benzo[a]pyrene...benzo[a]pyrenein iarc monograph volume 32 ( iarc, 1983 ) no evaluation was made of...
TRANSCRIPT
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111
1. Exposure Data
1.1 Identification of the agent
Chem. Abstr. Services Reg. No.: 50-32-8Chem. Abstr. Name: Benzo[a]pyreneIUPAC Systematic Name: Benzo[a]pyreneSynonyms: BaP; benzo[def]chrysene; 3,4-benzopyrene*; 6,7-benzopyrene*; benz[a]pyrene; 3,4-benz[a]pyrene*; 3,4-benzpyrene*; 4,5-benzpyrene* (*alternative numbering conventions)
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C20H12 Relative molecular mass: 252.31Description: Yellowish plates, needles from benzene/methanol; crystals may be mono-clinic or orthorhombicBoiling-point: 310–312 °C at 10 mm HgMelting-point: 179–179.3 °C; 178.1 °CSpectroscopy data: Ultraviolet/visual, infrared, fluorescence, mass and nuclear
magnetic-resonance spectral data have been reportedWater solubility: 0.00162 mg/L at 25 °C; 0.0038 mg/L at 25 °Clog Kow (octanol–water): 6.35Henry’s Law Constant: 0.034 Pa m3/mol at 20 °C
From IARC (2010)
1.2 Occurrence and exposure
Benzo[a]pyrene and other polycyclic aromatic hydrocarbons (PAHs) are widespread environ-mental contaminants formed during incomplete combustion or pyrolysis of organic material. These substances are found in air, water, soils and sediments, generally at trace levels except near their sources. PAHs are present in some foods and in a few pharmaceutical products based on coal tar that are applied to the skin. Tobacco smoke contains high concentrations of PAHs (IARC, 2010).
1.2.1 Exposure of the general population
The general population can be exposed to benzo[a]pyrene through tobacco smoke, ambient air, water, soils, food and pharmaceutical prod-ucts. Concentrations of benzo[a]pyrene in
BENZO[a]PYRENEBenzo[a]pyrene was considered by previous IARC Working Groups in 1972, 1983, and 2005 (IARC, 1973, 1983, 2010). Since that time new data have become available, which have been incorporated in this Monograph, and taken into consideration in the present evaluation.
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IARC MONOGRAPHS – 100F
sidestream cigarette smoke have been reported to range from 52 to 95 ng/cigarette — more than three times the concentration in mainstream smoke. Major sources of PAHs in ambient air (both outdoors and indoors) include residential and commercial heating with wood, coal or other biomasses (oil and gas heating produce much lower quantities of PAH), other indoor sources such as cooking and tobacco smoke, and outdoor sources like motor-vehicle exhaust (especially from diesel engines), industrial emissions and forest fires. Average concentrations of individual PAHs in the ambient air in urban areas typically range from 1 to 30 ng/m3; however, concentra-tions up to several tens of nanograms per cubic metre have been reported in road tunnels, or in large cities that make extensive use of coal or other biomass as residential heating fuel. Estimates of PAH intake from food vary widely, ranging from a few nanograms to a few micro-grams per person per day. Sources of PAHs in the diet include barbecued/grilled/broiled and smoke-cured meats; roasted, baked and fried foods (high-temperature processing); bread, cereals and grains (at least in part from gas/flame-drying of grains); and vegetables grown in contaminated soils, or in areas with surface contamination from atmospheric PAH fall-out (IARC, 2010).
1.2.2 Occupational exposure
Occupational exposure to PAHs occurs primarily through inhalation and via skin contact. Monitoring by means of ambient air-sampling or personal air-sampling at the workplace, to determine individual PAHs, sets of PAHs or surrogates (e.g. coal-tar pitch vola-tiles) has been used to characterize exposure via inhalation; more recently, biological monitoring methods have been applied to characterize the uptake of certain specific PAHs (e.g. benzo[a]pyrene) to be used as biomarkers of total expo-sure (IARC, 2010).
Industries where occupational exposure to benzo[a]pyrene has been measured and reported include: coal liquefaction, coal gasification, coke production and coke ovens, coal-tar distillation, roofing and paving (involving coal-tar pitch), wood impregnation/preservation with creosote, aluminium production (including anode manu-facture), carbon-electrode manufacture, chimney sweeping, and power plants. Highest levels of exposure to PAHs are observed in aluminium production (Söderberg process) with values up to 100 μg/m3. Mid-range levels are observed in roofing and paving (e.g. 10−20 μg/m3) and the lowest concentrations (i.e. at or below 1μg/m3) are observed in coal liquefaction, coal-tar distil-lation, wood impregnation, chimney sweeping and power plants (IARC, 2010).
2. Cancer in Humans
No epidemiological data on benzo[a]pyrene alone were available to the Working Group.
3. Cancer in Experimental Animals
Benzo[a]pyrene was considered by three previous Working Groups (IARC, 1973, 1983, 2010).
In IARC Monograph Volume 3 (IARC, 1973) it was concluded that benzo[a]pyrene produced tumours in all species tested (mouse, rat, hamster, guinea-pig, rabbit, duck, newt, monkey) for which data were reported following exposure by many different routes (oral, dermal, inhalation, intratracheal, intrabronchial, subcu-taneous, intraperitoneal, intravenous). Benzo[a]pyrene had both a local and a systemic carcino-genic effect, was an initiator of skin carcinogen-esis in mice, and was carcinogenic in single-dose studies and following prenatal and transplacental exposures.
112
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Benzo[a]pyrene
In IARC Monograph Volume 32 (IARC, 1983) no evaluation was made of studies of carcino-genicity in experimental animals published since 1972, but it was concluded that there is sufficient evidence for the carcinogenicity of benzo[a]pyrene in experimental animals.
Carcinogenicity studies with administra-tion of benzo[a]pyrene by multiple route of exposure, reported after the initial evaluations, were subsequently reviewed in IARC Monograph Volume 92 (IARC, 2010) and are summarized below (Table 3.1). See Table 3.2 for an overview of malignant tumours induced in different animal species.
3.1 Skin application
In several studies in which benzo[a]pyrene was applied to the skin of different strains of mice, benign (squamous cell papillomas and kerato-acanthomas) and malignant (mainly squamous-cell carcinomas) skin tumours were observed (Van Duuren et al., 1973; Cavalieri et al., 1977, 1988a; Levin et al., 1977; Habs et al., 1980, 1984; Warshawsky & Barkley, 1987; Albert et al., 1991; Andrews et al., 1991; Warshawsky et al., 1993). No skin-tumour development was seen in AhR−/− mice that lacked the aryl hydrocarbon receptor, whereas the heterozygous and wild-type mice developed squamous-cell carcinomas of the skin (Shimizu et al., 2000).
In a large number of initiation–promotion studies in mice, benzo[a]pyrene was active as an initiator (mainly of squamous-cell papillomas) when applied to the skin (IARC, 2010).
3.2 Subcutaneous injection
In subcutaneous injection studies of benzo[a]pyrene, malignant tumours (mainly fibro-sarcomas) were observed at the injection site in mice (Kouri et al., 1980; Rippe & Pott, 1989) and rats (Pott et al., 1973a, b; Rippe & Pott, 1989). No fibrosarcomas were observed in AhR−/− mice that
lacked the aryl hydrocarbon receptor, whereas the heterozygous and wild-type mice did develop these tumours (Shimizu et al., 2000).
In another study, male and female newborn Swiss mice that were given benzo[a]pyrene subcutaneously showed a significant increase in lung-adenoma incidence and multiplicity (Balansky et al., 2007).
A single study in 12 strains of hamsters resulted in sarcomas at the site of injection in both sexes of all 12 strains (Homburger et al., 1972).
3.3 Oral administration
After administration of benzo[a]pyrene by gavage or in the diet to mice of different strains (Sparnins et al., 1986; Estensen & Wattenberg, 1993; Weyand et al., 1995; Kroese et al., 1997; Culp et al., 1998; Hakura et al., 1998; Badary et al., 1999; Wijnhoven et al., 2000; Estensen et al., 2004), increased tumour responses were observed in lymphoid and haematopoeitic tissues and in several organs, including the lung, forestomach, liver, oesophagus and tongue.
Oral administration of benzo[a]pyrene to XPA–/– mice resulted in a significantly higher increase of lymphomas than that observed in similarly treated XPA+/– and XPA+/+ mice (de Vries et al., 1997). Benzo[a]pyrene given by gavage to XPA–/–/p53+/– double-transgenic mice induced tumours (mainly splenic lymphomas and forestomach tumours) much earlier and at higher incidences than in similarly treated single transgenic and wild-type counterparts. These cancer-prone XPA–/– or XPA–/–/p53+/– mice also developed a high incidence of tumours (mainly of the forestomach) when fed benzo[a]pyrene in the diet (van Oostrom et al., 1999; Hoogervorst et al., 2003).
Oral administration of benzo[a]pyrene by gavage to rats resulted in an increased incidence of mammary gland adenocarcinomas (el-Bayoumy et al., 1995).
113
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IARC MONOGRAPHS – 100F
114
Tabl
e 3.
1 Ca
rcin
ogen
icit
y st
udie
s of
ben
zo[a
]pyr
ene
in e
xper
imen
tal a
nim
als
Spec
ies,
stra
in (s
ex)
Dur
atio
n R
efer
ence
Dos
ing
regi
men
A
nim
als/
grou
p at
star
tIn
cide
nce
of tu
mou
rsR
esul
t or
sign
ifica
nce
Puri
ty (v
ehic
le)
Com
men
ts
Skin
app
licat
ion
Mou
se, S
wis
s IC
R/
Ha
(F)
52 w
k Va
n D
uure
n et
al.
(197
3)
0 (u
ntre
ated
), 0
(veh
icle
con
trol
), 5
μg/a
nim
al, 3
× /w
k, 5
2 w
k 50
/gro
up
Skin
T: 0
/50,
0/5
0, 2
3/50
(46%
; 13
P; 1
0 C
)+
NR
(ace
tone
)
Mou
se, S
wis
s (F)
38
–65
wk
Cav
alie
ri et
al.
(197
7)
0 an
d 0.
396
μmol
[0.1
mg]
per
an
imal
, tw
ice/
wk,
30
wk
40/g
roup
Skin
T: 0
% [0
/29]
, 78.
9% [3
0/38
] (7
P, 7
K, 3
6 C
, 1
mal
igna
nt S
chw
anno
ma)
+99
% (a
ceto
ne)
Mou
se, C
57BL
/6J (
F)
60 w
k Le
vin
et a
l. (1
977)
Expe
rim
ent 1
and
2: 0
(DM
SO/
acet
one)
, 0.0
2 [5
.28
μg],
0.1
[26.
43 μ
g], 0
.4 [1
05.7
5 μg
] μm
ol/
anim
al, o
nce/
2 w
k, 6
0 w
k (h
igh
dose
giv
en in
two
pain
tings
, 30
min
ap
art)
Expe
rim
ent 3
: 0 (a
ceto
ne/N
H4O
H),
0.02
5 [6
.6 μ
g], 0
.05
[13.
21 μ
g], 0
.1
[26.
43 μ
g] μ
mol
/ani
mal
, onc
e/2
wk,
60
wk
30/g
roup
Skin
T (m
ainl
y SC
C):
Expe
rim
ent 1
–0%
, 0%
, 38%
(13
T), 1
00%
(44
T)
Expe
rim
ent 2
–0%
, 4%
(1 T
), 50
% (1
5 T)
, 100
% (4
0 T)
Ex
peri
men
t 3–
0%, 7
% (2
T),
59%
(20
T), 9
1% (2
4 T)
+N
R (D
MSO
/ace
tone
(1:3
) or
acet
one/
NH
4OH
(1 0
00:1)
) Eff
ectiv
e nu
mbe
r of a
nim
als
not c
lear
ly sp
ecifi
ed
At m
ost,
seve
n an
imal
s/gr
oup
died
pre
mat
urel
y w
ithou
t a
skin
tum
our.
Mou
se, N
MR
I (F)
63
–109
wk
Hab
s et a
l. (1
984)
0, 2
, 4 μ
g/an
imal
, tw
ice/
wk
20/g
roup
Skin
T: 0
/20,
9/2
0 (4
5%; 2
P, 7
C),
17/2
0 (8
5%; 1
7 C
)+
> 96
% (a
ceto
ne)
Mou
se C
3H/H
eJ (M
) 99
wk
War
shaw
sky
&
Bark
ley
(198
7)
0 (u
ntre
ated
), 0
(veh
icle
con
trol
) or
12.5
μg/
anim
al, t
wic
e/w
k 50
/gro
up
Skin
T: 0
/50,
0/5
0, 4
8/50
(96%
; 47
C, 1
P)
+99
.5%
(ace
tone
)
Mou
se, S
wis
s (F)
42
wk
Cav
alie
ri et
al.
(198
8a)
0, 0
.1 [2
6.4
μg],
0.4
[105
.7 μ
g] μ
mol
/an
imal
, tw
ice/
wk,
20
wk
30/g
roup
Skin
T in
cide
nce:
0/3
0, 2
6/29
(90%
; SG
A, 3
P, 2
3 SC
C),
26/3
0 (9
0%; 2
P, 2
6 SC
C)
+Pu
rifie
d [N
R] (a
ceto
ne)
-
Benzo[a]pyrene
115
Spec
ies,
stra
in (s
ex)
Dur
atio
n R
efer
ence
Dos
ing
regi
men
A
nim
als/
grou
p at
star
tIn
cide
nce
of tu
mou
rsR
esul
t or
sign
ifica
nce
Puri
ty (v
ehic
le)
Com
men
ts
Mou
se, C
3H/fC
um
(M) E
xper
imen
t 1:
15 m
o Ex
peri
men
t 2:
18 m
o Ex
peri
men
t 3:
18 m
o K
ouri
et a
l. (1
980)
Expe
rim
ent 1
: 0 (t
rioc
tano
in
cont
rol),
0 (D
MSO
con
trol
), 0.
9 µm
ol [0
.23
mg]
in tr
ioct
anoi
n or
D
MSO
,
Fibr
oS a
t inj
ectio
n sit
e:
Expe
rim
ent 1
–0/1
6, 0
/20,
15/
18 (8
3%),
12/1
9 (6
3%)
+Pu
re (t
rioc
tano
in, D
MSO
)
Expe
rim
ent 2
: 0 (t
rioc
tano
in
cont
rol),
0 (D
MSO
con
trol
), 0.
9 µm
ol [0
.23
mg]
in tr
ioct
anoi
n or
in
DM
SO,
Expe
rim
ent 2
–0/2
0, 0
/18,
14/
18 (7
8%),
7/19
(37%
)
Expe
rim
ent 3
: 0 (t
rioc
tano
in/
DM
SO, 1
00:1)
, 0.9
µm
ol [0
.23
mg]
in
trio
ctan
oin/
DM
SO (1
00:1)
, 1 ×
20
or 4
0/gr
oup
Expe
rim
ent 3
–0/2
0, 3
6/40
(90%
)
Mou
se, N
R (F
) 78
wk
Rip
pe &
Pot
t (19
89)
0, 1
0, 1
00 μ
g/
anim
al, 1
× N
R/g
roup
S at
inje
ctio
n sit
e: 1
/30
(3%
), 13
/30
(43%
), 20
/30
(67%
)+
NR
(tric
apry
lin)
Mou
se, S
wis
s (n
ewbo
rn) (
M, F
) 75
–200
d
Bala
nsky
et a
l. (2
007)
0 an
d 1.
0 m
g/an
imal
, 1 ×
12
–15
M/g
roup
, 12–
15 F
/gro
upLu
ng A
: M –
0/1
5, 9
/12;
F –
0/1
5, 1
1/12
P
-
IARC MONOGRAPHS – 100F
116
Spec
ies,
stra
in (s
ex)
Dur
atio
n R
efer
ence
Dos
ing
regi
men
A
nim
als/
grou
p at
star
tIn
cide
nce
of tu
mou
rsR
esul
t or
sign
ifica
nce
Puri
ty (v
ehic
le)
Com
men
ts
Ham
ster
, Syr
ian,
RB
(ran
dom
ly b
red)
, BI
O in
bred
stra
ins
desig
nate
d as
: 1.5
, 4.
22, 4
.24,
7.88
, 12.
14,
15.16
, 45.
5, 5
4.7,
82.7
3,
86.9
3, 8
7.20
(M, F
) 53
wk
Hom
burg
er et
al.
(197
2)
500
μg/a
nim
al, 1
×
25 M
/gro
up, 2
5 F/
grou
pFi
broS
at i
njec
tion
site:
R
B–M
, 4/2
5 (1
6%);
F, 6
/23
(26%
) 1.
5–M
, 5/2
5 (2
0%);
F, 4
/23
(17%
) 4.
22–M
, 3/2
5 (1
2%);
F, 8
/25
(32%
) 4.
24–M
, not
test
ed; F
, 9/2
5 (3
6%)
7.88
–M, 1
3/25
(52%
); F,
5/2
3 (2
3%)
12.14
–M, 3
/25
(12%
); F,
9/2
2 (4
1%)
15.16
–M, 9
/25
(36%
); F,
16/
25 (6
4%)
45.5
–M, 1
2/25
(48%
); F,
7/1
5 (4
7%)
54.7
:–M
, 5/2
5 (2
0%);
F, 5
/25
(20%
) 82
.73–
M, 4
/21
(19%
); F,
4/2
4 (1
7%)
86.9
3–M
, 9/2
5 (3
6%);
F, 8
/25
(32%
) 87
.20–
M, 1
6/25
(64%
); F,
11/
25 (4
2%)
+N
R (tr
icap
rylin
) N
o su
bcut
aneo
us T
obs
erve
d in
his
tori
cal c
ontr
ols
Ora
l adm
inis
trat
ion
Mou
se, A
/J (F
) 26
0 d
Wey
and
et a
l. (1
995)
0, 1
6, 9
8 pp
m (t
otal
dos
e; 0
, 11,
67
mg)
in th
e di
et
30/g
roup
Lung
T: 4
/21
(19%
; 4 A
; 0.1
9 ±
0.09
A/a
nim
al),
9/25
(36%
*; 7
A, 2
AdC
; 0.4
8 ±
0.14
T/a
nim
al),
14/2
7 (5
2%*;
14 A
; 0.5
9 ±
0.12
A/a
nim
al)
Fore
stom
ach
T: (0
%) 0
/21,
(5/2
5) (2
0%; 3
P, 2
C;
0.24
± 0
.11**
T/a
nim
al),
27/2
7 (1
00%
**; 1
3 P,
14
C;
4.22
± 0
.41*
*)
*P <
0.0
5 **
P
-
Benzo[a]pyrene
117
Spec
ies,
stra
in (s
ex)
Dur
atio
n R
efer
ence
Dos
ing
regi
men
A
nim
als/
grou
p at
star
tIn
cide
nce
of tu
mou
rsR
esul
t or
sign
ifica
nce
Puri
ty (v
ehic
le)
Com
men
ts
Mou
se, C
SB–/
– or w
ild-
type
(CSP
± o
r CSB
+/+ )
(M
, F)
52 w
k W
ijnho
ven
et a
l. (2
000)
0 an
d 13
mg/
kg b
w b
y ga
vage
, 3 ×
/w
k, 1
3 w
k 6–
18 M
/gro
up, 6
–13
F/gr
oup
Wild
-typ
e: 5
/27
(14
M, 1
3 F;
19%
; 4 b
ronc
hiol
o-al
veol
ar A
, 2 ly
mph
oma)
, 17/
29* (
18 M
, 11
F; 5
9%;
6 br
onch
iolo
-alv
eola
r A, 1
0 fo
rest
omac
h P,
2
fore
stom
ach
SCC
, 2 h
istio
cytic
S, 2
hep
atoc
ellu
lar
A, 1
inte
stin
al A
dC, 1
skin
P)
CSB
–/– :
0/13
(6 M
, 7 F
), 7/
12**
(6 M
, 6 F
; 58%
; 2
bron
chio
lo-a
lveo
lar A
, 2 u
teri
ne S
, 1 fo
rest
omac
h SC
C, 1
inte
stin
al A
dC, 1
skin
his
tiocy
tic S
)
*P =
0.0
023
**P
= 0.
0017
NR
(soy
a oi
l)
Rat,
Crl:
CD
(SD
)BR
(F)
49 w
k el
-Bay
oum
y et
al.
(199
5)
0 an
d 50
μm
ol/a
nim
al, o
nce/
wk,
8
wk
by g
avag
e 30
/gro
up
Mam
mar
y T
inci
denc
e: 1
1/30
[37%
] [in
cide
nce
not c
lear
ly sp
ecifi
ed] (
8 de
smop
last
ic A
, 2 A
, 1
AdC
), 29
/30
(96.
7%; 8
fibr
oA**
, 17
desm
opla
stic
A*
, 7 A
, 22
AdC
**)
Num
bers
of m
amm
ary
T: c
ontr
ols,
14 d
esm
opla
stic
A, 2
A, 1
AdC
; tre
ated
ani
mal
s, 14
fibr
oA*,
35 d
esm
opla
stic
A, 1
1 A
, 56
AdC
**
*P <
0.0
5 **
P
-
IARC MONOGRAPHS – 100F
118
Spec
ies,
stra
in (s
ex)
Dur
atio
n R
efer
ence
Dos
ing
regi
men
A
nim
als/
grou
p at
star
tIn
cide
nce
of tu
mou
rsR
esul
t or
sign
ifica
nce
Puri
ty (v
ehic
le)
Com
men
ts
Vess
elin
ovitc
h et
al.
(197
5a, b
) C
ontd
.
C3A
/JF1
mic
e (a
ll ag
es c
ombi
ned)
: Li
ver T
(A a
nd h
epat
ocel
lula
r C)–
M
, 3/9
7 (3
%),
30/1
48 (2
0%),
33/1
37 (2
4%);
F, 0
/100
(0
%),
1.3%
2/1
26 (1
.3%
), 2/
153
1.3%
) Lu
ng T
(A a
nd A
dC)–
M
, 49/
97 (4
9%),
1 43
8/14
8 (9
3%),
125/
137
(91%
); F,
26
/100
(26%
), 11
5/12
6 (9
1%),
141/
153
(92%
) Fo
rest
omac
h T
(P a
nd S
CC
)–
M, 0
/97
(0%
), 18
/148
(12%
), 42
/137
(31%
); F,
0/1
00
(0%
), 18
/126
(14%
), 31
/153
(20%
) Ly
mph
oret
icul
ar T
(mai
nly
retic
ulum
-cel
l S)–
M
, 0/9
7 (0
%),
26/2
85 (9
%);
F, 2
/100
(2%
), 50
/278
(1
8%) (
high
- and
low
-dos
e gr
oups
com
bine
d)
+
Mou
se, C
D-1
(M, F
) 1
yr
Wis
lock
i et a
l. (1
986)
0 an
d 56
0 nm
ol [1
48 μ
g] (t
otal
dos
e;
give
n as
1/7
, 2/7
, 4/7
on
PND
0, 8
, 15
) 37
M/g
roup
, 27
F/gr
oup
Live
r T: M
, 2/2
8 (7
%; 2
A),
18/3
7* (4
9%; 1
1 A
, 7
C*)
; F, n
o liv
er T
foun
d Lu
ng T
: M, 1
/28
(4%
; 1 A
), 13
/37*
* (35
%; 1
3 A
); F,
0/
31, 1
3/27
** (4
8%) (
13 A
) M
alig
nant
lym
phom
a: M
, 1/2
8 (4
%),
2/37
(5%
); F,
1/
31 (3
%),
4/27
(15%
)
*P <
0.0
05
**P
99%
(DM
SO)
Mou
se, C
D-1
(M, F
) 52
wk
Lavo
ie et
al.
(198
7)
0 an
d 1.
1 μm
ol [2
90 μ
g] (t
otal
dos
e;
give
n as
1/6
, 2/6
, 4/6
on
PND
1, 8
, 15
) 17
M/g
roup
, 14–
18 F
/gro
up
Live
r T: M
, 1/1
7 (6
%; 1
H),
13/1
7* (7
6%; 9
hep
atic
A
, 4 H
); F,
0/1
8, 0
/14
Lu
ng A
: M, 0
/17,
14/1
7* (8
2%);
F, 0
/18,
9/1
4**
(64%
)
*P <
0.0
05
**[P
< 0
.000
5]>
99%
(DM
SO)
Mou
se, S
wis
s-W
ebst
er
BLU
: Ha(
ICR)
(M, F
) 26
wk
Busb
y et
al.
(198
9)
0 an
d 59
.5 μ
g (to
tal d
ose;
giv
en a
s 8.
5, 1
7, 34
μg
on P
ND
1, 8
, 15)
N
R/g
roup
Lung
T: M
, 12/
91 (1
3%; 1
2 A
, 1 A
dC; 0
.15
± 0.
04 T
/m
ouse
), 13
/28
(46%
; 13
A; 0
.71
± 0.
19 A
/mou
se);
F,
7/10
1 (7
%; 7
A; 0
.08
± 0.
03 A
/mou
se),
18/2
7 (6
7%;
18 A
, 1 A
dC; 1
.19
± 0.
21 T
/mou
se)
+>
99%
(DM
SO)
stat
istic
s NR
Mou
se, N
R, n
ewbo
rn
(M, F
) 30
wk
Rip
pe &
Pot
t (19
89)
0, 1
0, 1
00 μ
g/an
imal
, 1 ×
N
R/g
roup
Lung
T: 1
3% [5
/38]
(0.1
3 T/
anim
al),
16%
[5/3
1]
(0.2
3 T/
anim
al),
64%
[21/
33] (
2.52
T/a
nim
al)
+N
R (s
alin
e so
lutio
n +
1%
gela
tine
+ 0.
4% T
wee
n 20
) Ty
pe o
f lun
g tu
mou
r NR;
st
atis
tics N
RM
ouse
, A/J
(F)
260
d W
eyan
d et
al.
(199
5)
0 (u
ntre
ated
), 0
(veh
icle
con
trol
), 1.
79 m
g/an
imal
, 1 ×
29
–30/
grou
p
Lung
T: 7
/30
(23%
; 7 A
; 0.2
7 ±
0.12
A/a
nim
al),
11/3
0 (3
7%; 1
1 A
; 0.4
3 ±
0.11
A/a
nim
al),
29/2
9*
(100
%; 2
7 A
, 2 A
dC; 1
5.8
± 1.
28**
T/a
nim
al);
fore
stom
ach
T: 0
/30
(0%
), 0/
30 (0
%),
24/2
9** (
83%
; 15
P, 9
C; 1
.83
± 0.
25**
T/a
nim
al)
*P <
0.0
5 **
P
-
Benzo[a]pyrene
119
Spec
ies,
stra
in (s
ex)
Dur
atio
n R
efer
ence
Dos
ing
regi
men
A
nim
als/
grou
p at
star
tIn
cide
nce
of tu
mou
rsR
esul
t or
sign
ifica
nce
Puri
ty (v
ehic
le)
Com
men
ts
Mou
se, B
6C3F
1 , in
fant
(M
, F)
26 w
k, 3
9 w
k, 5
2 w
k Ro
drig
uez
et a
l. (1
997)
0 (u
ntre
ated
), 0
(veh
icle
con
trol
s),
125,
250
, 375
μg/
7 g
bw, 1
×
> 30
M/g
roup
, > 3
0 F/
grou
p
Live
r T (M
): A
t wk
26: 0
/41,
0/5
8, 0
/29,
0/2
5, 3
/34
(9%
; m
ultip
licity
, 1.0
); at
wk
39: 0
/34,
0/5
9, 6
/26
(23%
; m
ultip
licity
, 1.0
), 13
/34
(38%
; mul
tiplic
ity, 1
.9),
15/2
3 (6
5%; m
ultip
licity
, 1.9
); at
wk
52: 4
/64
(6%
; m
ultip
licity
, 1.0
), 3/
63 (5
%; m
ultip
licity
, 1.0
), 13
/29
(45%
; mul
tiplic
ity, 1
.8),
14/2
7 (5
2%; m
ultip
licity
, 2.
2), 1
9/24
(79%
; mul
tiplic
ity, 2
.5)
No
liver
T in
F
+N
R (c
orn
oil)
No
fore
stom
ach
tum
ours
Mou
se, C
D-1
(M)
12 m
o Vo
n Tu
ngel
n et
al.
(199
9)
0, 1
00, 4
00 n
mol
[26,
111
μg]
/an
imal
(tot
al d
ose;
giv
en a
s 1/7
, 2/7
, 4/
7 on
PN
D 1
, 8, 1
5)
24/g
roup
Live
r T: 3
/20
(15%
; 1 A
, 2 C
; 1.7
T/li
ver s
ectio
n),
5/21
(24%
; 4 A
, 1 C
; 1.5
T/li
ver s
ectio
n), 9
/20
(45%
; 7
A*, 2
C; >
2.3
T/li
ver s
ectio
n)
Lung
T: 4
/20
(20%
; 4 A
; 1.0
T/lu
ng se
ctio
n), 1
/21
(5%
; 1 A
; 1.0
T/lu
ng se
ctio
n), 9
/20
(45%
; 7 A
, 2 C
; 1.
9 T/
lung
sect
ion)
*P =
0.0
234
> 99
% (D
MSO
)
Rat,
Wis
tar (
F)
~112
wk
Rolle
r et a
l. (1
992)
0 an
d 5
mg/
anim
al, 1
×
NR
/gro
upA
bdom
inal
mes
othe
liom
a an
d S:
3/4
1 (7
.3%
), 33
/37
(89.
2%)
+N
R (3
:1 m
ixtu
re o
f tr
icap
rylin
/ bee
swax
) Li
mite
d re
port
ing
Rat,
Wis
tar (
F)
~116
wk
Rolle
r et a
l. (1
992)
5 m
g/an
imal
, 1 ×
N
R/g
roup
Abd
omin
al m
esot
helio
ma
and
S: 1
9/38
(50%
); hi
stor
ical
con
trol
s, 11
/369
(3%
)+
NR
(sal
ine
solu
tion)
N
o co
ntro
l; lim
ited
repo
rtin
g of
tum
our d
ata
Inha
lati
onH
amst
er, S
yria
n go
lden
(M)
Life
time
Thys
sen
et a
l. (1
981)
0, 2
.2, 9
.5, 4
6.5
mg/
m3,
4.5
h/d
, 7 d
/w
k, 1
0 w
k; th
erea
fter 3
h/d
, 7 d
/wk
(tota
l ave
rage
dos
es: 0
, 29,
127
, 383
m
g/an
imal
) 24
/gro
up (+
ani
mal
s add
ed d
urin
g th
e st
udy)
Resp
irat
ory
trac
t T:
(pol
yps,
P, S
CC
)–
0/27
, 0/2
7, 34
.6%
[9/2
6; 3
nas
al, 8
lary
ngea
l, 1
trac
heal
], 52
% [1
3/25
; 1 n
asal
, 13
lary
ngea
l, 3
trac
heal
; no
bron
chog
enic
T]
Upp
er d
iges
tive
trac
t T:
(pol
yps,
P, S
CC
)–
0/27
, 0/2
7, 26
.9%
[6/2
6; 6
pha
ryng
eal,
1 fo
rest
omac
h], 5
6% [1
4/25
; 14
phar
ynge
al,
2 oe
soph
agea
l, 1
fore
stom
ach]
+N
R (0
.1% sa
line
solu
tion)
; pa
rtic
le si
ze, >
99%
dia
met
er
0.2–
0.5
μm, >
80%
dia
met
er
0.2–
0.3
μm
Surv
ival
dec
reas
ed fo
r hig
h do
se-e
xpos
ed a
nim
als (
59
wk)
vs o
ther
gro
ups (
96 w
k).
Tabl
e 3.
1 (c
onti
nued
)
-
IARC MONOGRAPHS – 100F
120
Spec
ies,
stra
in (s
ex)
Dur
atio
n R
efer
ence
Dos
ing
regi
men
A
nim
als/
grou
p at
star
tIn
cide
nce
of tu
mou
rsR
esul
t or
sign
ifica
nce
Puri
ty (v
ehic
le)
Com
men
ts
Intr
apul
mon
ary
inje
ctio
nRa
t, O
M (F
) 64
(hig
h-do
se
grou
p)–1
33 w
k (u
ntre
ated
con
trol
s)
Deu
tsch
-Wen
zel e
t al.
(198
3)
0 (u
ntre
ated
), 0
(veh
icle
con
trol
), 0.
1, 0
.3, 1
.0 m
g/an
imal
, 1 ×
35
/gro
up
Lung
T: [
0/35
] (0%
), [0
/35]
(0%
), [1
0/35
] (28
.6%
) (4
epid
erm
oid
C; 6
ple
omor
phic
S),
[23/
35] (
65.7
%)
(21
epid
erm
oid
C; 2
ple
omor
phic
S),
[33/
35]
(94.
3%) (
33 e
pide
rmoi
d C
)
+99
.1% (1
:1 m
ixtu
re o
f bee
swax
an
d tr
ioct
anoi
n)
Rats
, F34
4/N
Slc
(M)
104
wk
Iwag
awa
et a
l. (1
989)
0, 0
.03,
0.1
, 0.3
, 1.0
mg/
an
imal
, 1 ×
N
R/g
roup
Lung
T: 0
/40,
1/2
9 (3
%; 1
und
iffer
entia
ted
T), 7
/30
(23%
; 6 S
CC
, 1 u
ndiff
eren
tiate
d T)
, 22/
29 (7
6%; 2
0 SC
C, 2
und
iffer
entia
ted
T), 9
/13
(69%
; 9 S
CC
)
+N
R (1
:1 m
ixtu
re o
f bee
swax
/tr
icap
rylin
)
Rat,
Osb
orne
-Men
del
(F)
134
wk
(low
-dos
e gr
oup)
–140
wk
(veh
icle
co
ntro
ls)
Wen
zel-H
artu
ng et
al.
(199
0)
0 (u
ntre
ated
), 0
(veh
icle
con
trol
), 30
, 100
, 300
μg/
an
imal
, 1 ×
35
/gro
up
Lung
T: [
0/35
] (0%
), [0
/35]
(0%
), [3
/35]
(8.6
%; 3
SC
C),
[11/
35] (
31.4
%; 1
1 SC
C),
[27/
35] (
77.1%
; 27
SCC
).
+99
.6%
(bee
swax
/tri
octa
noin
m
ixtu
re o
f var
ying
co
mpo
sitio
n)
SCC
pre
dom
inan
tly
kera
tiniz
ed
Rat,
F344
/DuC
rj (M
) 10
0 w
k H
orik
awa
et a
l. (1
991)
0, 5
0, 1
00, 2
00 μ
g/an
imal
, 1 ×
9–
10/g
roup
Lung
T: 0
/19,
0/1
0, 3
/10
(30%
; 2 S
CC
, 1 A
dSC
), 4/
9 (4
4.4%
; 3 S
CC
, 1 u
ndiff
eren
tiate
d T)
+N
R (1
:1 m
ixtu
re o
f bee
swax
/tr
icap
rylin
)
Intr
atra
chea
l ad
min
istr
atio
nRa
t, W
ista
r-W
U/
Kis
slegg
(F)
124–
126
wk
Pott
et a
l. (1
987)
0 an
d 1
mg/
anim
al, o
nce/
wk,
20
wk
NR
/gro
upLu
ng T
: 0/4
0, 7
/36
(19%
; 1 A
, 5 S
CC
, 1 m
ixed
A
dC/S
CC
)+
NR
(0.9
% sa
line
solu
tion)
Rat,
Spra
gue-
Daw
ley
(M, F
) C
ontr
ols,
131
wk;
tr
eate
d an
imal
s, 11
2 w
k St
einh
off et
al.
(199
1)
0 an
d 0
(phy
siolo
gica
l sal
ine)
, 7
mg/
kg b
w/in
still
atio
n (p
hysio
logi
cal s
alin
e w
ith T
wee
n 60
), on
ce/2
wk,
44
wk
20 o
r 50/
grou
p
M: 0
/50,
0/5
0, 1
9/20
(95%
; 19
mal
igna
nt lu
ng T
) F:
0/5
0, 0
/50,
19/
20 (9
5%; 1
8 m
alig
nant
, 1 b
enig
n lu
ng T
)
+N
R (p
hysio
logi
cal s
alin
e so
lutio
n w
ith o
r with
out
Twee
n 60
) Li
mite
d hi
stol
ogy
Tabl
e 3.
1 (c
onti
nued
)
-
Benzo[a]pyrene
121
Spec
ies,
stra
in (s
ex)
Dur
atio
n R
efer
ence
Dos
ing
regi
men
A
nim
als/
grou
p at
star
tIn
cide
nce
of tu
mou
rsR
esul
t or
sign
ifica
nce
Puri
ty (v
ehic
le)
Com
men
ts
Ham
ster
, Syr
ian
gold
en (M
, F)
78 w
k Fe
ron
(197
2)
0 (o
nly
for M
), 1
mg/
anim
al, o
nce/
wk,
36
wk
35/g
roup
Resp
irat
ory
trac
t T/a
deno
mat
oid
lesio
ns:
M–6
/27
(22%
; 1 tr
ache
al P
, 5 p
ulm
onar
y ad
enom
atoi
d le
sion)
, 19/
29 (6
6%; 1
trac
heal
P,
17 S
CC
, 26
pulm
onar
y ad
enom
atoi
d le
sion,
5 A
, 1
AdC
, 1 S
CC
) F–
22/2
7 (8
1%; 1
lary
ngea
l SC
C, 1
6 tr
ache
al S
CC
, 2
bron
chia
l A, 1
AdC
, 21
pulm
onar
y ad
enom
atoi
d le
sion,
8 A
, 1 A
dC)
+>
99%
(0.9
% sa
line
solu
tion)
N
o fe
mal
e co
ntro
ls; S
tatis
tics
NR
Ham
ster
, Syr
ian
gold
en (M
) 78
wk
Fero
n et
al.
(197
3)
0, 0
.062
5, 0
.125
, 0.2
5, 0
.5, 1
.0 m
g/an
imal
, onc
e/w
k, 5
2 w
k 30
/gro
up
Resp
irat
ory
trac
t T:
0/29
, 3/3
0 (1
0%; 3
trac
heal
P, 1
pul
mon
ary
A),
4/30
(13%
; 1 tr
ache
al P
, 4 p
ulm
onar
y A
), 9/
30
(30%
; 5 tr
ache
al P
, 7 p
ulm
onar
y A
), 25
/29
(86%
; 2
trac
heal
pol
yp, 9
P, 5
SC
C, 1
AdS
C, 1
fibr
oS,
2 br
onch
ial p
olyp
, 1 P
, 2 S
CC
, 1 A
dSC
), 26
/28
(93%
; 6 tr
ache
al P
, 11
SCC
, 1 A
dSC
, 1 b
ronc
hial
po
lyp,
2 P
, 4 S
CC
, 2 A
dSC
, 4 A
dC, 1
ana
plas
tic
C, 1
6 pu
lmon
ary
A, 4
SC
C, 3
AdS
C, 1
AdC
, 2
anap
last
ic C
)
+N
R (0
.9%
salin
e so
lutio
n)
Ham
ster
, Syr
ian
gold
en (M
, F)
M, 6
7–88
wk;
F, 6
0–88
w
k H
enry
et a
l. (1
973)
0, 1
3.3–
15.5
mg/
anim
al, o
nce/
wk,
8
wk
50/g
roup
, 25
cont
rols/
grou
p
Resp
irat
ory
trac
t T:
Con
trol
s–
1 tr
ache
al p
olyp
, 6 p
ulm
onar
y br
onch
iola
r ad
enom
atoi
d le
sions
/47
anim
als
Trea
ted
anim
als–
26
/65
(40%
; 1 n
asal
pol
yp; 6
lary
ngea
l pol
yps,
1 P,
1 A
, 1 A
dC, 7
trac
heal
pol
yps,
1 A
dC, 1
SC
C, 1
fibr
oS, 2
bro
nchi
al A
dC, 1
3 pu
lmon
ary
bron
chio
lar a
deno
mat
oid
lesio
n, 3
A, 5
AdC
, 1
SCC
, 2 a
napl
astic
C, 1
mix
ed C
, 1 m
yelo
geno
us
leuk
aem
ia, 1
neu
rofib
roS)
T
at o
ther
site
s: C
ontr
ols–
1
rena
l A
Trea
ted
anim
als–
3
blas
t-ce
ll le
ukae
mia
, 2 a
dren
ocor
tical
A, 1
rena
l A
dC, 1
oes
opha
geal
fibr
oS, 1
hae
man
giom
a
+N
R (0
.5%
gel
atin
e in
0.9
%
salin
e so
lutio
n)
Tum
our d
ata
for M
and
F
com
bine
d; st
atis
tics N
R
Tabl
e 3.
1 (c
onti
nued
)
-
IARC MONOGRAPHS – 100F
122
Spec
ies,
stra
in (s
ex)
Dur
atio
n R
efer
ence
Dos
ing
regi
men
A
nim
als/
grou
p at
star
tIn
cide
nce
of tu
mou
rsR
esul
t or
sign
ifica
nce
Puri
ty (v
ehic
le)
Com
men
ts
Ham
ster
, Syr
ian
gold
en (M
, F)
60 w
k K
obay
ashi
(197
5)
0 an
d 1
mg/
anim
al, o
nce/
wk,
30
wk
20–3
2 M
/gro
up, 2
0–28
F/g
roup
Resp
irat
ory
trac
t T:
M–0
/20,
11/
26 (4
2.3%
; 1 la
ryng
eal p
olyp
, 1
trac
heal
pol
yp, 1
P, 1
bro
nchi
al S
CC
, 9 lu
ng A
, 7
AdC
, 3 S
CC
, 1 a
napl
astic
C, 2
AdS
C)
F–0/
20, 1
4/26
(53.
8%; 1
lary
ngea
l P, 2
trac
heal
po
lyps
, 1 b
ronc
hial
SC
C, 1
0 lu
ng A
, 3 A
dC, 1
SC
C)
+N
R (0
.9%
salin
e)
Ham
ster
, Syr
ian
gold
en (M
, F)
78 w
k K
ruys
se &
Fer
on
(197
6)
0 (u
ntre
ated
), 0
(veh
icle
con
trol
s),
1 m
g/an
imal
, onc
e/2
wk,
52
wk
17 o
r 40/
grou
p
Resp
irat
ory
trac
t T:
M–0
/40,
0/4
0, 1
3/14
(93%
; 2 la
ryng
eal P
, 1 S
CC
, 4
trac
heal
P, 3
SC
C, 1
ana
plas
tic C
, 1 S
, 1 b
ronc
hial
SC
C, 1
AdC
, 5 p
ulm
onar
y A
, 1 A
dC)
F–0/
40, 0
/40,
7/1
2 (5
8%; 2
trac
heal
P, 3
SC
C,
1 br
onch
ial P
, 5 p
ulm
onar
y A
)
+>
99%
(sal
ine
solu
tion)
Ham
ster
, Syr
ian
gold
en (M
) 10
0 w
k Se
llaku
mar
et a
l. (1
976)
0 (u
ntre
ated
), 3
mg/
anim
al, o
nce/
wk,
10
wk
48/g
roup
Resp
irat
ory
trac
t T:
0/48
, 7/4
8 (1
5%; 2
lary
ngea
l P, 4
trac
heal
P, 1
lung
A
) T
at o
ther
site
s: 6/
48 (1
3%; 3
fore
stom
ach
P, 2
lym
phom
a, 1
an
apla
stic
C),
26/4
8 (5
4%; 2
1 fo
rest
omac
h P,
1 sk
in m
elan
oma,
1 li
ver h
aem
angi
oma,
1
adre
noco
rtic
oA, 3
adr
enoc
ortic
oC)
+>
99%
(0.9
% sa
line
solu
tion)
Ham
ster
, Syr
ian
gold
en (M
, F)
Expe
rim
ent 1
: up
to
89 w
k fo
r M a
nd 7
0 w
k fo
r F
Expe
rim
ent 2
: up
to
83 w
k fo
r M a
nd 6
8 w
k fo
r F
Ket
kar e
t al.
(197
7)
Expe
rim
ent 1
: 0,
4, 8
, 16
mg
in 0
.9%
salin
e so
lutio
n/an
imal
, 1 ×
30
/gro
up
Resp
irat
ory
trac
t T:
Expe
rim
ent 1
– M
0/2
4, 3
/30
(10%
; 1 la
ryng
eal P
, 1 tr
ache
al P
, 1
lung
S),
5/28
(18%
; 1 la
ryng
eal S
CC
, 1 tr
ache
al P
, 4
lung
S),
4/27
(15%
; 3 tr
ache
al P
, 1 lu
ng A
, 1 S
) F
0/28
, 3/2
9 (1
0%; 1
trac
heal
P, 2
lung
A),
1/30
(3
%; 1
lung
A),
3/28
(13%
; 1 la
ryng
eal P
, 2 lu
ng A
)
+97
% (0
.9%
salin
e so
lutio
n or
Tr
is b
uffer
)
Expe
rim
ent 2
: 0,
4, 8
, 16
mg
in T
ris b
uffer
/ an
imal
, 1 ×
30
/gro
up
Expe
rim
ent 2
– M
0/2
7, 5/
24 (2
1%; 1
trac
heal
P, 5
lung
A),
13/2
5 (5
2%; 1
lary
ngea
l P, 7
trac
heal
P, 4
lung
A, 3
AdC
), 8/
27 (3
0%; 2
lary
ngea
l P, 1
SC
C, 3
trac
heal
P, 3
lu
ng A
) F
0/27
, 3/2
7 (1
1%; 2
trac
heal
P, 1
lung
AdC
), 2/
29
(7%
; 2 tr
ache
al P
), 8/
29 (2
8%; 1
lary
ngea
l P, 4
tr
ache
al P
, 5 lu
ng A
)
+
Tabl
e 3.
1 (c
onti
nued
)
-
Benzo[a]pyrene
123
Spec
ies,
stra
in (s
ex)
Dur
atio
n R
efer
ence
Dos
ing
regi
men
A
nim
als/
grou
p at
star
tIn
cide
nce
of tu
mou
rsR
esul
t or
sign
ifica
nce
Puri
ty (v
ehic
le)
Com
men
ts
Ham
ster
, Syr
ian
gold
en (M
, F)
81 w
k Fe
ron
& K
ruys
se
(197
8)
0 (u
ntre
ated
), 0
(veh
icle
con
trol
s),
0.35
, 0.7
mg/
anim
al, o
nce/
wk,
52
wk
15 o
r 30/
grou
p
Resp
irat
ory
trac
t T:
M–0
/30
(unt
reat
ed a
nd v
ehic
le c
ontr
ols
com
bine
d), 4
/29
(14%
; 2 tr
ache
al P
, 1 b
ronc
hial
P,
2 p
ulm
onar
y A
), 19
/30
(63%
; 1 la
ryng
eal P
, 5
trac
heal
P, 1
SC
C, 1
ana
plas
tic C
, 1 S
, 2 b
ronc
hial
P,
1 A
dC, 1
1 pu
lmon
ary
A, 2
AdC
, 1 S
CC
, 1
anap
last
ic C
) F–
0/28
(unt
reat
ed a
nd v
ehic
le c
ontr
ols
com
bine
d), 3
/27
(11%
; 1 la
ryng
eal P
, 1 b
ronc
hial
P,
1 pu
lmon
ary
A),
7/24
(29%
; 1 tr
ache
al P
, 2 S
CC
, 1
bron
chia
l AdC
, 5 p
ulm
onar
y A
)
+>
99%
(0.9
% sa
line
solu
tion)
St
atis
tics N
R
Ham
ster
, Syr
ian
gold
en (M
, F)
Aver
age
surv
ival
up
to 4
1 w
k fo
r M a
nd 3
5 w
k fo
r F
Ket
kar e
t al.
(197
8)
0, 0
.1, 0
.33,
1.0
mg/
anim
al, o
nce/
wk
30/g
roup
Resp
irat
ory
trac
t T:
M–0
/29,
5/2
6 (1
9%; 5
bro
nchi
ogen
ic A
), 7/
29
(24%
; 5 tr
ache
al P
, 2 b
ronc
hiog
enic
A),
6/27
(22%
; 5
trac
heal
P, 2
bro
nchi
ogen
ic A
) F–
0/30
, 12/
30 (4
0%; 1
trac
heal
P, 1
SC
C, 1
0 br
onch
ioge
nic
A),
10/2
8 (3
6%; 7
trac
heal
P, 5
br
onch
ioge
nic
A, 1
SC
C),
6/30
(20%
; 3 tr
ache
al P
, 3
bron
chio
geni
c A
, 3 S
CC
)
+97
% (1
0% b
ovin
e se
rum
al
bum
in)
Aver
age
surv
ival
tim
e m
uch
low
er in
the
high
-dos
e gr
oup
than
in th
e ot
her g
roup
s
Ham
ster
, Syr
ian
gold
en (M
, F)
Life
time,
up
to 9
0 w
k St
enbä
ck &
Row
land
(1
978)
0, 3
mg
larg
e pa
rtic
les,
3 m
g sm
all
part
icle
s/an
imal
, onc
e/w
k, 1
8 w
k 48
(M +
F)/g
roup
Resp
irat
ory
trac
t T (M
+ F
com
bine
d): 0
/46,
31
/47
(66%
; 5 la
ryng
eal P
, 12
trac
heal
P, 2
0 SC
C,
2 un
spec
ified
T, 2
bro
nchi
al P
, 9 S
CC
, 3 A
, 2
anap
last
ic C
), 5/
46 (1
1%; 1
lary
ngea
l P, 1
SC
C,
4 tr
ache
al P
)
+99
.4%
(0.9
% sa
line
solu
tion)
; pa
rtic
le si
ze b
y w
eigh
t: la
rge-
98%
< 3
0 μm
, 90%
< 2
0 μm
, 36%
< 1
0 μm
, 10%
< 5
μm
; sm
all-9
8% <
10
μm, 7
9%
-
IARC MONOGRAPHS – 100F
124
Spec
ies,
stra
in (s
ex)
Dur
atio
n R
efer
ence
Dos
ing
regi
men
A
nim
als/
grou
p at
star
tIn
cide
nce
of tu
mou
rsR
esul
t or
sign
ifica
nce
Puri
ty (v
ehic
le)
Com
men
ts
Ham
ster
, Syr
ian
gold
en (M
, F)
105
wk
Fero
n et
al.
(198
0)
0 (u
ntre
ated
), 0
(gel
atin
e in
0.9
%
salin
e), 0
.5, 1
.0 m
g fin
e pa
rtic
les,
0.5,
1.0
mg
coar
se p
artic
les,
1.0
mg
wid
e-ra
nge
part
icle
s/an
imal
, onc
e/w
k, 5
2 w
k 30
–35/
grou
p
Resp
irat
ory
trac
t T:
M–0
/29,
2/3
4 (6
%; 2
lary
ngea
l P),
7/34
(21%
; 1
lary
ngea
l P, 6
trac
heal
P, 1
lung
A),
6/31
(19%
; 2
lary
ngea
l P, 1
trac
heal
P, 1
S,1
pul
mon
ary
A),
13/3
1 (4
2%; 2
lary
ngea
l P, 3
trac
heal
P, 9
pu
lmon
ary
A),
25/3
4 (7
4%; 2
lary
ngea
l P, 9
tr
ache
al P
, 4 S
CC
, 2 S
, 1 p
ulm
onar
y A
, 1 A
dC),
23/3
4 (6
8%; 2
lary
ngea
l P, 1
SC
C, 6
trac
heal
P, 2
SC
C, 1
bro
nchi
al P
, 1 S
CC
, 13
pulm
onar
y A
, 2
AdC
, 2 a
napl
astic
C)
F–0/
28, 2
/33
(6%
; 1 tr
ache
al P
, 1 p
ulm
onar
y A
), 2/
34 (6
%; 1
bro
nchi
al P
, 1 A
), 5/
32 (1
6%;
1 la
ryng
eal P
, 2 tr
ache
al P
, 3 p
ulm
onar
y A
), 9/
32
(28%
; 2 la
ryng
eal P
, 5 tr
ache
al P
, 6 p
ulm
onar
y A
), 19
/32
(31%
; 4 tr
ache
al P
, 1 S
CC
, 1 S
, 1 b
ronc
hial
P,
7 pu
lmon
ary
A, 1
AdC
), 11
/34
(34%
; 1 la
ryng
eal
P, 3
trac
heal
P, 2
bro
nchi
al P
, 7 p
ulm
onar
y A
, 1
AdC
)
+N
R; p
artic
les s
ize
by w
eigh
t: fin
e, 7
7% <
5.2
μm
, 60%
99%
(0.5
% g
elat
ine
in 0
.9%
sa
line
solu
tion)
Intr
atra
chea
l adm
inis
trat
ion
of c
ombi
nati
ons o
f ben
zo[a
]pyr
ene
and
‘par
ticl
es/fi
bres
’Ra
t, Sp
ragu
e-D
awle
y (M
, F)
Up
to 1
30 w
k St
einh
off et
al.
(199
1)
0, (u
ntre
ated
), 0
(phy
siolo
gica
l sa
line)
, 10–
40 m
g/kg
bw
Bay
ferr
ox
130
(96.
2% c
ubic
α-F
e 2O
3),
10–4
0 m
g/kg
bw
Bay
ferr
ox 9
20
(86.
1% fi
brou
s α-F
eOO
H),
7 m
g/kg
bw
, 7 m
g/kg
bw
+ 1
0–40
mg/
kg b
w
Bayf
erro
x 13
0, 7
mg/
kg b
w +
10
–40
mg/
kg b
w B
ayfe
rrox
920
, ~o
nce/
2 w
k, 4
4–~1
30 w
k 20
or 5
0/gr
oup
Lung
T:
M–0
/50,
0/5
0, 0
/50,
0/5
0, 1
9 m
alig
nant
T in
20
anim
als,
21 m
alig
nant
and
1 b
enig
n T
in 2
0 an
imal
s, 17
mal
igna
nt a
nd 1
ben
ign
T in
20
anim
als
F–0/
50, 0
/50,
0/5
0, 1
mal
igna
nt a
nd 1
ben
ign
T in
50
anim
als,
18 m
alig
nant
and
1 b
enig
n T
in 2
0 an
imal
s, 16
mal
igna
nt T
in 2
0 an
imal
s, 17
mal
igna
nt a
nd 2
ben
ign
T in
20
anim
als
+N
R (p
hysio
logi
cal s
alin
e so
lutio
n w
ith o
r with
out
Twee
n 60
); Ba
yfer
rox
130,
Ba
yfer
rox
920
Lim
ited
hist
olog
y
Tabl
e 3.
1 (c
onti
nued
)
-
Benzo[a]pyrene
125
Spec
ies,
stra
in (s
ex)
Dur
atio
n R
efer
ence
Dos
ing
regi
men
A
nim
als/
grou
p at
star
tIn
cide
nce
of tu
mou
rsR
esul
t or
sign
ifica
nce
Puri
ty (v
ehic
le)
Com
men
ts
Ham
ster
, Syr
ian
gold
en (M
, F)
Life
time
(up
to 1
40
wk)
Sa
ffiot
ti et
al.
(197
2)
Expe
rim
ent 1
0,
50
mg
ferr
ic o
xide
, 5 m
g +
45 m
g fe
rric
oxi
de, 1
2.5
mg
+ 37
.5 m
g fe
rric
oxi
de/ a
nim
al,
1 ×
Expe
rim
ent 2
(2
gro
ups/
dose
leve
l) 5
mg
+ 5
mg
ferr
ic o
xide
, 10
mg
+ 10
mg
ferr
ic o
xide
, 15
mg
+ 15
mg
ferr
ic o
xide
, onc
e/w
k, 1
5 w
k 23
–110
M/g
roup
, 18–
107
F/gr
oup
Expe
rim
ent 1
: Re
spir
ator
y tr
act T
– M
0/4
5, 0
/101
, 3/9
2 (3
%; 1
trac
heal
pol
yp, 1
P,
1 b
ronc
hial
A),
3/27
(11%
; 1 b
ronc
hial
A, 1
br
onch
ogen
ic S
CC
, 1 a
napl
astic
C)
F 0/
44, 0
/89,
4/9
7 (4
%; 1
trac
heal
pol
yp, 1
P, 1
br
onch
iola
r A, 1
AdC
), 6/
33 (1
8%; 1
bro
nchi
al
P, 1
A, 2
bro
ncho
geni
c SC
C, 1
ana
plas
tic C
, 2
bron
chio
lar A
) Fo
rest
omac
h P–
M
5/4
5 (1
1%; 6
T),
5/10
1 (5
%; 5
T),
15/9
2 (1
6%; 3
5 T)
, 8/2
7 (3
0%; 1
6 T)
F
2/44
(5%
; 2 T
), 2/
89 (2
%; 3
T),
5/97
(5%
; 5 T
), 4/
33 (1
2%; 6
T)
+N
R (0
.9%
salin
e so
lutio
n);
ferr
ic o
xide
Expe
rim
ent 2
: Re
spir
ator
y tr
act T
(M +
F c
ombi
ned)
– 7/
50 (1
4%; 2
trac
heal
P, 1
SC
C, 1
bro
nchi
al P
, 1 A
, 2
SCC
, 1 a
napl
astic
C, 1
pul
mon
ary
SCC
), 8/
58 (1
4%; 2
trac
heal
pol
yps,
1 br
onch
ial p
olyp
, 2
SCC
, 2 A
dC, 2
pul
mon
ary
A, 2
AdC
), 17
/61
(28%
; 2 tr
ache
al p
olyp
s, 2
P, 5
SC
C, 5
bro
nchi
al
SCC
, 1 p
ulm
onar
y A
, 1 S
CC
, 1 A
dC, 1
ana
plas
tic
C),
25/6
0 (4
2%; 4
trac
heal
pol
yps,
3 P,
3 S
CC
, 4
anap
last
ic C
, 1 b
ronc
hial
P, 1
SC
C, 2
ana
plas
tic
C, 4
AdC
, 1 A
, 2 p
ulm
onar
y SC
C, 2
ana
plas
tic
C, 6
A),
25/3
9 (6
4%; 1
trac
heal
P, 1
0 SC
C, 1
an
apla
stic
C, 3
bro
nchi
al P
, 7 S
CC
, 11
anap
last
ic
C, 2
AdC
, 2 p
ulm
onar
y SC
C, 2
A),
35/5
5 (6
4%;
2 la
ryng
eal S
CC
, 11
trac
heal
P, 1
pol
yp, 1
2 SC
C, 1
car
cino
S, 2
fibr
oS, 1
6 br
onch
ial S
CC
, 10
anap
last
ic C
, 6 A
dC, 3
A, 2
pul
mon
ary
A)
+
Fore
stom
ach
T–
M 8
/22
(36%
; 13
P, 1
SC
C),
6/
28 (2
1%; 9
P),
11/3
4 (3
2%; 2
8 P,
1 S
CC
), 11
/30
(37%
; 18
P), 5
/22
(23%
; 10
P), 1
/28
(4%
; 1 P
) F
9/28
(32%
; 14
P), 6
/30
(20%
; 9 P
), 5/
27 (1
9%; 2
0 P)
, 8/3
0 (2
7%; 1
0 P,
1 S
CC
), 5/
17 (2
9%; 1
1 P)
, 3/2
7 (1
1%; 3
P)
Tabl
e 3.
1 (c
onti
nued
)
-
IARC MONOGRAPHS – 100F
126
Spec
ies,
stra
in (s
ex)
Dur
atio
n R
efer
ence
Dos
ing
regi
men
A
nim
als/
grou
p at
star
tIn
cide
nce
of tu
mou
rsR
esul
t or
sign
ifica
nce
Puri
ty (v
ehic
le)
Com
men
ts
Ham
ster
, Syr
ian
gold
en (F
) Pr
esum
ably
life
time
Pott
et a
l. (1
973b
)
340
µg in
tric
apry
lin,
340
µg in
Tw
een
60/s
alin
e so
lutio
n,
340
µg in
Tw
een
60/s
alin
e so
lutio
n +
850
µg a
tmos
pher
ic d
ust/a
nim
al,
45 ×
with
in a
per
iod
of 6
.5 m
o (to
tal d
ose,
~15
mg;
dus
t, 38
mg)
48
/gro
up
Resp
irat
ory
trac
t T (b
enig
n an
d m
alig
nant
T o
f th
e la
rynx
, tra
chea
or b
ronc
hi):
2/48
(4%
), 14
/48
(29%
), 16
/48
(33%
)
+N
R (tr
icap
rylin
, Tw
een
60/
salin
e so
lutio
n); a
tmos
pher
ic
dust
from
Boc
hum
, Ger
man
y (p
artic
le si
ze <
5 μ
m)
Ham
ster
, Syr
ian
(M, F
) 10
0 w
k Se
llaku
mar
et a
l. (1
973)
0 (u
ntre
ated
), 3
mg
+ 3
mg
ferr
ic
oxid
e, 3
mg
+ 6
mg
ferr
ic o
xide
, 3
mg
+ 9
mg
ferr
ic o
xide
, onc
e/2
wk,
20
wk
36/g
roup
, 193
con
trol
s/gr
oup
Resp
irat
ory
trac
t T (M
+ F
com
bine
d):
0/19
3, 2
6/67
(39%
; 3 la
ryng
eal p
olyp
, 3 P
, 3 S
CC
, 7
trac
heal
pol
yp, 6
P, 2
SC
C, 2
bro
nchi
al p
olyp
, 5
SCC
, 9 A
dC, 1
ana
plas
ic C
, 7 lu
ng A
, 1 A
dC),
28/6
4 (4
4%; 1
lary
ngea
l pol
yp, 3
P, 6
SC
C, 3
tr
ache
al p
olyp
, 9 P
, 3 S
CC
, 3 b
ronc
hial
pol
yp, 1
P,
4 SC
C, 3
AdC
, 1 a
napl
astic
C, 7
lung
A, 4
AdC
), 26
/66
(39%
; 3 la
ryng
eal p
olyp
, 6 S
CC
, 6 tr
ache
al
poly
p, 1
1 P,
1 S
CC
, 1 b
ronc
hial
pol
yp, 1
P, 4
SC
C,
4 A
dC, 2
ana
plas
tic C
, 6 lu
ng A
, 6 A
dC)
Fore
stom
ach
T:
M–0
/193
(M +
F),
17/3
2 (5
3%; 3
7 P)
, 10/
31 (3
2%;
16 P
, 1 S
CC
), 6/
35 (1
7%; 1
5 P)
F–
0/19
3 (M
+ F
), 10
/35
(29%
; 30
P), 1
2/33
(36%
; 25
P),
15/3
1 (4
8%; 3
3 P)
+N
R (0
.9%
salin
e so
lutio
n);
ferr
ic o
xide
Ham
ster
, Syr
ian
gold
en (M
, F)
Life
time
(up
to 1
20
wk)
St
enbä
ck et
al.
(197
5)
0 (u
ntre
ated
),
2 m
g +
1 m
g m
agne
sium
oxi
de/
anim
al, o
nce/
wk,
20
wk,
3 m
g +
3 m
g fe
rric
oxi
de/a
nim
al, o
nce/
wk,
15
wk
48 o
r 90/
grou
p
Resp
irat
ory
trac
t tum
ours
(M +
F c
ombi
ned)
: 0/
89, 3
2/45
[71%
] (11
lary
ngea
l P, 3
SC
C, 1
tr
ache
al p
olyp
, 20
P, 5
SC
C, 1
AdC
, 1 b
ronc
hial
P,
3 A
, 8 A
dC, 9
SC
C, 1
AdS
C),
31/4
4 (7
0%;
10 la
ryng
eal P
, 4 S
CC
, 8 tr
ache
al P
, 12
SCC
, 2
anap
last
ic C
, 2 b
ronc
hial
P, 4
A, 2
AdC
, 17
SCC
, 3
anap
last
ic C
)
+N
R (0
.2%
salin
e so
lutio
n);
ferr
ic o
xide
, mag
nesiu
m
oxid
e
Tabl
e 3.
1 (c
onti
nued
)
-
Benzo[a]pyrene
127
Spec
ies,
stra
in (s
ex)
Dur
atio
n R
efer
ence
Dos
ing
regi
men
A
nim
als/
grou
p at
star
tIn
cide
nce
of tu
mou
rsR
esul
t or
sign
ifica
nce
Puri
ty (v
ehic
le)
Com
men
ts
Ham
ster
, Syr
ian
gold
en (M
, F)
Life
time
(up
to 1
00
wk)
St
enbä
ck &
Row
land
(1
979)
0 (u
ntre
ated
), 0
(sal
ine)
, 0 (g
elat
ine
in sa
line)
, 3 m
g si
licon
dio
xide
in
salin
e, 1
.5 m
g m
anga
nese
dio
xide
in
salin
e, 3
mg
in sa
line,
3 m
g in
ge
latin
e/sa
line,
3 m
g +
3 m
g si
licon
di
oxid
e in
salin
e, 1
.5 m
g +
1.5
mg
man
gane
se d
ioxi
de in
salin
e/an
imal
, onc
e/w
k, 2
0 w
k
50/g
roup
All
T (M
+ F
com
bine
d): 2
/100
(2%
; 2
lym
phom
a), 1
/48
(2%
; 2 fo
rest
omac
h P)
, 2/4
5 (4
%;
2 ly
mph
oma)
, 0/4
8 (0
%),
2/48
(4%
; 1 fo
rest
omac
h P,
1 ly
mph
oma)
, 18/
46 (3
9%; 1
lary
ngea
l P, 1
SC
C, 4
trac
heal
P, 1
5 fo
rest
omac
h P)
, 11/
47 (2
3%;
2 tr
ache
al P
, 1 S
CC
, 3 b
ronc
hial
SC
C, 1
sple
nic
haem
angi
oma,
1 a
dren
al c
ortic
al A
, 1 ly
mph
oma,
2
fore
stom
ach
SCC
), 25
/48
(52%
; 1 la
ryng
eal S
CC
, 8
trac
heal
P, 2
SC
C, 3
bro
nchi
al S
CC
, 6 lu
ng A
, 3
AdC
, 10
fore
stom
ach
P, 1
thyr
oid
A, 1
ute
rine
fib
rom
a, 1
A, 1
lym
phom
a), 2
0/48
(42%
; 1
lary
ngea
l P, 3
trac
heal
P, 1
SC
C, 1
bro
nchi
al S
CC
, 24
fore
stom
ach
P, 1
ova
rian
fibr
oma,
1 th
yroi
d A
, 2
fore
stom
ach
SCC
, 1 sq
uam
ous-
cell
fibro
ma)
+>
99%
(sal
ine,
0.5
% g
elat
ine
in sa
line)
; man
gane
se
diox
ide,
silic
on d
ioxi
de
Ham
ster
, Syr
ian
gold
en (M
, F)
82 w
k Re
ynde
rs et
al.
(198
5)
0 an
d 8
mg
+ 6
mg
ferr
ic o
xide
/an
imal
, onc
e/w
k, 6
wk
35/g
roup
Resp
irat
ory
trac
t T:
M–0
/32,
12/
24 (5
0%; 1
5 T:
3 la
ryng
eal P
, 1
trac
heal
P, 1
SC
C, 2
bro
nchi
al p
olyp
, 2 S
CC
, 1A
dC, 3
pul
mon
ary
SCC
, 1 A
dSC
, 1 A
dC)
F–0/
35, 9
/26
(35%
; 12
T: 1
lary
ngea
l P, 5
trac
heal
P,
2 b
ronc
hial
pol
yp, 2
pul
mon
ary
SCC
, 1 A
dSC
, 1
AdC
)
+N
R (0
.9%
salin
e so
lutio
n);
ferr
ic o
xide
Bucc
al p
ouch
Ham
ster
, Syr
ian
gold
en (M
) U
p to
40–
44 w
k w
ith
inte
rim
kill
s afte
r 5,
20, a
nd 2
4–32
wk
Solt
et a
l. (1
987)
Pain
ting
of b
oth
bucc
al p
ouch
with
0,
20
mM
solu
tion/
anim
al, t
wic
e/w
k, 2
0 w
k 28
/gro
up, 2
0 co
ntro
ls/gr
oup
Fore
stom
ach
P: 0
/6, 8
/10*
(afte
r 40–
44 w
k)
Bucc
al p
ouch
SC
C: 0
/6, 1
/10
(afte
r 40–
44 w
k)*[
P
99%
(no
vehi
cle)
Tabl
e 3.
1 (c
onti
nued
)
-
IARC MONOGRAPHS – 100F
128
Spec
ies,
stra
in (s
ex)
Dur
atio
n R
efer
ence
Dos
ing
regi
men
A
nim
als/
grou
p at
star
tIn
cide
nce
of tu
mou
rsR
esul
t or
sign
ifica
nce
Puri
ty (v
ehic
le)
Com
men
ts
Rat,
Spra
gue-
Daw
ley
(F)
45 w
k C
aval
ieri
et a
l. (1
988a
, b)
0 an
d 4
μmol
[1 m
g]/m
amm
ary
glan
d (2
nd, 3
rd, 4
th a
nd 5
th
mam
mar
y gl
and
on b
oth
sides
in
ject
ed),
1 ×
20
/gro
up
Epith
elia
l mam
mar
y T:
[3/2
0] (1
5%; 3
fibr
oA),
[14/
20] (
70%
; 13
AdC
, 3 fi
broA
); m
ultip
licity
: co
ntro
ls, 3
/3 [1
]; tr
eate
d ra
ts: A
dC, 1
8/13
[1.4
]; fib
roA
, 4/3
[1.3
] M
esen
chym
al (m
amm
ary)
T: [
0/20
] (0%
), [1
1/20
] (5
5%; 1
1 fib
roS;
mul
tiplic
ity, 2
0/11
[1.8
])
Skin
T: [
0/20
] (0%
), [9
/20]
(45%
; 9 S
CC
; m
ultip
licity
, 11/
9 [1
.2])
+>
99%
(tri
octa
noin
)
Rat,
Spra
gue-
Daw
ley
(F)
24 w
k C
aval
ieri
et a
l. (1
991)
0, 0
.25
[66
µg],
1 μm
ol [2
64 μ
g]/
mam
mar
y gl
and
(the
2nd,
3rd
, 4th
an
d 5t
h on
bot
h sid
es),
1 ×
20
/gro
up
Epith
elia
l mam
mar
y gl
and
T: 1
/18
(6%
; 1 fi
broA
), 1/
20 (5
%; 1
AdC
), 0/
20 (0
%)
Mes
ench
ymal
(mam
mar
y) T
: 0/1
8 (0
%),
6/20
(3
0%; 6
fibr
oS; m
ultip
licity
, 7/6
), 8/
20 (4
0%; 8
fib
roS;
mul
tiplic
ity, 1
0/8)
Sk
in T
: 0/1
8 (0
%),
0/20
(0%
), 1/
20 (5
%; 1
SC
C)
+>
99%
(tri
octa
noin
) St
atis
tics N
R
Intr
acol
onic
inst
illat
ion
Mou
se, S
wis
s alb
ino
(M, F
) 12
0 w
k To
th (1
980)
0, 2
00, 2
000
μg/g
bw
(tot
al d
oses
); co
ntro
l and
hig
h-do
se g
roup
, 10
× /
wk
inst
illat
ions
of 0
and
200
μg,
re
spec
tivel
y; lo
w-d
ose
grou
p,
1 in
still
atio
n
50/g
roup
/sex
Mal
igna
nt ly
mph
oma:
M
–0/5
0, 6
/50*
(12%
; 1 h
istio
cytic
, 4 ly
mph
ocyt
ic,
1 m
ixed
), 7/
50**
(14%
; 2 h
istio
cytic
, 3
lym
phoc
ytic
, 2 m
ixed
) F–
11/4
9 (2
2%; 5
his
tiocy
tic, 6
lym
phoc
ytic
), 21
/50*
** (4
2%; 5
his
tiocy
tic, 1
6 ly
mph
ocyt
ic),
18/4
9 (3
6%; 6
his
tiocy
tic, 8
lym
phoc
ytic
, 4 m
ixed
) O
esop
hagu
s T:
M–n
o tu
mou
r F–
0/49
, 0/5
0, 5
/49
(10%
) Fo
rest
omac
h T:
M
–0/5
0, 2
/50
(4%
; 2 P
), 10
/50*
*** (
20%
; 9 P
, 1
SCC
) F–
1/49
(2%
; 1 S
CC
), 5/
10 (2
0%; 3
P, 2
SC
C),
11/4
9***
* (22
%; 9
P, 2
SC
C)
*P <
0.0
4 **
P
-
Benzo[a]pyrene
129
Spec
ies,
stra
in (s
ex)
Dur
atio
n R
efer
ence
Dos
ing
regi
men
A
nim
als/
grou
p at
star
tIn
cide
nce
of tu
mou
rsR
esul
t or
sign
ifica
nce
Puri
ty (v
ehic
le)
Com
men
ts
Toth
(198
0)
Con
td.
Ana
l T :
M–0
/50,
0/5
0, 7
/50*
* (14
%; 4
P, 3
SC
C)
F–0/
49, 1
/50
(2%
; 1 P
), 6/
49* (
12%
; 1 P
, 4 S
CC
, 1
K)
Skin
T :
M–1
/50
(2%
; 1 K
), 0/
50, 1
3/50
****
* (26
%; 5
P,
7 SC
C, 1
K)
F–0/
49, 2
/50
(4%
; 2 S
CC
), 11
/49*
*** (
22%
; 4 P
, 5
SCC
, 2 K
)M
ouse
, C57
Bl/6
(F)
18 m
o A
nder
son
et a
l. (1
983)
0 (u
ntre
ated
, oliv
e oi
l or
β-na
phth
oflav
one
in o
live
oil),
1
mg/
anim
al (i
n ol
ive
oil),
onc
e/w
k, 1
4 w
k 45
–60/
grou
p
Fore
stom
ach
P: 7
/34
(21%
; mul
tiplic
ity, 1
.1 ±
0.4
), 17
/18*
(94%
; mul
tiplic
ity, 3
.2 ±
2.3
*)
Peri
tone
al S
: 0/4
0, 5
/32*
Ly
mph
oma:
1/4
0 (2
.5%
), 9/
32* (
28%
)
*P <
0.0
599
% (o
live
oil,
enzy
me
indu
cer β
-nap
htho
flavo
ne)
No
colo
n tu
mou
rs fo
und
Intr
avag
inal
app
licat
ion
Mou
se, C
57B1
(F)
5 m
o N
äslu
nd et
al.
(198
7)
Cot
ton
swab
soak
ed in
ace
tone
(c
ontr
ols)
or 1
% so
lutio
n of
be
nzo[
a]py
rene
in a
ceto
ne, t
wic
e/w
k 10
or 7
6/gr
oup
0/10
, 17/
76 (2
2%; i
nvas
ive
cerv
ical
C)
+N
R (a
ceto
ne)
Intr
afet
al in
ject
ion
Mou
se, S
wis
s (M
, F)
12 w
k Ro
ssi e
t al.
(198
3)
0, 0
.4, 4
.0, 9
.9, 1
9.8
nmol
[0
, 0.1
, 1, 2