Effect of butyl benzyl phthalate on reproduction and zinc metabolism

Janet Y. Uriu-Adams, C. Kevin Reece, Lan K. Nguyen, Benedetta J. Horvath, Rashmi Nair, Robert A. Barter, Carl L Keen

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Butyl benzyl phthalate (BBP) has been shown to be teratogenic. One mechanism contributing to the teratogenicity of several developmental toxicants, is chemical-induced changes in maternal zinc (Zn) metabolism which result in an increased synthesis of maternal liver metallothionein (Mt), and a subsequent reduction in Zn delivery to the conceptus. We investigated the effects of maternal BBP exposure on maternal-fetal Zn metabolism in Wistar rats. In study I, dams were gavaged with BBP (0,250, 1000, 1500 or 2000 mg/kg) on gestation days (GD) 11 through 13, and killed on GD 20. Maternal toxicity was evident in the three highest dose groups. Embryo/fetal death and small pup weights and lengths were noted in the 2000 mg BBP/kg group. Fetuses in the 1500 and 2000 mg/kg groups were characterized by poor skeletal ossification, and a high frequency of cleft palate. Rib anomalies were observed in the three highest dose groups. Maternal liver Mt concentrations were only slightly elevated in the 1500 and 2000 mg/kg groups. In study II, dams treated as above, were gavaged with 65Zn and killed 18 h later. While the 2000 mg/kg group had high percentages of 65Zn in some maternal tissues, sequestration of 65Zn in maternal liver was not evident. Thus, BBP is not a strong inducer of Mt, and the teratogenicity of BBP does not appear to be due to alterations in maternal and/or embryonic Zn metabolism.

Original languageEnglish (US)
Pages (from-to)55-68
Number of pages14
JournalToxicology
Volume159
Issue number1-2
DOIs
StatePublished - Feb 21 2001

Fingerprint

Metabolism
Reproduction
Zinc
Mothers
Metallothionein
Liver
Dams
Embryo Loss
Maternal Exposure
Pregnancy
Fetal Death
Toxicity
butylbenzyl phthalate
Rats
Cleft Palate
Ribs
Osteogenesis
Tissue
Wistar Rats
Fetus

Keywords

  • Zn metabolism
  • Butyl benzyl phthalate
  • Embryonic and fetal development
  • Metallothionein
  • Plasticizer
  • Rats
  • Teratogenicity

ASJC Scopus subject areas

  • Toxicology

Cite this

Uriu-Adams, J. Y., Kevin Reece, C., Nguyen, L. K., Horvath, B. J., Nair, R., Barter, R. A., & Keen, C. L. (2001). Effect of butyl benzyl phthalate on reproduction and zinc metabolism. Toxicology, 159(1-2), 55-68. https://doi.org/10.1016/S0300-483X(00)00403-0

Effect of butyl benzyl phthalate on reproduction and zinc metabolism. / Uriu-Adams, Janet Y.; Kevin Reece, C.; Nguyen, Lan K.; Horvath, Benedetta J.; Nair, Rashmi; Barter, Robert A.; Keen, Carl L.

In: Toxicology, Vol. 159, No. 1-2, 21.02.2001, p. 55-68.

Research output: Contribution to journalArticle

Uriu-Adams, JY, Kevin Reece, C, Nguyen, LK, Horvath, BJ, Nair, R, Barter, RA & Keen, CL 2001, 'Effect of butyl benzyl phthalate on reproduction and zinc metabolism', Toxicology, vol. 159, no. 1-2, pp. 55-68. https://doi.org/10.1016/S0300-483X(00)00403-0
Uriu-Adams JY, Kevin Reece C, Nguyen LK, Horvath BJ, Nair R, Barter RA et al. Effect of butyl benzyl phthalate on reproduction and zinc metabolism. Toxicology. 2001 Feb 21;159(1-2):55-68. https://doi.org/10.1016/S0300-483X(00)00403-0
Uriu-Adams, Janet Y. ; Kevin Reece, C. ; Nguyen, Lan K. ; Horvath, Benedetta J. ; Nair, Rashmi ; Barter, Robert A. ; Keen, Carl L. / Effect of butyl benzyl phthalate on reproduction and zinc metabolism. In: Toxicology. 2001 ; Vol. 159, No. 1-2. pp. 55-68.
@article{7ad0fb8104f448beadc1abefeedbe324,
title = "Effect of butyl benzyl phthalate on reproduction and zinc metabolism",
abstract = "Butyl benzyl phthalate (BBP) has been shown to be teratogenic. One mechanism contributing to the teratogenicity of several developmental toxicants, is chemical-induced changes in maternal zinc (Zn) metabolism which result in an increased synthesis of maternal liver metallothionein (Mt), and a subsequent reduction in Zn delivery to the conceptus. We investigated the effects of maternal BBP exposure on maternal-fetal Zn metabolism in Wistar rats. In study I, dams were gavaged with BBP (0,250, 1000, 1500 or 2000 mg/kg) on gestation days (GD) 11 through 13, and killed on GD 20. Maternal toxicity was evident in the three highest dose groups. Embryo/fetal death and small pup weights and lengths were noted in the 2000 mg BBP/kg group. Fetuses in the 1500 and 2000 mg/kg groups were characterized by poor skeletal ossification, and a high frequency of cleft palate. Rib anomalies were observed in the three highest dose groups. Maternal liver Mt concentrations were only slightly elevated in the 1500 and 2000 mg/kg groups. In study II, dams treated as above, were gavaged with 65Zn and killed 18 h later. While the 2000 mg/kg group had high percentages of 65Zn in some maternal tissues, sequestration of 65Zn in maternal liver was not evident. Thus, BBP is not a strong inducer of Mt, and the teratogenicity of BBP does not appear to be due to alterations in maternal and/or embryonic Zn metabolism.",
keywords = "Zn metabolism, Butyl benzyl phthalate, Embryonic and fetal development, Metallothionein, Plasticizer, Rats, Teratogenicity",
author = "Uriu-Adams, {Janet Y.} and {Kevin Reece}, C. and Nguyen, {Lan K.} and Horvath, {Benedetta J.} and Rashmi Nair and Barter, {Robert A.} and Keen, {Carl L}",
year = "2001",
month = "2",
day = "21",
doi = "10.1016/S0300-483X(00)00403-0",
language = "English (US)",
volume = "159",
pages = "55--68",
journal = "Toxicology",
issn = "0300-483X",
publisher = "Elsevier Ireland Ltd",
number = "1-2",

}

TY - JOUR

T1 - Effect of butyl benzyl phthalate on reproduction and zinc metabolism

AU - Uriu-Adams, Janet Y.

AU - Kevin Reece, C.

AU - Nguyen, Lan K.

AU - Horvath, Benedetta J.

AU - Nair, Rashmi

AU - Barter, Robert A.

AU - Keen, Carl L

PY - 2001/2/21

Y1 - 2001/2/21

N2 - Butyl benzyl phthalate (BBP) has been shown to be teratogenic. One mechanism contributing to the teratogenicity of several developmental toxicants, is chemical-induced changes in maternal zinc (Zn) metabolism which result in an increased synthesis of maternal liver metallothionein (Mt), and a subsequent reduction in Zn delivery to the conceptus. We investigated the effects of maternal BBP exposure on maternal-fetal Zn metabolism in Wistar rats. In study I, dams were gavaged with BBP (0,250, 1000, 1500 or 2000 mg/kg) on gestation days (GD) 11 through 13, and killed on GD 20. Maternal toxicity was evident in the three highest dose groups. Embryo/fetal death and small pup weights and lengths were noted in the 2000 mg BBP/kg group. Fetuses in the 1500 and 2000 mg/kg groups were characterized by poor skeletal ossification, and a high frequency of cleft palate. Rib anomalies were observed in the three highest dose groups. Maternal liver Mt concentrations were only slightly elevated in the 1500 and 2000 mg/kg groups. In study II, dams treated as above, were gavaged with 65Zn and killed 18 h later. While the 2000 mg/kg group had high percentages of 65Zn in some maternal tissues, sequestration of 65Zn in maternal liver was not evident. Thus, BBP is not a strong inducer of Mt, and the teratogenicity of BBP does not appear to be due to alterations in maternal and/or embryonic Zn metabolism.

AB - Butyl benzyl phthalate (BBP) has been shown to be teratogenic. One mechanism contributing to the teratogenicity of several developmental toxicants, is chemical-induced changes in maternal zinc (Zn) metabolism which result in an increased synthesis of maternal liver metallothionein (Mt), and a subsequent reduction in Zn delivery to the conceptus. We investigated the effects of maternal BBP exposure on maternal-fetal Zn metabolism in Wistar rats. In study I, dams were gavaged with BBP (0,250, 1000, 1500 or 2000 mg/kg) on gestation days (GD) 11 through 13, and killed on GD 20. Maternal toxicity was evident in the three highest dose groups. Embryo/fetal death and small pup weights and lengths were noted in the 2000 mg BBP/kg group. Fetuses in the 1500 and 2000 mg/kg groups were characterized by poor skeletal ossification, and a high frequency of cleft palate. Rib anomalies were observed in the three highest dose groups. Maternal liver Mt concentrations were only slightly elevated in the 1500 and 2000 mg/kg groups. In study II, dams treated as above, were gavaged with 65Zn and killed 18 h later. While the 2000 mg/kg group had high percentages of 65Zn in some maternal tissues, sequestration of 65Zn in maternal liver was not evident. Thus, BBP is not a strong inducer of Mt, and the teratogenicity of BBP does not appear to be due to alterations in maternal and/or embryonic Zn metabolism.

KW - Zn metabolism

KW - Butyl benzyl phthalate

KW - Embryonic and fetal development

KW - Metallothionein

KW - Plasticizer

KW - Rats

KW - Teratogenicity

UR - http://www.scopus.com/inward/record.url?scp=0035925068&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035925068&partnerID=8YFLogxK

U2 - 10.1016/S0300-483X(00)00403-0

DO - 10.1016/S0300-483X(00)00403-0

M3 - Article

C2 - 11250055

AN - SCOPUS:0035925068

VL - 159

SP - 55

EP - 68

JO - Toxicology

JF - Toxicology

SN - 0300-483X

IS - 1-2

ER -