Prechronic Toxicity Studies on 2-Ethylhexanol in F334 Rats and B6C3F1 Mice
| Autor: | J. R. Hodgson, R. Gingell, Chr. Gembardt, W. Mellert, K. Deckardt, S. R. Murphy, B. D. Astill, T. R. Tyler, D. Guest |
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| Rok vydání: | 1996 |
| Předmět: |
Male
medicine.medical_specialty Ratón Administration Oral Spleen Biology Toxicology Microbodies Mice Plasticizers Oral administration Internal medicine Toxicity Tests medicine Animals Transaminases Kidney Palmitoyl Coenzyme A Stomach Body Weight Proventriculus Organ Size Rats Inbred F344 Rats medicine.anatomical_structure Endocrinology Liver Chemistry Clinical Toxicity Female medicine.symptom Hexanols Weight gain |
| Zdroj: | Toxicological Sciences. 29:31-39 |
| ISSN: | 1096-0929 1096-6080 |
| Popis: | Data on the subchronic toxicity of 2-ethylhexanol (2EH) were required to establish the dose vehicle and dose levels for oncogenicity studies. In preliminary studies 2EH was given subacutely (11 days) to male and female Fischer 344 rats and B6C3F1 mice as an aqueous emulsion by oral gavage (0, 100, 330, 1000, and 1500 mg/kg/day). Clinical observations were made, body weights, food consumption, clinical chemistries, hematologies, and selected organ weights were measured, and gross and micropathologies were performed. Target organs were the central nervous system, liver, forestomach, spleen, thymus, and kidney in rats and the central nervous system, liver, and forestomach in mice. 2EH was then administered by oral gavage to male and female F344 rats and B6C3F1 mice as an aqueous emulsion (0, 25, 125, 250, and 500 mg/kg/day) for 13 weeks. At 500 mg/kg/day in the rat there was reduced body weight gain (6% male, 7% female), increased relative liver (29% male, 15% female), kidney (16% male, 6% female), stomach (11% male, 16% female), and testes (6%) weights, and moderate gross and microscopic changes in the liver and forestomach. There were no behavioral effects or effects on the spleen or thymus. A no-effect level for target organ effects in the rat was 125 mg of 2EH/kg/day. At 500 mg of 2EH/kg/day in the mouse the only effects were increased relative stomach weights in males (13%) and a low incidence of gross and microscopic findings in the forestomach (male and female) and liver (female). A no-effect level for target organ effects in the mouse was 125 mg of 2EH/kg/day. 2EH was a peroxisome proliferator in the rat but not in the mouse at subchronic dose levels of 500 mg/kg/day. Dose levels in oncogenicity studies were set at 50 mg/kg/day for the absence of treatment-related effects in rats and mice, and 500 and 750 mg/kg/day, respectively, in rats and mice as high doses producing minimal toxicity without altering the life span. |
| Databáze: | OpenAIRE |
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