Pattern of neurotoxicity of n-hexane, methyl n-butyl ketone, 2,5- hexanediol, and 2,5-hexanedione alone and in combination with O- ethyl O-4-nitrophenyl phenylphosphonothioate in hens.
Abou-Donia-MB; Makkawy-HM; Campbell-GM
J Toxicol Environ Health 1985 Jan; 16(1):85-100
Studies were conducted to investigate whether subchronic dermal exposure to n-hexane (110543), methyl-n-butyl-ketone (591786) (MnBK), 2,5-hexanediol (2935446) (2,5-HDOH), or 2,5-hexanedione (110134) (2,5-HD) produced neuropathy in the hen when applied alone; to determine the joint neurotoxic action resulting from binary dermal application of O-ethyl-O-4-nitrophenyl-phenylphosphonothioate (2104645) (EPN) and each of these aliphatic hexacarbons when applied at the same or different sites; and to characterize the morphology and distribution of the neuropathologic lesions induced by single and binary treatments. Adult leghorn-hens were treated with the test substances applied on the back of the neck for 90 days. Hens were observed for 30 days after the end of the exposure period. All hens treated with dermal doses of EPN or n-hexane type chemicals alone or in combinations suffered a slight loss of weight at onset of ataxia. Most was regained. Severe ataxia developed in hens treated with a 1.0mg/kg daily dermal dose of EPN. At sacrifice, no changes were observed in the major tissues. Histopathological changes noted in the spinal cord depended on the treatment. Neither subchronic treatment with daily dermal doses of EPN nor n-hexane produced any histopathologic lesions in the spinal cord. Hens treated with daily doses of EPN dissolved in MnBK exhibited changes in the spinal cord. Treatment with EPN on the same or at different sites from 2,5-HDOH caused an equivocal and an unequivocal histopathological change in each group of hens. Multiple foci of axonal degeneration with phagocytes containing myelin debris were noted in longitudinal sections of the spinal cord of a hen from the group treated dermally with EPN and 2,5-HDOH. These findings suggested the need for protection to prevent skin contact in industrial and agricultural workers with potential exposure.
NIOSH-Publication; NIOSH-Grant; Neurotoxic-effects; Organic-solvents; Skin-exposure; Skin-absorption; Nervous-system-disorders; Laboratory-animals; Organo-phosphorus-pesticides; Agricultural-chemicals; Insecticides
Pharmacology Duke University Department of Pharmacology Durham, N C 27710
110-54-3; 591-78-6; 2935-44-6; 110-13-4; 2104-64-5
Journal of Toxicology and Environmental Health
Duke University, Durham, North Carolina