Estimation of the dermal carcinogenic activity of petroleum fractions using a modified Ames assay

Blackburn, Gary R.; Deitch, Robin A.; Schreiner, Ceinwen A.; Mehlman, Myron A.; Mackerer, Carl R.

doi:10.1007/bf00125566

Cited by 62 publications

(36 citation statements)

References 8 publications

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“…Workplace exposures were compared to tank fume condensates from the same bitumen source based on simulated distillation, UV fluorescence, PAC profile and selected ion GC/MS fingerprinting. Tank emissions were also tested for mutagenicity index (Blackburn et al 1984(Blackburn et al , 1996. The tank roofing and paving samples selected for skin painting closely matched the composition of worker exposure samples.…”

Section: Case Study 1 -Evaluating Carcinogenic Potential Of Bitumen Ementioning

confidence: 99%

“…This material showed significantly higher levels of 4-6 ring PACs [232 mg/kg], high fluorescence activity (336 EU/g) a mutagenicity index of 3.3 and the tumorigenic response was consistent with that seen previously (Niemeier et al 1988). Mutagenicity Index, derived using the modified Ames test (Blackburn 1984(Blackburn , 1996, is predictive of carcinogenic potential in mouse skin; complex petroleum substances with values >1.0 are considered to be carcinogenic, while those <1.0 are unlikely to be active.…”

Section: Case Study 1 -Evaluating Carcinogenic Potential Of Bitumen Ementioning

confidence: 99%

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

Kriech¹,

Schreiner²,

Osborn³

et al. 2017

Critical Reviews in Toxicology

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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. Here, we synthesize findings from published studies to explain the differences and discuss critical factors in cancer hazard evaluation for complex petroleum substances. Using these critical factors, we reviewed relevant human genetic toxicity, mammalian toxicity and mechanistic studies with bitumen to understand the divergence in results. We assess the most reliable and scientifically supported information on the potential carcinogenic hazards of bitumen emissions and comment on quality and completeness of data. Human hazard data are typically considered highest priority because they eliminate the need for interspecies extrapolation and reduce the range of high -to low-dose extrapolation during the risk assessment process. Finally, two well-conducted comprehensive animal studies are discussed that have well-defined test material, exposure concentration and composition representative of worker exposure, evidence of systemic uptake, no confounding exposures and provide consistency across all elements within both studies. Studies that allow effective read-across from human, animal and mechanistic components, control for confounders and are well-validated analytically against workplace exposures, provide the strongest evidence base for evaluating cancer hazard. ARTICLE HISTORY

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Section: Case Study 1 -Evaluating Carcinogenic Potential Of Bitumen Ementioning

confidence: 99%

Section: Case Study 1 -Evaluating Carcinogenic Potential Of Bitumen Ementioning

confidence: 99%

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

Kriech¹,

Schreiner²,

Osborn³

et al. 2017

Critical Reviews in Toxicology

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“…Aromatic extracts are not acutely toxic, highly irritating, or sensitizing, but, as shown by previous studies 79 as well as studies conducted as part of the HPV work, distillate aromatic extracts can produce the target organ and developmental effects that are characteristic of PAC-containing 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.…”

Section: Characterization Of Toxicological Hazard Information For Majmentioning

confidence: 99%

The Mammalian Toxicological Hazards of Petroleum-Derived Substances

McKee

White

2013

Int J Toxicol

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Petroleum-derived substances are complex and composed of aliphatic (normal-, iso-, and cycloparaffins), olefinic, and/or aromatic constituents. Approximately 400 of these complex substances were evaluated as part of the US Environmental Protection Agency voluntary High Production Volume (HPV) Challenge program. The substances were separated into 13 groups (categories), and all available data were assessed. Toxicology testing was conducted as necessary to fully address the end points encompassed by the HPV initiative. In a broad sense, volatile hydrocarbons may cause acute central nervous system effects, and those that are liquids at room temperature pose aspiration hazards if taken into the lungs as liquids and may also cause skin irritation. Higher boiling substances may contain polycyclic aromatic constituents (PACs) that can be mutagenic and carcinogenic and may also cause developmental effects. Substances containing PACs can also cause target organ and developmental effects. The effects of aliphatic constituents include liver enlargement and/or renal effects in male rats via an a-2u-globulin-mediated process and, in some cases, small but statistically significant reductions in hematological parameters. Crude oils may contain other constituents, particularly sulfur-and nitrogen-containing compounds, which are removed during refining. Aside from these more generic considerations, some specific petroleum substances may contain unusually toxic constituents including benzene, 1,3-butadiene, and/or n-hexane, which should also be taken into account if present at toxicologically relevant levels.

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“…Recommendations by Palmer (1990) include a proposed amendment to the military specification for fog oils to include a requirement for tests demonstrating the absence of carcinogens. Furthermore, Palmer recommends the following: (1) at a minimum, mutagenicity data, as determined by the modified Ames assay of Blackburn (1984) or PAH content, as determined by the FDA analytical test for white oil purity (Falk et al 1964), should be provided by the manufacturer. (2) Stockpiles of conventionally-refined oils purchased before the Military Specification was amended to exclude carcinogens should no longer be used for production of smokes to which military personnel are exposed.…”

Section: Human Health Riskmentioning

confidence: 99%