(Imming et al., 1969) resulted in teratogenesis. Notably, that teratogenesis was seen at doses similar to those at which fetotoxicity was not seen. Doses of 0.2–20 mg/kg per day on gestational days 20–38 resulted in no consistent evidence of fetotoxicity (Coulston et al., 1974).

More recently, effects on estrogenic and progesterone systems and the ability of carbamate insecticides to act as general endocrine modulators have been described. Klotz and colleagues (1997) reported, on the basis of in vitro studies, that the carbamates alone weakly activated estrogen- and progesterone-responsive reporter genes in breast and endometrial cancer cells. In whole-cell competition binding assays, the carbamates showed little capacity to displace radiolabeled estrogen or progesterone from its receptors. The effect of two carbamates, benomyl and carbendazim (at 500 and 1000 mg/kg for 5 days), on growth of decidua (the endometrium of the pregnant uterus) in pseudopregnant rats was assessed in an in vivo study. Both produced reductions in uterine decidual weight and uterine protein content, but serum estradiol and progesterone and the binding capacities of cytosolic estrogen and progesterone receptors were unchanged. The authors interpreted the findings as suggesting that antigrowth and antimitotic activities of the compounds on the decidua were direct and did not involve steroidal or receptor mechanisms.

Several reports have described effects on sperm due to carbaryl. When carbaryl at 50 and 100 mg/kg was fed to rats 5 days/week for 60 or 90 days, dose- and age-dependent declines in sperm count and motility and increased abnormal sperm structure were observed. The effects were more pronounced in young animals than in adults (Pant et al., 1995, 1996). Luca and Balan (1987) reported genotoxic effects in a sperm-abnormality assay in rats fed carbaryl for 3, 6, 9, 12, 15, and 18 months at 12.5, 25, and 250 mg/kg per day. Effects were generally dose-related, but they were not consistently observed for all exposure durations; maximal effects occurred at 6 and 15 months.

Other Health Effects

Chronic studies of carbaryl’s effects on the immune system have revealed several effects. Doses of 2–8 mg/kg per day for 4 weeks resulted in immunosuppression in rabbits (Street and Sharma, 1975). A 9-month oral exposure of rats at 2 mg/kg per day resulted in changes in serum complement-fixing activity, lysozyme activity, and immune functions of the reticuloendothelial system, neutrophils, skin, and mucosa. That dose is less than 1% of the oral LD50 for rats. It is not clear from those reports to what extent the effects are accompanied by overt toxicity, loss of body weight, or other toxic outcomes. Furthermore, the studies did not determine the extent to which such effects are progressive or reversible.

Interactions with Other Agents

The aryl hydrocarbon receptor (AhR) is a transcription factor that activates gene expression, including expression of cytochrome P450 enzymes (such as CYP1A1), in a ligand-dependent manner. The environmental chemical dioxin is one of the most potent AhR ligands ever found. Data from an in vitro study indicate that carbaryl can induce CYP1A1 in human HepG2 and HaCaT cell lines (Ledirac et al., 1997), but that the effect occurs via AhR-independent mechanisms. More recent work (Denison et al., 1998), however, indicates that carbaryl indeed is a weak AhR ligand and inducer of AhR-dependent and dioxin-response-element-dependent gene expression in cell lines from other species. Whether that



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