Binge toluene exposure in pregnancy and pre-weaning developmental consequences in rats

Abstract

Binge Toluene Exposure in Pregnancy and Pre-weaning Developmental Consequences in Rats. Bowen, S.E. and Hannigan, J.H. The persistent rate of abuse of inhaled organic solvents, especially among women of child-bearing age, raises the risk for teratogenic effects of maternal toluene abuse. In this study, timed-pregnant Sprague Dawley rats were exposed from Gestation Day (GD) 8 to GD20 to 12,000 or 8000 parts per million (ppm) toluene, or 0ppm (controls) for 30min twice daily, 60min total daily exposure. Pups were assessed from postnatal day (PN) 4 to PN21 using a developmental battery measuring growth (i.e., body weight), maturational milestones (e.g., eye opening & incisor eruption), and biobehavioral development (e.g., negative geotaxis & surface righting). Pups exposed in utero to 12,000ppm or 8000ppm toluene weighed significantly less than the non-exposed control pups beginning at PN4 and PN12 (respectively) until PN21. Toluene resulted in significant increases in an index of poor perinatal outcome, specifically a composite of malformations, defined "runting" and neonatal death. No significant delays were observed in reaching maturational milestones. The results reveal that brief, repeated, prenatal exposure to high concentrations of toluene can cause growth retardation and malformations in rats. A comparison of the present, conservative results with findings in previous studies implies that binge patterns of toluene exposure in pregnant rats modeling human solvent abuse can result in developmental and morphological deficits in offspring. These results do not exclude the possibility that maternal toxicity as well as teratogenic effects of toluene may contribute to outcomes. The results suggest that abuse of inhaled organic solvents like toluene may result in similar early developmental outcomes in humans.

Keywords: Gestational toluene exposure; Rats; Toluene.

Figure 1

Effects of 0 ppm, 8,000 ppm, or 12,000 ppm toluene exposure on percent weight gain in pregnant rats. Shown are means ± SEM of percent weight gain from GD4 through GD20. Inset graph shows mean ± SEM of dam weights (grams) on PN20. Toluene 8,000 (#) and 12,000 (*) ppm groups significantly different from sham exposure group (p < 0.05).

Figure 2

Effects of 0 ppm, 8,000 ppm, or 12,000 ppm toluene exposure on pup weight gain. Shown are means ± SEM of percent weight gain from PN1 through PN21. Inset graph shows mean ± SEM of pup weights (grams) on PN1. Toluene 8,000 (#) and 12,000 (*) ppm groups significantly different from sham exposure group (p < 0.05).

Figure 3

Effects of prenatal 0 ppm, 8,000 ppm, or 12,000 ppm toluene exposure on forelimb grip strength. Shown are means ± SEM of pup strength (grams) for PN12 (left) and PN16 (right). The inset depicts effects of prenatal 0 ppm, 8,000 ppm, or 12,000 ppm toluene exposure collapsed across Day.