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2581. Oestrogenic effects of DDT
912
AGRICULTURAL CHEMICALS
given 50 ppm D D T and in 16 females and six males of the parent generation and three females and one male of the F1 generation fed 250 ppm DDT. These responses were generally apparent only in mice over 70 wk old. Liver tumours were more numerous in the males of all the four groups treated with D D T than in those of the control group. The increase was most marked in the 250 ppm group, in which the incidence was also significantly increased in females. Only a slight increase in liver tumours was seen in females fed 10 to 50 ppm DDT. The percentages of tumourbearing animals (based in each group on the number surviving when the first tumour was observed at any site) were, in males and females respectively, 84 and 80 ~o in the P generation and 62 and 85 ~o in the F1 generation of the untreated controls, 88 and 90 Yo (P generation) and 92 and 95 ~o (FI generation) in the group given 250 ppm D D T and 96 and 93 ~o (P generation) and 97 and 97 ~o (F~ generation) in a urethane-treated positive-control group. In the latter group, the increase in tumour incidence was associated only with lung tumours. The incidence of tumours at sites other than the liver did not appear to be affected by D D T treatment. Liver tumours generally appeared at an earlier age in the DDT-treated animals than in untreated controls and also appeared earlier in the F1 than in the parent generations of the D D T groups. The age at which the mice with liver tumours died, as well as the incidence of such tumours, appeared to be related to the dose of DDT. Only four of the liver tumours metastasized, and although they all occurred in DDT-treated animals the small number involved prevented any conclusion being drawn from this. Histologically the liver tumours took the form of well-differentiated nodular growths, either pressing on the surrounding liver parenchyma without infiltration or obliterating the liver structures and forming glandular or trabecular patterns.
2581. Oestrogenic effects of DDT Clement, J. G. & Okey, A. B. (1972). Estrogenic and anti-estrogenic effects of D D T administered in the diet to immature female rats. Can. J. Physiol. Pharmac. 50, 971. We referred recently to the oestrogenic and anti-oestrogenic properties of D D T in connexion with a demonstration that this insecticide can prolong the reproductive life of ageing female rats (Cited in F.C.T. 1973, 11, 690). The paper cited above is concerned with its effect on female rats at the other end of their life cycle. Immature female Wistar rats were fed diets containing 500-3000 ppm o,p'-DDT from days 23-30 after birth and were then killed for determination of uterine wet and dry weights and protein and glycogen levels. Diethylstilboestrol (DES) at a level of 100 ppb (b = 109) was given to a positive control group, while other rats received the basic diet alone. The administered D D T had a clearly oestrogenic effect, producing increases in uterine weights, protein and glycogen. The dose response was linear over the range tested. The increases were statistically significant, however, only at dietary levels of 1000 ppm or more. All the D D T levels caused some premature vaginal opening, a sensitive indicator of oestrogenic activity but again the effect was only statistically significant at 1000 ppm and above. All the open vaginas contained the cornified epithelial cells characteristic of mature females during the onset of oestrus. A lower dietary level of o,p'-DDT (100 ppm) given over the same period significantly reduced the oestrogenic effect on uterine glycogen exerted by oestradiol injected sc from day 23 in a dose of 0.5/~g/day, probably by stimulating hepatic
AGRICULTURAL CHEMICALS
given 50 ppm D D T and in 16 females and six males of the parent generation and three females and one male of the F1 generation fed 250 ppm DDT. These responses were generally apparent only in mice over 70 wk old. Liver tumours were more numerous in the males of all the four groups treated with D D T than in those of the control group. The increase was most marked in the 250 ppm group, in which the incidence was also significantly increased in females. Only a slight increase in liver tumours was seen in females fed 10 to 50 ppm DDT. The percentages of tumourbearing animals (based in each group on the number surviving when the first tumour was observed at any site) were, in males and females respectively, 84 and 80 ~o in the P generation and 62 and 85 ~o in the F1 generation of the untreated controls, 88 and 90 Yo (P generation) and 92 and 95 ~o (FI generation) in the group given 250 ppm D D T and 96 and 93 ~o (P generation) and 97 and 97 ~o (F~ generation) in a urethane-treated positive-control group. In the latter group, the increase in tumour incidence was associated only with lung tumours. The incidence of tumours at sites other than the liver did not appear to be affected by D D T treatment. Liver tumours generally appeared at an earlier age in the DDT-treated animals than in untreated controls and also appeared earlier in the F1 than in the parent generations of the D D T groups. The age at which the mice with liver tumours died, as well as the incidence of such tumours, appeared to be related to the dose of DDT. Only four of the liver tumours metastasized, and although they all occurred in DDT-treated animals the small number involved prevented any conclusion being drawn from this. Histologically the liver tumours took the form of well-differentiated nodular growths, either pressing on the surrounding liver parenchyma without infiltration or obliterating the liver structures and forming glandular or trabecular patterns.
2581. Oestrogenic effects of DDT Clement, J. G. & Okey, A. B. (1972). Estrogenic and anti-estrogenic effects of D D T administered in the diet to immature female rats. Can. J. Physiol. Pharmac. 50, 971. We referred recently to the oestrogenic and anti-oestrogenic properties of D D T in connexion with a demonstration that this insecticide can prolong the reproductive life of ageing female rats (Cited in F.C.T. 1973, 11, 690). The paper cited above is concerned with its effect on female rats at the other end of their life cycle. Immature female Wistar rats were fed diets containing 500-3000 ppm o,p'-DDT from days 23-30 after birth and were then killed for determination of uterine wet and dry weights and protein and glycogen levels. Diethylstilboestrol (DES) at a level of 100 ppb (b = 109) was given to a positive control group, while other rats received the basic diet alone. The administered D D T had a clearly oestrogenic effect, producing increases in uterine weights, protein and glycogen. The dose response was linear over the range tested. The increases were statistically significant, however, only at dietary levels of 1000 ppm or more. All the D D T levels caused some premature vaginal opening, a sensitive indicator of oestrogenic activity but again the effect was only statistically significant at 1000 ppm and above. All the open vaginas contained the cornified epithelial cells characteristic of mature females during the onset of oestrus. A lower dietary level of o,p'-DDT (100 ppm) given over the same period significantly reduced the oestrogenic effect on uterine glycogen exerted by oestradiol injected sc from day 23 in a dose of 0.5/~g/day, probably by stimulating hepatic