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Developmental toxicity of 2,4,5-trichlorophenoxyacetic acid (2,4,5-T). II. Multireplicated dose-response studies with
C J Nelson1, J F Holson, T B Gaines
1USEPA (MD-56), Research Triangle Park, North Carolina 27711.
Abstract:
A series of multireplicated developmental toxicity studies were conducted in four-way outcross mice and CD-1 outbred mice administered either analytical or technical grades of 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) by gavage on Gestational Days 6 through 14. The formulations of 2,4,5-T differed by a factor of 10-fold in 2,3,7,8-tetrachlorodibenzo-p-dioxin levels. Reduced fetal weight and increased incidences of cleft palate and embryolethality were the most significant prenatal effects of both formulations of 2,4,5-T observed in all strains/stocks of mice. Both the outcross and outbred mice exhibited a dose-response relationship with each of the above endpoints and the dose-response curves were parallel. There were no embryotoxic or fetotoxic differences between the technical and analytical grades of 2,4,5-T with regard to extent of fetal weight reduction, resorption rate, or cleft palate incidence. There was little difference in the results between the four-way outcross mouse and the CD-1 outbred mouse.
Insights
Developmental toxicity studies in mice revealed that 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) caused reduced fetal weight, cleft palate, and embryolethality. These effects occurred regardless of 2,4,5-T formulation purity or mouse strain.
Area of Science:
- Toxicology
- Developmental Biology
- Environmental Health
Background:
- 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) is a herbicide with potential developmental toxicity concerns.
- The presence of dioxins, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin, in 2,4,5-T formulations can influence toxicity.
- Understanding the dose-response relationship and effects across different mouse models is crucial for risk assessment.
Purpose of the Study:
- To evaluate the developmental toxicity of analytical and technical grades of 2,4,5-T in mice.
- To compare the effects of 2,4,5-T formulations with varying dioxin levels.
- To assess potential differences in susceptibility between mouse strains.
Main Methods:
- Multireplicated developmental toxicity studies were conducted in four-way outcross mice and CD-1 outbred mice.
- Administration of 2,4,5-T (analytical or technical grade) via gavage on Gestational Days 6-14.
- Evaluation of endpoints including fetal weight, cleft palate incidence, and embryolethality.
Main Results:
- Reduced fetal weight, increased cleft palate incidence, and embryolethality were observed with both 2,4,5-T formulations.
- A clear dose-response relationship was evident for these endpoints in both mouse strains.
- No significant differences in toxicity were found between analytical and technical grades of 2,4,5-T, nor between the mouse strains.
Conclusions:
- 2,4,5-T exhibits significant developmental toxicity in mice, manifesting as reduced fetal weight, cleft palate, and embryolethality.
- The purity of the 2,4,5-T formulation, specifically dioxin levels, did not alter the observed toxicological outcomes.
- Both four-way outcross and CD-1 outbred mice demonstrated similar sensitivity to 2,4,5-T developmental toxicity.
