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

Journal Article · Tue Jan 01 00:00:00 EST 1985 · J. Toxicol. Environ. Health; (United States)

DOI:https://doi.org/10.1080/15287398509530721· OSTI ID:6228526

Abou-Donia, M B; Makkawy, H M; Campbell, G M

This investigation was designed to study the neurotoxicity produced in hens by the aliphatic hexacarbons n-hexane, methyl n-butyl ketone (MnBK), 2,5-hexanediol (2,5-HDOH), and 2,5-hexanedione (2,5-HD) following daily dermal application of each chemical alone and in combination with O-ethyl O-4-nitrophenyl phenylphosphonothioate (EPN). Dermal application was carried out on the unprotected back of the neck. To assess whether the joint neurotoxic action of various chemicals is caused by the enhancement of absorption through the skin or by interaction at the molecular level, two additional experiments were performed. Dermal application was carried out for 90 d followed by a 30-d observation period. The results show that (1) hens treated with EPN developed severe ataxia followed by improvement during the observation period; (2) n-hexane produced leg weakness with subsequent recovery, whereas the same dose of MnBK, 2,5-HDOH, or 2,5-HD produced clinical signs of neurotoxicity characterized by gross ataxia; (3) concurrent dermal application of EPN with n-hexane of 2,5-HDOH at the same site or at different sites produced an additive neurotoxic action; (4) simultaneous dermal application of EPN and MnBK at different sites resulted in an additive effect, whereas it caused potentiation when applied at the same site; and (5) concurrent topical application of EPN and 2,5-HD produced a potentiating neurotoxic effect. While no histopathologic lesion was produced at the end of the observation period when any test chemical was applied alone, binary treatments of EPN and aliphatic hexacarbons resulted in histopathologic changes in some hens, with morphology and distribution characteristic of EPN neurotoxicity. The mechanism of this joint action seems to be related both to enhancing skin absorption of EPN and/or to its metabolic activation by n-hexane and its related chemicals.

• Research Organization: Duke Univ. Medical Center, Durham, NC
• OSTI ID: 6228526
• Journal Information: J. Toxicol. Environ. Health; (United States), Vol. 16:1
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
HYDROCARBONS
TOXICITY
NERVOUS SYSTEM
MORPHOLOGICAL CHANGES
PATHOLOGICAL CHANGES
RESPONSE MODIFYING FACTORS
NITRO COMPOUNDS
CHICKENS
HEXANE
KETONES
SKIN
SKIN ABSORPTION
ABSORPTION
ALKANES
ANIMALS
BIRDS
BODY
FOWL
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
UPTAKE
VERTEBRATES
560305* - Chemicals Metabolism & Toxicology- Vertebrates- (-1987)