Combined endocrine effects of in utero exposure to the antiandrogens butylbenzyl phthalate (BBP) and linuron (Lin) on fetal testosterone (T) synthesis and reproductive tract development
Parks, LG; Hotchkiss, AK; Ostby, JS; Lambright, CR; Gray, LE, Jr
HERO ID
675372
Reference Type
Journal Article
Year
2001
Language
English
| HERO ID | 675372 |
|---|---|
| In Press | No |
| Year | 2001 |
| Title | Combined endocrine effects of in utero exposure to the antiandrogens butylbenzyl phthalate (BBP) and linuron (Lin) on fetal testosterone (T) synthesis and reproductive tract development |
| Authors | Parks, LG; Hotchkiss, AK; Ostby, JS; Lambright, CR; Gray, LE, Jr |
| Journal | Toxicologist |
| Volume | 60 |
| Issue | 1 |
| Page Numbers | 225 |
| Abstract | Lin and BBP are toxicants that induce malformations in the male rat when administered in utero. However, the mechanism of action for both compounds had not been described. We suspected that BBP would decrease fetal T production because another phthalate ester (PE), diethylhexyl phthalate, has been shown to act via this mechanism. In addition, we wanted to determine if Lin (a weak androgen receptor (AR) antagonist) would also reduce fetal T production because the pattern of malformations that it induces more closely resemble a PE than an AR antagonist. A second objective of this study was to determine if a mixture of BBP and Lin would produce additive effects when administered at doses that singularly elicited minimal effects. BBP, a non-AR mediated antiandrogen, is approximately ten fold less potent than is Lin. Pregnant Sprague-Dawley rats were dosed daily on gestational day (GD) 14 through GD 18 with either BBP (500 mg/kg dam body weight (BW)), Lin (75 mg/kg dam BW), a combination (BBP 500 mg/kg & Lin 75 mg/kg) or vehicle control (2.5 mL corn oil). Two thirds of the dams were sacrificed on GD 18 and fetuses removed to assess male testicular T and progesterone (P) production, testicular T levels and whole body T levels. Offspring from the remaining litters were assessed for anogenital distance (AGD) on postnatal day (PND) 2, the number of areolas on PND 13, and for reproductive malformations in the adult rat. In utero exposure to Lin or BBP decreased T production. BBP plus Lin decreased T production and other fetal endocrine measures in an additive manner. In addition, BBP and Lin in combination produced additive effects on the incidence of reproductive malformations and reductions in reproductive organ weights in adult F1 male rats. |
| Is Certified Translation | No |
| Dupe Override | No |
| Comments | Authoring Organization: MONSANTO APPLIED SCI DIV |
| Is Public | Yes |
| Language Text | English |
| Keyword | Pregnancy; Rats; Animal; Female; Sprague-Dawley; Phthalic Acids TOXICITY; Linuron TOXICITY; Testosterone BIOSYNTHESIS; Androgen Antagonists TOXICITY; Genitalia; Male ABNORMALITIES; Abnormalities; Drug-Induced; Organ Weight DRUG EFFECTS; Fetus DRUG EFFECTS; Fetus METABOLISM; 85-68-7; No cas rn; 330-55-2; 57-85-2 |
| Is Qa | No |