Assessing cancer hazards of bitumen emissions - a case study for complex petroleum substances.

When assessing cancer hazard and risk associated with a complex petroleum substance, like bitumen emissions, there are often conflicting results related to human, animal and mechanistic studies. Validation of the complex composition to assure that it matches real-world exposures and control of confounders are pivotal factors in study design to allow the necessary read-across during assessments. Several key studies on bitumen emissions in two-year dermal cancer assays reported variable outcomes ranging from high cancer incidence to no cancer incidence.

Health assessment of gasoline and fuel oxygenate vapors: subchronic inhalation toxicity.

Sprague Dawley rats were exposed via inhalation to vapor condensates of either gasoline or gasoline combined with various fuel oxygenates to assess whether their use in gasoline influences the hazard of evaporative emissions. Test substances included vapor condensates prepared from an EPA described "baseline gasoline" (BGVC), or gasoline combined with methyl tertiary butyl ether (G/MTBE), ethyl t-butyl ether (G/ETBE), t-amyl methyl ether (G/TAME), diisopropyl ether (G/DIPE), ethanol (G/EtOH), or t-butyl alcohol (G/TBA). Target concentrations were 0, 2000, 10,000 or 20,000mg/m(3) and exposures were for 6h/day, 5days/week for 13weeks.

Health assessment of gasoline and fuel oxygenate vapors: neurotoxicity evaluation.

Sprague-Dawley rats were exposed via inhalation to vapor condensates of either gasoline or gasoline combined with various fuel oxygenates to assess potential neurotoxicity of evaporative emissions. Test articles included vapor condensates prepared from "baseline gasoline" (BGVC), or gasoline combined with methyl tertiary butyl ether (G/MTBE), ethyl t-butyl ether (G/ETBE), t-amyl methyl ether (G/TAME), diisopropyl ether (G/DIPE), ethanol (G/EtOH), or t-butyl alcohol (G/TBA). Target concentrations were 0, 2000, 10,000 or 20,000mg/mg(3) and exposures were for 6h/day, 5days/week for 13weeks.

Health assessment of gasoline and fuel oxygenate vapors: micronucleus and sister chromatid exchange evaluations.

Micronucleus and sister chromatid exchange (SCE) tests were performed for vapor condensate of baseline gasoline (BGVC), or gasoline with oxygenates, methyl tert-butyl ether (G/MTBE), ethyl tert butyl ether (G/ETBE), t-amyl methyl ether (G/TAME), diisopropyl ether (G/DIPE), t-butyl alcohol (TBA), or ethanol (G/EtOH). Sprague Dawley rats (the same 5/sex/group for both endpoints) were exposed to 0, 2000, 10,000, or 20,000mg/m(3) of each condensate, 6h/day, 5days/week over 4weeks. Positive controls (5/sex/test) were given cyclophosphamide IP, 24h prior to sacrifice at 5mg/kg (SCE test) and 40mg/kg (micronucleus test).

Health assessment of gasoline and fuel oxygenate vapors: developmental toxicity in rats.

Gasoline-vapor condensate (BGVC) or condensed vapors from gasoline blended with methyl t-butyl ether (G/MTBE), ethyl t-butyl ether (G/ETBE), t-amyl methyl ether (G/TAME) diisopropyl ether (G/DIPE), ethanol (G/EtOH), or t-butyl alcohol (G/TBA) were evaluated for developmental toxicity in Sprague-Dawley rats exposed via inhalation on gestation days (GD) 5-20 for 6h/day at levels of 0 (control filtered air), 2000, 10,000, and 20,000mg/m(3). These exposure durations and levels substantially exceed typical consumer exposure during refueling (<1-7mg/m(3), 5min). Dose responsive maternal effects were reduced maternal body weight and/or weight change, and/or reduced food consumption.

Health assessment of gasoline and fuel oxygenate vapors: reproductive toxicity assessment.

Vapor condensates of baseline gasoline (BGVC), or gasoline-blended with methyl tertiary butyl ether (G/MTBE), ethyl t-butyl ether (G/ETBE), t-amyl methyl ether (G/TAME), diisopropyl ether (G/DIPE), ethanol (G/EtOH), or t-butyl alcohol (G/TBA) were evaluated for reproductive toxicity in rats at target concentrations of 2000, 10,000, or 20,000mg/m(3), 6h/day, 7days/week. BGVC and G/MTBE were assessed over two generations, the others for one generation. BGVC and G/MTBE F1 offspring were evaluated for neuropathology and changes in regional brain glial fibrillary acidic protein content.

Health assessment of gasoline and fuel oxygenate vapors: immunotoxicity evaluation.

Female Sprague Dawley rats were exposed via inhalation to vapor condensates of either gasoline or gasoline combined with various fuel oxygenates to assess potential immunotoxicity of evaporative emissions. Test articles included vapor condensates prepared from "baseline gasoline" (BGVC), or gasoline combined with methyl tertiary butyl ether (G/MTBE), ethyl t-butyl ether (G/ETBE), t-amyl methyl ether (G/TAME), diisopropyl ether (G/DIPE), ethanol (G/EtOH), or t-butyl alcohol (G/TBA). Target concentrations were 0, 2000, 10,000 or 20,000mg/mg(3) administered for 6h/day, 5days/week for 4weeks.

Characterization of the noncancer hazards of gas oils.

Gas oils, used to manufacture diesel fuel and residential heating oil, are complex hydrocarbon substances with carbon numbers of C9-C30 and boiling ranges of approximately 150 °C to 450 °C. Target organ (liver enlargement, reduced thymus weights, and reductions in hematological parameters) and developmental (reduced fetal viability, increased resorption frequency, and reduced fetal weights) effects are associated with aromatic constituents present in some gas oils. Two types of gas oils were tested for repeated-dose and developmental toxicity following repeated dermal administration.

Genetic toxicity of high-boiling petroleum substances.

There are several specific types of high-boiling petroleum substances (HBPS) having final boiling points >343°C), in which genetic toxicity can be related to the content of polycyclic aromatic compounds (PACs), specifically crude oils, gas oils, heavy fuel oils, lubricant base oils, waxes and aromatic extracts. Evaluation of optimized Salmonella tests covering over 250 samples from 43 types of HBPS revealed that gene mutation can be determined for these substances using a protocol optimized for the detection of mutagenic PAC. The outcomes of modified Salmonella assays can be predicted using HBPS compositional information as input to a newly developed statistical model.

Asphalt fume dermal carcinogenicity potential: II. Initiation-promotion assay of Type III built-up roofing asphalt.

Clark et al. (accepted for publication) reported that a sample of field-matched fume condensate from a Type III built-up roofing asphalt (BURA) resulted in a carcinogenic response in a mouse skin bioassay, with relatively few tumor-bearing animals, long tumor latency and chronic skin irritation. This mouse skin initiation/promotion study was conducted to assess possible mechanisms, i.

Review of mechanistic studies relevant to the potential carcinogenicity of asphalts.

Heating of asphalts to facilitate use in paving and roofing applications produces fumes containing polycyclic aromatic compounds (PAC). Regulatory organizations have suggested asphalt fumes of concern to humans due to possible carcinogenic effects but data are inadequate to classify. Two-year rodent inhalation studies and recent European epidemiology research have shown that asphalt fume alone does not pose a carcinogenic risk to humans.

Genetic toxicity of naphthalene: a review.

Results of five previously unpublished studies of the genotoxicity of naphthalene are presented and extensively discussed in relation to the large database that exists in the published literature. According to the published literature, naphthalene has not induced gene mutations in bacterial assays or in a metabolically competent human cell line. However, naphthalene has caused cytotoxicity in some cell lines, and induced clastogenicity in Chinese hamster ovary (CHO) cells, in a human lymphoblastoid cell line, and in preimplantation mouse embryos.