The relative neurotoxicities of n-hexane, methyl n-butyl ketone, 2,5- hexanediol, and 2,5-hexanedione following oral or intraperitoneal administration in hens.
Abou-Donia-MB; Makkawy-HA; Graham-DG
Toxicol Appl Pharmacol 1982 Mar; 62(3):369-389
The neurotoxicity of n-hexane (110543), methyl-n-butyl-ketone (591786) (MnBK), 2,5-hexanediol (2935446) (2,5-HDOH) and 2,5- hexanedione (110134) (2,5-HD) were studied in leghorn-hens following oral (po) or intraperitoneal (ip) injection. Groups of hens were given daily oral doses of 100 milligrams per kilogram (mg/kg) of one of the test compounds for a period of 90 days. For ip administration, groups of hens received 100 or 200mg/kg of the test compounds daily for 90 days. After a 30 day observation period birds were sacrificed. The sciatic, tibial, peripheral and peroneal nerves and the spinal cord were prepared for histopathological examination. The neurotoxic potential of the compounds was measured by a neurotoxicity index based on the clinical condition of the hen, the time of onset of clinical signs, and the intensity of histopathologic changes. Subchronic po or ip administration of n- hexane caused weakness which subsided after cessation of exposure. Subchronic exposure of the other compounds caused neurotoxicity characterized by ataxia which sometimes progressed to paralysis. Generally, ip injection caused more severe effects than po administration. Histopathological examination of nervous tissue from hens treated with 2,5-HD, 2,5-HDOH and MnBK showed giant paranodal axonal swelling followed by Wallerian degeneration of axons and myelin in peripheral nerves and spinal cord; this pathological change was absent in n-hexane treated hens. The neurotoxic potency of the tested compounds were in descending order of 2-5-HD, 2,5- HDOH, MnBK and n-hexane. The authors conclude that hens, through generally sensitive to hexa-carbon neurotoxicity, exhibit selectivity toward specific compounds within this chemical group.
NIOSH-Publication; NIOSH-Grant; Comparative-toxicology; Neurotoxins; Chronic-toxicity; Animal-studies; Neurotoxicity; Invivo-study
Pharmacology Duke University Department of Pharmacology Durham, N C 27710
110-54-3; 591-78-6; 2935-44-6; 110-13-4
Toxicology and Applied Pharmacology
Duke University, Durham, North Carolina