Non-additive developmental toxicity in mixtures of trichloroethylene (TCE), di(2-ethylhexyl)phthalate (DEHP), and heptachlor (HEPT)
Narotsky, MG; Hamby, BT; Mitchell, DS; Weller, E; Chinchilli, VM; Kavlock, RJ
HERO ID
1334065
Reference Type
Journal Article
Subtype
Abstract
Year
1992
Language
English
| HERO ID | 1334065 |
|---|---|
| Material Type | Abstract |
| In Press | No |
| Year | 1992 |
| Title | Non-additive developmental toxicity in mixtures of trichloroethylene (TCE), di(2-ethylhexyl)phthalate (DEHP), and heptachlor (HEPT) |
| Authors | Narotsky, MG; Hamby, BT; Mitchell, DS; Weller, E; Chinchilli, VM; Kavlock, RJ |
| Journal | Teratology |
| Volume | 45 |
| Issue | 5 |
| Page Numbers | 489-490 |
| Abstract | In order to investigate the developmental effects of chemicals in mixture, three compounds were combined using five dosages of each agent (a 5x5x5 design). Due to the large number of treatment groups (125), the experiment was divided into five replicates, each consisting of five blocks. To date, four of the five blocks have been completed with over 1200 rats treated and 1000 litters examined. F-344 rats were gavaged on gestation days (GD) 6-15 with TCE (0, 10.1, 32, 101, and 320 mg/kg/d), DEHP (0, 24.7, 78, 247, and 780 mg/kg/d), and HEPT (0, 0.25, 0.8, 2.5, and 8.0 mg/kg/d) in corn oil. The dams were allowed to deliver and their pups were weighed and examined on days 1 and 6. Implants were counted to determine prenatal loss. Linear and logistic regression models were used to analyze continuous and proportional endpoints, respectively. Preliminary data analysis after four replicates revealed TCE and DEHP main effects and synergism for reduced maternal weight gain during GD 6-8; however, DEHP and HEPT were antagonistic. Full-litter resorptions were associated with main effects and a two-way synergism of DEHP and HEPT. Eye defects were associated with TCE and DEHP main effects. Decreased pup weights were associated with a main effect of each agent and DEHP antagonisms with the other two agents. Post-natal loss was associated with a HEPT main effect and a TCE-DEHP-HEPT three-way synergism. Results will be discussed in terms of study design and implications for risk assessment. |
| Doi | 10.1002/tera.1420450503 |
| Url | http://onlinelibrary.wiley.com/doi/10.1002/tera.1420450503/abstract |
| Is Certified Translation | No |
| Dupe Override | No |
| Conference Location | Boca Raton, Florida |
| Conference Name | The Teratology Society Thirty-second Annual Meeting and The Neurobehavioral Teratology Society Sixteenth Annual Meeting |
| Conference Date | June 27–July 2, 1992 |
| Is Public | Yes |
| Language Text | English |
| Keyword | Pregnancy; Trichloroethylene/ TOXICITY; Diethylhexyl Phthalate/ TOXICITY; Heptachlor/ TOXICITY; Drug Synergism; Dose-Response Relationship, Drug; Fetus/ DRUG EFFECTS; Body Weight/DRUG EFFECTS |
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