Document NG73K9pY4xzkL65wXO02Z6Mxb

R&S 025270  ... - 318 - the drinking-water. The sodium nitrite was kept constant at a level of 0*3$ in the food pellets to maintain an optimal ratio for combination with MU or EUt since ad lib, feeding did not ensure the simultaneous presence of both the nitrite and the alkylurea in the stomach. Vith the highest dose of 0-03 MU there was also a 2%)6 increase in lymphomas. Except for a diffuse spongio blastoma and an orbital neurinoma of the optic nerve, all the neurogenic neoplasms observed were similar to those previously produced with MNU or ENU in the same strain of rat. The hazard of possible consumption of harmless preoureors and the intragastric synthesis of potent nitrosourea carcinogens will have to be considered in any programme of cancer prevention. TERATOGENIC EVALUATION OF LEAL COMPOUNDS IN MICE AND RATS G-L. Kennedy, D.V. Arnold and J.O. Calandra Industrial DIO-TEST Laboratories, Inc., Northbrook, Illinois 60062, USA (Received 13 April 1975) Abstract--Groups of pregnant albino mice and rats were treated by gavage with doses up to 714 mg lead acetate/kg or 10 mg tetraethyllead (TEL)/kg. The compounds were administered daily during the period of rapid organogeneBis (days 5-15 of pregnancy for mice and days 6--16 for rats). Maternal toxicity was observed and foetal resorption and general retardation of development were encountered at the higher dosage levels. Neither lead compound caused any congenital malformations. Foetuses derived from lead--exposed females Wore examined grossly and for internal structural and skeletal development, but no teratogenio response was evident, even at dose levels at which frank signs of maternal toxicity were observed. It 1b concluded that lead, as the acetate or as tetraethyllead, is not teratogenio to the mouse or rat. ` OBSERVATIONS ON THE ORAL ADMINISTRATION AND TOXICITY OF J 71 / VINYL CHLORIDE IN HATS V.J. Feron, A.J. Speek, Marianne I. Willems, D. van Battum and A.P. de Groot Central Institute for Nutrition and Food Research (CIVO) TNO, Utrechteoweg ' ' 48, Zeiot, The Netherlands (Heoeived 1 April 1975) Abstract--Various possibilities were studied for administering vinyl chloride monomer (VCM) orally to rate. Upon storage, solutions of VCM in soya-bean oil appeared to be stable with respect to their VCM content and the fatty acid composition of the oil. In addition no oligomers of vinyl chloride or reaction products of VCM with components of the oil were deteoted. Stomach Intubation of such solutions was considered an acceptable method of oral administration of VCM to ratB in abort-term toxicity studies. Within a period of 4 hr following intragastrio intubation of VCM in Boya-bean oil (300 mg VO0cg body weight), over $2% of the VCM administered was recovered from the gases excreted (mainly exhaled?) by the animals. Eructation did not appear to be involved in the excretion of VCM. VCM dissolved in soya-bean oil was administered by gavage to male and female rats at levels of 0 (controls), 30, 100 and 300 mg/kg body weight, ones dnily on 6 days/wk for a period of ij wk. Several haematological, l 4 I V. 'V-t 7,, t #r 3s S k v; i R&S 025271 - 519 - biochemical and organ-weight values differed to a statistically significant degree from those of the controls, but these differences were considered to have only minor> if any, toxicological significance. A slight increase in livor-to-body weight ratio occurred in males and females on the highest dose level. This increase was not accompanied by liver damage, as was evident from hiatological examination, enzyme histochemistry and electron microscopy. The no-effect level in thiB 90-day study was conservatively placed at 50 mg VCM/kg body weight, but was probably higher since the effects occurring at 100 and 500 mg/kg body weight were of doubtful toxicological significance. Indications were obtained that the feeding of rats on diets containing polyvinyl chloride (PTC) powder with a high VCM contont is a more practical method for the long-tom oral exposure of ratB to TCM than is stomach intub ation of VCM in oil. TCM was almost completely released from FTC powder during passage through the digestive tract. BIOLOGICAL TESTING OP POOD GROWN IN TEE TRANSKEI I.F.H. Purchase, R.C. Tustin and S.J. vo- Rensburg National Research Institute for Nutritional Diseases, SA Medical Research Council, PO Box 70, Tiervlei, Cape Province, South Afrioa (Received 11 April 1975) Abstract--Oesophageal cancer is the commonest form of cancer occurring in the Tranakei, South Africa. In an attempt to identify carcinogens contributing to this high incidence, food collected from gardens belonging to families in which a member had developed oesophageal cancer was fed to BD DC rats from ooneeption until dsath. One group was fed a diet consisting of maize, beans and a salt mixture while the second group received a full Tranakei diet con sisting of the same ingredients with the addition of imi fino (Solatium nigrum and Sonchus oleraoeus). The latter group developed severe liver leeionB (characterized by bile-duct proliferation and hyperplastic nodules) and epithelial-cell dysplasia of the oesophagus. This group also suffered from an increased incldenoe of tumours of various types. It proved impossible to breed suooessfully from rate on the full Tranakei diet. The liver leBlons were exacerbated by supplying distillate, eolleoted when the diets were dried, to the rats as drinking-water. The effeot of the distillate was probably not duo to the presence of nitrosamines. The possibility that the full Tranakei diet was producing these effects indirectly by the interaction of nitrites and secondary amines in the Htomach was tested by the addition of sodium nitrite to the diets but this did not induce liver lesions. These results suggest that the diet collected from the Tranakei contains toxic factors which produce liver and oesophageal lesions and an increased Incldenoe of oancer in rats. These same factors may also contribute to the high in cidence of oesophageal and liver oancer occurring in man in the Tranakei.