International Agency for Research on Cancer (IARC) - Summaries & Evaluations

(Group 2B)

For definition of Groups, see Preamble Evaluation.

VOL.: 45 (1989) (p. 159)

CAS No.: 8006-61-9 (for natural gasoline)
Chem. Abstr. Name: not assigned

5. Summary of Data Reported and Evaluation

5.1 Exposure data

Gasoline is a complex mixture of volatile hydrocarbons, predominantly in the C4-C12 range, with a boiling range of 50-200 oC. Most automotive gasoline is produced by blending naphtha process streams, such as light straight-run [3], reformed [15], alkylate [13], isomerization [14] and thermally [28, 29] and catalytically cracked [22, 23] naphthas. Alkylate naphtha [13] is typically the main component used in the production of aviation gasoline. Saleable gasolines may contain numerous additives, such as alkyllead compounds, 1,2-dibromoethane (ethylene dibromide), 1,2-dichloroethane (ethylene dichloride), alkyl phosphates, phenols, alcohols and methyl-tert-butyl ether, in order to meet product specifications. Automotive gasoline may contain 0-7%, and typically contains 2-3%, benzene. Occupational exposure to gasoline vapours occurs during production in petroleum refineries and during transport and distribution to retailers. Exposures to vapours are in most cases principally to lighter hydrocarbons, C6 or lower. Personal 8-h time-weighted average exposures of bulk and drum gasoline loaders and tank cleaners have been reported as 40-850 mg/m3 total hydrocarbons and 1-27 mg/m3 benzene, and for bulk loaders up to 6 mg/m3 1,3-butadiene. Higher levels of exposure to benzene have been reported for gasoline rail-loading and for some gasoline storage tank cleaning operations. Service station attendants and customers are exposed to lower levels of gasoline vapours.

5.2 Experimental data

A sample of totally volatilized unleaded gasoline was tested for carcinogenicity in one strain of mice and in one strain of rats by inhalation, producing an increase in the incidence of hepatocellular adenomas and carcinomas in female mice; no such increase was observed in males. Exposure of male rats resulted in an increased incidence of adenomas and carcinomas of the kidney; no such tumour was found in females. One sample of light straight-run naphtha [3] and one sample of light catalytically cracked naphtha [22] produced skin tumours in mice. (See the monograph on occupational exposures in petroleum refining.)

5.3 Human data

This section describes studies of occupations in which exposure to gasoline may occur, including service station attendants and motor vehicle mechanics. None of the studies provided detailed data concerning exposure to gasoline. Furthermore, it was not possible to distinguish the effects of the combustion products from those of gasoline itself.

In a large UK cohort study on oil distribution workers, some of whom had presumably had occupational exposure to gasoline, a lower total cancer mortality was found than expected on the basis of national rates, but there was a slightly elevated number of deaths from neoplasms of the lymphatic and haematopoietic tissues. A Swedish register-based cohort study on pancreatic cancer showed moderately increased incidence among service station workers.

Two US proportionate mortality studies showed some consistency regarding elevated risks for some types of lymphopoietic cancers in motor vehicle mechanics, although not all findings were significant. For service station workers, the proportionate mortality ratio for leukaemia and aleukaemia was increased in one study but not in another.

In a US case-control study on kidney cancer, there was some evidence of a positive trend in risk with duration of employment as a service station attendant. Another US study showed a nonsignificant deficit in risk for renal-cell carcinoma among people classified as exposed to gasoline, but an increase in risk was suggested among heavy smokers with employment in service stations. A case-control study of cancer at many sites in Canada revealed an elevated risk for kidney cancer in men exposed to aviation gasoline; there were indications of a dose-response relationship.

Several case-control studies have investigated risks for cancer of the lower urinary tract in different occupations with possible exposure to gasoline. An early study from the USA revealed no excess risk among workers in occupations involving exposure to petroleum products. In a Danish study on bladder cancer, an elevated risk was associated with 'oil or gasoline work'. Nonsignificantly increased risks were found in two US studies on bladder cancer among motor vehicle mechanics, while no increase was seen in a third study. There was a significantly elevated risk for bladder cancer among garage workers and service station attendants in one of these studies, and another showed a nonsignificant elevation in risk for workers in the gasoline service industry. A US study on cancer of the renal pelvis suggested an elevated risk for workers exposed to unspecified petroleum, tar or pitch products.

A Swedish study, similar in design to a case-control study, indicated an increased risk for acute nonlymphocytic leukaemia in men with occupational exposure to petroleum products. One hospital-based case-control study in the USA revealed an increased risk for testicular cancer in service station attendants and garage workers; another showed an increased risk for pancreatic cancer in men with occupational exposure to dry cleaning agents or gasoline. Another US case-control study demonstrated an increased risk for liver cancer in service station attendants, particularly for hepatocellular carcinoma. A case-control study of cancer at many sites in Canada revealed an elevated risk only for stomach cancer among men exposed to automotive gasoline.

Nine case-control studies from four countries provide data on paternal occupations involving exposure to hydrocarbons and the risk for cancer in children. There was no consistent association between father's occupation and risk for childhood cancer, although significant results appeared in a few of the studies. Only one study gave detailed data on maternal occupations involving exposure to hydrocarbons during pregnancy; this suggested an increased risk for leukaemia in their children. No study specifically assessed exposure to gasoline, but paternal occupations such as motor vehicle mechanic and service station attendant were not consistently associated with an increase in risk.

5.4 Other relevant data

Urinary thioether excretion was increased in samples taken from service station attendants after work. The half-life of antipyrine was reduced in such workers.

No report specifically designed to study genetic and related effects in humans following exposures to gasoline was available to the Working Group.

Male, but not female, rats developed nephropathy after exposure to unleaded gasoline, with hyaline droplet accumulation, necrosis and degeneration of proximal convoluted tubules. The extent and severity of hyaline droplet accumulation paralleled the extent and localization of renal tubular cell proliferation.

Two samples of unleaded gasoline (one described as PS-6, the other as having a boiling range of 31-192 oC) were tested in a series of assays for genetic and related effects. Neither sample induced chromosomal aberration in the bone marrow of rats treated in vivo. The PS-6 sample induced unscheduled DNA synthesis in vivo in male and female mouse hepatocytes, but not in male rat hepatocytes or in male or female rat kidney cells, nor did it induce sister chromatid exchange or mutation in cultured human lymphocytes. Neither sample induced mutation in cultured mammalian cells; however, an extract of and the residue from the evaporation of the PS-6 sample did induce mutation in cultured mammalian cells. The PS-6 sample induced unscheduled DNA synthesis in vitro in mouse, rat and human hepatocytes but not in rat kidney cells. A leaded gasoline induced somatic mutation in insects. The other sample of unleaded gasoline, an extract of the PS-6 sample and the residue from the evaporation of the PS-6 sample did not induce mutation in bacteria.

5.5 Evaluation

There is inadequate evidence for the carcinogenicity in humans of gasoline.

There is limited evidence for the carcinogenicity in experimental animals of unleaded automotive gasoline.

In making the overall evaluation, the Working Group also took note of the following supporting evidence. Unleaded gasoline induces unscheduled DNA synthesis in hepatocytes from male and female mice treated in vivo and in cultured mouse, rat and human hepatocytes. There is limited evidence for the carcinogenicity in experimental animals of light straight-run naphtha and of light catalytically-cracked naphtha (see the monograph on occupational exposures in petroleum refining). Benzene is carcinogenic to humans (Group 1); for 1,3-butadiene, there is inadequate evidence for carcinogenicity in humans and sufficient evidence for carcinogenicity in experimental animals (Group 2B) (IARC, 1987).

Overall evaluation

Gasoline is possibly carcinogenic to humans (Group 2B).

For definition of the italicized terms, see Preamble Evaluation.

Synonyms for Automotive gasoline

Synonyms for Aviation gasoline

Last updated 01/21/98

    See Also:
       Toxicological Abbreviations
       Gasoline (ICSC)