A comparison of developmental toxicity evident at term to postnatal growth and survival using ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, and ethanol

Abstract

This study was designed to compare an abbreviated evaluation of uterine contents at term (teratology probe) with a modified Chernoff-Kavlock assay (postnatal study), [Chernoff N, Kavlock RJ: J Toxicol Environ Health 10:541-550, 1982]. Mice were intubated during gestation and were evaluated for signs of toxicity. In the teratology probe, uterine contents were examined at term. In the postnatal study, offspring were examined and weighed through day 22 postpartum. Ethylene glycol monoethyl ether (EGEE) produced embryo lethality and malformations, and decreased fetal weight at a dose level which was not maternally toxic in the teratology probe. In the postnatal study, EGEE decreased litter size and neonatal body weight; while litter size continued to decrease beyond the neonatal period, body weights of surviving pups were not significantly different from control. Pups exposed prenatally to EGEE developed kinked tail which was not apparent in fetuses or neonates. Maternally toxic dose levels of ethylene glycol monobutyl ether and ethanol were associated with increased embryo lethality in teratology probe studies. In postnatal studies, there were no significant effects on pup growth or survival at maternally toxic dose levels. Preliminary conclusions regarding maternal and developmental toxicity were comparable based on the teratology probe or postnatal study. Both assays measure litter size and offspring weight, but the teratology probe measures resorption incidence which may be a more sensitive index of prenatal death than number of live born. Neither fetal weight nor neonatal weight reliably predict permanent alteration of growth. A postnatal study permits detection of internal malformations or functional defects which reduce postnatal survival and gross abnormalities which appear postnatally.

Use of Biological Markers and Pharmacokinetics in Human Health Risk Assessment

“…Based on existing observations ofrelationships between sperm concentrations and male fertility performance [which are not without controversy among andrologists (50) Table 5 are a) a uniform multiplicative sperm reduction effect across the entire distribution of sperm counts, b) a linear relationship between the multiplicative spenn count "reduction factor" and the excess infertility risk for a "reduction factor" of 1.24, and c) a one-hit killing function for spenn progenitors in relation to dose rate. It can be seen in Table 5 (53,54) seemed to be compatible with a linear doseresponse relationship (Figs. 4 and 5).…”

Interactive effect of combined exposure to ethylene glycol ethers and ethanol on hematological parameters in rats

“…These ethers may cause local toxicity, i.e., skin irritation and sensitization in susceptible humans [1] and also, systemic toxicity. The primary systemic toxicity of these chemicals in animals include reproductive, developmental and hematological effects [2][3][4][5][6]. Similar effects have been observed in exposed workers.…”

Ethylene glycol monoethyl ether [MAK Value Documentation, 2008]

“…A NOAEL of 23 mg/kg body weight and day was found for both ingestion and subcutaneous injection (Stenger et al 1971). In mice, ingestion of the lowest dose of 1000 mg/kg body weight and day from days 8 to 14 of gestation led to reduced foetal weight, and 1800 mg/kg body weight and day caused an increased incidence of resorptions and malformations (Wier et al 1987).…”

“…The postnatal survival rate was decreased at 1200 mg/kg body weight and day (Wier et al 1987; Table 4). …”