Inhalation Two-Generation Reproductive Toxicity Study of Methyl Isobutyl Ketone in Rats
| Autor: | Ralph Gingell, D. C. Topping, M. D. Nemec, E. J. Rauckman, K. L. Pavkov, S. B. Harris, J. A. Pitt |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Male
medicine.medical_specialty Time Factors Litter Size 010501 environmental sciences Toxicology 030226 pharmacology & pharmacy 01 natural sciences Muscle hypertrophy Nephropathy Rats Sprague-Dawley 03 medical and health sciences Sex Factors 0302 clinical medicine Internal medicine Administration Inhalation Animals Lactation Medicine Sexual maturity 0105 earth and related environmental sciences Dose-Response Relationship Drug Sperm Count Inhalation business.industry Reproduction Body Weight Methyl n-Butyl Ketone Organ Size medicine.disease Rats Dose–response relationship Endocrinology Toxicity Solvents Sperm Motility Gestation Female business Reproductive toxicity |
| Zdroj: | International Journal of Toxicology. 23:127-143 |
| ISSN: | 1092-874X 1091-5818 |
| DOI: | 10.1080/10915810490436351 |
| Popis: | To evaluate whether methyl isobutyl ketone (MIBK) affects reproductive performance, a two-generation reproduction study was conducted. MIBK was administered to 30 Sprague-Dawley rats/sex/group via whole-body inhalation at concentrations of 0, 500, 1000, or 2000 ppm, 6 h daily, for 70 days prior to mating. F0 and F1 females were exposed from mating through gestation day 20 and from postnatal day 5; F2 litters were maintained through post-natal day 21. No treatment-related mortality of adult animals occurred. There was a dose-related increase in adult animals with no or a decreased response to a sound stimulus at 1000 and 2000 ppm; however, no adverse clinical signs occurred 1 h after exposure, suggesting this was a transient sedative effect. Clinical signs of central nervous system (CNS) depression in the pups were observed and one F1 pup died after initial exposure to 2000 ppm on postnatal day 22; subsequently exposure was delayed until postnatal day 28. Decreased body weight gain and slight decreased food consumption were observed during the first 2 weeks of exposure in both generations at 2000 ppm. There were no adverse effects on male and female reproductive function or landmarks of sexual maturation. Increased F0 and F1 liver weights with associated centrilobular hypertrophy occurred in rats at 2000 ppm, indicative of an adaptive response. Increased male kidney weights at all exposure concentrations, associated with hyaline droplets, were indicative of male rat-specific nephropathy. Other than acute sedative effects, the no-observed-adverse-effect level (NOAEL) for parental systemic effects (excluding male rat kidney) was 1000 ppm, based on transient decreased body weight and food consumption; for reproductive effects, 2000 ppm, the highest concentration tested; and for neonatal toxicity, 1000 ppm (based on acute CNS depressive effects). |
| Databáze: | OpenAIRE |
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