Dermal carcinogenic activity of petroleum-derived middle distillate fuels

Biles, Robert W.; McKee, Richard H.; Lewis, Stephen; Scala, Robert A.; DEPASS, LINVAL R.

doi:10.1016/0300-483x(88)90222-3

Cited by 32 publications

(25 citation statements)

References 18 publications

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“…Additionally, when these samples were separated further, the saturated constituents were more carcinogenic than the aromatics. Later studies [Biles et al, 1988;Clark et al, 1988;Witschi et al, 19871 confirmed these initial findings.…”

Section: Introductionsupporting

confidence: 62%

“…Because the distillation points of the known carcinogenic species are above 370°C, and the distillation range of PMDs is -170-300°C, PMDs generally contain low levels of carcinogenic PAH [e.g., Biles et al, 1988;King et al, 19821. However, certain products that contain higher boiling, cracked material may have concentrations of PAH that are sufficiently high to produce biological activity.…”

Section: Discussionmentioning

confidence: 99%

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Evaluation of the genetic toxicity of middle distillate fuels

McKee

Amoruso

Freeman

et al. 1994

Environ and Mol Mutagen

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Petroleum middle distillate (PMD) fuels are mixtures of hydrocarbons that distill between approximately 170-370 degrees C. Commercial products that fall into this category include kerosine, diesel fuel, jet fuel, and home heating oil. These products contain both saturated (paraffins and cycloparaffins) and aromatic species, but because of the boiling range normally contain very small amounts of the 3-6 ring polycyclic aromatic hydrocarbon (PAH) constituents, which are considered to be carcinogenic. Nevertheless, there is evidence of weak tumorigenic activity when these materials are repeatedly applied to mouse skin. In the current studies representative products were tested in two commonly used, short-term assays for genetic toxicity, the Salmonella/mammalian microsome mutagenicity assay and the mouse bone marrow micronucleus test. All samples were inactive in the micronucleus assay, and three were clearly inactive in the Salmonella test. Of the remaining two, one was marginally active in the Salmonella assay, and one was equivocal. The marginally active sample contained detectable levels of PAH due to the use of catalytically cracked materials as blending stocks. The results indicated that PMDs that do not contain cracked material were not mutagenic. Thus they may produce tumors via nongenotoxic processes. Those products that do contain cracked stocks may have sufficient PAH to be mutagenic in the Salmonella assay, and in those cases the PAH might also contribute to tumor formation.

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Section: Introductionsupporting

confidence: 62%

Section: Discussionmentioning

confidence: 99%

Evaluation of the genetic toxicity of middle distillate fuels

McKee

Amoruso

Freeman

et al. 1994

Environ and Mol Mutagen

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“…9 Prolonged and repeated application of petroleum middle distillates in mice results in the development of skin tumors. 14,31 An interesting aspect of these kerosene exposure studies pertinent to the present jet fuel investigations relates to the hydrocarbon fractions purported to be most active. The n-alkanes demonstrate a maximal skin tumor promotion activity at a chain length of C12-C14.…”

mentioning

confidence: 99%

Effects of short‐term high‐dose and low‐dose dermal exposure to Jet A, JP‐8 and JP‐8 + 100 jet fuels

Monteiro‐Riviere

Inman

Riviere

2001

J of Applied Toxicology

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Occupational and environmental exposures to jet fuel recently have become a source of public and regulatory concern. This study investigates the cutaneous toxicity of three fuels used in both civilian and military aircraft. Pigs, an accepted animal model for human skin, were exposed to low-dose (25 microl or 7.96 microl cm(-2)) or high-dose (335 microl or 67 microl cm(-2)) Jet A, JP-8 and JP-8 + 100 under occluded (Hill Top) chamber or cotton fabric) and non-occluded conditions for 5 h, 24 h and 5 days. To mimic occupational exposure, fuel-soaked fabric (high dose) was used. Erythema, edema, transepidermal water loss (TEWL) and epidermal thickness were quantified. High-dose fabric occluded sites had slight erythema at 5 h with increased erythema at 5 days. No erythema was noted in any of the occluded (Hill Top) or non-occluded sites at any of the time points. Morphological assessments depicted slight intracellular epidermal edema at all time points. An increase in change in TEWL (DeltaTEWL) was observed at the 5-h and 24-h fabric and Hill Top occluded treatments and a decrease at the 5-day fabric and Hill Top occluded sites. In all 5-day JP-8 + 100 fabric sites, intracorneal microabscesses filled with inflammatory cells were observed. Epidermal thickening was significant (P < 0.05) in all three jet fuels at the high-dose fabric sites, with JP-8 + 100 being the thickest. The epidermal rete peg depth increased significantly (P < 0.05) at 24 h and 5 days with Jet A, JP-8, and JP-8 + 100 in the fabric sites. No significant differences were noted in the 5-day non-occluded fabric and Hill Top occluded and non-occluded sites. Jet fuel JP-8 + 100 tended to have the greatest proliferative response. In conclusion, the high-dose fabric-soaked exposure at 5 days to Jet A, JP-8 and JP-8 + 100 fuels caused the greatest increase in cutaneous erythema, edema, epidermal thickness and rete peg depth compared with high-dose non-occluded or low-dose exposure under Hill Top occluded and non-occluded conditions.

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“…No tumours were found (Esso Research, 1960). White mineral oils have been used as negative controls (non-tumorigenic material) for many carcinogenicity studies of other petroleum products (Biles et al, 1988;McKee et al, 1987aMcKee et al, , 1987b. EFSA Journal 2009;7(11):1387…”

Section: Studies In Micementioning

confidence: 99%

Scientific Opinion on the use of high viscosity white mineral oils as a food additive

Publication¹

2009

EFSA Journal

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The Panel on Food Additives and Nutrient Sources added to Food (ANS) provides a scientific opinion on the safety of high viscosity white mineral oils (HVMO) (CAS Registry Number 8042-47-5) when used as food additives. HVMO have previously been evaluated by the EC Scientific Committee for Food (SCF) (1995) and the Joint FAO/WHO Expert Committee on Food Additives (JECFA) (1995, 2002). The SCF allocated a Temporary Group ADI of 0-4 mg/kg bw/day for white paraffinic oils which included white mineral oils with a viscosity higher than 8.5 cSt at 100°C. In 2002, JECFA recommended an ADI of 0 -20 mg/kg bw/day for HVMO. Dietary exposure to HVMO did not produce adverse effects in subchronic toxicity and chronic toxicity/carcinogenicity studies in rats. Infiltration of histiocytes (granulomas) in mesenteric lymph nodes and oil deposition in the liver were considered to be an indication of exposure to white mineral oils rather than an adverse effect. The NOAEL for HVMO was considered to be 1200 mg/kg bw/day, the highest dose tested. Using this NOAEL and applying an uncertainty factor of 100 the Panel established an ADI of 12 mg/kg bw/day for HVMO (kinematic viscosity ≥ 11 mm²/s (cSt) at 100 °C, a carbon number > 28 at 5 % distillation point and an average molecular weight > 500 g/mol). The Panel considered the dietary exposure to HVMO from current uses as well as proposed uses, and estimated that the potential dietary exposures for high level consumers (95 th /97.5 th ) would reach up to approximately 13 mg/kg bw/day for adults and 19 mg/kg bw/day for children. The Panel considers these estimates to be very conservative since high levels of exposure from different sources, in consumers only, have been added up. KEY WORDSHigh viscosity white mineral oils; CAS Number 8042-47-5; Liquid paraffin; Paraffinum Liquidum. SUMMARYFollowing a request from the European Commission to the European Food Safety Authority, the Scientific Panel on Food Additives and Nutrient Sources added to Food (ANS) was asked to evaluate the safety-in-use of high viscosity white mineral oils as food additives.In 1995, the EC Scientific Committee for Food (SCF) (1995) evaluated the safety of mineral and synthetic hydrocarbon oils and waxes for use as food additives, in food processing and for use in food packaging materials. The SCF did not allocate an Acceptable Daily Intake (ADI) for those products which, in F344 rats, showed accumulation of hydrocarbons in the liver and lymph nodes associated with a granulomatous response, since it was felt that from the 90-day studies available at that time it was not possible to set a safe level for intake from food. These products included white mineral oils with a viscosity equal to or less than 8.5 cSt at 100°C. For the mineral hydrocarbon products which showed no or minimal accumulation and no toxicity within the duration of a 90-day study in rats the SCF allocated a Temporary Group ADI of 0-4 mg/kg bw for white paraffinic oils. These products included white mineral oils with a viscosity higher than 8.5 ...

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Dermal carcinogenic activity of petroleum-derived middle distillate fuels

Cited by 32 publications

References 18 publications

Evaluation of the genetic toxicity of middle distillate fuels

Evaluation of the genetic toxicity of middle distillate fuels

Effects of short‐term high‐dose and low‐dose dermal exposure to Jet A, JP‐8 and JP‐8 + 100 jet fuels

Scientific Opinion on the use of high viscosity white mineral oils as a food additive

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