Reproductive Toxicity Study of Clarified Slurry Oil in the Rat

Abstract

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.

The Toxicological Effects of Heavy Fuel Oil Category Substances

“…22 The dermal route was also used to relate these data to results of previous dermal application tests in which the toxicological properties of these substances were established. 12 –21 The results of present studies confirmed the types of toxicological effects produced by these oils and demonstrated that CCCO is a reasonable worst-case example for HFO category members.…”

Use of a Statistical Model to Predict the Potential for Repeated Dose and Developmental Toxicity of Dermally Administered Crude Oil and Relation to Reproductive Toxicity

“…In the studies of clarified slurry oil, there were no effects on fertility following dermal administration of “clarified slurry oil” at doses of 0.1, 1, 10, 50, or 250 mg/kg/d, the highest level tested. 30 These data suggest that the PAC constituents in high-boiling petroleum-derived substances are unlikely to affect fertility. In contrast, in developmental toxicity studies of clarified slurry oil dermal treatment at levels between 1 and 250 mg/kg/d resulted in both maternal and fetal effects of which the most profound were significant increases in resorption and significantly reduced maternal and fetal body weights.…”

“…30,31 This type of substance contains the highest levels of PACs of any of the petroleum-derived substances. In the studies of clarified slurry oil, there were no effects on fertility following dermal administration of ''clarified slurry oil'' at doses of 0.1, 1, 10, 50, or 250 mg/kg/d, the highest level tested.…”

The Mammalian Toxicological Hazards of Petroleum-Derived Substances

“…80 Aromatic extracts are also mutagenic in appropriately modified Salmonella tests 28,29 and produce skin tumors when repeatedly applied to mouse skin. 25,30,81 Based on the results of Hoberman et al, 63,74 aromatic extracts are not expected to be reproductive toxicants.…”

“…[55][56][57] The gas oil streams that do not contain high levels of PACs can also induce mouse skin tumors; however, these substances are not tumorinitiating agents and appear to act via a promotional process related to repeated skin irritation. 56,57 Although gas oils have not been tested in 2-generation reproductive toxicity tests, it seems unlikely that they would affect fertility, given the absence of reproductive effects in studies of substances in categories containing both lower (ie, jet fuels) 59 and higher (ie, heavy fuel oils [HFOs]) 63 boiling constituents. As part of the HPV program, 2 types of gas oils, a blend of commercial diesel fuels (ultralow sulfur diesel [ULSD]), and aromatic-rich streams from a catalytic cracking process were tested for target organ and developmental effects in repeated dermal application studies.…”