A 15-week, whole-body inhalation study of the vapors of a distillate (LCCN-D) of light catalytic cracked naphtha (CAS no. 64741-55-5, LCCN) was conducted with Sprague-Dawley rats. Target exposure concentrations were 0, 750, 2500, and 7500 ppm for 6 hours/day, 5 days/week. Over the course of the study, animals received at least 65 exposures. For a portion of the control and 7500-ppm groups, a 4-week postexposure period was included in the study. Subchronic toxicity was evaluated using standard parameters. During life, neurotoxicity was evaluated by motor activity assessment and a functional observational battery. Selected tissues from animals in all exposure groups were examined microscopically. Neuropathologic examination of selected neuronal tissues from animals in the control and high-exposure groups was also conducted. No compound-related effects were seen on survival, clinical chemistry, food consumption, or physical signs. No evidence of neurotoxicity was seen at any exposure level. Slight decreases in hematocrit and hemoglobin concentrations were seen in male rats at the end of exposure to 7500 ppm LCCN-D. However, values were within normal physiological ranges and recovery occurred. Slight decreases in mean body weights and body weight gain were observed in high-exposure females during the first 7 weeks of exposure, but this decrease was not seen during the second half of the study. Male rat nephropathy involving hyaline droplet formation and alpha-2micro-globulin accumulation was seen in mid- and high-exposure males, an effect not relevant to humans. The incidence and severity of goblet cell hypertrophy/hyperplasia and respiratory epithelium hyperplasia in nasoturbinal tissues were greater in high-exposure animals, but recovery occurred. None of the effects observed were considered toxicologically significant. The no-observable-adverse-effect level (NOAEL) for subchronic and neurotoxicity of LCCN-D was > or = 7500 ppm.

A 13-week dermal repeat-dose toxicity study was conducted with hydrodesulfurized (HDS) kerosene, a test material that also met the commercial specifications for aviation turbine fuel (jet A). The objectives were to assess the potential for target organ toxicity and neurotoxicity. The HDS kerosene was applied to the shaved backs of Sprague-Dawley CD rats, 12/sex/group, 6 h/d, 5 d/wk in doses of 0 (vehicle control), 165 mg/kg (20% HDS kerosene), 330 mg/kg (40% HDS kerosene), or 495 mg/kg (60% HDS kerosene). Additional rats (12/sex) from the control and the high-dose groups were held without treatment for 4 weeks to assess recovery. Standard parameters of toxicity were investigated during the in-life phase. At necropsy, organs were weighed and selected tissues were processed for microscopic evaluation. Neurobehavioral evaluations included tests of motor activity and functional observations that were conducted pretest, at intervals during the exposure period and after recovery. No test substance-related effects on mortality, clinical observations (except dermal irritation), body weight, or clinical chemistry values were observed. A dose-related increase in skin irritation, confirmed histologically as minimal, was evident at the dosing site. The only statistically significant change considered potentially treatment related was an increase in the neutrophil count in females at 13 weeks. No test article-related effects were observed in the neurobehavioral assessments or gross or microscopic findings in the peripheral or central nervous system tissues in any of the dose groups. Excluding skin irritation, the no observed adverse effect level value for all effects was considered 495 mg/kg/d.

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Hydrodesulfurized kerosine (HDS kerosine), applied dermally, was tested for reproductive and developmental toxicity in Sprague-Dawley rats, using a modified OECD Guideline 421, Reproductive/Developmental Toxicity Screening Protocol. A preliminary acute dermal irritancy test demonstrated that dilution of HDS kerosine in either a light (100 Saybolt universal seconds, SUS) or moderate viscosity (340 SUS) USP mineral oil reduced irritation of the neat material comparably. Similar dermal absorption was observed in vitro for neat HDS kerosine or diluted in either of the mineral oils. HDS kerosine diluted to 494 (60%), 330 (40%), or 165 (20%) mg/kg/day in Squibb mineral oil (340 SUS) was applied daily at 1 ml/kg to the shaved backs of rats for 7 wk (premating, mating to d 19 of gestation) to females and 8 wk to males. Dams and litters were sacrificed on postpartum d 4 and males were sacrificed within the following week. HDS kerosine produced slight to moderate skin irritation at the highest dose in both sexes but no apparent maternal, reproductive, or developmental toxicity. No clinical signs of toxicity and no effects on body weight, food consumption, or absolute organ weights were observed. Relative kidney weights were heavier in male rats at the high dose. Skin changes were observed microscopically in male rats in all groups and in females at the high dose. No microscopic changes were observed in reproductive organs of parental animals. There were no differences in mean number of corpora lutea, implantation sites, and live pups per litter, and no gross anomalies were observed. Pups born from treated dams showed comparable body weights and weight gains to controls. The viability index on postpartum d 4 was > or = 93%. In conclusion, the no observable adverse effect level (NOAEL) for HDS kerosine for reproductive and developmental toxicity in rats is 494 mg/kg/d.

A distillate of light catalytic reformed naphtha (CAS number 64741-63-5, LCRN-D) administered by inhalation was tested for reproductive and developmental toxicity in Sprague-Dawley rats, following a modified OECD Guideline 421, Reproductive/Developmental Toxicity Screening protocol. LCRN-D was administered as a vapor, 6 h/d, 7 d/wk at target concentrations of 0, 750, 2500 or 7500 ppm to female rats for approximately 6 wk from 2 wk prior to mating, during mating through gestational d 19, and to males beginning 2 wk prior to mating for approximately 7 consecutive weeks. Dams and litters were sacrificed on postnatal d 4 and males were sacrificed within the week after the last litter was necropsied. Parental systemic effects observed at the 7500 ppm exposure level included slightly lower body weights for males throughout the study. Increased kidney to body weight and increased liver to body weight ratio in male rats exposed to 7500 ppm LCRN-D may be related to slightly lower final mean body weights. Body and organ weight data for female rats in all exposure groups were comparable to controls. No test-material-related microscopic changes were observed in the reproductive organs or nasal turbinate tissue of either sex. Reproductive performance was unaffected by exposure to LCRN-D. The mating and fertility indices were 100% in all groups. There were no significant exposure-related differences in implantation sites or live pups per litter, and no gross abnormalities were observed in pups from treated dams. Pups born from LCRN-D-exposed dams showed comparable body weights and weight gain to control pups. The viability index on postpartum d 4 was > or =97%. Under conditions of this study, the no-observed-adverse-effect level (NOAEL) for exposure to light catalytic reformed naphtha distillate for parental effects was 2500 ppm and the NOAEL for reproductive and developmental toxicity was 7500 ppm.