Naphtha (petroleum), hydrotreated heavy

Immunotoxicity

Description of key information

Gasoline exposure does not affect the immune system in experimental animals at levels up to 20000 mg/m3.

Key value for chemical safety assessment

Effect on immunotoxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no study available

Effect on immunotoxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Effect on immunotoxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

A number of authors have suggested that exposure to hydrocarbons including gasoline could be a causal factor in the development of end stage glomerular nephritis (Bierne and Brennan, 1972; Zimmerman et al., 1975; Finn et al., 1980; Kleinknecht et al., 1980). These publications reported a greater percentage of exposure among patients than controls. The majority of these publications were summaries of case reports. A subsequent review of the literature on this subject (Churchill et al., 1983) concluded that there were serious methodological deficiencies in most of the studies which limited their utility. Churchill identified 4 major weaknesses; (1) the use of inappropriate control groups; (2) the use of unblinded interviewers; (3) failure to consider recall bias; and (4) failure to define a credible measure of hydrocarbon exposure. Churchill noted that among the case reports suggesting a relationship between "hydrocarbon" exposure and either Goodpasture's syndrome or antiglomerular basement membrane disease, 4 involved exposure to gasoline specifically (Sprecace, 1963; Heale et al., 1969; and D'Apice et al., 1978). There is one additional case reported in Zimmerman et al. (1975). One of the 4 cases identified by Churchill was an 18 year old girl who had sold gasoline for 2 weeks prior to the onset of symptoms (D'Apice, 1978). Among the other 3, one washed cars (Heale et al., 1969), one was a cotton loom turner (Heale, 1969), and one was an army clerk in an ordinance warehouse (Sprecace, 1962). No unusual exposures to gasoline are apparent in the documentation of any of these cases. In the case reported by Zimmerman et al. (1975), exposure was listed as to "petroleum fuels" without further specification, and a renal biopsy was not carried out to confirm the diagnosis.

 

An additional methodological weakness, not identified by Churchill, was the lack of precision in the definition of "hydrocarbon vapors." As one example, Zimmerman et al. (1975) presented as a typical case a woman employed in a dry cleaning facility, removing stains with carbon tetrachloride, and Kleinknecht et al. (1980) described two women who were exposed to a domestic solvent containing sodium hydroxide, carboxymethyl cellulose, nonylphenol, ethylene oxide, and butane. Some of these substances are organic solvents, but only butane is a hydrocarbon. There is also reference to an animal model based on exposure to N'N'-diacetyl benzidine that is neither a hydrocarbon nor a solvent. Thus the human literature on this subject can best be described as inconclusive.

The possible relationship between "hydrocarbon" exposure and end stage renal disease has been under discussion for more than 30 years. There are some case reports in humans, but, at least as these pertain to gasoline, the number of cases is small and the relationship to gasoline exposure is uncertain. The experimental data in animals indicate that gasoline exposure does not affect the immune system at levels up to 20,000 mg/m³(approximately 4000 ppm). Thus it seems unlikely that there would be a relationship between exposure and the development of autoimmune disease (ie, Goodpasture's disease) and subsequent end stage renal disease except under conditions resulting in frank pulmonary injury. In principal, pulmonary injury could be associated with aspiration of liquid gasoline into the lung but is unlikely to be caused by gasoline vapor exposure except under conditions of extreme over-exposure at levels exceeding the lower explosive limit.

For full citations to the references, please see record 'Exposure related observations in humans.0.14/immunotoxicity' in section 7.10.5.

Justification for selection of effect on immunotoxicity via inhalation route endpoint:

one of 2 studies on immunotoxicity of gasoline