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This report focuses on recent studies that investigated the effects of kerosine dermal exposure on neurotoxicity and reproductive/developmental toxicity. Background toxicity information will also be reviewed for kerosine range mid distillates. The kerosine range mid distillates have a carbon range of C9-C16 and have a boiling range of 302-554 degrees F (150-290 degrees C). This category includes kerosine, aviation fuels (e.g., Jet A, JP-5 and JP-8), no. 1 fuel oil and diesel fuel oil. In general, the kerosine range mid distillates demonstrate relatively low acute toxicity by any route of exposure. High inhalation exposures can induce central nervous system depression characterized by ataxia, hypoactivity and prostration. Kerosines are known to cause skin irritation and inflammation under conditions of acute and repeated exposure in animals and humans, but are only slightly irritating to the eye and are not skin sensitizers. In addition, the absorption of kerosine range mid distillates through the skin has been demonstrated to be fairly rapid, but limited to approximately 10-15% of the applied dose after 24 hours. The kerosine range mid distillates are generally inactive in genetic toxicity tests although positive studies have been reported. Positive results, while at times equivocal, have been reported for straight run kerosine and jet fuel A in the mouse lymphoma assay with metabolic activation, and hydrodesulfurized kerosine (mouse) and jet fuel A (rat) in the bone marrow cytogenetic assay. Effects on the nervous and reproductive systems have been reported in humans and experimental animals under conditions where inhalation and dermal exposure to specific kerosine type fuels are sometimes difficult to separate. Recent laboratory studies have addressed this point and examined the effects of dermal exposure. In these studies, rats were exposed to hydrodesulfurized kerosine by skin application to determine the potential of dermal contact to cause reproductive/developmental toxicity (OECD Guideline 421) or neurotoxicity (TSCA Guidelines on subchronic inhalation and neurotoxicity studies). These studies demonstrated that the highest dose level of kerosine does not induce reproductive/developmental or neurotoxicity effects by skin exposure in rodent studies. The dermal NOEL for HDS kerosine in rats was > or = 494 mg/kg for both neurotoxicity, and reproductive/developmental toxicity.

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Clarified slurry oil (CSO, CAS #64741–62-4; also termed carbon black oil), a residual product from the fluidized catalytic cracker in petroleum refining, has the potential to be absorbed through the skin. The reproductive toxicity of CSO in male and female rats was evaluated by the topical route of exposure. CSO was administered dermally to male rats at dosages of 0 (vehicle), 0.1, 1, 10, 50, and 250 mg/kg/day for 70 days before a cohabitation period with untreated female rats. CSO was administered also to female rats at the same dosages for 14 days prior to a 7-day cohabitation period and continuing until Day 0 of gestation (day spermatozoa was present in a smear of the vaginal contents or a copulatory plug was observed in situ). The dosage volume in both experiments was 1 ml/kg, adjusted on each day of dosage based on individual body weights recorded immediately before application of CSO. Under the conditions of these experiments, the paternal no-observable-adverse-effect-level (NOAEL) for CSO administered dermally was 1 mg/kg/day. The 10, 50, and 250 mg/kg/day dosages of CSO caused body weight losses and/or decreased body weight gains and reduced feed consumption. The 50- and 250-mg/kg/day dosages also caused adverse clinical effects. No mating, fertility, or testicular end points in male rats were affected by the highest dosages tested; therefore, the reproductive NOAEL for male rats is <250 mg/kg/day. The maternal NOAEL for CSO administered dermally was 10 mg/kg/day. The 50-and 250-mg/kg/day dosages of CSO reduced body weight gains; 250 mg/kg/day also reduced feed consumption. There were no adverse effects on gonadal function, estrous cycles, mating behavior, conception rates, or reproductive organ weights; therefore, the reproductive NOAEL for female rats administered CSO dermally is at least 250 mg/kg/day.

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.