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Developmental and reproductive toxicity evaluation of toluene vapor in the rat II. Developmental toxicity.
Reprod Toxicol. 2007 Jun; 23(4):521-31.RT

Abstract

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 (<or=2.5%) of various malformations occurred in the 250, 1500, and 3000ppm groups; there was no increase in the incidence of specific or total malformations with increased exposure and thus these were not attributed to toluene. In this Toluene study, the maternal toxicity NOAEL was 750ppm with a defined maternal and developmental toxicity LOAEL of 1500ppm.

Authors+Show Affiliations

American Petroleum Institute Developmental Workgroup, Washington, DC, United States.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17360154

Citation

Roberts, L G., et al. "Developmental and Reproductive Toxicity Evaluation of Toluene Vapor in the Rat II. Developmental Toxicity." Reproductive Toxicology (Elmsford, N.Y.), vol. 23, no. 4, 2007, pp. 521-31.
Roberts LG, Nicolich MJ, Schreiner CA. Developmental and reproductive toxicity evaluation of toluene vapor in the rat II. Developmental toxicity. Reprod Toxicol. 2007;23(4):521-31.
Roberts, L. G., Nicolich, M. J., & Schreiner, C. A. (2007). Developmental and reproductive toxicity evaluation of toluene vapor in the rat II. Developmental toxicity. Reproductive Toxicology (Elmsford, N.Y.), 23(4), 521-31.
Roberts LG, Nicolich MJ, Schreiner CA. Developmental and Reproductive Toxicity Evaluation of Toluene Vapor in the Rat II. Developmental Toxicity. Reprod Toxicol. 2007;23(4):521-31. PubMed PMID: 17360154.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Developmental and reproductive toxicity evaluation of toluene vapor in the rat II. Developmental toxicity. AU - Roberts,L G, AU - Nicolich,M J, AU - Schreiner,C A, Y1 - 2007/02/12/ PY - 2006/09/26/received PY - 2007/01/12/revised PY - 2007/01/31/accepted PY - 2007/3/16/pubmed PY - 2007/7/14/medline PY - 2007/3/16/entrez SP - 521 EP - 31 JF - Reproductive toxicology (Elmsford, N.Y.) JO - Reprod Toxicol VL - 23 IS - 4 N2 - 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 (<or=2.5%) of various malformations occurred in the 250, 1500, and 3000ppm groups; there was no increase in the incidence of specific or total malformations with increased exposure and thus these were not attributed to toluene. In this Toluene study, the maternal toxicity NOAEL was 750ppm with a defined maternal and developmental toxicity LOAEL of 1500ppm. SN - 0890-6238 UR - https://www.unboundmedicine.com/medline/citation/17360154/Developmental_and_reproductive_toxicity_evaluation_of_toluene_vapor_in_the_rat_II__Developmental_toxicity_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0890-6238(07)00028-7 DB - PRIME DP - Unbound Medicine ER -