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Reproductive and developmental toxicity of inhaled 2,3-dichloro-1,3-butadiene in rats.
Reprod Toxicol. 2006 Nov; 22(4):613-22.RT

Abstract

Inhalation developmental and reproductive toxicity studies were conducted with 2,3-dichloro-1,3-butadiene (DCBD), a monomer used in the production of synthetic rubber. In the reproductive toxicity study, Crl:CD(SD)IGS BR rats (24/sex/group) were exposed whole body by inhalation to 0, 1, 5, or 50 ppm DCBD (6 h/day) for approximately 10-11 weeks total, through premating (8 weeks; 5 days/week), cohabitation of mating pairs (up to 2 weeks, 7 days/week), post-cohabitation for males (approximately 7 days) and from conception to implantation (gestation days 0-7 [GD 0-7]), followed by a recovery period (GD 8-21) for presumed pregnant females. Estrous cyclicity was evaluated during premating (last 3 weeks) and cohabitation. Reproductive organs and potential target organs, sperm parameters, and GD 21 fetuses (viability, weight, external alterations) were evaluated. In the developmental study, pregnant Crl:CD(SD)IGS BR rats (22/group) were exposed whole body by inhalation to 0, 1, 10, or 50 ppm DCBD (6 h/day) on GD 6-20; dams were necropsied on GD 21 (gross post-mortem only) and fetuses were evaluated (viability, weight, and external, visceral and skeletal exams). During the in-life portion of the studies, body weight, food consumption, and clinical observation data were collected. At 50 ppm, gasping and labored breathing occurred in both studies during the first few exposures; body weight and food consumption parameters were affected in parental animals from both studies, but were more severely affected in the developmental study. Fetal weight was decreased in the developmental study at 50 ppm. Degeneration of the nasal olfactory epithelium was observed in the reproduction study at 50 ppm. There were no effects on reproductive function, embryo-fetal viability, or increases in fetal structural alterations in either study. The no-observed-adverse-effect level (NOAEL) for reproductive toxicity was 50 ppm. The NOAEL for systemic toxicity in the reproduction study was 5 ppm based on adverse effects on body weight and food consumption parameters and nasal olfactory epithelial toxicity at 50 ppm in parental rats. The NOAEL for maternal and developmental toxicity was 10 ppm based on reduced maternal weight gain and food consumption and reduced fetal weight at 50 ppm in the developmental toxicity study.

Authors+Show Affiliations

DuPont Haskell Laboratory for Health and Environmental Sciences, Newark, DE 19711, USA. eve.mylchreest@usa.dupont.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16716565

Citation

Mylchreest, E, et al. "Reproductive and Developmental Toxicity of Inhaled 2,3-dichloro-1,3-butadiene in Rats." Reproductive Toxicology (Elmsford, N.Y.), vol. 22, no. 4, 2006, pp. 613-22.
Mylchreest E, Malley LA, O'Neill AJ, et al. Reproductive and developmental toxicity of inhaled 2,3-dichloro-1,3-butadiene in rats. Reprod Toxicol. 2006;22(4):613-22.
Mylchreest, E., Malley, L. A., O'Neill, A. J., Kegelman, T. A., Sykes, G. P., & Valentine, R. (2006). Reproductive and developmental toxicity of inhaled 2,3-dichloro-1,3-butadiene in rats. Reproductive Toxicology (Elmsford, N.Y.), 22(4), 613-22.
Mylchreest E, et al. Reproductive and Developmental Toxicity of Inhaled 2,3-dichloro-1,3-butadiene in Rats. Reprod Toxicol. 2006;22(4):613-22. PubMed PMID: 16716565.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reproductive and developmental toxicity of inhaled 2,3-dichloro-1,3-butadiene in rats. AU - Mylchreest,E, AU - Malley,L A, AU - O'Neill,A J, AU - Kegelman,T A, AU - Sykes,G P, AU - Valentine,R, Y1 - 2006/05/23/ PY - 2006/02/16/received PY - 2006/04/05/accepted PY - 2006/5/24/pubmed PY - 2007/2/6/medline PY - 2006/5/24/entrez SP - 613 EP - 22 JF - Reproductive toxicology (Elmsford, N.Y.) JO - Reprod Toxicol VL - 22 IS - 4 N2 - Inhalation developmental and reproductive toxicity studies were conducted with 2,3-dichloro-1,3-butadiene (DCBD), a monomer used in the production of synthetic rubber. In the reproductive toxicity study, Crl:CD(SD)IGS BR rats (24/sex/group) were exposed whole body by inhalation to 0, 1, 5, or 50 ppm DCBD (6 h/day) for approximately 10-11 weeks total, through premating (8 weeks; 5 days/week), cohabitation of mating pairs (up to 2 weeks, 7 days/week), post-cohabitation for males (approximately 7 days) and from conception to implantation (gestation days 0-7 [GD 0-7]), followed by a recovery period (GD 8-21) for presumed pregnant females. Estrous cyclicity was evaluated during premating (last 3 weeks) and cohabitation. Reproductive organs and potential target organs, sperm parameters, and GD 21 fetuses (viability, weight, external alterations) were evaluated. In the developmental study, pregnant Crl:CD(SD)IGS BR rats (22/group) were exposed whole body by inhalation to 0, 1, 10, or 50 ppm DCBD (6 h/day) on GD 6-20; dams were necropsied on GD 21 (gross post-mortem only) and fetuses were evaluated (viability, weight, and external, visceral and skeletal exams). During the in-life portion of the studies, body weight, food consumption, and clinical observation data were collected. At 50 ppm, gasping and labored breathing occurred in both studies during the first few exposures; body weight and food consumption parameters were affected in parental animals from both studies, but were more severely affected in the developmental study. Fetal weight was decreased in the developmental study at 50 ppm. Degeneration of the nasal olfactory epithelium was observed in the reproduction study at 50 ppm. There were no effects on reproductive function, embryo-fetal viability, or increases in fetal structural alterations in either study. The no-observed-adverse-effect level (NOAEL) for reproductive toxicity was 50 ppm. The NOAEL for systemic toxicity in the reproduction study was 5 ppm based on adverse effects on body weight and food consumption parameters and nasal olfactory epithelial toxicity at 50 ppm in parental rats. The NOAEL for maternal and developmental toxicity was 10 ppm based on reduced maternal weight gain and food consumption and reduced fetal weight at 50 ppm in the developmental toxicity study. SN - 0890-6238 UR - https://www.unboundmedicine.com/medline/citation/16716565/Reproductive_and_developmental_toxicity_of_inhaled_23_dichloro_13_butadiene_in_rats_ DB - PRIME DP - Unbound Medicine ER -