assay, beagle

dogs

� 300 mg/kg/day [79]

92. Cerivastatin(143201-11-0)


(hepatocellular adenomas)

+ 9.1 mg/kg/day [18]


93. Cetirizine(83881-51-0)


(liver tumours)

+ 16 mg/kg/day [9]


rats

� 20 mg/kg/day [9]


94. Cevimeline(107233-08-9)


mice

� NR [9]


male rats

� 100 mg/kg/day [9]


female rats (uterus adenocarcinomas)

+ 100 mg/kg/day [9]

Humans: basal cell and squamous

carcinomas

(+) [9]

95. Chloral hydrate(302-17-0)

(Group 3)


male mice (liver tumours)

(+) 10 mg/kg � 1 po [80]



+ 166 mg/kg � 1 po [80]



+ 13.5 mg/kg/day [80]



+ 25 mg/kg/day po [80]



(+) 0.165 mg/neonatal mouse ip [80]


female mice (pituitary tumours and

lymphomas)

+ 100 mg/kg/day po [80]


female mice

� 0.165 mg/neonatal mouse ip [80]


mice (hepatocellular carcinomas)

+ 1.28 g/l in dr. wt. [81]


mice (pituitary tumours)

+ 71.4 mg/kg/day [81]


Dawley rats

�(x0.8) 135 mg/kg/day po [80]

Long-term carcinogenesis assay, F344 rats �(x0.9) 162.6 mg/kg/day po [80]


96. Chlorambucil(305-03-3)

(Group 1)


mice (skin papillomas)

+ 0.1% on skin [60]

Long-term carcinogenesis assay, A/J mice

(lung tumours)

+ 37 mg/kg � 3/week ip � 4

weeks

[60]


Webster mice (lung tumours)

+ 1.5 mg/kg � 3/week ip � 6

months

[60]





Dawley male rats (hematopoietic tumours)

(+) 2.2 mg/kg � 3/week ip � 6

months

[60]


Dawley female rats

� 4.5 mg/kg � 3/week ip � 6

months

[60]

Humans: acute nonlymphocytic leukaemia (+) [17,60]

97. Chloramphenicol(56-75-7)

(Group 2A)


mice (lymphomas)

(+) 2 g/l in dr. wt [36]

Long-term carcinogenesis assay, C57BL/6N

mice (lymphomas)

(+) 0.5 g/l in dr. wt. [36]

Long-term carcinogenesis assay, BALB/

c � AF1 mice

(+) 2.5 mg/mouse ip � 5/

week � 5 weeks

[36]

Humans: leukaemias (+) [17]

98. Chlormadinone(302-22-7)

(Group 2B)

Long-term carcinogenesis assay, CF-LP

mice

� 200–400 MRHD/kg/day [83,84]

Long-term carcinogenesis assay, mice of

various strains

?(x1.9) 8 mg/kg of diet [83,84]

Long-term carcinogenesis assay, rats � 400 MRHD/kg/day [83,84]


female dogs

+ NR [83,84]

99. Chlorozotocin(54749-90-5)

(Group 2A)


Dawley rats (sarcomas and

mesotheliomas)

+ 0.4 mg/kg/week � 114 weeks [36]


male rats (nervous system, lung and

forestomach tumours)

(+) 9.15 mg/m2 iv every 6

weeks � 10 times

[36]

100. Chlorphenamine(132-22-9)


male mice

�(x23.3) 50 mg/kg/day [85]


female mice

? 200 mg/kg/day [85]


male rats

�(x21.3) 30 mg/kg/day [85]


female rats

� 60 mg/kg/day [85]


101. Chlorpromazine(50-53-3)


Syrian hamsters

(+) on the skin [87]

Humans: ovarian cancer � [19]

102. Chlorpropamide(94-20-2)


mice

�(x6.4) 10,000 ppm in diet [10,25,88]

Long-term carcinogenesis assay, F344 rats �(x7.8) 6000 ppm in diet [10,25,88]

103. Ciclopirox(29342-05-0)


mice

� 5% sol. on skin � 50 weeks [9]

104. Cilostazol(73963-72-1)

Long-term carcinogenesis assay, mice � 1 g/kg/day [9]


105. Cimetidine(51481-61-9)

(Group 3)


female mice (lymphomas)

?(x0.5) 226 mg/kg/day [36]

Long-term carcinogenesis assay, cdr rats

(Leydig cells tumours)

(+) 378 mg/kg/day [9,36]

Long-term carcinogenesis assay, dogs ? 144 mg/kg/day [10]

Humans: stomach cancer ? [36]

Lung cancer ? [36]

106. Ciprofibrate(52214-84-3)


(hepatocellular carcinomas)

+ 10 mg/kg in diet [25,89]


107. Ciprofloxacin(85721-33-1)



108. Cisapride(81098-60-4)



109. Cisplatin(15663-27-1)

(Group 2A)


female mice (tumours at various sites)

+ 1.62 mg/kg ip/week � 10

times

[17,60]

Long-term carcinogenesis assay, A/Jax

female mice (lung adenomas)

+ 103–108 mmol/kg ip [17,60]

Humans: leukaemias ? [90]


110. Citalopram(59729-32-7)

Long-term carcinogenesis assay, NMRI/

BOM mice

�(x19.2) 240 mg/kg/day [9]

Long-term carcinogenesis assay, COBS WI

rats (small intestine carcinomas)

+ 8 mg/kg/day [9]


Ovarian cancer ?, (+), � [19,20,32]






111. Clemastine(15686-51-8)


Long-term carcinogenesios assay, rats � 84 mg/kg/day [10,92]

112. Clindamycin(18323-44-9)

Long-term carcinogenesis assay, mice � 1% on the skin � 2 years [9]

113. Clobazam(22316-47-8)

Long-term carcinogenesis assay, rats � 300 mg/kg/day � 9 months [93]


(thyroid tumours)

+ 100 mg/kg/day [94]


114. Clofazimine(2030-63-9)

Long-term carcinogenesis assay, animals

(species not specified)

� NR [18]

115. Clofibrate(637-07-0)

Long-term carcinogenesis assay, mice �(x1.2) 5000 ppm in diet [95]

Long-term carcinogenesis assay, mice �(x0.8) 350 mg/kg in diet [95]



+ 250 mg/kg/day [95]



+ 5000 ppm in diet [95]


Dawley rats (liver neoplastic nodules)

(+) 400 mg/kg/day [95]

Long-term carcinogenesis assay,

marmosets

� 263 mg/kg/day [95]


116. Clomiphene(911-45-5)

(Group 3)


Dawley newborn female rats (uterus

tumours)

(+) 10–500 mg sc [83]

Humans: liver and testes tumours (+) [17]

117 Clomipramine(303-49-1)



Humans: breast cancer �, �, �, ?, ? [27,28,30,31]

Ovarian cancer �, ?, (+), ? [19,20,32]



118. Clonazepam(1622-61-3)


mice

� 0.136% in diet [96]


rats

� 300 mg/kg/day [97]


119. Clonidine(4205-90-7)



120. Clopidogrel(113665-84-2)


Long-term carcinogenesis assay, rats �(x10.1) 77 mg/kg/day [9,10]

121. Clorazepate(23887-31-2)

Long-term carcinogenesis assay, dogs � 75 mg/kg/day [9]

Long-term carcinogenesis assay, monkeys �(x12.9) 36 mg/kg/day [9]

122. Clozapine(5786-21-0)



123. Codeine(76-57-3)


mice

�(x5.3) 400 mg/kg/day [98]


124. Colesevelam(182815-44-7)


mice

�(x3.8) 3 g/kg/day [9]


Dawley male rats (pancreas adenomas)

+ >1.2 g/kg/day [9]


Dawley female rats (thyroid adenomas)

+ 2.4 g/kg/day [9]

125. Cromolyn(16110-51-3)

Long-term carcinogenesis assay, mice � 150 mg/kg � 3/week ip � 12

months

[9]

Long-term carcinogenesis assay, rats � 75 mg/kg/day sc � 12 months [9]

Long-term carcinogenesis assay, hamsters � 53 mg/kg � 3/week ip � 12

months

[9]

126. Cyclobenzaprine(303-53-7)

Long-term carcinogenesis assay, rats � 40 MRHD/day [9]

127. Cyclophosphamide(6055-19-2)

(Group 1)


hybrid female mice (nervous system,

urinary bladder and hematopoietic tissues

tumours)

+ 5.7 mg/kg/day sc [60]


hybrid mice (various types of tumours)

(+) 8 mg/kg/day sc [60]




Long-term carcinogenesis assay, NMR1

female mice (various types of tumours)

+ 26 mg/kg/week sc [60]


(lung tumours)

+ 34 mg/kg � 3/week ip � 4

weeks

[60]

Long-term carcinogenesis assay, dd and A

mice (liver and lung tumours)

+ 5 mg/kg � 2/week ip � 15

weeks

[60]


Webster mice (lung and bladder tumours)

(+) 15–25 mg/kg � 3/week ip � 6

months

[60]


female mice (urinary bladder tumours)

? 200 mg/kg ip � 1–3 times [60]


newborn mice (lung tumours)

(+) 4 mg/kg � 3 times [60]


Dawley rats (nervous system, urinary

bladder and hematopoietic tissues

tumours)

+ 0.63 mg/kg/day in dr. wt. [60]


rats (mammary tumours)

+ 5–10 mg/kg � 3/week ip � 6

months

[60]

Long-term carcinogenesis assay, BR 46

male rats (various types of tumours)

+ 15 mg/kg/week iv � 52 weeks [60]


male rats (benign and malignant tumours)



Dawley male rats (various types of

tumours)


Humans: leukaemias +, +, +, + [17,35,99,100]

Cancer at any site + [101]

Urinary bladder cancer +, +, + [17,102,103]

128. Cyclosporin A(59865-13-3)

(Group 1)


(lymphomas and liver tumours)

+ 1–16 mg/kg/day [9,10]

Long-term carcinogenesis assay, OF1 mice �(x0.02) 16 mg/kg of diet [10,36,104]

Long-term carcinogenesis assay, AKR mice

(thymic lymphomas)

+ 150 mg/kg of diet [36]


and pancreas tumours)

+ 0.5–8 mg/kg/day [9,10,104]

Long-term carcinogenesis assay, OFA rats �(x0.02) 8 mg/kg of diet [36]


dogs

�(x4.3) 45 mg/kg/day [104]

Humans: lymphomas and Kaposi’s

sarcomas

+ [36]

lymphoproliferative disorders + [105]

129. Cyproterone(2098-66-0)


(liver and stomach tumours)

+ 96–104 mg/kg/day [84]

130. Dacarbazine(4342-03-4)

(Group 2B)


Webster mice (lung, spleen, and uterus

tumours, and lymphomas)

+ 25–50 mg/kg � 3/week ip � 8

months

[60]


Dawley rats (various types of tumours)

+ 50–100 mg/kg � 3/week

ip � 6 months

[60]


Dawley female rats (various types of

tumours)

+ 2.5 mg/rat � 3/week iv � 12

weeks

[60]


Dawley weanling rats (various types of

tumours)

+ 346 mg/rat in diet (total dose) [60]

Long-term carcinogenesis assay, Buffalo

weanling female rats (mammary and

thymic tumours)

+ 500 mg/kg of diet � 9 weeks [60]


131. Dactinomycin(50-76-0)


(local sarcomas)

+ NR sc, ip [9]

Long-term carcinogenesis assay, rats (local

sarcomas)

+ NR sc, ip [9]


(mesenchymal tumours)

+ 50 mg/kg � 5/week � 18

weeks

[9]

132. Danthron(117-10-2)

(Group 2B)

Long-term carcinogenesis assay, C3H/HeN


+ 0.2% in diet [25,36,106]


(large intestine tumours)

+ 1% in diet [25,36]

133. Dantrolene(7261-97-4)



Dawley female rats (liver and mammary

tumours)

+ 15–60 mg/kg/day [9,10]


Dawley rats

� NR [9]




Long-term carcinogenesis assay, F344 rats � NR [9]

Long-term carcinogenesis assay, hamsters � NR [9]

134. Dapsone(80-08-0)

(Group 3)


mice

�(x1.6) 1000 ppm in diet [10,95,107]


mice (mother and offspring)

�(x1.6) 100 mg/kg/day to mother;

52 g/kg total dose in offspring

[95]


mice

? 2.65 g/kg (total dose) [95]

Long-term carcinogenesis assay, TgAG

transgenic mice

� 10% topically [18]


male rats (sarcomas of spleen and

peritoneum)

+ 600 ppm in diet [95,107]


female rats

�(x3.9) 1200 ppm in diet [95,107]

Long-term carcinogenesis assay, BDIV rats

mother and offspring (thyroid tumours)

+ 100 mg/kg/day to mother;

52 g/kg total dose in offspring

[10,95]


Wistar rats (tumours at multiple sites)

+ 0.025–0.030% in diet [95]



Dawley female rats

� 100 mg/rat � 1 po [95]


Dawley female rats

� 30 mg/rat � 10 po [95]

Humans: oral cavity and bladder tumours + [17,108]

lymphomas + [17]

135. Daunorubicin(20830-81-3)


(fibrosarcomas at injection site)

+ NR sc [9]


(peritoneal sarcomas)

+ 1/70 HD ip � 3/week � 6

months

[9]


(mammary adenocarcinomas)

+ 1.6 MRHD iv [9]


136. Deferasinox(201530-41-8)

Long-term carcinogenesis assay, p53(+/�)

transgenic mice

�(x0.8) 200–300 mg/kg/day [18]

Long-term carcinogenesis assay, Wistar �(x0.3) 60 mg/kg/day [18]

137. Delavirdine(136817-59-9)


(liver and urinary bladder tumours)

+ 500 mg/kg/day [9]


mice (liver tumours)

+ 250 mg/kg/day [9]


138. Deserpidine(131-01-1)


139. Desloratadine(100643-71-8)

*(tested as loratadine)

Long-term carcinogenesis assay, male mice � 16 mg/kg/day [18]


mice

� 32 mg/kg/day [18]


mice* (liver tumours)

+ 40 mg/kg/day [9]


mice*

� 40 mg/kg/day [9]

Long-term carcinogenesis assay, male rats*

(liver tumours)

+ 10 mg/kg/day [9,18]


rats* (liver tumours)

+ 25 mg/kg/day [9,18]

140. Dexamethasone(50-02-2)


141. Dexmethylphenidate(40431-64-9)

(tested as methylphenidate)



+ 60 mg/kg/day [9]

Long-term carcinogenesis assay, F344 rats � 45 mg/kg/day [9]

142. Diazepam(439-14-5)

(Group 3)

Long-term carcinogenesis assay, CF1 mice

(liver tumours)

(+) 75 mg/kg/day in diet [25,109]


rats

�(x18.3) 75 mg/kg/day in diet [25,109]

Long-term carcinogenesis assay, hamsters � 120 mg/kg/day [109]

Long-term carcinogenesis assay, gerbils � 10 mg/animal po weekly [109]


143. Diclofenac(15307-86-5)


Long-term carcinogenesis assay, mice � 0.035% topically [18]

Long-term carcinogenesis assay, mice �(x0.02) 0.3–1 mg/kg/day [18]


Long-term carcinogenesis assay, gerbils � 10 mg/gerbil po weekly [18]









144. Didanosine(69655-05-6)

(Group 3)

Long-term carcinogenesis assay, mice � 1.2 g/kg/day [9]

Long-term carcinogenesis assay, rats � 1 g/kg/day [9]


145. Dienoestrol(84-17-3)

(Group 1)

Long-term carcinogenesis assay, CC57W

female mice (ovary tumours)

+ 0.46–0.735 mg/mouse

intravaginally (total dose)

[83]


guinea pigs (uterus leiomyomas)

+ 1 mg/kg/day [83]


146. Diethylstilboestrol(56-53.1)

(Group 1)

Long-term carcinogenesis assay, C3H male

mice (mammary tumours)

+ 4.25–14.25 mg/mouse po

(total dose)

[83]

Long-term carcinogenesis assay, ZD8F and

AZF1 male mice (mammary tumours)

+ 0.5 mg/mouse/day po [83]

Long-term carcinogenesis assay, C3H and A


+ 50 mg/kg in diet [83]


castrated male mice (mammary tumours)

+ 0.5–1 mg/kg po � 2–28 days

cycles

[83]

Long-term carcinogenesis assay, C3H/An

castrated male mice (mammary tumours)

+ 0.25 mg/kg of diet [83]

Long-term carcinogenesis assay, C3H/HeJ


(+) 0.1 mg/kg of diet [83]

Long-term carcinogenesis assay, MTV+/

C3H mice (mammary tumours)

+ 4 mg/mouse sc (total dose) [83]

Long-term carcinogenesis assay, BC female

mice (cervix or vagina tumours)

(+) 0.25 mg/week sc � 25–41

weeks

[83]

Long-term carcinogenesis assay, RIL male

mice (leukaemias)

+ 50 mg/mouse/week � 7

months

[83]

Long-term carcinogenesis assay, C mice

(mammary and lymphoid tumours)

(+) 0.3–4 mg sc in pellets [83]


male mice (testes tumours)

+ 1 mg sc in pellets [83]

Long-term carcinogenesis assay, C3H/

MTV+ male mice (mammary tumours)

+ 0.6 mg sc in pellets [83]


RIII � C57L MTV+ female mice (mammary

tumours)

+ 1.4–1.6 mg sc in pellets [83]

Long-term carcinogenesis assay, C3H/

MTV+ female mice (mammary tumours)

+ 0.1 mg sc in pellets [83]


of pregnant treated CD-1 mice (uterus,

cervix and vagina tumours)

(+) 0.01–100 mg/kg sc on days 9–

16 of pregnancy

[83]


of pregnant treated ICR/Jcl mice (lung

tumours and ovary tumours)

+ 10 mg/kg sc on day 15–19 of

pregnancy

[83]


female mice (cervix and/or vagina

tumours)

+ 2 mg/mouse sc [83]

Long-term carcinogenesis assay, BC and

C57 female mice (vagina and/or cervix

tumours)

(+) 1–4 mg/mouse

intravaginally � 3/week

[83]


Dawley weanling rats (mammary

tumours)

(+) 0.2 mg/kg in diet [83]


Dawley rats (pituitary tumours)

+ 20 mg/rat sc [83]

Long-term carcinogenesis assay, various

strains of rats (mammary, adrenal and

bladder tumours)

+ 4–5 mg/rat sc in pellets [83]

Long-term carcinogenesis assay, Ax C

hysterectomized and ovariectomized rats

(mammary tumours)

+ sc implant [83]


newborn rats (squamous cell carcinomas)

(+) 70 mg/rat sc (total dose) [83]


golden hamsters (kidney tumours)

+ 0.6 mg/hamster every other

day � 36 weeks

[83]


Syrian hamsters (kidney tumours)

+ 6 mg/hamster sc � 3/week [83]


hamsters (kidney tumours)

+ 20 mg/hamster sc in pellets [83]





of treated pregnant Syrian golden

hamsters (genital tract tumours)

+ 20–40 mg/hamster on day 15

of gestation

[83]


dogs (ovary tumours)

+ 15–60 mg/dog sc every 7–8

weeks

[83]


dogs (ovary tumours)

+ 60–495 mg/dog sc [83]

Long-term carcinogenesis assay, squirrel

female monkeys (uterus tumours)

+ 60 mg pellets sc [83]

Long-term carcinogenesis assay, frogs

(liver and haematopoietic tissues tumours)

+ 40–200 mg/week sc [83]

Humans: vagina, cervix and breast

tumours in women exposed in utero

(+) [83,84,99]

147. Diflunisal(22494-42-4)








148. Diltiazem(42399-41-7)


Long-term carcinogenesis assay, rats �(x2) 100 mg/kg/day [9,18]

Humans: cancer at any site �, � [23,26]

149. Diphenhydramine(58-73-1)


mice

�(x2.9) 313 ppm in diet [25,110]

Long-term carcinogenesis assay, F344 rats � 2000 ppm in diet [25,86]


male rats

?(x12.2) 625 ppm in diet [25,110]


female rats

?(x6.1) 313 ppm in diet [25,110]

150. Dipyridamole(58-32-2)



151. Dipyrone(68-89-3)


(C57BL6 � C3H)F1 mice

+ 0.5–1% in dr. wt. [25,111]


male rats

�(x2.3) 0.4% in dr. wt. [25,112]


rats

�(x8.5) 3000 ppm in diet [25,113]

152. Disopyramide(3737-09-5)


153. Disulfiram(97-77-8)



+ 100 mg/kg/day 323 mg/kg of

diet

[114]

Long-term carcinogenesis assay, (C57BL/

6 � AKR)F1 mice (subcutaneous sarcomas)

+ 100 mg/kg/day 323 mg/g of

diet

[114]


6 � AKR)F1 female mice (reticulum cell

sarcomas)

+ 1 g/kg sc [114]


male mice

�(x0.9) 2000 ppm in diet [10,115]


female mice

�(x0.5) 500 ppm in diet [10,115]



Dawley male rats

?(x9.8) 500 mg/kg po � 2/week [114]

Long-term carcinogenesis assay, F344 rats �(x1.2) 600 ppm in diet [114]

154. Dofetilide(115256-11-6)



155. Dolasetron(115956-12-2)



+ 150 mg/kg/day [9]


Dawley rats

� 150 mg/kg/day [9]

156. Donepezil(120014-06-4)


mice

� 180 mg/kg/day [9]


Dawley rats

� 30 mg/kg/day [9]

157. Dorzolamide(120279-96-1)



Dawley male rats (urinary bladder

papillomas)

+ 20 mg/kg/day [9,18]


Dawley female rats

� 20 mg/kg/day [9,18]




158. Doxazosin(74191-85-8)

Long-term carcinogenesis assay, mice �(x4) 120 mg/kg/day [18]

Long-term carcinogenesis assay, rats �(x8) 40 mg/kg/day [18]

159. Doxefazepam(40762-15-0)


Dawley rats (liver tumours)

(+) 30 mg/kg/day in diet [25,109,116]

160. Doxylamine(469-21-6)

(Group 3)


mice (liver and thyroid tumours)

+ 375–750 ppm in diet [9,10,25,117]


male rats (liver tumours)

+ 115 mg/kg/day [9,10,25,118]


female rats

� 144 mg/kg/day [9,10,25,118]

161. Dronabinol(1972-08-3)


mice (thyroid adenomas)

? 125 mg/kg/day [9,10,25,119]

Long-term carcinogenesis assay, F344 rats � 50 mg/kg/day [9,10,25,119]

162. Drospirenone(67392-87-4)


(harderian gland tumours)

+ 10 mg/kg/day [9]

Long-term carcinogenesis assay, rat

(pheochromocytomas)

+ 10 mg/kg/day [9]

163. Duloxetine(116539-59-4)

Long-term carcinogenesis assay, male mice �(x7) 100 mg/kg/day [9]



+ 140 mg/kg/day [9]

Long-term carcinogenesis assay, rats �(x5.1) 27–36 mg/kg/day [9]

Humans: breast cancer �, �, �, ? [27–30]

Ovarian cancer �, �, (+) [19,32,40]



164. Dutasteride(164656-23-9)


male mice

� 500 mg/kg/day [9]


female mice (hepatocellular adenomas)

+ 250 mg/kg/day [9]

Long-term carcinogenesis assay, Han

Wistar male rats (Leydig cell tumours)

+ 7.5 mg/kg/day [9]

Long-term carcinogenesis assay, Han

Wistar female rats

� 15 mg/kg/day [9]

165. Ebastine(90729-43-4)




166. Efavirenz(154598-52-4)




+ 150 mg/kg/day [9]

167. Eflornithine(67037-37-0)


mice

� 650 mg/kg/day on skin [9]

168. Eletriptan(143322-58-1)



+ 400 mg/kg/day [9]


(testicular adenomas)

+ 75 mg/kg/day [9]

169. Enalapril(75847-73-3)

Long-term carcinogenesis assay, male mice �(x10.8) 90 mg/kg/day [9,18]


mice

�(x21.6) 180 mg/kg/day [9,18]



170. Enoxolone(471-53-4)


male rats

� 96 mg/kg/day [25]

171. Entacapone(130929-57-6)

Long-term carcinogenesis assay, mice ?(x1.7) 600 mg/kg/day [9]


(kidney tumours)

+ 400 mg/kg/day [9]


rats

�(x2.3) 400 mg/kg/day [9]

172. Entecavir(142217-69-4)


(lung tumours)

+ 3 MRHD/kg/day [10]


mice (lung and vascular tumours)



(brain tumours)

+ 24–35 MRHD/kg/day [10]


rats (liver, skin and vascular tumours)

+ 24–35 MRHD/kg/day [10]

173. Ephedrine(299-43-2)


mice

�(x1.2) 250 ppm in diet [10,120]

Long-term carcinogenesis assay, F344 rats �(x1.2) 250 ppm in diet [10,120]

174. Epinastine(80012-43-7)






175. Epirubicin(56420-45-2)


(subcutaneous fibromas)

(+) 0.5 mg/kg � 10 times, every 3

weeks iv

[9]



(+) 3.6 mg/kg iv [9]


rats (unspecified tumours)

(+) 0.75–1 mg/kg � 4 days, 8

doses

[9]

Humans: myelogenous leukaemias + [9]

176. Eplerenone(107724-20-9)

Long-term carcinogenesis assay, P53

deficient mice

� 1 g/kg/day [18]


(thyroid tumours)

(+) 75 mg/kg/day [18]



(+) 250 mg/kg/day [18]


177. Eprosartan(133040-01-4)

Long-term carcinogenesis assay, mice �(x12) 2 g/kg/day [9,18]


178. Erythromycin(114-07-8)


179. Estazolam(29975-16-4)


mice

�(x24) 10 mg/kg/day in diet [9,109,121]


Dawley CD rats

� 10 mg/kg/day in diet [9,109,121]


180. Eszopiclone(138729-47-2)


mice (lung and skin tumours)

+ 100 mg/kg/day [18]

Long-term carcinogenesis assay, CD1 mice � 100 mg/kg/day [18]

Long-term carcinogenesis assay, p53

transgenic mice

� 300 mg/kg/day [18]


Dawley rats (mammary and thyroid

tumours)

+ 100 mg/kg/day [18]

Humans: cancer at any site (+) [122]

181.Etanercept(185243-69-0)

Carcinogenesis in animals no data [9]

Humans: lymphomas + [9]

182. Ethacrynic acid(6500-81-8)



183. Ethenzamide(938-73-8)


6 � C3H)F1 male mice

+ 1.2% in diet [123]


6 � C3H)F1 female mice

? 1.2% in diet [123]

184. Ethinyloestradiol(57-63-6)

(Group 1)



+ 200–400 MRHD/kg/day [83]

Long-term carcinogenesis assay, Mead

female rats

�(x16.9) 0.053 mg/kg/day [83]


tumours)

+ 200–400 MRHD/kg/day [83]

Humans: liver tumours (+) [83,84]

185. Ethionamide(536-33-4)


mice

�(x1) 2000 ppm in diet [10,124]


female mice (thyroid tumours)

+ 2 mg/mouse po [10,58]


186. Ethynodiol(297-76-7)

(Group 2B)



+ 200–400 MRHD/kg/day [83]

Long-term carcinogenesis assay, castrated


+ 0.68 mg/kg/day [83]

Long-term carcinogenesis assay, rats + 200–400 MRHD/kg/day [83]

Humans ? [83,84]

187. Etidronate(2809-21-4)


188. Etodolac(41340-25-4)


mice

�(x0.07) 15 mg/kg/day [18,25,125]

Long-term carcinogenesis assay, CD rats �(x0.14) 15 mg/kg/day [18,25,125]






189. Etoposide(33419-42-0)

(Group 2A)

Long-term carcinogenesis assay, NF1

transgenic knockout mice

� 100 mg/kg/week po � 6

weeks

[13]




Humans: myeloid leukaemias + [13]

190. Ezetimibe(163222-33-1)



rats

� 500 mg/kg/day [9]

Long-term carcinogenesis assay, male rats � 1.5 g/kg/day [9]

191. Famciclovir(104227-87-4)




rats (mammary adenocarcinomas)

+ 600 mg/kg/day [9]

192. Famotidine(76824-35-6)

Long-term carcinogenesis assay, mice � 2 g/kg/day [9,18]


193. Felbamate(25451-15-4)


(liver adenomas)

+ 1.2 g/kg/day [10,25]


(testes tumours)

+ 300 mg/kg/day [10,25]


rats (liver adenomas)

+ 100 mg/kg/day [10,25]

194. Felodipine(72509-76-3)


Long-term carcinogenesis assay male rats

(testes interstitial tumours)

(+) 23.1 mg/kg/day [18]


rats

� 69.3 mg/kg/day [16]


195. Fenofibrate(49562-28-9)


(liver tumours)

+ 200 mg/kg/day [9]


pancreas and testes tumours)

+ 200 mg/kg/day [9]


196. Feprazone(30748-29-8)

Long-term carcinogenesis assay, rats � 540 mg/kg/day � 6 months [126]

Long-term carcinogenesis assay, dogs � 375 mg/kg/day � 1 year [126]

197. Finasteride(98319-26-7)


male mice (Leydig cell tumours)

+ 250 mg/kg/day [25]


Dawley rats

� 160–320 mg/kg/day [9]

Humans: male breast and prostate

tumours

? [9]

198. Flecainide(54143-56-5)



199. Fluconazole(86386-73-4)




+ 5 mg/kg/day [9]


rats

�(x7) 10 mg/kg/day [9]

200.Flunisolide(3385-03-3)


(lung adenomas)

(+) NR po [9]

Long-term carcinogenesis assay, male rats � NR po [9]


rats (mammary adenocarcinomas)

+ NR po [9]

201. 5-Fluorouracil(51-21-8)

(Group 3)

Long-term carcinogenesis assay, A/Jax

mice

� 1 mg/mouse iv � 16 weeks [60]


rats

? 0.01–3 mg/rat/day [60]

Long-term carcinogenesis assay, BR46 rats � 33 mg/kg/week � 1 year [60]


202. Fluoxetine(54910-89-3)


mice

�(x0.7) 12 mg/kg/day [25,127]


Dawley rats

�(x1.2) 10 mg/kg/day [25,127]


Ovarian cancer ?, (+), � [19,20,32]



203. Fluphenazine(69-23-8)


Dawley female rats

�(x0.23) 0.2 mg/rat 3 times/week [10,128]


204. Flurbiprofen(5104-49-4)











205. Fluticasone(80474-14-2)

Long-term carcinogenesis assay, mice �(x4) 1 mg/kg/day po [9]

Long-term carcinogenesis assay, rats �(x1) 57 mg/kg/day (inhalation) [9]

206. Fluvastatin(93957-55-2)


male mice

� 350 mg/kg/day [9,10,129]


female mice (forestomach papillomas)

+ 30 mg/kg/day [9,10,129]


(stomach tumours)

+ 15 mg/kg/day [9,10]

Long-term carcinogenesis assay, male CD


+ 24 mg/kg/day [9,10,129]

Long-term carcinogenesis assay, female CD

rats

�(x5.8) 24 mg/kg/day [9,10,129]




207. Fluvoxamine(54739-18-3)


Long-term carcinogenesis assay, hamsters � 240 mg/kg/day [18]

Humans: breast cancer �, �, �, ?, ? [27,28,30,31]

Ovarian cancer ?, (+), � [19,20,32]



208. Formoterol(73573-87-2)

Long-tern carcinogenesis assay, mice

(adrenal tumours)

+ 69 mg/kg/day in dr.wt. [9]


(hepatocarcinomas)

+ 50 mg/kg/day in diet [9]


mice (hepatocarcinomas)



mice (uterine tumours)



rats (ovarian tumours)

+ 15 mg/kg/day in dr.wt. [9]



+ 0.5 mg/kg/day in diet [9]

209. Fosfosal(6064-83-1)


Dawley rats

� 500 mg/kg/day [10,130]

210. Fosinopril(97825-24-6)



(mesentery lipomas)

? 400 mg/kg/day [18]


rats

� 400 mg/kg/day [18]


211. Frovatriptan(158747-02-5)



transgenic mice (subcutaneous sarcomas)

? 400 mg/kg/day [18]


(pituitary adenomas)

+ 85 mg/kg/day [18]


rats

� 85 mg/kg/day [18]


212. Fulvestrant(129453-61-8)



+ 15 mg/rat � 30days im [9]


rats (ovary tumours)

+ 10 mg/rat � 15 days im [9]

213. Furosemide(54-31-9)

(Group 3)


male mice

�(x1.1) 1400 ppm in diet [25,131,132]


female mice (mammary adenocarcinomas)

(+) 1400 ppm in diet [25,131,132]



?(x0.6) 350 ppm in diet [25,131,132]


female rats

�(x1.1) 700 ppm in diet [25,131,132]

Humans: lung and other sites tumours ? [36]

214. Gabapentin(60142-96-3)



male rats (pancreas tumours)

+ 2 g/kg/day [9,10,133]





female rats

�(x16.2) 2 g/kg/day [9,10,133]

215. Galantamine(357-70-0)



deficient transgenic mice

�(x4.6) 20 mg/kg/day [9]



rats (endometrial adenocarcinomas)

(+) 10 mg/kg/day [9]

216. Ganciclovir(82410-32-0)


(forestomach, liver, preputial and

harderian gland tumours)

(+) 20 mg/kg/day [9]

217. Gatifloxacin(160738-57-8)


mice

� 81–90 mg/kg/day [9]

Long-term carcinogenesis assay, F344 rats � 47–139 mg/kg/day [9]

218. Gemfibrozil(25812-30-0)


mice (hepatocellular carcinomas)

(+) 30 mg/kg in diet [10,109]

Long-term carcinogenesis assay, CD male

rats (adrenal, liver, pancreas and testes

tumours)

+ 30 mg/kg in diet [10,109]


rats

�(x0.2) 30 mg/kg in diet [10,109]

Humans: skin basal cell carcinomas ? [109]


219. Glatiramer(28704-27-0)


(fibrosarcomas at the injection site)

? 60 mg/kg/day sc [9]

Long-term carcinogenesis assay, rats �(x15) 30 mg/kg/day sc [9]

220. Glibenclamide(10238-21-8)


221. Glimepiride(93479-97-1)

Long-term carcinogenesis assay, mice + >320 ppm im [9]

222. Glipizide(29094-61-9)



223. Goserelin(65807-02-5)


(histiocytic sarcomas)

+ 2.4 mg/kg/day sc [9]


(pituitary adenomas)

+ 50–150 mg/kg sc every 4

weeks � 1 year

[9]

224. Granisetron(109889-09-0)

Long-term carcinogenesis assay, mice ? NR [9]


(liver tumours)

+ 5 mg/kg/day [9]


rats (liver tumours)

+ 25 mg/kg/day [9]


tumours)

+ 100 mg/kg/day [9]

225. Griseofulvin(126-07-8)

(Group 2B)

Long-term carcinogenesis assay, AP mice ?(x6.4) 0.5–1% in diet [16]

Long-term carcinogenesis assay, CR mice

(hepatomas)

+ 1% in diet [16,134]


mice (hepatomas)

+ 3% in diet [134]

Long-term carcinogenesis assay, infant

mice (hepatomas)

+ 3 mg/mouse (total dose) [16,134]


rats

?(x2.6) 200 mg/kg/day � 12 days [16]



+ NR [134,135]


Dawley female rats

? NR [135]

Long-term carcinogenesis assay, Syrian

hamsters

? NR [134,135]

Humans: thyroid tumours +, � [134]

226. Guanabenz(5051-62-7)

Long-term carcinogenesis assay, mice �(x1) 11.5 mg/kg/day [18]


227. Guanadrel(40580-59-4)



(interstitial testes tumours)

+ 100 mg/kg/day [10]


rats

�(x15.2) 100 mg/kg/day [10]

228. Guanfacine(29110-47-2)

Long-term carcinogenesis assay, mice �(x12) 150 � MRHD [18]

Long-term carcinogenesis assay, rats �(x16.5) 100 � MRHD [18]




229. Haloperidol(52-86-8)


male mice

�(x0.3) 5 mg/kg/day [9]


female mice (mammary and pituitary

tumours)

+ 5 mg/kg/day [9]


rats

�(x0.6) 5 mg/kg/day [9]

230. Hydralazine(86-54-4)


mice (lung tumours)

+ 0.125% in dr. wt. [10,136]

(Group 3) Long-term carcinogenesis assay, Sprague-

Dawley rats

�(x1.7) 0.035% in diet [137]



(+) 60 mg/kg/day [135]


rats (liver neoplastic nodules)

(+) 30 mg/kg/day [135]

Humans: breast cancer � [138]


Colorectal cancer (+) [139]

231. Hydrochlorothiazide(58-93-5)

(Group 3)



?(x12) 5000 ppm in diet [18,25,36,140,141]


female mice

�(x12) 5000 ppm in diet [18,25,36,140,141]

Long-term carcinogenesis assay, F344 rats �(x4.9) 1000 ppm in diet [25,36,142]

Long-term carcinogenesis assay, F344 rats �(x9.8) 2000 ppm in diet [18,25,36,142]


232. Hydroxyurea(127-07-1)

Long-term carcinogenesis assay, XVII/G

newborn mice

� 10 mg/mouse/day ip [13]


Squamous cell carcinoma (+) [143]

233. Hyoscine(51-34-3)


mice

� 25 mg/kg/day [25,144]

Long-term carcinogenesis assay, F344 rats � 25 mg/kg/day [25,144]

234. Ibandronate(114084-78-5)


mice

� 40 mg/kg/day [18]


male mice

� 80 mg/kg/day [18]


female mice (adrenal tumours)

+ 80 mg/kg/day [18]


rats

� 15 mg/kg/day [18]

235. Ibuprofen(15687-27-1)


male rats

�(x0.06) 16 mg/kg/day [25]






236. Imiquimod(99011-02-6)


(liver tumours)

+ 5 mg/kg on skin � 3/week [9]

Long-term carcinogenesis assay, rats � 6 mg/kg po � 2/week [9]

237. Indapamide(268807-65-8)




238. Indinavir(150378-17-9)

Long-term carcinogenesis assay, mice � NR [9,10]


(thyroid adenomas)

+ 640 mg/kg/day [9,10]


rats

�(x1) 640 mg/kg/day [9,10]

239. Indomethacin(53-86-1)




Long-term carcinogenesis assay, F344 rats �(x0.11) 2 mg/kg in diet [25]


Dawley female rats (mammary tumours)

+ 0.89 mg/kg/day in dr. wt. [25]






Bladder cancer (+) [145]

240. Ipratropium(22254-24-6)






241. Irbesartan(138402-11-6)


Long-term carcinogenesis assay, male rats �(x16.2) 500 mg/kg/day [9,18]


rats

� 1 g/kg/day [9,18]

242. Irinotecan(97682-44-5)



+ 2–25 mg/kg/rat/week iv � 13

weeks

[9]

243. Irsogladine(57381-26-7)

Long-term carcinogenesis assay, male rats � 4 mg/kg/day [25]

244. Isoniazid(54-85-3)

(Group 3)

Long-term carcinogenesis assay, male mice ? NR [146]

Long-term carcinogenesis assay, AKR mice ?(x1.6) 200 mg/kg/day po [146]


female mice (lung tumours)

+ NR [146]


mice

? NR [146]


male mice (lung tumours)

+ NR [146]

Long-term carcinogenesis assay, CBA mice

(lung tumours)

+ 34 mg/kg/day po [25,146]

Long-term carcinogenesis assay, C1 albino

mice

? NR [146]

Long-term carcinogenesis assay, C3H black

mice

?(x1.6) 200 mg/kg/day [146]

Long-term carcinogenesis assay, dd male

mice

? NR [146]


female mice

+ 100 mg/kg/day po [146]


female mice

? NR sc [146]


mice (lung tumours)

+ 83–200 mg/kg/day po [146]


mice transplacental (lung tumours)

+ NR po [146]


Swiss mice (lung tumours)

+ 37 mg/kg/day [146]


Swiss mice

? NR po [146]


Swiss mice

? NR sc [146]

Long-term carcinogenesis assay, SWR mice ? NR ip [146]

Long-term carcinogenesis assay, dd mice + 0.06% in diet [25]

Long-term carcinogenesis assay, Osborne-

Mendel rats

? NR ip [146]

Long-term carcinogenesis assay, rats �(x0.5) 30 mg/kg/day po [25]

Long-term carcinogenesis assay, Cb/Sc rats

(lung and mammary tumours)

+ 99–149 mg/kg/day po [25]


hamsters

? 0.3% in dr. wt. [146]

Long-term carcinogenesis assay, hamsters ? 0.25% in dr. wt. [25]

Humans: cancer at any site �, �, �, ? [17,147–149]

Esophageal cancer (+) [149]

245. Isonixin(57021-61-1)


Dawley rats

� 1.6 g/kg/day � 6 months [150]


rabbits

� 2 g/kg/day [150]

246. Isophosphamide(3778-73-2)

(Group 3)


hybrid mice (lymphomas)

+ 0.2–2 mg/mouse sc every 7

weeks

[60]


mice (various types of tumours)

+ 10 mg/kg � 3/week ip [60]


mice (lung tumours)

+ 18.8 mg/kg � 3/week ip � 8

weeks

[60]


Dawley rats (various types of tumours)

+ 6–12 mg/kg � 3/week ip [60]

247. Isosorbide mononitrate(16051-77-7)


Long-term carcinogenesis assay, rats � 500–900 mg/kg/day [10,18]

248. Isotretinoin(4759-48-2)


(pheochromocytomas)

(+) 8–32 mg/kg/day [10,18]

249. Isradipine(75695-993-1)


male mice (hepatocellular carcinomas)

? 80 mg/kg/day [9,18]


female mice

� 80 mg/kg/day [9,18]


male rats (testes interstitial tumours)

(+) 12.5 mg/kg/day [9,18]





female rats

� 62.5 mg/kg/day [9,18]


250. Itraconazole(84625-61-6)



(soft tissue sarcomas)

(+) 25 mg/kg/day [9]


rats (lung carcinomas)

(+) 50 mg/kg/day [9]

251. Ketoprofen(22071-15-4)



male rats

�(x0.5) 8 mg/kg/day [25]







252. Ketorolac(74103-06-3)








253. Labetalol(36894-69-6)




254. Lamivudine(131086-21-0)



255. Lamotrigine(84057-84-1)




256. Lansoprazole(103577-45-3)


male mice (liver and testes tumours)

+ 75–300 mg/kg/day [9,10]


female mice (liver tumours)

+ 150 mg/kg/day [9]

Long-term carcinogenesis assay Sprague-

Dawley male rats (gastric and testes

tumours)

+ 15–150 mg/kg/day [9]


Dawley female rats (stomach tumours)

+ 15–150 mg/kg/day [9]


rats (stomach tumours)

+ NR [10]

257. Leflunomide(75706-12-6)


(lymphoma)

+ 15 mg/kg/day [9,10]


258. Letrozole(112809-51-5)


(liver and ovary tumours)

+ 0.6–60 mg/kg/day [9]


(ovary tumours)

+ 10 mg/kg/day [9]

259. Leuprolide(53714-56-0)


(pituitary tumours)

+ 60 mg/kg/day [9]


(pancreas, pituitary and testes tumours)

+ 0.6–4 mg/kg/day [9]

260. Levetiracetam(102767-28-2)


Long-term carcinogenesis assay, rats �(x4.9) 1.8 g/kg/day [18]

261. Levobunolol(47141-42-4)


male mice

� 200 mg/kg/day [151]


female mice (uterus leiomyomas)

(+) 200 mg/kg/day [151]


rats

� 180 mg/kg/day [151]

262. Levodopa(59-92-7)

Long-term carcinogenesis assay, rats �(x0.65) MRHD � 4 [9]

263. Levofloxacin(100968-85-4)


264. Lisinopril(76547-98-3)

Long-term carcinogenesis assay, mice �(9.5) 135 mg/kg/day [9,18]






265. Lofexidine(31036-80-3)


266. Loperamide(53179-11-6)

Long-term carcinogenesis assay, rats � MRHD � 133 [9]

267. Loratadine(79794-75-5)


(liver tumours)

+ 40 mg/kg/day [10]


mice

�(x19.2) 40 mg/kg/day [10]


(liver tumours)

+ 10 mg/kg/day [10]



+ 25 mg/kg/day [10]

Humans cancer at any site � [14]

268. Lorazepam(846-49-1)

Long-term carcinogenesis assay, CD rats � 0.48% in diet [152]

269. Lornoxicam(70374-39-9)


Dawley rats

�(x0.2) 0.25 mg/kg/day [153]


270. Losartan(114978-26-4)


Long-term carcinogenesis assay, male rats � 270 mg/kg/day [9,10,18]


rats (pancreas adenomas)

? 270 mg/kg/day [9,10,18]

271. Lovastatin(75330-75-5)

Long-term carcinogenesis assay mice

(liver, lung and stomach tumours)

+ 500 mg/kg/day [9,36,154]


and thyroid tumours)

+ 30–180 mg/kg/day [9,36,154]


Long-term carcinogenesis assay, monkeys � 60 mg/kg/day [154]




272. Lubiprostone(136790-76-6)


mice

�(x4.2) 0.5 mg/kg/day [18]


Dawley male rats (testes adenomas)

+ 0.4 mg/kg/day [18]


Dawley female rats (hepatocellular

adenomas)

+ 0.4 mg/kg/day [18]

273. Lynestrenol(52-76-6)

(Group 2B)


mice (liver and mammary tumours)

+ 200–400 MRHD/kg/day [83,84]



+ 200–400 MRHD/kg/day [83,84]

Humans ? [17,84]

274. Manidipine(126229-12-7)

Long-term carcinogenesis assay, ICR mice �(x11.2) 40 mg/kg/day [25,155]

Long-term carcinogenesis assay, CD-1 rats �(x3.4) 6 mg/kg/day [25,156]

275. Medroxalol(70161-10-3)


male mice

�(x3.1) 500 mg/kg/day [157]


female mice (uterine leiomyomas)

+ 250 mg/kg/day [158]

Long-term carcinogenesis assay, Long

Evans rats

�(x6.3) 500 mg/kg/day [157]

276. Medroxyprogesterone(71-58-9)

(Group 2B)

Long-term carcinogenesis assay, Marsh

female mice

� 5 mg/mouse � 2 im [83,84]


mice (pancreas tumours)

+ 1–5 mg/kg/day [83,84]


beagle dogs (mammary tumours)

+ 62.5 mg/kg every 3 months [84]

Humans: breast, ovary and uterus tumours ? [159]

277. Mefloquine(53230-10-7)



278. Megestrol(595-33-5)

Long-term carcinogenesis assay, rats � NR [17,84]


beagle dogs (mammary tumours)

+ 0.1 mg/kg/day [17,84]

279. Meloxicam(71125-38-7)


Long-term carcinogenesis assay, rats �(x1.2) 0.8 mg/kg/day [9,25]









280. Melphalan(148-82-3)

(Group 1)


(lung adenomas and skin papillomas)

+ 0.001–0.1% sol. on the skin,

10 weekly applications

[17,160]


(lung tumours)

+ 0.27 mg/kg � 3/week ip � 4

weeks

[17,160]


mice (lung tumours)

+ 0.75 mg/kg ip � 6 months [17,160]

Long-term carcinogenesis assay, rats CD

(peritoneal sarcomas)

+ 0.9 mg/kg � 3/week ip � 6

months

[17,160]

Humans: leukaemias +, + [99,100]

281. Memantine(19982-08-2)


Long-term carcinogenesis assay, rats �(x17) 20–40 mg/kg/day [9]

282. Mephobarbital(115-38-8)


(liver tumours)

+ NR [9]


tumours)

+ NR [9]

283. Mepyramine(91-84-9)


mice

�(x9.6) 1500 ppm in diet [161]


Dawley female rats

�(x13) 1000 ppm in dr.wt. [10,162]


Long-term carcinogenesis assay, F344 rats � 2000 ppm in dr.wt. [164]



tumours)

+ NR [92]

284. Mequinol(170-96-3)


mice

� 80 mg/kg/day on skin [9]

285. 6-Mercaptopurine(50-44-2)

(Group 3)

Long-term carcinogenesis assay, mice � 10 mg on skin � 3/week 10

applications

[17,60]

Long-term carcinogenesis assay, C57BL

newborn mice (thymic lymphomas)

+ 20 mg/kg/week ip � 10 times [17,60]


(leukaemias and lymphomas)

+ 15–30 mg/kg � 3/week ip � 6

months

[17,60]


female rats

? 2.5–25 mg/week sc � 26

weeks

[17,60]

Long-term carcinogenesis assay, BR46

male rats (benign tumours)

(+) 16.5 mg/kg/week ip � 52

weeks

[17,60]


286. Mesalazine(89-57-6)

Long-term carcinogenesis assay, mice �(x4.7) 2 g/kg/day [9]


mice

�(x5.8) 2.5 g/kg/day [9]


rats

�(x1.5) 320 mg/kg/day [9]


rats

�(x2.3) 480 mg/kg/day [9]

287. Mesoridazine(5588-33-0)




288. Mestranol(72-33-3)

(Group 1)


MTV� female mice (cervix carcinomas)

+ 10–12.5 mg/mouse/day [83,84]


(C3H � RIII)F1 MTV+ castrated male mice

(mammary tumours)

(+) 30–40 mg/mouse/day [83,84]


MTV� female mice (chromophobe

adenomas)

+ 20 mg/kg of diet [83,84]


MTV+ female mice (cervix and vagina

tumours)

(+) 20 mg/kg of diet [83,84]


MTV� female mice (cervix and vagina

tumours)

(+) 10–12.5 mg/mouse/day [83,84]


(C3H � RIII)F1 male mice (mammary

tumours)

+ 1 mg/kg of diet [83,84]

Long-term carcinogenesis assay, (C3H

xRIII)F1 male mice (mammary tumours)

+ 75 mg/kg of diet [83,84]



+ NR [83,84]


Webster and CF-LP mice

� 200 mg/kg/day [83,84]





MTV+ mice (mammary tumours)

+ 0.1 mg/mouse � 2/week � 20

months

[83,84]


female rats

� 3 mg/rat � 6/week � 50

weeks

[83,84]


(mammary tumours)

+ NR � 104 weeks po [83,84]


Syrian golden hamsters

� 34 mg/kg � 3/week [83,84]

Long-term carcinogenesis assay, dogs ? 0.5 mg/kg/day [83,84]

Long-term carcinogenesis assay, monkeys ? 1 mg/day [83,84]

289. Metaproterenol(5874-97-5)


mice (ovary tumours)

+ 320–640 MRHD/day [9]


rats (ovary leiomyomas)

(+) 640 MRHD/day [9]

290. Metformin(657-24-9)

Long-term carcinogenesis assay, mice �(x2.4) 1.5 g/kg/day [10,135]



rats (uterus polyps)

+ 900 mg/kg/day [10,135]

291. Methadone(76-99-3)


mice

�(x9.6) 60 mg/kg/day [18,165]


male rats

�(x15) 46 mg/kg/day [18,165]


female rats

� 88 mg/kg/day [18,165]

292. Methapyrilene(91-80-5)


(liver tumours)

+ 125 ppm in diet [164]


Dawley rats

� 1000 ppm in diet [162]


(liver tumours)

+ 0.1% in diet [166]

293. Methimazole(60-56-0)

(Group 3)

Long-term carcinogenesis assay, C3H mice �(x8) 35–500 mg/l in dr. wt. [134]

Long-term carcinogenesis assay, C3H mice

(thyroid adenomas)

+ 250–500 mg/l in dr. wt. and

low iodine diet

[134]


(thyroid tumours)



294. Methotrexate(59-05-2)


mice (haemangiomas, lymphomas and

lung tumours)

+ 3–10 mg/kg of diet [17,60]

(Group 3) Long-term carcinogenesis assay, XVII/Bln

male mice (lung tumours)

+ 0, 1 mg/kg in dr. wt. [17,60]


Webster mice

? 0.5–1 mg/kg � 3/week � 6

months

[17,60]


Dawley rats

? 0.625 mg/kg ip weekly [17,60]


Dawley CD male rats (pituitary and testes

tumours)

(+) 0.15–0.3 mg/kg ip � 3/

week � 6 months

[17,60]


Dawley CD female rats (adrenal, mammary

and pituitary tumours)

? 0.15–0.6 mg/kg ip � 3/

week � 6 months

[17,60]



(+) 1 mg/kg/week iv � 52 weeks [17,60]


golden hamsters

? 20 mg/kg of diet [17,60]

Humans: non-melanoma skin cancer (+) [17]

295. Methoxsalen(298-81-7)

(Group 1)

Long-term carcinogenesis assay, mice of

various strains

� 1 g/kg of diet [95]


Swiss mice

� 0.4 mg/mouse/day � 10

months ip

[95]


296. Methyldopa(555-30-6)


male mice (kidney tumours)

?(x1.5) 6300 ppm in diet [9,10,25,167]


female mice

�(x3) 12,500 ppm in diet [9,10,25,167]

Long-term carcinogenesis assay, F344 rats �(x3) 6300 ppm in diet [9,10,25,167]

297. Methylphenidate(113-45-1)

Long-term carcinogenesis assay, B6C3H1


+ 60 mg/kg/day [9,10,25,168]

Long-term carcinogenesis assay, p53 +/�transgenic mice

�(x6.9) 60–74 mg/kg/day [9,10,168]

Long-term carcinogenesis assay, F344 rats �(x8.5) 45 mg/kg/day [9,10,25,168]




298. Methylthiouracil(56-04-2)

(Group 2B)

Long-term carcinogenesis assay, C3H/FIB


+ 1 g/l in dr. wt. and low iodine

diet

[134]

Long-term carcinogenesis assay, Long-

Evans female rats (thyroid carcinomas)

+ 2.5 mg/rat/day and low

iodine diet

[134]


FBI rats (thyroid tumours)

+ 0.1–0.25% in dr. wt. [134]

Long-term carcinogenesis assay, random-

bred rats (thyroid tumours)

+ 0.1% in dr. wt. [134]

Long-term carcinogenesis assay, hamsters

(thyroid adenomas)

+ 0.2% in dr. wt. [134]

Humans: brain, oral and thyroid cancers ? [134]

299. Metolazone(1756051-9)




300. Metoprolol(54163-88-1)


male mice

�(x9) 750 mg/kg/day [9,18]


female mice (lung adenomas)

(+) 750 mg/kg/day [9,18]


mice

�(x9) 750 mg/kg/day [9,18]


301. Metronidazole(443-48-1)

(Group 2B)


mice (lung tumours)

+ 0.06% in diet [58]


Dawley weanling female rats (mammary

tumours)

? 0.135% in diet [58]

Humans: lung and cervix tumours ? [17]

Cancer at any site (+), ?, ?, � [101,169–171]

302. Mexiletine(318-2871-4)



303. Mibefradil(116644-53-2)


Long-term carcinogenesis assay, rats (oral

cavity squamous carcinoma)

?(x3.4) 35 mg/kg/day [18]

304. Midazolam(59467-70-8)


(liver tumours)



(thyroid tumours)

+ 80 mg/kg/day [10]


305. Midodrine(4279476-3)

Long-term carcinogenesis assay, mice � 4 MRHD/kg/day [9,18]


306. Minocycline(10118-90-8)


(thyroid tumours)

+ NR po [9]

307. Minoxidil(30304-91-5)


(liver nodules)



mice (malignant lymphomas)


Long-term carcinogenesis assay, male mice �(x9) 80 mg/kg/day dermal study [18]



+ 8 mg/kg/day dermal study [10,18]

Long-term carcinogenesis assay, rats � 15 MRHD/kg/day po [10,18]


(pheochromocytomas and preputial gland

adenomas)

+ NR dermal study [10,18]

308. Mirtazapine(61337-67-5)


(liver tumours)

+ 200 mg/kg/day [18]


mice

�(x21.3) 200 mg/kg/day [18]


(liver and thyroid tumours)

+ 60 mg/kg/day [18]



+ 20 mg/kg/day [18]


Ovarian cancer �, �, (+) [19,32,40]

309. Misoprostol(59122-46-2)


mice

� 16 mg/kg/day [18,25]

Long-term carcinogenesis assay, rats � 2.4 mg/kg/day [18,25]

310. Mitoxantrone(65271-80-9)

(Group 2B)


(liver tumours)

+ 0.1 mg/kg iv every 3 weeks [9,13]


(auditory canal tumours)

+ 0.3 mg/kg iv every 3 weeks [9,13]




Humans: leukaemias (+) [9]

311. Moclobemide(71320-77-9)



312. Modafinil(68693-11-8)

Long-term carcinogenesis assay, mice ?(x1.4) 60 mg/kg/day [9]


313. Moexipril(103775-10-6)


Webster mice

�(x7.2) 75 mg/kg/day [9,18,172]


Dawley rats

�(x14.6) 75 mg/kg/day [9,18,172]


314. Mometasone(105102-22-5)

Long-term carcinogenesis assay, Swiss CD-

1 mice

�(x2) 160 mg/kgday � inhalation [9]


Dawley rats

�(x2) 67 mg/kg/day � inhalation [9]

315. Montelukast(158966-92-8)



Dawley rats

� 200 mg/kg/day [9]

316. Morphine(57-27-2)


mice

�(x0.07) 10 mg/kg/week po [173]

Long-term carcinogenesis assay, CBA mice ?(x0.6) 0.3 mg/mouse sc [173]


mice

�(x0.04) 0.06 mg/mouse on skin [173]


golden hamsters

? 0.284 mg/hamster

intratracheal

[173]

317. Mycophenolate mofetil(116680-01-4)



Humans: lymphomas and skin tumours (+) [9]

318. Nabumetone(42924-53-8)








319. Nadolol(4220033-9)


mice

�(x3.8) 500 mg/kg/day [174]

Long-term carcinogenesis assay, CD rats �(x15.2) 1 g/kg/day [174]

320. Nafenopin(3771-19-5)


F344 rats (liver tumours)

+ 40 mg/kg/day [25]


Sprague-Dawley rats (pancreas tumours)

+ 20 mg/kg/day [25]



+ 100 mg/kg/day [25]


hamsters

� 230 mg/kg/day [25]

321. Nalbuphine(4394-00-7)



322. Naltrexone(16590-41-3)


(mesotheliomas and vascular tumours)

+ NR [18]

323. Naproxen(2220453-1)







324. Naratriptan(121679-13-8)



(thyroid adenomas)

+ 90 mg/kg/day [9]

325. Nateglinide(105816-04-4)


mice

�(x4.1) 400 mg/kg/day [9]


Dawley rats

�(x19) 900 mg/kg/day [9]

326. Nedocromil(69049-73-6)


rats

�(x17.4) 24 mg/kg/day [18]

327. Nefazodone(83366-66-9)




Ovarian cancer �, �, (+) [19,32,40]




328. Nelfinavir(159984-64-7)

Long-term carcinogenesis assay, mice �(x9) 1 g/kg/day [9]


(thyroid tumours)

+ 300 mg/kg/day [9]


mice (thyroid tumours)

+ 1 g/kg/day [9]

329. Nevirapine(129618-40-2)


(liver tumours)

+ 50 mg/kg/day [9,10]



+ 375 mg/kg/day [9,10]


(liver tumours)

+ 3.5 mg/kg/day [9,10]



+ 35 mg/kg/day [9,10]

330. Niacinamide(59-67-6)

Long-term carcinogenesis assay, mice �(x8) 1% in dr.wt. [9]

331. Nicardipine(55985-32-5)



(thyroid tumours)

+ 15 mg/kg/day [9,18]

Long-term carcinogenesis assay, dogs �(x7.3) 25 mg/kg/day [18]


332. Nifedipine(21829-25-4)



rats

� 210 mg/kg/day [9,175]


333. Nilutamide(63612-50-0)



+ 45 mg/kg/day [9]

334. Nimodipine(66085-59-4)

Long-term carcinogenesis assay, male mice �(x7.3) 546 mg/kg/day [9,18,175]


mice

�(x10.3) 774 mg/kg/day [9,18,175]



?(x2.5) 91 mg/kg/day [9,18,175]


rats (uterus adenocarcinonas)

?(x3.3) 121 mg/kg/day [9,18,175]

335. Nisoldipine(63675-72-9)


(stomach papillomas)

?(x19.6) 163 mg/kg/day [9,18,175]


mice

� 217 mg/kg/day [9,18,175]

Long-term carcinogenesis assay, male rats �(x20) 82 mg/kg/day [9,18,175]


rats

� 111 mg/kg/day [9,18,175]

336. Nitrendipine(39562-70-0)

Long-term carcinogenesis assay, male mice � 410 mg/kg/day [175]


mice

� 509 mg/kg/day [175]



rats

� 166 mg/kg/day [175]

337. Nitrofurantoin(67-20-9)

Long-term carcinogenesis assay, BDF1

mice

� 3 g/kg of diet [36]


male mice (lymphomas)



female mice

� 200 mg/kg of diet [36]


mice (ovary and tubular tumours)

+ 2.5 g/kg of diet [36]


female mice

� 500 mg/kg/day [36]

Long-term carcinogenesis assay, ICR/Jcl

offspring of pregnant mice (lung adenoma)

(+) 75 mg/kg sc � 3 times in

mothers

[36]


Dawley weanling female rats

� 1870 ! 1000 mg/kg of

diet � 72 weeks

[36]


Dawley weanling male rats (mammary

tumours)

(+) 1870 mg/kg of diet � 104

weeks

[36]


male rats (kidney adenomas)

(+) 1300 mg/kg of diet [36]

Humans: female genital tract and nervous

system tumours

? [36]

bladder tumours �, � [36,102]

338. Nitrofurazone(59-87-0)


male mice

� 310 mg/kg of diet [36]


female mice (ovary tumours)






offspring of pregnant mice

� 75 mg/kg sc � 3 times in

mothers

[36]


newborn mice (lung tumours)

(+) 75 mg/kg sc � 3 times in

mothers and � 4 times after

birth

[36]



+ 1 g/kg of diet [36]


(mammary and testes tumours, and

leukaemias)



339. Nitroglycerin(55-63-0)



(hepatocarcinomas and testes interstitial

tumours)

+ 434 mg/kg/day [9,18]


tumours)

+ 1% in diet [176]


340. Nizatidine(76963-41-2)

Long-term carcinogenesis assay, male mice � 2 g/kg/day [9]



(+) 2 g/kg/day [9]


341. Norethisterone(68-22-4)

(Group 2B)



+ 200–400 MRHD/kg/day [83,84]


CF-LP mice (pituitary tumours)

+ 200–400 MRHD/kg/day [83,84]


(liver and mammary tumours)

+ 200–400 MRHD/kg/day [83,84]

Humans: liver tumours (+) [84]

342. Norethynodrel(68-23-5)

(Group 2B)


Humans: liver tumours

(+)

+

200–400 HD [83,84]

343. Norfloxacin(70458-96-7)

Long-term carcinogenesis assay, rats � 8–9 HD/day [9]

344. d-Norgestrel(797-63-7)

(Group 2B)


mice

� 200–400 MRHD/kg/day [83,84]



+ 0.5 mg/kg/day [83,84]


Humans: liver tumours (+) [84]

345. Octreotide(83150-76-9)



(tumours at the injection site and uterus

tumours)

+ 1.25 mg/kg/day sc [9]

346. Oestradiol(50-28-2)

(Group 1)



+ 0.5 mg/l in dr. wt. [83]


MTV+ mice (mammary tumours)


Long-term carcinogenesis assay, Strong A

male mice (testes tumours)

+ 50 mg/week sc � 6 months [83]

Long-term carcinogenesis assay, C57

MTV�� CBA MTV+ mice (lymphoid,

mammary and pituitary tumours)

+ 16.6–50 mg/week

sc � lifespan

[83]

Long-term carcinogenesis assay, RIII MTV+

male mice (mammary tumours)

+ 50 mg/week sc � 20 weeks [83]

Long-term carcinogenesis assay, Marsh-

Buffalo MTV+ female mice (lymphoid

tumours)

+ 80 mg � 2/week sc or im � 6

months

[83]

Long-term carcinogenesis assay, C3H � PM

female mice (cervix tumours)

+ 16.6 mg/week [83]


C57 � CBA female mice (cervix and

mammary tumours)

+ 16.6–50 mg/week [83]


(C3H � RIII)F1 MTV+ castrated male mice

(mammary tumours)

+ 0.5–1 mg pellet sc [83]


male mice (thymic lymphosarcomas)

+ 1–2 mg pellet sc [83]


female mice (cervix and/or vagina

tumours)

+ 5 mg pellet sc [83]





(C3H � RIII)F1 MTV+ castrated mice

(mammary tumours)

+ 0.64 mg pellet sc [83]


mice (vaginal hyperplastic lesions)

(+) 5 mg/day � 5 days [83]


cfC3H MTV+ newborn mice (mammary

tumours)

+ 5 mg/day � 5 days [83]


MTV� female mice (mammary dysplasias)

? 40 mg/day � 5 days [83]





rats (pituitary tumours)



ovariectomized guinea-pigs (fibromas)

+ 20–80 mg � 3/week [83]


guinea-pigs (abdomen, spleen and

stomach tumours)

+ 80 mg � 3/week sc [83]


ovariectomized guinea pigs (uterus and

mesentery fibromyomas)

+ 20–50 mg pellet [83]


(kidney tumours)

+ 1 or more 20 mg pellet sc

every 21 weeks

[83]


monkeys

� 575–825 mg pellet sc every

5–6 weeks

[83]


347. Oestriol(50-27-1)

(Group 1)


(C3H � RIII) F1 MTV+ castrated mice

(mammary tumours)

+ 0.64–0.85 mg pellet sc [83]


(kidney tumours)

+ 20 mg pellet sc every 150

days

[83]

Humans: ? [84]

348. Oestrone(53-16-7)

(Group 1)


MTV� gonadectomized male mice

(mammary tumours)

+ 0.125 mg/l in dr. wt. [83]


(C3H � RIII) F1 MTV+ castrated male mice

(mammary tumours)

+ 6 mg/mouse/day [83]



+ 0.01% sol. on skin � 2/

week � 16 weeks

[83]



+ 0.6 mg/mouse/week by

injection for more than 5

months

[83]

Long-term carcinogenesis assay, A MTV+


(+) 30–50 mg/week sc � 43

weeks

[83]

Long-term carcinogenesis assay, CBA

MTV� male mice

� 30–50 mg/week sc � 43

weeks

[83]


MTV+ male mice (mammary tumours)

(+) 50 mg/week sc � 24 weeks [83]

Long-term carcinogenesis assay, A and C3H





+ 50–200 mg/day by injection [83]

Long-term carcinogenesis assay, rats of

various strains (mammary tumours)



Copenhagen rats (bladder cancers)



rats of various strains (mammary tumours)



male golden hamsters (kidney tumours)

+ NR [83]

Long-term carcinogenesis assay, intact and

castrated male Syrian hamsters (kidney

tumours)



349. Olanzapine(132539-06-1)




+ 3 mg/kg/day [9]




+ >2 mg/kg/day [9]




+ 8 mg/kg/day [9]




350. Olmesartan(144689-24-7)


knockout mice

� 1 g/kg/day [9,18]

Long-term carcinogenesis assay, Hras2

transgenic mice

� 1 g/kg/day [9,18]


351. Olopatadine(113806-05-6)



352. Olsalazine(605498-4)

Long-term carcinogenesis assay, male CD-

1 mice (liver tumours)

?(x9.6) 2 g/kg/day [9]


CD-1 mice

�(x9.6) 2 g/kg/day [9]


Wistar rats (urinary bladder carcinomas)

(+) 0.8 g/kg/day [9]


Wistar rats

�(7.8) 0.8 g/kg/day [9]

353. Omeprazole(73590-58-6)


mice

? NR [9,25]


transgenic mice

� NR [9]


(gastric carcinoids)

+ 1.7–140.8 mg/kg/day [9]


rats

�(x1.1) 13.8 mg/kg/day [9]


Sprague-Dawley rats (ECL cells carcinoids

and brain astrocytomas)

(+) 0.4–16 mg/kg/day [9,25]


Sprague-Dawley rats

�(x1.3) 0.4–16 mg/kg/day [9,25]

Humans: gastric cancer � [177]

354. Ondansetron(99614-02-5)



355. Orciprenaline(586-06-1)

Long-term carcinogenesis assay, male mice � 640 � MRHD [9]


mice (ovarian tumours)

+ 320 � MRHD [9]

Long-term carcinogenesis assay, male rats � NR [9]


(hepatic adenomas)

+ NR [10]


rats

? 640 � MRH D [9]

356. Orlistat(96829-58-2)


Long-term carcinogenesis assay, rats � 1 g/kg/day [9]

357. Oseltamivir(196618-13-0)

Long-term carcinogenesis assay, FVB/

Tg:AC transgenic mice

� 780 mg/kg/day [9]

358 Oxaprozin(21256-18-8)



+ NR [18]


mice

� NR [18]







359. Oxazepam(604-75-1)

(Group 2B)



+ 2500 ppm in diet [109,178]



+ 2500 ppm in diet [178,179]

Long-term carcinogenesis assay, F344/N

rats (kidney adenomas)

+ 2500 ppm in diet [180,181]


360. Oxcarbazepine(28721-07-5)



+ 100 mg/kg/day [9]


(liver and testes tumours)

+ >250 mg/kg/day [9]


rats (liver and vagina tumours)

+ >25 mg/kg/day [9]

361. Oxprenolol(6452-71-7)

Long-term carcinogenesis assay, CF1 mice �(x2.6) 150 mg/kg/day [25,182]


362. Oxybutinin(5633-20-5)





363. Oxymetholone(434-07-1)


male rats

?(x4.9) 150 mg/kg/day [9,183]


female rats (various types of tumours)

+ 30–100 mg/kg/day [9,183]

Humans: liver tumours + [58]

364. Oxymorphone(76-41-11)


mice

� 150 mg/kg/day [184]

Long-term carcinogenesis assay, Crl:CD

IGS BR rats

� 25 mg/kg/day [184]

365. Palonosetron(135729-56-5)


mice

� 60 mg/kg/day [9]


Dawley male rats (adrenal, pancreas and

pituitary tumours)

+ 15–60 mg/kg/day [9]


Dawley female rats (liver and thymus

tumours)

+ 15–90 mg/kg/day [9]

366. Pamidronate(40391-99-9)



(pheochromocytomas)

+ HD [9,18]


rats

� NR [9,18]

367. Pantoprazole(138786-67-1)


transgenic mice

� NR [9,10]


male mice

�(x18) 150 mg/kg/day [9,10]



+ 150 mg/kg/day [9,10]


Dawley rats (stomach, liver and thyroid

tumours)

+ 50–200 mg/kg/day [9,10]


(stomach tumours)

+ 5–50 mg/kg/day [9,10]

368. Paracetamol(103-90-2)

(Group 3)

Long-term carcinogenesis assay, IF mice

(liver tumours)

+ 1 g/kg of diet [36]


mice

�(x1) 6 g/kg of diet [36]


mice

�(x1.6) 10 g/kg of diet [185]


Dawley male rats

?(x1.7) 5.53 g/kg of diet [185]

Long-term carcinogenesis assay, Leeds rats

(liver and bladder tumours)

(+) 5/10 g/kg of diet [185]


male rats

�(x2) 6 g/kg of diet [36]


female rats (leukaemias)

(+) 6 g/kg of diet [36]

Humans: kidney and urinary bladder

tumours

(+), �, (+), ?,

(+), (+), (+), �[185–188,

42–44,189]

Breast cancer � [41]

Ovarian cancer (+) [47]


Esophageal cancer � [45]

Pharynx cancer + [190]

Melanoma (+) [190]

369. Paroxetine(61869-08-7)



(reticulum cell sarcoma)

+ 20 mg/kg/day [9,10]


rats

�(x3.9) 20 mg/kg/day [9,10]

Humans: breast cancer ?, ?, ?, � [27,28,30]

Ovarian cancer ?, (+), � [19,20,32]



370. Pemoline(2152-334-3)


371. Penbutolol(38363-41-6)



372. Penicillamine(52-67-5)

Long-term carcinogenesis assay, NZB

hybrid mice (lymphocytic leukaemias)

+ 400 mg/kg � 5/week 9 [9]

373. Pentoxifylline(6493-05-6)






374. Pergolide(66104-22-1)

Long-term carcinogenesis assay, male mice � 36.4 mg/kg/day [9]


mice (uterus tumours)

+ 40.8 mg/kg/day [9]

Long-term carcinogenesis assay, male rats �(x2.9) 0.88 mg/kg/day [9]



+ 1.42 mg/kg/day [9]

375. Paricalcitol(131918-61-1)


CD-1 mice (uterus tumours)

+ 1–10 mg/kg sc [9]


(pheochromocytomas)

+ 0.15–1.5 mg/kg sc [9]

376. Perindopril(82834-16-0)




377. Phenacetin(62-44-2)

Long-term carcinogenesis assay, BD I and

BD III rats

? 40–50 mg/rat/day in diet [95]


Dawley female rats (mammary and ear

duct carcinomas)

+ 0.535% in diet [95]


Dawley rats (urinary tract and nasal cavity

tumours)

+ 1.25% in diet [95]

Humans: kidney and/or urinary tract

tumours

+, +, +, +,

+, +, +, +, ?

[17,44,58,99,102,

186,187,189,191]

378. Phenazopyridine(94-78-0)

(Group 2B)


mice

+ 0.6 g/kg in diet [95,192]

Long-term carcinogenesis assay, A/Hc mice � 1.55 g/kg/week ip [95,192]


(colon or rectum tumours)

+ 3.7 g/kg in diet [95,192]


379. Phenelzine(51-71-8)


male mice (lung and blood vessel tumours)

+ 0.015% in dr. wt. [95]


Dawley rats

�(x2.5) 0.02–0.035% in diet [137]


Breast cancer (+) [91]

380. Phenobarbital(50-06-6)

(Group 2B)


(liver tumours)

+ 0.05% in diet [134]

Long-term carcinogenesis assay, CF-1 mice

(liver tumours)

+ 0.05% in diet [134]

Long-term carcinogenesis assay, CF-1 mice

(liver tumours)

+ 0.05% in dr. wt. [134]


mice

�(x3.7) 0.05% in dr. wt. [134]

Long-term carcinogenesis assay, Avy/A


+ 0.05% in diet [134]


(liver tumours)

+ 0.02% in diet [134]

Long-term carcinogenesis assay, C3H mice ?(x3.1) 85 mg/kg/day [134]

Long-term carcinogenesis assay, C57BL/6

mice

?(x3.1) 85 mg/kg/day [134]

Long-term carcinogenesis assay, C-myc


+ 0.05% in diet [134]


p53 heterozygous mice

�(x3.7) 0.1% in diet [134]

Long-term carcinogenesis assay, MT42

transgenic mice (liver tumours)

+ 0.05% in dr. wt. [134]



+ 0.05% in dr. wt. [134]

Long-term carcinogenesis assay, F344 rats ?(x3.8) 0.05% in diet [134]

Long-term carcinogenesis assay, F344 rats ?(x7.5) 0.05% in dr. wt. [134]


Lung cancer ? [193]

381. Phenolphthalein(77-09-8)

(Group 2B)


mice (lymphomas and sarcomas)

+ 3–6 g/kg of diet [10,13,194]

Long-term carcinogenesis assay, p53 (+/�)

mice (lymphomas)

+ 3 g/kg of diet [10,13,194]


(lymphomas and pheochromocytomas)

+ 12.5 g/kg of diet [10,13,194]

Humans: colon tumours ? [10]

382. Phenoxybenzamine(59-96-1)

Long-term carcinogenesis assay, A/Hc mice

(lung tumours)

+ 40 mg/kg � 4 ip [195]





mice (peritoneal sarcomas)

+ 25 mg/kg � 3/week ip [196]


Dawley male rats (peritoneal sarcomas)

+ 5 mg/kg � 3/week ip [196]


Dawley female rats (peritoneal sarcomas)

+ 10 mg/kg � 3/week ip [196]

383. Phenylbutazone(50-33-9)

(Group 3)


male mice (hepatocellular adenomas)

+ 300 mg/kg/day [197]


female mice

� 300 mg/kg/day [197]



? 100 mg/kg/da y [197]


female rats

(+) 100 mg/kg/day [197]

Humans: lymphoproliferative

malignancies

? [17]

384. Phenytoin(57-41-0)

(Group 2B)

Long-term carcinogenesis assay, various

strains of female mice (lymphomas and

reticular cell sarcomas)

+ 60 mg/kg/day [109]

Long-term carcinogenesis assay, C3H mice �(x1.3) 2 mg/mouse [109]


mice

�(x0.2) 0.012% in diet [109]

Long-term carcinogenesis assay, C3H male

mice

�(x0.5) 300 ppm in diet [109]



+ 200 ppm in diet [109]


(liver tumours)

+ 210–300 ppm in diet

perinatal/adult exposure

[109]



+ 70–200 ppm in diet perinatal/

adult exposure

[109]

Long-term carcinogenesis assay, male mice �(x0.3) 210 ppm in diet perinatal

exposure

[109]


mice

�(x0.3) 210 ppm in diet perinatal

exposute

[109]


(liver tumours)

+ 0.6 mg/mouse ip � 66 days [109]


adult rats

�(x7.8) 2400 ppm in diet [109]



(+) 2400 ppm in diet perinatal/

adult exposure

[109]


female rats

�(x7.8) 2400 ppm in diet perinatal/

adult exposure

[109]

Long-term carcinogenesis assay, F344 rats �(x2) 630 ppm in diet perinatal

exposure

[109]

Humans: lymphomas +, � [19,101]

Brain and lung tumours, myelomas ? [19,101]

Liver tumours � [19,101]

Cancer at any site (+), (+) [19,101]

385. Pilocarpine(137071-32-0)


mice

�(x4.8) 30 mg/kg/day [9]


Dawley rats (liver adenomas and

phechromocytomas)

+ 18 mg/kg/day [9]

386. Pimecrolimus(137071-32-0)

Long-term carcinogenesis assay, mice � 4 mg/kg/day (dermal study) [9]


(lymphomas)

+ 25 mg/kg/day (dermal study) [9]


(lymphomas)



(thyroid adenomas)

+ 2 mg/kg/day (dermal study) [9]


(thymomas)



(thymomas)


387. Pimozide(2062-78-4)

Long-term carcinogenesis assay, male mice � NR [9]


mice (pituitary and mammary tumours)

+ NR [9]


388. Pindolol(13523-86-9)

Long-term carcinogenesis assay, mice � 100 MRHD/kg/day [10,135]


389. Pioglitazone(111025-46-8)






(urinary bladder tumours)

+ 4 mg/kg/day [9,10,18]


rats

�(x15.9) 63 mg/kg/day [9,10,18]

390. Pirazinamide(98-96-4)


male mice

�(x2.3) 10,000 ppm in diet [9,10]


391. Pirbuterol(38677-81-5)

Long-term carcinogenesis assay, mice �(x15) 10 mg/kg/day in diet [9]


Dawley rats

� 10 mg/kg/day in diet [9]

392. Piroxicam(36322-90-4)


female rats

�(x9.1) 16 mg/kg/day [25]






393. Polythiazide(346-18-9)

Long-term carcinogenesis assay, rats � MRHD � 100 [9,18]


394. Posaconazole(171228-49-2)




rats

�(x3.5) 20 mg/kg/day [18]

395. Potassium canrenoate(4138-96-9)


Dawley rats (myelocytic leukaemia)

+ 20 mg/kg/day [18]


396. Practolol Long-term carcinogenesis assay, Wistar

rats

� 300 mg/kg/day [198]

Long-term carcinogenesis assay, rodents (+) NR [21]

397. Pramipexole(104632-26-0)

Long-term carcinogenesis assay, Chbb/

NMRI mice

�(x8) 10 mg/kg/day [9]


rats

�(x13) 8 mg/kg/day [9]

398. Pravastatin(81093-37-0)


(liver and lung tumours)

+ 250 mg/kg/day [9]



+ 100 mg/kg/day [9]


rats

�(x24.3) 100 mg/kg/day [9]




399. Prazepam(2955-38-6)

Long-term carcinogenesis assay, CF1 mice �(x6) 75 mg/kg/day in diet [25,109]


rats

�(x12.2) 75 mg/kg/day in diet [25,109]

400. Praziquantel(55268-74-1)


Long-term carcinogenesis assay, golden

hamsters

� NR [9]

401. Prazosin(1923784-4)


402. Prednimustine(29069-24-7)


Dawley female rats (auditory canal

squamous cell carcinomas)

(+) 12 mg/kg po � 9/month [36]

403. Prednisolone(50-24-8)


Dawley male rats (liver tumours)

+ 40 mg/ml in dr. wt. [25]


Dawley female rats

�(x0.004) 468 mg/kg (total dose) [25]

404. Prednisone(53-03-2)

(Group 3)


mice

?(x2.3) 12–25 mg/kg/day [17,25,60]

Long-term carcinogenesis assay, ICR mice �(x0.5) 5 mg/kg/day [17,25,60,199]

Long-term carcinogenesis assay, Charles

River rats

?(x8.5) 22–45 mg/kg/day [17,25,60]

405. Pregabalin(148553-50-8)


and CD1 mice (haemoangiosarcomas)


406. Primidolol(67227-55-8)


male mice

� 50 mg/kg/day [200]


female mice

(+) 50 mg/kg/day [200]


407. Primidone(125-33-7)


mice (liver and thyroid tumours)

+ 600 ppm in diet [10,201]





male rats (kidney and thyroid tumours)

+ 1300 ppm in diet [10,201]


female rats

�(x4.9) 2500 ppm in diet [10,201]

408. Probenecid(57-66-9)


male mice

�(x1.9) 400 mg/kg/day [10,25,202]


female mice (liver adenomas)

(+) 100–400 mg/kg/day [10,25,202]


rats

�(x3.9) 400 mg/kg/day [10,25,202]

409. Procarbazine(366-70-1)

(Group 2A)

Long-term carcinogenesis assay, CD2 F1

mice (lung tumours and leukaemias)

+ 450–1800 mg/kg once or

258 mg/kg/week po � 8

weeks

[17,60]

Long-term carcinogenesis assay, albino


+ 300 mg/kg/week po � 8

weeks

[17,60]

Long-term carcinogenesis assay, CD F1

male mice (lung tumours and leukaemias)

+ 300 mg/kg/week po � 4–8

weeks

[17,60]


female mice (lung tumours and

leukaemias)

+ 2.58–10.24 mg/mouse po 1–5

times/week � 10 weeks

[17,60]

Long-term carcinogenesis assay, CD2 F1

mice (lung tumours)

+ 300 mg/kg once ip [17,60]



+ 300 mg/kg/week ip � 8 weeks [17,60]



+ 28.4 mg/mouse ip (total dose) [17,60]


Webster mice (lung, kidney, uterus

tumours and lymphomas)

+ 12–25 mg/kg � 3/week ip � 6

months

[17,60]


mice (lung, nervous system and

haematopoietic tumours)

+ 6 mg/kg � 3/week ip � 52

weeks

[17,60]



+ 50–150 mg/rat once or

50 mg/rat � 3 times po

[17,60]


Mendel female rats (mammary tumours)

+ 500 mg/kg/week po � 10

weeks

[17,60]



+ 50 mg/kg/week ip � 10 weeks [17,60]


Mendel female rats (mammary tumours)

+ 500 mg/kg once or 50 mg/kg/

week � 10 weeks ip

[17,60]

Long-term carcinogenesis assay, R female

rats (mammary, ear duct and uterus

tumours)

+ 15 mg/rat ip � 15 times [17,60]


Dawley CD rats (mammary tumours,

lymphomas and leukaemias)

+ 30–60 mg/kg � 3/week ip � 6

months

[17,60]


Dawley rats (neuroepithelial, mammary,

lymphoreticular and haematopoietic

tumours)

+ 30 mg/kg � 3/week ip � 26

weeks

[17,60]



+ 24 mg/kg/week iv � 52 weeks [17,60]

Long-term carcinogenesis assay, BD-IX

offspring rats (brain tumours)

+ 125 mg/kg iv in pregnant

mothers

[17,60]

Humans: acute nonlymphocytic leukaemia ? [17]

410. Progesterone(57-83-0)

(Group 2B)



+ 2.5 mg/mouse/week sc � 19

weeks

[83]

Long-term carcinogenesis assay, C3H � A

MTV+ mice (mammary carcinomas)

+ 14 mg pellet sc every 4

weeks � 104 weeks

[83]


mice (endometrium sarcomas)

+ 18–900 mg/day from sc

pellets

[83]


Crgl MTV� newborn female mice (genital

tract tumours)

+ 100 mg/mouse sc � 5 days [83]


female dogs

? 22.5 mg/day sc [83]

411. Promethazine(60-87-7)


male mice

�(x2.2) 45 mg/kg/day [10,25,203]


female mice

�(x0.7) 15 mg/kg/day [10,25,203]

Long-term carcinogenesis assay, F344 rats �(x3.2) 33.3 mg/kg/day [10,25,203]

412. Propafenone(54063-53-5)



413. Propranolol(525-66-6)


mice

�(x0.7) 100 mg/kg/day [16,25,204]






Evans rats

�(x0.6) 37.5 mg/kg/day [18,25,204]

Long-term carcinogenesis assay, rats �(x2.3) 150 mg/kg/day [9,18,25]

414 Propylthiouracil(51-52-5)

(Group 2B)

Long-term carcinogenesis assay, A male

mice (thyroid tumours)

+ 0.8% in diet [134]


mice (pituitary adenomas)

+ 10 g/kg of diet [25,134]


(thyroid tumours)

(+) 0.1% in dr. wt. [25,134]



+ 0.2–0.25% in dr. wt. [25,134]


Evans rats (thyroid tumours)

+ 0.1% in diet [25,134]


(thyroid tumours)

+ 0.006% in dr. wt. [25,134]


golden hamsters (thyroid tumours)

+ 0.2% in dr. wt. [25]


guinea pigs (thyroid tumours)

+ 0.03% in dr. wt. [25]

Humans: thyroid tumours ? [134]

415. Pyribenzamine(154-69-8)


Dawley rats

� 1000 ppm in dr. wt. 5 days/

week

[10,162]

416. Pyrimethamine(58-14-10)


B6C3F1 mice

� 1000 ppm in diet [10,205]


(lung tumours)

+ 25 mg/kg ip [10,205]

Long-term carcinogenesis assay, F344 rats � 400 ppm in diet 5 days/week [10,205]

Humans: ?

417. Quazepam(36735-22-5)

Long-term carcinogenesis assay, mice �(x22.4) 120 mg/kg/day po [206]

Long-term carcinogenesis assay, hamsters � 120 mg/kg/day po [206]


418. Quercetine(117-39-5)

(Group 3)

Long-term carcinogenesis assay, ddY mice � 2% in diet � 842 days [207]

Long-term carcinogenesis assay, A/JJms

mice

� 5% in diet � 23 weeks [207]

Long-term carcinogenesis assay, ICR/HA

Swiss female mice

� 25 mg/mouse on skin � 3/

week � 368 days

[207]

Long-term carcinogenesis assay, F344 rats � 0.1% in diet � 540 days [185]

Long-term carcinogenesis assay, F344/

DuCrj rats (caecum and colon tumours)

� 5% in diet � 104 weeks [185]


rats (kidney tumours)

(+) 40 g/kg of diet [185]


rats (intestinal and bladder tumours)

+ 0.1% in diet � 58 weeks [207]

Long-term carcinogenesis assay, ACI rats

(caecum tumours)

(+) 10% in diet � 850 days [207]

Long-term carcinogesis assay, female

golden hamsters

� 10% in diet � 735 days [207]


419. Quetiapine(111974-69-7)


male mice (thyroid adenomas)

+ 250 mg/kg/day [9]


female mice

�(x4.5) 750 mg/kg/day [9]


male rats (thyroid adenomas)

+ 250 mg/kg/day [9]


female rats (mammary adenocarcinomas)

+ 25 mg/kg/day [9]

420. Quinapril(85441-61-8)

Long-term carcinogenesis assay, mice �(x4.5) 75 mg/kg/day [9,10,18,25]

Long-term carcinogenesis assay, male rats �(x12.2) 100 mg/kg/day [9,10,18,25]


rats (mesenteric lymphonode

hemangiomas and skin subcutaneous

lipomas)

(+) 100 mg/kg/day [9,10,18,25]


421. Rabeprazole(117976-89-3)


mice

�(x4.7) 100 mg/kg/day [9,10]


Dawley male rats

�(x5.7) 60 mg/kg/day [9,10]


Dawley female rats (ECL cell carcinoid

tumours)

+ 5 mg/kg/day [9,10]




422. Raloxifene(84449-90-1)


(prostate and testes tumours)

+ 41–210 mg/kg/day [9]


mice (ovary tumours)

+ 9–242 mg/kg/day [9]


(ovary tumours)

+ 279 mg/kg/day [9]

423. Ramipril(87333-19-5)

Long-term carcinogenesis assay, mice � 1 g/kg/day [9,18]



424. Ranitidine(66357-35-5)



425. Rasagiline(136236-51-6)

Long-term carcinogenesis assay, CD1 mice

(lung tumours)

+ 15 mg/kg/day [18]


Dawley male rats

�(x20) 3 mg/kg/day [18]


Dawley female rats

� 17 mg/kg/day [18]

426. Repaglinide(135062-02-1)



(liver and thyroid adenomas)

+ 30–60 mg/kg/day [9]


rats

� 120 mg/kg/day [9]

427. Reserpine(50-55-5)

(Group 3)


male mice (seminal vesicles carcinomas)

+ 10 ppm in diet [17,25,95,209]


female mice (mammary carcinomas)

+ 5 ppm in diet [17,25,95,209]


male rats (adrenal pheochromocytomas)

+ 5 ppm in diet [17,25,95,209]


female rats

�(x16.2) 10 ppm in diet [17,25,95,209]

Humans: breast carcinomas (+) [17]

428. Ribavirin(36791-04-5)

Long-term carcinogenesis assay, p53 (+/�)

transgenic mice

� 100 mg/kg/day [9]

429. Rifabutin(72559-06-9)



430. Rifampicin(13292-46-1)

Long-term carcinogenesis assay, C3Hf

male mice

�(x0.5) 0.06% in dr.wt [95]

Long-term carcinogenesis assay, C3Hf


+ 0.03% in dr. wt. [95]


mice

�(x0.5) 0.06% in dr. wt. [95]


mice

�(x0.05) 0.3 mg/mouse sc [95]


rats

�(x1) 0.06% in dr. wt. [95]

Humans: lung tumours ? [95]

431. Riluzole(1744-22-5)



432. Ripazepam(26308-28-1)


mice

(+) 150 mg/kg/day in diet [25,109,210]

Long-term carcinogenesis assay, CD rats ?(x18.3) 150 mg/kg/day in diet [25,109,210]

433. Risedronate(105462-24-6)



434. Risperidone(106266-06-2)


male mice

�(x3.5) 10 mg/kg/day [9]


female mice (pituitary and mammary

tumours)

+ 0.63 mg/kg/day [9]


male rats (pancreas and mammary

tumours)

+ 2.5 mg/kg/day [9]


female rats (mammary adenocarcinomas)

+ 0.63 mg/kg/day [9]

435. Ritonavir(15521367-5)


(liver tumours)

+ 50–200 mg/kg/day [9]


mice

� 200 mg/kg/day [9]


436. Rivastigmine(123441-03-2)






437. Rizatriptan(144034-80-0)



438. Rofecoxib(162011-90-7)

Long-term carcinogenesis assay, mice �(x5.8) 30–60 mg/kg/day [9,10]


439. Ropinirole(91374-21-9)


male mice

�(x11.7) 50 mg/kg/day [9]


female mice (uterus tumours)

+ 50 mg/kg/day [9]


Dawley male rats (Leydig cell tumours)

+ 1.5 mg/kg/day [9]


Dawley female rats

�(x23.7) 50 mg/kg/day [9]

440. Rosiglitazone(122320-73-4)


mice

�(x3.6) 6 mg/kg/day [9]


Dawley rats (lipomas)

+ >0.3 mg/kg/day [9]

441. Rosuvastatin(287714-41-4)


(liver tumours)

+ 200 mg/kg/day [9]


rats (uterus polyps)

+ 80 mg/kg/day [9]





442. Salbutamol(18559-94-9)


1 mice

� 500 mg/kg/day [9,10,25]


Dawley female rats (leiomyomas)

+ 20 mg/kg/day [9,10,25]

Long-term carcinogenesis assay, golden

hamsters

� 50 mg/kg/day [9,10]

443. Salmeterol(89365-50-4)


mice

? 1.4 mg/kg/day [9,10]


Dawley rats (mesovarian leiomyomas)

+ 0.68 mg/kg/day [9,10]

444. Saquinavir(127779-20-8)



445. Sertraline(7961-96-2)


male mice (liver adenomas)

+ 10 mg/kg/day [9]


female mice

�(x1) 40 mg/kg/day [9]


Evans male rats

�(x2) 40 mg/kg/day [9]


Evans female rats (uterus and thyroid

tumours)

+ 40 mg/kg/day [9]

Humans: breast cancer ?, ?, ?, � [27–30]

Ovarian cancer ?, (+), � [19,20,32]



446. Sevelamer(52757-95-0)

Long-term carcinogenesis assay, mice �(x1.4) 9 g/kg/day [9,18]



+ 300 mg/kg/day [9,16]

447. Sibutramine(106650-56-0)



(testes tumours)

+ 9 mg/kg/day [9]


rats

�(x5.8) 9 mg/kg/day [9]

448. Sildenafil(139755-83-2)


Long-term carcinogenesis assay, rats � 29–42 MRHD/kg/day [9,18]

449. Silver sulfadiazine(22199-08-2)

Long-term carcinogenesis assay, mice � 10 HD/day on skin [9]

Long-term carcinogenesis assay, rats � 10 HD/day on skin [9]

450. Simvastatin(79902-63-9)


(liver and lung tumours)

+ 100 mg/kg/day [9]


rats (thyroid adenomas)

+ 25 mg/kg/day [9]



and thyroid tumours)

+ 50 mg/kg/day [9]







451. Sirolimus(553123-88-9)


(liver tumours)

+ 1–6 mg/kg/day [9]


mice (malignant lymphomas)

+ 6–12.5 mg/kg/day [9]


(testes adenomas)

+ 0.2 mg/kg/day [9]

452. Sodium cromoglycate(16110-51-3)

Long-term carcinogenesis assay, mice �(x0.9) 150 mg/kg/day ip � 3 weeks [9]

Long-term carcinogenesis assay, rats �(x0.9) 75 mg/kg/day sc [9]

Long-term carcinogenesis assay, hamsters � 17.5–33 mg/kg/day ip � 3

weeks

[9]

453. Sotalol(3930-20-9)


mice

�(x9) 600 mg/kg/day [25,204]



Evans rats

�(x8.4) 275 mg/kg/day [18,25,204]

454. Spironolactone(52-01-7)

(Group 3)


Dawley rats (thyroid and testes tumours)

+ 150 mg/kg/day [18,134,211]

Humans: pharyngeal carcinomas + [134]

Breast and thyroid tumours � [134]

455. Stavudine(3056-17-5)


(liver tumours)

+ human dose � 250 [9,10]


(liver and urinary bladder tumours)

+ human dose � 732 [9,10]



+ human dose � 732 [9,10]


456. Sucralfate(54182-58-0)


Long-term carcinogenesis assay, rats �(x1.4) 1 g/kg/day [9]

457. Sulfafurazole(127-69-5)

(Group 3)


mice

� 2 g/kg/day po � 103 weeks [95]

Long-term carcinogenesis assay, F344 rats � 400 mg/kg/day po � 103

weeks

[95]


458. Sulfamethazine(57-68-1)

(Group 3)



+ 4.8 g/kg of diet � 24 months [95,134]


(thyroid tumours)

+ 1.2 g/kg of diet � 24 months [95,134]

459. Sulfamethoxazole(723-46-6)

(Group 3)

Long-term carcinogenesis assay, CD rats

(thyroid adenomas)

+ 50 mg/kg/day po [95,134]

Humans: cancer at any site ? [95,134]

460. Sulfasalazine(599-79-1)



+ 2.7 g/kg/day [10,25,213]


(urinary tract tumours)

+ 337.5 mg/kg/day [10,25,213]

461. Sumatriptan(103628-46-2)



462. Tacrolimus(104987-11-3)



Humans: squamous cell carcinoma ? [214]

463. Tadalafil(171596-29-5)



464. Tamoxifen(10540-29-1)

(Group 1)


Park 1 mice (ovary and testes tumours)

+ 50 mg/kg/day po � 3 months [109]

Long-term carcinogenesis assay, C3H/OUJ

female mice

� 125 mg/mouse/day sc � 6

months

[109]


Park Wistar rats (liver tumours)

+ 5 mg/kg/day po � 2 years [109]


Dawley Crl:CD(BR) rats (liver tumours)

+ 11.3 mg/kg/day po � 12

months

[109]


Dawley female rats (liver tumours)

+ 45 mg/kg/day po � 12

months

[109]



+ 36 mg/kg/day po � 24

months

[109]


rats of various strains (liver tumours)

(+) 420 mg/kg of diet [109]





Dawley female rats (uterus tumours)

(+) 45 mg/kg/day po � 52 weeks [109]

Humans: endometrial tumours + [109,215–217]

Hepatocellular cancer ? [217]

465. Tamsulosin(106133-20-4)


male mice

� 127 mg/kg/day [9,18]



+ 45 mg/kg/day [9,18]


male rats

� 43 mg/kg/day [9,18]



+ 5.4 mg/kg/day [9,18]

466. Tegaserod(145158-71-0)


(small intestine adenocarcinomas)

+ 600 mg/kg/day [9,18]


467. Telmisartan(144701-48-4)


mice

� 1 g/kg/day [9,18]

Long-term carcinogenesis assay, F344 rats �(x12.2) 100 mg/kg/day [9,18]

468. Temazepam(846-50-4)


mice

? 160 mg/kg/day in diet [25,109,218]

Long-term carcinogenesis assay, CD rats � 160 mg/kg/day in diet [25,109,218]


469. Temozolamide(85622-93-1)


(various types of tumours)

+ 125 mg/m2� 5 days/

month � 6 cycles

[9]

470. Teniposide(29767-20-2)

(Group 2A)

Carcinogenesis in animals

Humans: leukaemias

no data

+

[76]

[76]

471. Tenofovir(147127-20-6)


mice (liver adenomas)

+ 16 HD/kg/day [9]

Long-term carcinogenesis assay, male mice � 16 HD/kg/day [9]

Long-term carcinogenesis assay, rats � 5 HD/kg/day [9]

472. Terazosin(63590-64-7)



(adrenal tumours)

(+) 250 mg/kg/day [9,18]


rats

� 250 mg/kg/day [9,18]

473. Terbinafine(91161-71-6)


(liver tumours)

+ 69 mg/kg/day [9]

474. Terbutaline(23031-25-6)



+ 84.2 mg/kg/day [25]

475. Terfenadine(50679-08-8)

Long-term carcinogenesis assay, mice ?(x6) 150 mg/kg/day [10,219]

Long-term carcinogenesis assay, rats ?(x12) 150 mg/kg/day [10,219]


476. Testosterone(58-22-0)


MTV+ male mice

� 1.25 mg/week sc for life [83]


ovariectomized mice

� 3 mg pellet sc [83]


(C57BL � dba)F1 female mice (cervix

tumours)

+ 1–2 mg pellet � 2/week sc for

life

[83]


cCrgl newborn female mice (vaginal

tumours)

+ 25 mg/day sc � 5 days [83]


cfC3H MTV+ newborn female mice

(mammary tumours)

+ 5 mg/day sc � 5 days [83]

Long-term carcinogenesis assay, SHN

MTV+ newborn female mice (mammary

tumours)

+ 200 mg/day sc � 5 day [83]


(prostate carcinomas)

+ 1–3 mg pellet sc � 4 times in

6 months

[83]


female albino rats (ovary tumours)

(+) 0.5–2.5 mg/week sc [83]


rabbits (endometrium polyps)

? 15 mg on alternate weeks im [83]

Humans: hepatocellular carcinomas (+) [17]

477. Thenyldiamine(91-79-2)


Dawley rats

� 1000 ppm in dr. wt [162]


male rats

� 17.6 mg/kg/day [25]


female rats

� 25.1 mg/kg/day [25]

478.Theophylline(58-55-9)


male mice

�(x1.4) 150 mg/kg/day [25,66,220]





female mice

�(x0.7) 75 mg/kg/day [25,66,220]

Long-term carcinogenesis assay, F344 rats �(x1.4) 75 mg/kg/day [25,66,220]

479. Thiabendazole(148-79-8)

Long-term carcinogenesis assay, animals

not specified

� 15 HD/day [9]

480. Thiotepa(52-24-4)

(Group 1)


mice (lung tumours)

+ total dose 19 mg/kg ip [36]


mice (leukaemias and lymphomas)

+ 2.3 mg/kg � 3/week ip � 52

weeks

[36]


Dawley rats (uterus and mammary

tumours, lymphomas and leukaemias)

+ 0.7–1.4 mg/kg � 3/week

ip � 52 weeks

[36]



+ 1 mg/kg iv � 52 weeks [36]

Humans: leukaemias + [36]

481. Thiouracil(141-90-2)

(Group 2B)

Long-term carcinogenesis assay, A, C57

and I mice (thyroid tumours)

+ 0.1% in diet per various

periods up to 81 weeks

[134]


female mice (thyroid tumours)

+ 0.375–0.5% in diet � 464 days [134]

Long-term carcinogenesis assay, C3H TM

mice (hepatomas)

+ 0.3% in diet � 17 months [134]

Long-term carcinogenesis assay, Stanford

albino rats (benign thyroid tumours)

+ 0.1% in diet � 120–312 days [134]


Dawley male rats (thyroid adenomas)

+ 0.2% in dr. wt � 24 months [134]

Humans: thyroid, brain and oral tumours (+) [134]

482. Tiagabine(115103-54-3)



(hepatocellular adenomas and Leydig cell

tumours)

+ 200 mg/kg/day [9]

483. Ticlopidine(55142-85-3)



484. Tilidine(20380-58-9)

Long-term carcinogenesis assay, CF-1 mice �(x2.4) 100 mg/kg/day [25]


Dawley rats

�(x4.9) 100 mg/kg/day [25]

485. Timolol(26839-75-8)

Long-term carcinogenesis assay, male mice � 500 mg/kg/day [9,18]


mice (lung, uterine and mammary

tumours)

+ 500 mg/kg/day [9,18]


(adrenal pheochromocytomas)

+ 300 mg/kg/day [9,18]


rats

� 300 mg/kg/day [9,18]

486.Tiotropium(186691-13-4)

Long-term carcinogenesis assay, male mice �(x0.5) 0.002 mg/kg/day [9]


mice

� 0.145 mg/kg/day [9]

Long-term carcinogenesis assay, rats � 0.059 mg/kg/day [9]

487. Tizanidine(51322-75-9)



488. Tocainide(41708-72-9)



489. Tolazamide(1156-19-0)


mice

�(x4.8) 10,000 ppm in diet [25,221]


490. Tolbutamide(64-77-7)


mice

�(x12) 50,000 ppm in diet [25,222]


491. Tolcapone(134308-13-7)



(uterus and kidney tumours)

+ 250 mg/kg/day [9]

492. Tolmetin(26171-23-3)











493. Tolterodine(124937-51-5)




rats

� (x0.4) 20 mg/kg/day [9]

494. Topiramate(97240-79-4)



+ 300 mg/kg/day [9]


495. Toremifene(89778-26-7)


(bone, ovary and testes tumours)

+ 30 mg/kg/day [9]



496. Torsemide(56211-40-6)




rats (kidney tumours)

(+) 9 mg/kg/day [9,18]


497. Tramadol(27203-92-5)


(lung and liver tumours)

(+) 30 mg/kg/day [9]


498. Trandolapril(87679-37-6)




499. Tranexamic acid(1197-18-18)


(biliary system tumours)


Long-term carcinogenesis assay, rats � 1 MRHD/kg/day [18]

500. Travoprost(157263-68-6)

Long-term carcinogenesis assay, mice � 0.1 mg/kg/day sc [9]

Long-term carcinogenesis assay, rats � 0.1 mg/kg/day sc [9]

501. Trazodone(19794-93-5)



Ovarian cancer �, �, (+) [19,32,40]

502. Treosulphan(299-75-2)

(Group 1)

Carcinogenesis in animals

Humans: leukaemias

no data

+

[17,60]

[17,60]

503. Tretinoin(302-79-4)


mice (skin and liver tumours)

+ 100–299 HD/day on skin [9]

504. Triamcinolone(124-94-7)




(liver tumours)

+ 6.39 mg/kg/day [9,10,25]

505. Triamterene(396-01-0)



(+) 400 ppm in diet [9,10,18,223]



(+) 150 ppm in diet [9,10,18,223]


female rats

�(x2.9) 600 ppm in diet [9,10,18,223]


506. Triaziquone(68-76-8)

(Group 3)


male rats (malignant tumours at various

sites)

+ 0.03 mg/kg/week iv � 52

weeks

[159]


male rats (malignant tumours at various

sites)

+ 0.03 mg/kg/week � 25 weeks

iv and � 33 weeks ip

[159]


507. Triazolam(28911-01-5)



508. Trichlormethine(817-09-4)

(Group 2B)


(lung tumours)

(+) 1 mg/kg/week sc � 10 weeks [36]


SPF rats (sarcomas at the injection site)

+ 0.1 mg/kg/day or 1 mg/kg/

week sc

[36]

509. Triprolidine(486-12-4)


mice

� 4000 ppm in diet [10,224]

Long-term carcinogenesis assay, F344 rats � 2000 ppm in diet [10,225]

510. Triptorelin(57773-63-4)

Long-term carcinogenesis assay, mice � 6 mg/kg every 4 weeks � 18

months

[9]


(pituitary tumours and histiosarcomas)

+ 0.12–30 mg/kg every 4

weeks � 13–19 months

[9]

511. Troglitazone(97322-87-7)


(hemangiomas)

+ 800 mg/kg/day [18]





mice (hemangiomas and

hepatocarcinomas)

+ 400 mg/kg/day [18]

Long-term carcinogenesis assay, ras H2

male mice

� 6000 ppm in diet [226]

Long-term carcinogenesis assay, ras H2

female mice (vascular tumours)

(+) 6000 ppm in diet [226]



rats

�(x12) 200 mg/kg/day [18]

512. Trospium(10405-02-4)



513. Uracil mustard(66-75-1)

(Group 2B)


mice (lung tumours)

+ 8 mg/kg ip � 7 times in 24

weeks

[17,159]


(lung tumours)

+ 0.76 mg/kg ip � 3/week � 4

weeks

[17,159]


mice (liver, lung and ovary tumours)

+ 0.12 mg/kg ip � 3/week � 6

months

[17,159]

Long-term carcinogenesis assay, CD rats

(ovary and pancreas tumours, lymphomas

and sarcomas)

+ 0.15 mg/kg ip � 3/week � 6

months

[17,159]


514. Ursodiol(128-13-2)




Dawley female rats (pheochromocytomas)

+ 300 mg/kg/day [9]

515. Valacyclovir(124832-26-4)



516. Valdecoxib(181695-72-7)

Long-term carcinogenesis assay, mice � 25–50 mg/kg/day [9,18]

Long-term carcinogenesis assay, rats �(x8.5) 1.5–7.5 mg/kg/day [9,18]






517. Valproic acid(99-66-1)

Long-term carcinogenesis assay, ICR mice

(lung adenomas)

+ 170 mg/kg/day [9]


male rats

�(x1.9) 500 mg/kg/day [227]


female rats (uterus adenocarcinomas)

+ 250 mg/kg/day [227]


Dawley male rats (fibrosarcomas and other

tumours)

+ 80 mg/kg/day [9]


Dawley female rats (various types of

tumours)

+ 80 mg/kg/day [9]

518. Valsartan(137862-53-4)



519. Vardenafil(224785-90-4)

Long-term carcinogenesis assay, male mice � 21 MRHD/day [9,10,18]


mice

� 37 MRHD/day [9,10,18]

Long-term carcinogenesis assay, male rats � 400 MRHD/day [9,10,18]


rats

� 170 MRHD/day [9,10,18]

520. Venlafaxine(93413-69-5)



Humans: breast cancer ?, ?, ?, � [27–30]

Ovarian cancer ?, (+), � [19,20,32]



521. Verapamil(52-53-9)



522. Vinblastine(143-67.3)

(Group 3)


Webster mice

? 0.18 mg/kg ip � 3/week � 6

months

[60]


Dawley CD rats (various types of tumours)

(+) 0.2 mg/kg ip � 3/week � 6

months

[60]





male rats (benign and malignant tumours)

(+) 0.33 mg/kg iv every 2

weeks � 5 times

[60]


523. Vincristine(2068-78-2)

(Group 3)


Webster mice

? 0.15 mg/kg ip � 3/week � 6

months

[60]


Dawley CD rats

� 0.12 mg/kg ip � 3/week � 6

months

[60]


524. Voriconazole(137234-62-9)


(liver tumours)

+ 100 mg/kg/day [9]


tumours)

+ 6 mg/kg/day [9]

525. Zafirlukast(107753-78-6)


(liver adenomas and histocytic sarcomas)

+ 300 mg/kg/day [18]



+ 2 g/kg/day [18]

526. Zalcitabine(7481-89-2)

(Group 2B)


male mice (thymic lymphomas)

+ 500 mg/kg/day [9,13]


female mice (thymic lymphomas)

+ 500 mg/kg/day [9,13]

Long-term carcinogenesis assay, NIH Swiss

mice (thymomas)

+ 500 mg/kg/day [9,13]


527. Zaleplon(151319-34-5)





Long-term carcinogenesis assay, rats �(x6.5) 20 mg/kg/day in diet [9]



528. Zanamivir(139110-80-8)

Long-term carcinogenesis assay, mice � 22 HD/day � inhalation � 2

years

[9]

Long-term carcinogenesis assay, rats � 25 HD/day � inhalation � 2

years

[9]

529. Zidovudine(30516-87-1)

(Group 2B)

Long-term carcinogenesis assay, male CD1

mice

�(x1) 120 mg/kg/day [13]


CD1 mice (vaginal carcinomas)

+ 120 mg/kg/day [13]


B6C3F1 mice (kidney and harderian gland

tumours)

+ 30–120 mg/kg/day [13]


B6C3F1 mice (vaginal tumours)

+ 60 mg/kg/day [13]


1 mice, transplacental exposure

�(x0.3) 40 mg/kg/day [13]


CD-1 mice, transplacental exposure

(vaginal carcinomas)

+ 40 mg/kg/day [13]


1 mice, transplacental exposure (lung

tumours)

+ 25 mg/mouse [13]


CD-1 mice, transplacental exposure (skin

tumours)

+ 25 mg/mouse [13]

Long-term carcinogenesis assay,female

CD-1 female mice, transplacental exposure

(vaginal carcinomas)

+ 8 mg intravaginally [13]


rats

�(x9.8) 600 mg/kg/day [13]


rats (vaginal carcinomas)

+ 600 mg/kg/day [13]

Humans: non Hodgkin lymphoma ? [212]

530. Zileuton(111406-87-2)


(liver tumours)

(+) 450 mg/kg/day [18]


mice (liver, kidney and vascular tumours)

+ 450 mg/kg/day [18]


(kidney tumours)

+ 170 mg/kg/day [18]

531. Ziprasidone(146939-27-7)


male mice

�(x5.6) 200 mg/kg/day [9]


female mice (pituitary and mammary

tumours)

+ 50 mg/kg/day [9]


Evans rats

�(x0.7) 12 mg/kg/day [9]




532. Zolendronate(118072-93-8)


(harderian gland tumours)

+ 0.1 mg/kg/day [9]


533. Zolmitriptan(139264-17-8)



(thyroid adenomas)

(+) 400 mg/kg/day [9]


rats

� 400 mg/kg/day [9]

534. Zolpidem(82626-48-0)



(kidney tumours)

? 80 mg/kg/day [9]


535. Zonisamide(68291-97-4)



Note.a +, positive; (+), weakly positive; �, negative; ?, equivocal.b NR, not reported; sc, subcutaneously; ip, intra-peritoneally; iv, intravenously; po, oral route; HD, usual human dose; MRHD, maximum recommended human dose.

The number in parentheses indicates the ratio [high animal dose (mg/m2)/maximum recommended human dose (mg/m2)].

Table 2Summary of results of carcinogenesis assay of 535 drugs.

Tested for carcinogenicity in mice 443 (82.8%)

Positive 99 (18.5%/22.3%)a

Negative 267 (49.9%/60.3%)

Discordant 77 (14.4%/17.4%)

Tested for carcinogenicity in rats 489 (91.4%)

Positive 129 (24.1%/26.4%)

Negative 277 (51.8%/56.6%)

Discordant 83 (15.5%/17.0%)

Tested for carcinogenicity in both mice and rats 408 (76.3%)

Positive 113 (21.1%/27.7%)

Negative 185 (34.6%/45.3%)

Discordant 110 (20.6%/27.0%)

Tested for carcinogenicity in other species 52 (9.7%)

Positive 16 (3.0%/30.8%)

Negative 36 (6.7%/69.2%)

With at least one positive result in animal 279 (52.1%)

Carcinogenicity in humans 186 (34.8%)

Positive 104 (19.4%/55.9%)

Negative or equivocal 82 (15.3%/44.1%)

With contrasting results in the same organ 46 (8.6%/24.7%)

a The first of the two percentages is relative to 535 drugs considered; the second

to the number of drugs tested in the indicated species.


inadequate for 63; 10 drugs were not tested for carcinogenicity. Ina review of Snyder and Green [7] on the genotoxicity of marketedpharmaceuticals, based on information obtained from the 1999edition of the Physicians’ Desk Reference as well as from the peer-reviewed published literature, only 201 drugs had both genetictoxicity data and rodent carcinogenicity data. These premisesindicate that in prescribing most drugs the evaluation of thebenefit/carcinogenic effects ratio is impossible. Therefore wedeemed it useful to examine whether data allowing a morecomplete assessment can be retrieved. One of the aims of thisreview was also to examine the extent of correlation existingbetween carcinogenicity in experimental animals and, whenavailable, information provided by epidemiological studies inhumans.

2. Methods

This review is a compendium of all the carcinogenicity data that have been found in

an extensive search. For each drug considered the search term was carcinogenic

activity. The search was conducted primarily in peer-reviewed journals using

Medline, Toxline, and the Registry of Toxic Effects of Chemicals Substances [8].

Additional unpublished data were obtained from Micromedex and from the following

websites: http://www.toxnet.nlm.nih.gov, http://www.ntp.server.niehs.nih.gov,

http://www.potency.berkeley.edu, http://www.fda.gov/cder, http://www.scirus.

com, http://www.inchem.org, http://www.updateusa.com, http://www.osha.gov.

Concerning data that are not published in peer-reviewed journals, in some cases

the tests were conducted under the oversight of authoritative bodies, such as the U.S.

National Toxicology Program; in the other cases the carcinogenicity data are those

reported by the Physician’s Desk Reference [9] or in the final package insert approved

by the Center for Drug Evaluation and Research of the Food and Drug Administration.

3. Results and discussion

In our extensive search for carcinogenicity of marketed drugs,whose expected clinical use is continuous for at least 6 months orare used in an intermittent manner, we retrieved at least one resultfor 535 pharmaceuticals. Only a very limited number of them havebeen recently retired from the commerce after a long period of use.For each of the 535 drugs considered, the carcinogenicity assays inanimals and, when available, the epidemiological findings arereported in Table 1. The result is indicated as + (positive), (+)(weakly positive), � (negative), and ? (equivocal or inconclusive).In this table the name of each drug is followed by thecorresponding Chemical Abstract Service (CAS) number. For eachassay the corresponding reference is reported; when the same

result is reported by more than one article, we indicate thereference of each article.

As shown in Table 2, of the 535 drugs examined 443 (82.8%)have at least one result of carcinogenicity assays in mice, and 489(91.4%), in rats; 408 (76.3%) were tested in both species. Only 52drugs (9.7%) were tested in other species (monkeys, dogs, rabbits,hamsters, guinea pigs, gerbils, marmosets, and frogs). The drugswith at least one positive result in animals number 279 (52.1%).Concerning information on carcinogenicity in humans, data wereretrieved for only 186 drugs (34.8%), and for 104 of them indicationof potential carcinogenic activity was retrieved to a variable extent.Concerning the predictivity of carcinogenicity between mice andrats, 113 drugs gave at least one positive result in both species and185 tested negative in both species. However, 63 drugs werecarcinogenic in at least one study in rats but tested negative inmice, and 47 gave a positive result in mice but were noncarcino-genic in rats. A similar degree of correlation was found to occurbetween results of in vitro and in vivo genotoxicity assays andcarcinogenicity in mice and rats. Of 472 drugs considered in a

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http://www.ntp.server.niehs.nih.gov/

Table 3Correlation between carcinogenicity in animals and carcinogenicity in human.

Drugs with positive result(s) in both animals

and humans

58 (31.2%)

Drugs with positive result(s) in animals and

negative or equivocal in humans

53 (28.5%)

Drugs with positive finding(s) in humans and

negative or equivocal in animals

41 (22.0%)

Drugs negative or equivocal in both animals

and humans

29 (15.6%)

Drugs with positive finding(s) in humans

without data in animals

5 (2.7%)


previous review [228] 304 are among those listed in Table 1. Ofthese drugs, 112 tested negative in both genotoxicity andcarcinogenicity assays, 69 gave a positive result in at least onegenotoxicity assay and in at least one carcinogenicity assay, 79were carcinogenic in at least one study but failed to induce positiveresults in genotoxicity assays; and 44 tested positive in at least onegenotoxicity assay but gave negative results in carcinogenicityassays.

With respect to the correlation between results obtained inanimals and epidemiological findings, Table 3 shows that 58 drugs(31.2%) display at least one positive result in animals and tovariable extent epidemiological findings of potential carcinogenic-ity in humans. Fifty-three drugs (28.5%) gave at least one positiveresult in animals in the absence of positive finding in humans, 41drugs (22.0%) gave one or more findings indicating potentialcarcinogenicity in humans but tested negative in animals, and 29drugs (15.6%) gave only negative or equivocal results in bothanimals and humans. For five drugs findings of potentialcarcinogenicity in humans were retrieved but there were no datain animals.

The information provided by this review suggests the followingconsiderations. For a relevant fraction (65.2%) of the drugsconsidered no studies were retrieved on carcinogenicity inhumans; therefore it is not possible to assess for these drugsthe capability of carcinogenesis assays performed in animals topredict carcinogenic effects in humans. However, this assessmentis possible for the 186 drugs with data in both animals and humans.The assessment indicates that the capability of results obtained inanimals of predicting the effect in humans is quite limited, since fora relevant number of drugs they are discordant from epidemiologi-cal findings. Of these drugs, 29 tested negative in carcinogenicityassays performed in mice and or rats and did not provide evidenceof carcinogenicity in humans; 58 were carcinogenic in mice and/orrats and in humans; 53 were carcinogenic in mice and or rats butnot in humans; and 41 were non carcinogenic in mice and/or ratsbut gave evidence of carcinogenicity in humans. The capacity ofdrugs to cause cancer became apparent in the early 1970s [35,99],and the need to perform lifetime rodent studies on all drugs inclinical use was advocated by Rall [229] in the year 1975. Anextensive survey study of 25,000 patients, published in the year1977 [230], revealed that less than 1% of the cancers identified inthis study was likely to be caused by any recent regular use ofdrugs. However, in a first screening for carcinogenicity of 95commonly used drugs and drug groups in relation to 56 primarycancer sites and combination of sites, performed by Friedman andUry [190], statistically significant positive associations with atleast one site were found for 41 drugs or drug groups with amorbidity ratio ranging in 18 cases from 7.4 to 25.7. Whenscreening analyses for the same drugs and drug groups wererepeated [50], several drug-cancer associations had either gainedor lost statistical significance but such an association was presentfor 20 drugs or drug groups. Moreover, the screening of 120additional less commonly used drugs revealed 43 positive drug-cancer associations.

The information provided in this review on the carcinogenicityof marketed pharmaceuticals in animals and humans clearlyindicates the need to evaluate the benefit/carcinogenic risk ratiobefore prescribing a drug, and the need to take this ratio intoaccount in the choice among drugs with the same pharmacologicalactivity. Obviously, the prescription of a drug found to be devoid ofcarcinogenic activity in both animals and humans should befavoured.

Conflict of interest

None declared.

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update of carcinogenicity studies in animals and humans of 535 marketed pharmaceuticals

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