The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program. The findings may not have been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by NTP in March 2009. For more information, see the Explanation of Levels of Evidence for Developmental Toxicity. The findings and conclusions for this study should not be construed to represent the views of NTP or the U.S. Government.
Naphthalene is a polyaromatic hydrocarbon produced from petroleum and coal tar. NAP is widely used in the manufacture of dyes, synthetic tanning agents, and lubricants; it is also a common constituent of mothbalIs. Exposure to NAP can occur in the home and workplace, and ingestion or inhalation can cause severe toxicity in humans, especially in infants and individuals with a deficiency in the enzyme glucose-6-phosphate dehydrogenase. Because of the large population at risk, and since NAP readily crosses the placenta, it was evaluated as a developmental toxicant. Accordingly, NAP (0, 20, 80, or 120 mg/kg/day) was administered in corn oil by gavage to pregnant rabbits during the major period of organogenesis (gd 6-19). Maternal clinical signs, weight, and food consumption were monitored from gd 0 to 30. On gd 30, fetuses were removed from the does and examined for effects of NAP on growth, viability, and morphological development.
There was no maternal mortality in the control or NAP groups and each group contained 20-23 pregnant does at necropsy. Maternal body weights in the NAP-treated groups were comparable to controls at all gestational ages. Maternal corrected gestational weight gain and food consumption in all three NAP groups was also comparable to controls throughout gestation.
Examination of the uterine contents revealed that NAP was not fetotoxic. Average live litter size and average fetal body weight in the NAP-treated groups were normal. There was no effect of NAP on the incidence of malformations (external, visceral, or skeletal). The incidence of variations or defects (fetuses with one or more malformation or variation) on a per fetus or litter basis was similarly unaffected in the NAP-treated groups.
The results from this study provide no definitive evidence for NAP being toxic to the fetus or doe at doses as high as 120 mg/kg/day. Higher doses were not examined in this study due to the reported incidence of 40% maternal mortality following administration of 150 mg/kg/day NAP to pregnant rabbits in a range-finding study (NTP, 1990).