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 language | English (US) |
|---|---|
| Pages (from-to) | 55-68 |
| Number of pages | 14 |
| Journal | Toxicology |
| Volume | 159 |
| Issue number | 1-2 |
| DOIs | |
| State | Published - Feb 21 2001 |
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Keywords
- Zn metabolism
- Butyl benzyl phthalate
- Embryonic and fetal development
- Metallothionein
- Plasticizer
- Rats
- Teratogenicity
ASJC Scopus subject areas
- Toxicology
Cite this
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 journal › Article
}
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 -