Kerosine (petroleum)

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vivo

Description of key information

All in vitro assays were negative for genotoxicity, except for one assay done with straight run kerosine which was positive (similar to OECD 471, 476, 479).  All in vivo chromosome aberration and dominant lethal assays were negative for genotoxicity (OECD 475, 478), while one in vivo sister chromatid exchange assay (modified OECD 479) was positive for genotoxicity in male, but not in female mice.  Because most studies were negative and the data on various individual components of kerosines and jet fuels were negative, the overall conclusion is that kerosines and jet fuels are not mutagenic or genotoxic.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vivo:

The weight of evidence from in vitro and in vivo mutagenic studies indicates that kerosine and jet fuels are likely not mutagens.

In vitro gene mutation studies in bacteria

A number of standard tests, with and without metabolic activation by inclusion of rat liver S9, were conducted on straight-run kerosines, deodorised kerosine and Jet A.  A rather wide variety of tester strains, both of prokaryotic species (Salmonella typhimurium) and eukaryotic species (Saccharomyces cerevisiae), were used, and also various solvents were applied to dissolve the test product. In a study by the American Petroleum Institute (1977) (Klimisch score = 1), strains of S. typhimurium (TA-1535, TA-1537, TA-1538, TA-98 and TA-100) and S. cerevisiae (D4) were exposed to kerosine in DMSO with or without metabolic activation by Aroclor 1254-induced rat liver microsomes at dose concentrations from 0.001 to 5.0 μL/plate. Results were invariably negative; however, they must be regarded with caution since the standard Ames test is considered to be inappropriate for testing the mutagenicity of water insoluble petroleum products. Blackburn and colleagues (1986) modified the standard assay in order to evaluate the mutagenic polycyclic aromatic hydrocarbons in high boiling petroleum derived substances, namely unrefined lubricant base oils. The modified assay can be used as a screening tool for other petroleum products, however the results should be evaluated carefully since the assay has only been validated for other lubricant base oils.  In a modified assay (Klimisch score = 1; CONCAWE Butler, 1991),S. typhimurium were exposed to straight-run kerosines and hydrotreated kerosines dissolved in DMSO at concentrations of 50 μL/mL. Substances were considered positive if they showed a mutagenicity index (MI) greater than 1.0.  Data from CONCAWE show negative results for both straight-run and hydrodesulfurised kerosine. Data from Blackburn et al show negative results for hydrotreated kerosine, but positive results (MI values of 1.7 and 2.9) for straight run kerosine. These last results are not only rather unexpected but also difficult to interpret since no actual data were given in the original publication.

 

In vitro gene mutation in mammalian cells

Key in vitro gene mutation studies in mammalian cells were identified. In a study by the American Petroleum Institute (API, 1984b), cultures of mouse lymphoma cells were exposed to hydrodesulfurised kerosine with or without metabolic activation by Aroclor 1254-induced rat liver S9 fraction. Under non-activation conditions the test material induced a good range of toxicities for evaluation (relative growths ranged from 2.8% to 65.3%). None of the assays induced a mutant frequency that exceeded the minimum criterion (40.8 x 10-6). The test material was not mutagenic under non-activation conditions. In the presence of metabolic activation a wide range of toxicities was induced (6.1 to 107.9% relative growths). The minimum criterion mutant frequency of 69.0 x 10-6 was not exceeded. The test material was therefore considered non mutagenic under activation conditions.  In a study by API (1977) (Klimisch score = 1), mouse lymphoma L5178Y cells were exposed to straight-run kerosine in acetone vehicle at concentrations ranging from 0.04 to 0.065 μL/mL (with metabolic activation) or 0.006 to 0.13 μL/mL (without activation). There was no evidence that straight-run kerosine induced mutant colonies over background levels.

  

In vitro cytogenicity in mammalian cells

Hydrodesulfurised kerosine was tested in the sister chromatid exchange assay using Chinese hamster ovary cells (API, 1988a).  The assay was conducted with Aroclor-induced rat liver S-9 activation system. A small but statistically significant increase in the frequency of sister chromatid exchanges was observed at the high and low concentrations with metabolic activation.  These increases appeared to be random and of no biological significance. There were no significant increases observed at any concentration in the absence of metabolic activation. Under the conditions of the study, hydrodesulfurised kerosine is considered to be negative in the sister chromatid exchange assay with Chinese hamster ovary cells.

 

In vivo cytogenicity

Based on weight of evidence kerosine substances were found to be non mutagenic through cytogenic investigations.

In six in vivo bone marrow cytogenetic studies in the rat, there were no indications of chromosomal aberrations.  Although an in vivo Sister Chromatid Exchange study in the mouse gave positive findings in the male group (but not in the females) the positive findings in the males were associated with signs of toxicity (lethargy and weight loss) at the very high top dose used in the study (4000mg/kg ), both on the day of the administration of the kerosine and the day after (when they were sacrificed). 

 

In a rat bone marrow micronucleus assay (API, 1985c, Klimisch score = 1), straight run kerosine (CAS# 800-20-6) was administered to Sprague Dawley rats.  Straight run kerosine was not considered to induce chromosomal aberrations in bone marrow cells of rats. In another bone marrow micronucleus assay (API, 1984b, Klimisch score = 1), hydrodesulfurised kerosine (CAS# 64742-81-0) was administered to rats. No clinical signs of toxicity were exhibited by the rats, and there was no significant increase in frequency of micronucleated polychromatic erythrocytes in bone marrow as compared to control.  In a study by API (1977) (Klimisch score = 1), straight-run kerosine (CAS# 8008-20-6) was administered to 45 male rats. No significant increase in the frequency of micronucleated polychromatic erythrocytes was observed. 

 

In vivo gene mutation

Key in vivo gene mutation studies were identified. In a sperm cell dominant lethal mutation assay (API, 1980b, Klimisch score = 1), Jet Fuel A was administered via inhalation route to male mice at concentrations of 100 or 400 ppm for a 6-hour exposure period, 5 days per week for 8 weeks. Males were mated with females, and the uteri of pregnant females were examined for living and dead implants. Jet Fuel A did not increase the incidence of post-implantation deaths. In another study by API (1973) (Klimisch score = 1), deodorised kerosine was administered subcutaneously to 10 male Swiss-Webster mice in corn oil vehicle or intraperitoneally to 10 Long-Evans rats undiluted at a dose of 1.0 mL/kg. Males were mated with females, and no pattern of decreased pregnancy rate or increased embryo loss was observed in the females.

 

Summary

 

There were no studies located that described mutagenic or genotoxic effects of kerosine or jet fuels in humans. The weight of evidence from in vitro and in vivo mutagenic studies indicates that kerosine and jet fuels are likely not mutagens.

 

The in vivo cytogenicity testing produced some contradictory results in that for hydrodesulfurised kerosine negative results were obtained in rats and female mice, but positive results were obtained in male mice.  Although these studies were done under GLP and should be considered as valid, the male mice in the hydrodesulfurised kerosine study suffered a significant body weight loss compared to both the positive and negative controls. The loss of body weight must be seen as a general indicator of toxicity, which may have impacted the study. Taking into account that the great majority of the studies were negative and that the data on various individual components of kerosines and jet fuels were negative, the overall conclusion is that kerosines and jet fuels are not mutagenic or genotoxic.

 

Additional data support that kerosines are not mutagens (Blackburn et al., 1984; API, 1985d; CONCAWE, 1991). This information is presented in the dossier.

 

Justification for selection of genetic toxicity endpoint

one of 11 in-vitro and 6 in-vivo studies

Justification for classification or non-classification

There were no studies located that described mutagenic or genotoxic effects of kerosine or jet fuels in humans. Because most of the experimental studies were negative and the data on various individual components of kerosines and jet fuels were negative, the weight of evidence from in vitro and in vivo mutagenic studies indicates that kerosine and jet fuels are likely not mutagens and are not classified as mutagens under the EU CLP Regulation (EC No. 1272/2008).