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The effect of repeated methyl iso-butyl ketone vapor exposure on schedule-controlled operant behavior in rats.
Neurotoxicology. 1999 Aug; 20(4):583-93.N

Abstract

Methyl iso-butyl ketone (MiBK), a commercial solvent, was selected by the US Environmental Protection Agency (US EPA) for testing under the Multi-Substance Rule for the Testing of Neurotoxicity (US EPA, 1993) using schedule-controlled operant behavior (SCOB) to determine if subchronic exposure to MiBK vapor had the potential to alter behavior as an indicator of neurotoxicity. Food-restricted and ad libitum-fed Sprague-Dawley male rats were exposed to 0, 250, 750, or 1500 ppm MiBK for 6 h/day, 5 d/wk for 13 weeks. SCOB testing of food-restricted animals, using a multiple fixed ratio (FR)/fixed interval (FI) schedule (FR20:FI120), was conducted prior to each exposure to maintain the operant behavior; the data from Weeks -1, 4, 8, and 13 were evaluated for evidence of neurotoxicity. SCOB testing was also evaluated for two weeks following the cessation of exposures. Ad libitum-fed animals were included to assess systemic effects using routine indicators such as changes in body weight, food consumption, and organ weight. No significant differences were seen in fixed-ratio run rate, FR pause duration, fixed-interval response rate, and index of curvature values at any concentration. Animals exposed to 750 and 1500 ppm MiBK exhibited clinical signs associated with transient reduced activity levels, but only during exposure. No signs of reduced activity were observed immediately after exposure for either group. No other treatment-related abnormalities were observed during exposure. Food-restricted animals did not demonstrate any increased or decreased sensitivity to the CNS depressive effects of MiBK relative to the ad libitum-fed animals. No treatment-related body weight differences were observed within either the food-restricted groups or the ad libitum-fed groups, although body weights of the former were clearly depressed compared with those of the latter. Relative and absolute liver, and relative kidney weights were significantly greater for the 750 and 1500 ppm ad libitum-fed animals. No differences in kidney weight were observed for food-restricted animals, but absolute and/or relative liver weights were significantly higher for all the treated food-restricted groups. The results of this study indicate that repetitive exposures to high concentrations of MiBK vapors do not result in adverse effects on operant behavior in the rat.

Authors+Show Affiliations

Health and Environment Laboratories, Eastman Kodak Company, Rochester, New York 14652-6272, USA. davidtox@kodak.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

10499357

Citation

David, R M., et al. "The Effect of Repeated Methyl Iso-butyl Ketone Vapor Exposure On Schedule-controlled Operant Behavior in Rats." Neurotoxicology, vol. 20, no. 4, 1999, pp. 583-93.
David RM, Bernard LG, Banton MI, et al. The effect of repeated methyl iso-butyl ketone vapor exposure on schedule-controlled operant behavior in rats. Neurotoxicology. 1999;20(4):583-93.
David, R. M., Bernard, L. G., Banton, M. I., Tyler, T. R., Topping, D. C., Gill, M. W., & O'Donoghue, J. L. (1999). The effect of repeated methyl iso-butyl ketone vapor exposure on schedule-controlled operant behavior in rats. Neurotoxicology, 20(4), 583-93.
David RM, et al. The Effect of Repeated Methyl Iso-butyl Ketone Vapor Exposure On Schedule-controlled Operant Behavior in Rats. Neurotoxicology. 1999;20(4):583-93. PubMed PMID: 10499357.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The effect of repeated methyl iso-butyl ketone vapor exposure on schedule-controlled operant behavior in rats. AU - David,R M, AU - Bernard,L G, AU - Banton,M I, AU - Tyler,T R, AU - Topping,D C, AU - Gill,M W, AU - O'Donoghue,J L, PY - 1999/9/28/pubmed PY - 1999/9/28/medline PY - 1999/9/28/entrez SP - 583 EP - 93 JF - Neurotoxicology JO - Neurotoxicology VL - 20 IS - 4 N2 - Methyl iso-butyl ketone (MiBK), a commercial solvent, was selected by the US Environmental Protection Agency (US EPA) for testing under the Multi-Substance Rule for the Testing of Neurotoxicity (US EPA, 1993) using schedule-controlled operant behavior (SCOB) to determine if subchronic exposure to MiBK vapor had the potential to alter behavior as an indicator of neurotoxicity. Food-restricted and ad libitum-fed Sprague-Dawley male rats were exposed to 0, 250, 750, or 1500 ppm MiBK for 6 h/day, 5 d/wk for 13 weeks. SCOB testing of food-restricted animals, using a multiple fixed ratio (FR)/fixed interval (FI) schedule (FR20:FI120), was conducted prior to each exposure to maintain the operant behavior; the data from Weeks -1, 4, 8, and 13 were evaluated for evidence of neurotoxicity. SCOB testing was also evaluated for two weeks following the cessation of exposures. Ad libitum-fed animals were included to assess systemic effects using routine indicators such as changes in body weight, food consumption, and organ weight. No significant differences were seen in fixed-ratio run rate, FR pause duration, fixed-interval response rate, and index of curvature values at any concentration. Animals exposed to 750 and 1500 ppm MiBK exhibited clinical signs associated with transient reduced activity levels, but only during exposure. No signs of reduced activity were observed immediately after exposure for either group. No other treatment-related abnormalities were observed during exposure. Food-restricted animals did not demonstrate any increased or decreased sensitivity to the CNS depressive effects of MiBK relative to the ad libitum-fed animals. No treatment-related body weight differences were observed within either the food-restricted groups or the ad libitum-fed groups, although body weights of the former were clearly depressed compared with those of the latter. Relative and absolute liver, and relative kidney weights were significantly greater for the 750 and 1500 ppm ad libitum-fed animals. No differences in kidney weight were observed for food-restricted animals, but absolute and/or relative liver weights were significantly higher for all the treated food-restricted groups. The results of this study indicate that repetitive exposures to high concentrations of MiBK vapors do not result in adverse effects on operant behavior in the rat. SN - 0161-813X UR - https://www.unboundmedicine.com/medline/citation/10499357/The_effect_of_repeated_methyl_iso_butyl_ketone_vapor_exposure_on_schedule_controlled_operant_behavior_in_rats_ L2 - https://antibodies.cancer.gov/detail/CPTC-TIMP1-2 DB - PRIME DP - Unbound Medicine ER -