I-~rop. ,7. Cancer Vol. 14, pp, 1403-1404. 00t4-2964/78/1201 1403 $ 02.00/0 ( Pergamon Press Ltd. 1978. Printed in (;reat Britain

Letter to the Editor

Rotenone'. A Carcinogen?

Possible Environmental

MARIO GOSALVEZ and JUAN J. DIAZ-GIL

Bioquimica Experimental, Clinica Puerta Hierro, Universidad Autbnoma, Madrid, Spain

1N a PrEY[Orals paper [1] we reported that the respiratory inhibitor rotenone induces a high incidence of mammary fibroadenomas in the albino rat. In a second report [2] we pointed out that rotenone was also inducing the tu- mors when administered orally. We now re- port information about the uses of rotenone as an insecticide, pesticide and piscicide which may induce the consideration of this com- pound as an environmental carcinogen.

Initially [1] we mentioned the use of ro- tenone as an insecticide in small quantities because the Section of Agricultural Plagues of the Spanish Ministry of Agriculture evaluated the world consumption of rotenone extrapolat- ing for the world population the low Spanish consumption. Further investigations through various state agencies in the United States and an exhaustive bibliographic search in the not readily available literature revealed, ho- wever, that: 1. There is a massive consumption of ro-

tenone as an insecticide in superindustria- lized countries, especially in the U.S., Great Britain, Sweden, Denmark, Finland, Israel, Canada and Norway. The United States does not produce all rotenone need- ed for its consumption and must import substantial quantities of rotenone yearly. A minimum of ten million pounds of rotenone and rotenone products (cube and derris powder) were imported in the U.S. in 1950. The importation of rotenone dimin- ished since then, reaching one million pou- nds in 1972. The total yearly consumption of rotenone in the U.S. presently is esti- mated at 15 million pounds.

2. Rotenone is used in the U.S. mainly as an agricultural insecticide and as a piscicide. The use as an agricultural insecticide is small, presently in fields (mainly fruit) but,

Accepted 14 June 1978.

however, is massively used in private house- hold gardens of the American home [3, 4]. As a piscicide, rotenone is used for total killing or for selective killing in lakes, ri- vers, fisheries, water reservoirs and water plants [5-9]. Through this use, rotenone contaminates drinking water. The concen- tration of rotenone in drinking water is not available at present but it is enough to cause a characteristic odor and taste [5, 6].

3. Rotenone is also used in the U.S.A. tot parasitic controls in cats, dogs and cows but with this use no ingestion of rotenone by humans is foreseen.

Figure 1 depicts the uses of rotenone and its possible ways of arrival to the human female in the U.S.A. The ingestion in consumed fresh or cooked vegetables grown in private household gardens and the ingestion with drinking water are considered the main possible environmental hazards. In 'Fable 1 an experiment is shown in which we have investigated the content of rotenone in green beans cultivated in winter in our laboratory under household garden con- ditiozas, using a commercial insecticide contain- ing rotenone. The treated beans contained from 14 to 58/~g of rotenone per gram of beans when ready to be cooked. This amount is well within the order of magnitude of the carcinogenic potency of rotenone (0.1 mg ofrotenone daily during 30 days is enough to cause tumours in the rat).

As rotenone is carcinogenic in the ra( at very low doses by oral administration and the ingestion of rotenone by humans in substantial amounts, it is more than a possibility, we believe, that rotenone could possibly be con- sidered as an environmental carcinogen. Such a consideration, however, would not guaran- tee that rotenone is a causative agent of the human mammary tumors in the absence of well founded epidemiological studies.

1403

1404 Letter to the Editor

Table l. Content of rotenone in green beans treated with rotex 2.5

Beans Leaves S tems Roots

Control plants N.D. N.D. N.D. N.D.

Experiment A 58 850 N.D. N.D.

Experiment B 14 420 N.D. N.D.

N.D.: Not detectable. The numbers express micrograms of rotenone per wet weight of plant material. Each experiment is the average of the data obtained from two flowerpots. Rotex 2.5 is a Spanish brand (Grima Laboratories, Valencia, Spain)of insecticide containing 2.5°o rotenone. The beans were cultivated in Madrid (Spain) during the winter months, exposed to the sun, air and rain and were collected at a size of 5-10cm. The plants in experiment A received, in the last two months of growth, three pulverizations with Rotex 2.5, one every 15days. The plants in experiment B received two pulverizations, one every 30 days. The plants we're sprayed according to norms for the use of Rotex 2.5 in agriculture. The determination of the rotenone content was made by gas chromatography as previously described [7] except that we included a previous purification of the chloroform extracts in thin layer chromatography [gJ.

Al though an epidemiological study of ro- tenone in household gardens and m a m m a r y tumor incidence would be highly desirable, this may be perhaps an impossible study since

most individuals would not remember what pesticide they used in their garden 10, 20 or 30 yr ago. The purpose of this report is to call

to the attention of the scientific communi ty and state organizations with interest in poss- ible environmental hazards to the fact that rotenone is a rat carcinogen by oral route and which is possibly reaching the human female in certain countries in substantial amounts.

ROTENONE

AGRICULTURAL USE FISH CONTROL FARMS, GARDENS, LAKES, RIVERS, FISHERIES, HOUSEHOLO GARDENS WATER RESERVOIRES, WATER PLANTS

PA~T~ONTROL

ooos / \

CONSUMED KILLING KILLING VEGETABLES / /

/ WATER \

HUMAN FEMALE

t;,ie. 1.

REFERENCES

1. M. GOSALVEZ and J. MERCHAN, Induction of rat mammary adenomas with the respiratory inhibitor rotenone. Cancer Res. 33, 3047 (1973).

2. M. GosALvez, J. DIAz-GIL, J. COLOMA and L. SALOANICOFF, Spectral and metabolic characteristics of mitochondrial fractions isolated ti-om rotenone tumors. Brit. J . Cancer 36, 243 (1977).

3. C . E . CUSHINO and J. R. OLIVE, Effects of toxaphene and rotenone upon the macroscopic bottom fauna of two Northern Colorado reservoirs. Trans. Amer. Fish. Soc. 86, 294 (1950).

4. A . J . LEmaAN, A toxicological evaluation of household insecticides. Assoc. Food and Drug officials of U.S. Quart. Bull. 18, 3 {1954).

5. E. W. BONN and L. R. HOLBERT, Some effects of rotenone products on municipal water supplies. Trans. Amer. Fish. Soc. 90, 287 (1961).

6. J. M.'CoHEN, Q. H. PICKERINO, R. L. WOODWARD and W. VAN HEVVELIN, Effect of fish poisons on water supplies. 2. Odor Problems. J. Amer. l/Vat. Wks A.rr 53, 49 (1965).

7. M. E. DELFEL, Gas-liquid chromatographic determination of rotenone and dequeline in plant extracts and commercial insecticides. J. Ass. offic, agr. Chem. 56 (6), 1343 (1973).

~}. ~'V. F. SIGLER, The ecology and use of carp in Utah. Utah State University, Utah agr. Exp. Sta. Bull. 405, Dec. (1958).

9. J. FUKAMI, 1, YAMAMOTO and J. E. CASmDA, Metabolism of rotenone in vitro by tissue homogenates from mammals and insects. Science 155, 713 (1967).