Developmental toxicity evaluation of inhaled toluene diisocyanate vapor inCD rats

Mated female CD(R) (Sprague-Dawley) rats, 25/group, were exposed to toluene diisocyanate (TDI) vapor, for six h/day on gestational days (gd) 6 through 15, at 0.00, 0.02, 0.10, or 0.50 p.p.m.. Maternal clinical signs, body wei ghts, and feed and water consumption were recorded throughout gestation. At termination (gd 21), maternal body, gravid uterine, and liver weights were recorded. Corpora lutea were counted, and implantation sites were identifi ed: resorptions and dead and live fetuses. All live fetuses were examined f or external alterations. One-half of the live fetuses/litter were examined for visceral (including craniofacial) alterations. The remaining intact fet uses/litter were stained with alizarin red S and examined for ossified skel etal alterations. Maternal toxicity at 0.50 ppm consisted of reduced body w eights, body weight gains, feed consumption, and clinical signs of toxicity . Water consumption was unaffected. Gestational parameters exhibited no sig nificant treatment-related changes, including pre- and postimplantation los s, sex ratio/litter, or fetal body weights/litter. Incidences of individual malformations, malformations by category (external, visceral, and skeletal ), total malformations, individual external and visceral variations, variat ions by category, and total variations were unaffected. Of 111 skeletal var iants observed, only 1, incidence of poorly ossified cervical centrum 5, wa s increased at 0.50 ppm, indicating possible minimal fetotoxicity, although it occurred in the absence of any other indications of developmental toxic ity. Therefore, exposure to TDI vapor by inhalation, during major organogen esis in CD(R) rats, resulted in maternal toxicity and minimal fetotoxicity at 0.50 ppm no observed adverse effect level (NOAEL) for maternal and devel opmental toxicity was 0.10 ppm. No treatment-related embryotoxicity or tera togenicity was observed.