Assessment of adult and neonatal reproductive parameters in Sprague-Dawley rats exposed to propylene glycol monomethyl ether vapors for two generations
Autor: | J. W. Crissman, C M Clements, A. B. Liberacki, William J. Breslin, Edward W. Carney |
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Rok vydání: | 1999 |
Předmět: |
Litter (animal)
Male medicine.medical_specialty Time Factors Offspring Physiology Weanling Ovary Biology Toxicology Rats Sprague-Dawley Random Allocation Fetus Pregnancy Internal medicine Lactation Administration Inhalation medicine Animals Maternal-Fetal Exchange Estrous cycle Dose-Response Relationship Drug Reproduction Body Weight Age Factors Teratology Rats Survival Rate medicine.anatomical_structure Endocrinology Animals Newborn Propylene Glycols Toxicity Female |
Zdroj: | Toxicological sciences : an official journal of the Society of Toxicology. 50(2) |
ISSN: | 1096-6080 |
Popis: | This study evaluated propylene glycol monomethyl ether (PGME) in a rat 2-generation reproduction study, which included non-traditional study end points, such as sperm count and motility, developmental landmarks, estrous cyclicity, and weanling organ weights. Groups of 30 male and 30 female Sprague-Dawley rats (6-weeks-old) were exposed to 0, 300, 1000, or 3000 ppm of PGME vapors via inhalation for 6 hours/day, 5 days/week prior to mating, and 6 hours/day, 7 days/week during mating, gestation, and lactation, for 2 generations. These concentrations corresponded to estimated oral equivalent doses of 0, 396, 1325, or 3974 mg/kg/day. At 3000 ppm, toxicity in the P1 and P2 adults was marked, as evidenced by sedation during and after exposure, and mean body weights which were as much as 21% lower than controls. This marked parental toxicity was accompanied by lengthened estrous cycles, decreased fertility, decreased ovary weights, and histologic ovarian atrophy in maternal rats. In the offspring from these dams, decreased body weights, reduced survival and litter size, slight delays in puberty onset, and histologic changes in liver and thymus in the F1 and F2 offspring were observed. The nature of the reproductive/neonatal effects and their close individual animal correlation with decreased maternal body weights suggested that these effects were secondary to general toxicity and/or nutritional stress. No such reproductive/neonatal effects were observed at 1000 ppm, a concentration which caused less marked, but significant body weight effects without sedation. There were no treatment-related effects of any kind noted at 300 ppm of PGME. Therefore, the no-observable-effect level (NOEL) for reproductive/neonatal effects was 1000 ppm, and that for parental toxicity was 300 ppm. |
Databáze: | OpenAIRE |
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