- Email: [email protected]
Animal bedding and toxicity studies
Information Section
Cancers of the blood from benzene A study of nearly 75,000 Chinese workers exposed to benzene and followed up for periods of up to 16 years found increases in various cancers of the blood system associated with relatively low-level exposures. Exposure to less than 10 ppm, or cumulatively to less than 40 ppm-years, was associated with an approximate doubling of the risk of developing these types of cancer (Hayes R.B. et aL, Journal of the National Cancer Institute 1997, 89, 1065).
The importance of benzene oxide in benzene carcinogenesis It had been thought that benzene oxide, a putative benzene metabolite, was not sufficiently stable to play a significant role in benzene-induced leukaemias. A study has now confirmed not only that benzene oxide is an important metabolite in rats dosed orally but that it is sufficiently stable (half-life in blood 8 rain) to be distributed throughout the body (Lindstrom A.B. et aL, Carcinogenesis 1997, 18, 1637).
5-ethylidene-2-norbornene and 5-vinyl2-norbornene toxicity in rats and rabbits The thyroid gland was the principal target organ identified in a 14-week study in which groups of 20 rats were exposed to the vapour of 5-ethylidene-2norbornene for 6 hours/day, 5 days/week. The effects included colloid depletion in 18, 10 and two animals exposed at 150, 25 and 5 ppm, respectively, and changes in the follicular epithelium at the two higher concentrations. The biological significance of these findings is uncertain, as there were no clear indications of thyroid dysfunction (based on clinical chemistry and thyroid function tests). Additional studies revealed that this chemical, as well as its structural isomer, 5-vinyl-2-norbornene, was of low acute oral and inhalation toxicity in rats, of low dermal toxicity in rabbits, moderately irritating to rabbit skin and slightly irritating to the rabbit eye (Ballantyne B. et aL, Journal of Applied Toxicology 1997, 17, 197 and 211).
Ethyl tert-butyl ether ( ~ B E ) - - repeated inhalation study in rats In a US study, rats were repeatedly exposed for 6 hr (on 65 occasions over a 14-week period) to this gasoline additive at atmospheric levels up to 5000 ppm. Shaky movements and unsteady gait (ataxia), which resolved half-way through the study, were the only neurological effects seen at 5000 ppm. Eye damage (corneal mineralization) was
931
also evident at the top exposure level. There was no convincing evidence of my neurotoxic activity at 1750 ppm (Dorman D.C. et al., Journal of Atrplied Toxicology 1997, 17, 235). {Ref: 102869}
A phthalate reduces breast cancer in rats Benzyl butyl phthalate (BBP), given to female rats by stomach tube for 1 week, reduced the incidence of breast cancer induced by the subsequent administration of a standard carcinogen. The protective action was seen at the lowest tested dose of 250 mg/kg body weight/day. In supplementary studies in which BBP was administered by intraperitoneal injection, it was shown to reduce the formation of DNA adducts with the carcinogen (Singletary K. et al., Carcinogenesis 1997, 18, 1669).
Liver carcinogens m Comet 6 Bone marrow micronucleus 0 The Comet assay detects genotoxicity as DNA fragments derived from single-strand breaks and alkali-labile damage. Japanese investigators have devised a modified protocol that allows genotoxicity to be studied in the liver, lung, kidney, spleen and bone marrow of mice. Seven rodent liver carcinogens that are inactive in the bone marrow micronucleus assay in mice were subjected to this new methodology. Six of these gave positive Comet assay responses, suggesting that the test may be useful for detecting in rive activity of chemicals whose genotoxicity is not expressed in the bone marrow micronucleus assay. The response was most marked in the liver but was also observed in other tissues. The seventh liver carcinogen, benzene hexachloride, gave no response in any tissue, reflecting its inactivity in in vitro tests (Sasaki Y.F. et al., Mutation Research 1997, 391,201).
Animal bedding and toxicity studies Investigators from Finland have highlighted the influence that bedding type might play in the results of animal studies. Using in vitro assays, pine shavings beddings ~commonly used all over the world", were shown to be highly cytotoxic and potent inducers of cytochrome P-450 (an important enzyme in drug metabolism). Although the fact that bedding may bias results and increase variations in pharmacological and toxicological studies carried out in different laboratories has been suggested over many years, it was pointed out that quality requirements for bedding are generally not specified in international test guidelines (Pelkonen K.H.O. and H~inninen O.O.P., Toxicology 1997,
122, 73).
Cancers of the blood from benzene A study of nearly 75,000 Chinese workers exposed to benzene and followed up for periods of up to 16 years found increases in various cancers of the blood system associated with relatively low-level exposures. Exposure to less than 10 ppm, or cumulatively to less than 40 ppm-years, was associated with an approximate doubling of the risk of developing these types of cancer (Hayes R.B. et aL, Journal of the National Cancer Institute 1997, 89, 1065).
The importance of benzene oxide in benzene carcinogenesis It had been thought that benzene oxide, a putative benzene metabolite, was not sufficiently stable to play a significant role in benzene-induced leukaemias. A study has now confirmed not only that benzene oxide is an important metabolite in rats dosed orally but that it is sufficiently stable (half-life in blood 8 rain) to be distributed throughout the body (Lindstrom A.B. et aL, Carcinogenesis 1997, 18, 1637).
5-ethylidene-2-norbornene and 5-vinyl2-norbornene toxicity in rats and rabbits The thyroid gland was the principal target organ identified in a 14-week study in which groups of 20 rats were exposed to the vapour of 5-ethylidene-2norbornene for 6 hours/day, 5 days/week. The effects included colloid depletion in 18, 10 and two animals exposed at 150, 25 and 5 ppm, respectively, and changes in the follicular epithelium at the two higher concentrations. The biological significance of these findings is uncertain, as there were no clear indications of thyroid dysfunction (based on clinical chemistry and thyroid function tests). Additional studies revealed that this chemical, as well as its structural isomer, 5-vinyl-2-norbornene, was of low acute oral and inhalation toxicity in rats, of low dermal toxicity in rabbits, moderately irritating to rabbit skin and slightly irritating to the rabbit eye (Ballantyne B. et aL, Journal of Applied Toxicology 1997, 17, 197 and 211).
Ethyl tert-butyl ether ( ~ B E ) - - repeated inhalation study in rats In a US study, rats were repeatedly exposed for 6 hr (on 65 occasions over a 14-week period) to this gasoline additive at atmospheric levels up to 5000 ppm. Shaky movements and unsteady gait (ataxia), which resolved half-way through the study, were the only neurological effects seen at 5000 ppm. Eye damage (corneal mineralization) was
931
also evident at the top exposure level. There was no convincing evidence of my neurotoxic activity at 1750 ppm (Dorman D.C. et al., Journal of Atrplied Toxicology 1997, 17, 235). {Ref: 102869}
A phthalate reduces breast cancer in rats Benzyl butyl phthalate (BBP), given to female rats by stomach tube for 1 week, reduced the incidence of breast cancer induced by the subsequent administration of a standard carcinogen. The protective action was seen at the lowest tested dose of 250 mg/kg body weight/day. In supplementary studies in which BBP was administered by intraperitoneal injection, it was shown to reduce the formation of DNA adducts with the carcinogen (Singletary K. et al., Carcinogenesis 1997, 18, 1669).
Liver carcinogens m Comet 6 Bone marrow micronucleus 0 The Comet assay detects genotoxicity as DNA fragments derived from single-strand breaks and alkali-labile damage. Japanese investigators have devised a modified protocol that allows genotoxicity to be studied in the liver, lung, kidney, spleen and bone marrow of mice. Seven rodent liver carcinogens that are inactive in the bone marrow micronucleus assay in mice were subjected to this new methodology. Six of these gave positive Comet assay responses, suggesting that the test may be useful for detecting in rive activity of chemicals whose genotoxicity is not expressed in the bone marrow micronucleus assay. The response was most marked in the liver but was also observed in other tissues. The seventh liver carcinogen, benzene hexachloride, gave no response in any tissue, reflecting its inactivity in in vitro tests (Sasaki Y.F. et al., Mutation Research 1997, 391,201).
Animal bedding and toxicity studies Investigators from Finland have highlighted the influence that bedding type might play in the results of animal studies. Using in vitro assays, pine shavings beddings ~commonly used all over the world", were shown to be highly cytotoxic and potent inducers of cytochrome P-450 (an important enzyme in drug metabolism). Although the fact that bedding may bias results and increase variations in pharmacological and toxicological studies carried out in different laboratories has been suggested over many years, it was pointed out that quality requirements for bedding are generally not specified in international test guidelines (Pelkonen K.H.O. and H~inninen O.O.P., Toxicology 1997,
122, 73).