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Developmental toxicity and uterotrophic studies with di-2-ethylhexyl terephthalate.
Birth Defects Res B Dev Reprod Toxicol. 2007 Oct; 80(5):396-405.BD

Abstract

BACKGROUND

These studies were conducted to evaluate the potential adverse effects of di-2-ethylhexyl terephthalate (DEHT) exposure on in utero development in mice and rats. In addition, a uterotrophic assay for estrogenic activity was conducted in sexually immature rats.

METHODS

In the developmental toxicity studies, diet containing DEHT was fed to four groups of mated female Crl:CD(SD)IGS BR rats (25/group) from gestation day (GD) 0-20 or Crl:CD1(ICR) mice (25/group) from GD 0-18. Concentrations within the feed were 0, 0.3, 0.6, and 1.0% for the rats and 0, 0.1, 0.3, and 0.7% for the mice. Laparohysterectomies were carried out on the last day of exposure and the numbers of fetuses, early and late resorptions, total implantations, and corpora lutea were recorded. The fetuses were weighed, sexed, and examined for external, visceral and skeletal malformations, and developmental variations. The dose rate from dietary DEHT exposure was 0, 226, 458, and 747 mg/kg/day in the rats and 197, 592, and 1382 mg/kg/day in the mice for the control, low, mid, and high-exposure groups, respectively.

RESULTS

DEHT exposure did not affect clinical observations. A slight reduction in body weight gain was noted in the high-dose level rat group; the remaining groups were unaffected. At necropsy, increased liver weights were noted in the high-dose rat group and the mid- and high-dose mouse groups. Mean numbers of implantation sites and viable fetuses, mean fetal weights, and mean litter proportions of preimplantation loss, early resorptions, late resorptions, and fetal sex ratios were unaffected by DEHT exposures. No test article-related malformations or variations were observed at any concentration level in the rat and mouse developmental toxicity studies. In the uterotrophic assay for estrogenic activity, sexually immature female rats received oral gavage doses 20, 200, or 2000 mg DEHT/kg bw/day from postnatal day (PND) 19-21. A slight reduction in rate of body weight gain was noted on the first day of dosing in the high dose group, but no other indications of toxicity were evident. DEHT exposure did not affect wet or blotted uterine weight parameters in any of these dose groups. The NOEL for developmental toxicity in rats was 747 mg/kg/day and 1382 mg/kg/day in mice. The NOEL for estrogenic activity was 2000 mg/kg/day. The NOEL for maternal toxicity was 458 mg/kg/day in rats and 197 mg/kg/day in mice.

CONCLUSIONS

The lack of adverse developmental effects with DEHT exposure are in contrast to the adverse developmental effects noted after di-2-ethylhexyl phthalate (DEHP) exposure. The difference between the effects noted with the ortho-constituent (DEHP) and the lack of effects reported with the para-constituent (DEHT) is due most likely to differences in metabolism and the formation of the stable monoester, mono-2-ethylhexyl phthalate (MEHP) from the DEHP moiety.

Authors+Show Affiliations

WFTC, LLC, Victor, NY 14564, USA. wfaber@msn.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17849488

Citation

Faber, Willem D., et al. "Developmental Toxicity and Uterotrophic Studies With Di-2-ethylhexyl Terephthalate." Birth Defects Research. Part B, Developmental and Reproductive Toxicology, vol. 80, no. 5, 2007, pp. 396-405.
Faber WD, Deyo JA, Stump DG, et al. Developmental toxicity and uterotrophic studies with di-2-ethylhexyl terephthalate. Birth Defects Res B Dev Reprod Toxicol. 2007;80(5):396-405.
Faber, W. D., Deyo, J. A., Stump, D. G., Navarro, L., Ruble, K., & Knapp, J. (2007). Developmental toxicity and uterotrophic studies with di-2-ethylhexyl terephthalate. Birth Defects Research. Part B, Developmental and Reproductive Toxicology, 80(5), 396-405.
Faber WD, et al. Developmental Toxicity and Uterotrophic Studies With Di-2-ethylhexyl Terephthalate. Birth Defects Res B Dev Reprod Toxicol. 2007;80(5):396-405. PubMed PMID: 17849488.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Developmental toxicity and uterotrophic studies with di-2-ethylhexyl terephthalate. AU - Faber,Willem D, AU - Deyo,James A, AU - Stump,Donald G, AU - Navarro,Lisa, AU - Ruble,Karen, AU - Knapp,John, PY - 2007/9/13/pubmed PY - 2007/12/7/medline PY - 2007/9/13/entrez SP - 396 EP - 405 JF - Birth defects research. Part B, Developmental and reproductive toxicology JO - Birth Defects Res B Dev Reprod Toxicol VL - 80 IS - 5 N2 - BACKGROUND: These studies were conducted to evaluate the potential adverse effects of di-2-ethylhexyl terephthalate (DEHT) exposure on in utero development in mice and rats. In addition, a uterotrophic assay for estrogenic activity was conducted in sexually immature rats. METHODS: In the developmental toxicity studies, diet containing DEHT was fed to four groups of mated female Crl:CD(SD)IGS BR rats (25/group) from gestation day (GD) 0-20 or Crl:CD1(ICR) mice (25/group) from GD 0-18. Concentrations within the feed were 0, 0.3, 0.6, and 1.0% for the rats and 0, 0.1, 0.3, and 0.7% for the mice. Laparohysterectomies were carried out on the last day of exposure and the numbers of fetuses, early and late resorptions, total implantations, and corpora lutea were recorded. The fetuses were weighed, sexed, and examined for external, visceral and skeletal malformations, and developmental variations. The dose rate from dietary DEHT exposure was 0, 226, 458, and 747 mg/kg/day in the rats and 197, 592, and 1382 mg/kg/day in the mice for the control, low, mid, and high-exposure groups, respectively. RESULTS: DEHT exposure did not affect clinical observations. A slight reduction in body weight gain was noted in the high-dose level rat group; the remaining groups were unaffected. At necropsy, increased liver weights were noted in the high-dose rat group and the mid- and high-dose mouse groups. Mean numbers of implantation sites and viable fetuses, mean fetal weights, and mean litter proportions of preimplantation loss, early resorptions, late resorptions, and fetal sex ratios were unaffected by DEHT exposures. No test article-related malformations or variations were observed at any concentration level in the rat and mouse developmental toxicity studies. In the uterotrophic assay for estrogenic activity, sexually immature female rats received oral gavage doses 20, 200, or 2000 mg DEHT/kg bw/day from postnatal day (PND) 19-21. A slight reduction in rate of body weight gain was noted on the first day of dosing in the high dose group, but no other indications of toxicity were evident. DEHT exposure did not affect wet or blotted uterine weight parameters in any of these dose groups. The NOEL for developmental toxicity in rats was 747 mg/kg/day and 1382 mg/kg/day in mice. The NOEL for estrogenic activity was 2000 mg/kg/day. The NOEL for maternal toxicity was 458 mg/kg/day in rats and 197 mg/kg/day in mice. CONCLUSIONS: The lack of adverse developmental effects with DEHT exposure are in contrast to the adverse developmental effects noted after di-2-ethylhexyl phthalate (DEHP) exposure. The difference between the effects noted with the ortho-constituent (DEHP) and the lack of effects reported with the para-constituent (DEHT) is due most likely to differences in metabolism and the formation of the stable monoester, mono-2-ethylhexyl phthalate (MEHP) from the DEHP moiety. SN - 1542-9733 UR - https://www.unboundmedicine.com/medline/citation/17849488/Developmental_toxicity_and_uterotrophic_studies_with_di_2_ethylhexyl_terephthalate_ L2 - https://doi.org/10.1002/bdrb.20130 DB - PRIME DP - Unbound Medicine ER -