The Role of Maternal Variation in the Assessment of Developmental Toxicity
Public Deposited- Last Modified
- February 28, 2019
- Creator
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Hassett-Sipple, Beth M.
- Affiliation: Gillings School of Global Public Health, Department of Environmental Sciences and Engineering
- Abstract
- Intraspecies variability is an important component in evaluating public health risks. In developmental toxicity studies, such variation may occur among litters within a treatment group. This study examined the degree of similarity across three breedings of female mice (CD-1) with respect to their responses to two known developmental toxicants. Each female was mated to the same male (CD-1) and exposed to the same dosing regimen during each pregnancy. Litters were evaluated for postnatal viability and growth. The known murine teratogens dinocap and all-trans retinoic acid were chosen because of the existence of adequate historical data on these compounds. Two doses of each chemical were chosen to produce marginal or severe developmental toxicity. Five treatment groups (22-29 animals per group) were dosed by gastric intubation as follows: control (corn oil, gestation days 10 through 13); dinocap (20 or 40 mg/kg/day in corn oil, gestation days 10 through 13); and all-trans retinoic acid (10 or 20 mg/kg/day in corn oil, gestation days 11 through 13). Litters were examined on postnatal days 1 and 3 for viability, evidence of developmental toxicity, and growth (body weight). Gross abnormalities observed included abdominal ballooning in the high dose litters and limb defects in the all-trans retinoic acid treated animals. Intergroup differences were assessed using the multiple t-test of least square means. A rank test of independence was performed to assess whether or not a given dam's response was consistent across litters and intraclass correlation coefficients were calculated to assess between versus within dam variability. These analyses indicated that maternal variability contributed to interlitter difference in untreated CD-1 mice, in many cases up to 40 percent. Treatment with either of two known development toxicants, however, decreased the role that maternal variability played with respect to interlitter differences, frequently dropping by greater than 50 percent.
- Date of publication
- August 1991
- DOI
- Resource type
- Rights statement
- In Copyright
- Advisor
- Ball, Louise
- Turner, Alvis G.
- Sulik, Kathleen K.
- Degree
- Master of Science in Public Health
- Academic concentration
- Environmental Management and Policy
- Degree granting institution
- University of North Carolina at Chapel Hill
- Graduation year
- 1991
- Language
- Deposit record
- ad7e9272-7c4f-43e0-afeb-7a5f2526ad76
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