Related Experiment Videos
Teratogenicity/fetotoxicity of DEHP in mice
Abstract:
The embryonic/fetotoxic effects of DEHP on pregnant mice (ddY-Slc female x CBA male) were studied. DEHP was administered orally in dosages of 0.05 ml/kg to 30.0 mg/kg on day 6, 7, 8, 9 or 10 of gestation. A single administration of DEHP over 0.1 ml/kg (1/300 of LD50) on day 7 of gestation decreased the numbers and the body weight of living fetuses, whereas no significant changes in the numbers of living fetuses (with no gross and skeletal abnormalities) were observed compared with those of the control group, when 0.05 ml/kg (1/600 of LD50) of DEHP was administered. The fetotoxicity (fetal death) was dose dependent. The LD50 and the nonfetolethal maximum dosage of DEHP in its single, oral administration was 592 mg/kg and 64 mg/kg, respectively. The latter value is much higher than an estimated DEHP intake from commercial foodstuffs in men, which is approximately 0.03 mg/kg/day.
Insights
Diethylhexyl phthalate (DEHP) can cause embryonic and fetotoxic effects in pregnant mice, leading to decreased fetal weight and numbers at higher doses. However, lower doses showed no significant impact on fetal development or abnormalities.
Area of Science:
- Toxicology
- Developmental Biology
- Reproductive Science
Background:
- Diethylhexyl phthalate (DEHP) is a common plasticizer with potential endocrine-disrupting properties.
- Understanding the reproductive and developmental risks of DEHP exposure is crucial for public health.
- Previous studies have indicated potential adverse effects of phthalates on fetal development.
Purpose of the Study:
- To investigate the embryonic and fetotoxic effects of oral DEHP administration during critical periods of gestation in mice.
- To determine the dose-dependent relationship between DEHP exposure and fetal outcomes.
- To establish the lethal dose 50 (LD50) and the maximum non-fetotoxic dose of DEHP.
Main Methods:
- Pregnant mice (ddY-Slc female x CBA male) were administered varying oral doses of DEHP (0.05-30.0 mg/kg) on days 6-10 of gestation.
- Fetal viability, body weight, and the presence of gross or skeletal abnormalities were assessed.
- LD50 and maximum non-fetotoxic dosage were calculated based on observed effects.
Main Results:
- A single oral DEHP dose exceeding 0.1 ml/kg (1/300 LD50) on day 7 of gestation significantly reduced fetal numbers and body weight.
- Lower doses (0.05 ml/kg, 1/600 LD50) did not result in significant changes in fetal viability or abnormalities compared to controls.
- Fetotoxicity, including fetal death, was found to be dose-dependent, with an LD50 of 592 mg/kg and a maximum non-fetotoxic dose of 64 mg/kg.
Conclusions:
- DEHP exhibits dose-dependent fetotoxic effects in mice, with significant adverse outcomes observed at doses higher than 0.1 ml/kg.
- The maximum non-fetotoxic dose of DEHP (64 mg/kg) is substantially higher than estimated human daily intake from food.
- These findings highlight the importance of dose in assessing DEHP's reproductive risks, suggesting a margin of safety for typical human exposure levels.