Developmental and reproductive toxicity evaluation of toluene vapor in the rat : II. developmental toxicity

• Published in: Reproductive toxicology (Elmsford, N.Y.) N.Y.), 2007-06, Vol.23 (4), p.521-531
• Main Authors: ROBERTS, L. G, NICOLICH, M. J, SCHREINER, C. A
• Format: Article
• Language: English
• Subjects: Abnormalities, Drug-Induced; Air Pollutants - chemistry; Air Pollutants - toxicity; Animals; Biological and medical sciences; Body Weight - drug effects; Bone and Bones - abnormalities; Chemical and industrial products toxicology. Toxic occupational diseases; Dose-Response Relationship, Drug; Drinking - drug effects; Eating - drug effects; Embryology: invertebrates and vertebrates. Teratology; Female; Fetal Resorption - chemically induced; Fetal Weight - drug effects; Fundamental and applied biological sciences. Psychology; Gestational Age; Inhalation Exposure; Male; Medical sciences; Motor Activity - drug effects; No-Observed-Adverse-Effect Level; Organogenesis - drug effects; Pregnancy; Rats; Rats, Sprague-Dawley; Reproduction - drug effects; Risk Assessment; Solvents; Teratology. Teratogens; Toluene - chemistry; Toluene - toxicity; Toxicology; Volatilization
• ISSN: 0890-6238; 1873-1708
• DOI: 10.1016/j.reprotox.2007.01.009

The developmental toxicity of toluene was evaluated via whole body inhalation exposure, in pregnant Sprague Dawley rats exposed to toluene (99.9% pure) from gestation day (GD) 6-15 inclusive, 6h/day, at concentrations of 0, 250, 750, 1500 and 3000ppm (0, 938, 2812, 5625 and 11250mg/m(3)). Doses were selected from a preliminary study performed over a range of concentrations from 0 to 5000ppm, in which maternal and fetal toxicity were observed at 2000ppm and above. This study has been cited in various regulatory documents and is presented here to allow greater accessibility to results and conclusions. Toluene induced clinical signs in pregnant dams (ataxia, hyper-responsivity, increased water intake, decreased food consumption) at 3000ppm, ataxia and hyper-responsivity at 1500ppm, and reduced maternal body weight gain at 1500 during the exposure period only and at 3000ppm from initiation of exposure to GD20. At Caesarean section on GD20, no adverse effects on implantation, number and viability of fetuses, or fetal sex distribution were observed. Litter weight and mean fetal weight was reduced at 3000ppm and mean fetal weight was reduced at 1500ppm. Instances of reduced or unossified skeletal elements occurred at the same dose levels. Mean fetal weight was also reduced at 250ppm but not at 750ppm. Extensive statistical analysis of fetal body weight data support the conclusion that there is no toxicologically significant dose-related effect on fetal body weight at or below 750ppm. Low incidences (