Petroleum naphtha fraction, co-processed with renewable hydrocarbons of plant and/or animal origin

Carcinogenicity

Description of key information

Carcinogenicity - NOEL, 0.05 ml. Chronic dermal application of blended gasoline did not significantly change the incidence of skin tumours,  liver haemangiomas, lung adenomas, or of malignant lymphomas in treated animals compared to negative and historical controls.

Carcinogenicity - NOEL, 292 ppm (~1400 mg/m3). Male rat kidney tumors and female mouse liver tumors were observed following chronic inhalation exposure (OECD TG 453). If these effects are discounted as not being relevant to humans, NOAEL is 9689 mg/m3.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no study available

Carcinogenicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEC

9 869 mg/m³

Study duration:

chronic

Species:

rat

Quality of whole database:

No tumours were observed that are considered relevant to human health

Carcinogenicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

0.038 mg/kg bw/day

Study duration:

chronic

Species:

mouse

Justification for classification or non-classification

The chronic toxicity studies were conducted by standard procedures and under good laboratory practice guidelines. The majority of the mechanistic data have been published in the open literature. No further testing for carcinogenic potential is necessary. With respect to regulatory purposes, one important question relates to the relevance of data on “wholly vaporized gasoline” to humans who are exposed predominantly to the more volatile constituents. This is particularly important in assessing the significance of the female mouse liver tumors as they were apparently the consequence of increased metabolic activity in the liver. The substances that have the largest effects on metabolism are the higher boiling aromatic constituents that constitute a very small fraction of gasoline vapor but a much more substantial fraction of wholly vaporized gasoline. An analogous situation pertains to the kidney tumors in male rats. The constituents that are the most potent inducers of tumors of this type are high molecular weight isoparaffins which are present in wholly vaporized gasoline but not gasoline vapor. Considering the questions about the relevance of the various tumor types produced, as well as questions relating to the exposure conditions, it seems more appropriate to rely on data from gasoline vapor studies than the data from wholly vaporized gasoline for human health risk assessment. As the volatile fraction of gasoline has not been tested in chronic studies, the results of repeated dose and developmental and reproductive toxicity studies of gasoline "light ends" should be used as the basis for risk assessment. According to EU CLP Regulation (EC No. 1272/2008), the data do not support classification of gasoline per se for carcinogenic potential, although there is a regulatory requirement to classify gasoline as carcinogenic as it contains > 0.1% benzene.

Additional information

The animal data indicate that gasoline exposure by inhalation at high levels can produce kidney tumors in male rats and liver tumors in female mice. The mechanistic data suggest that both the male rat kidney tumors and the female mouse liver tumors were the consequence of promotional processes. The male rat kidney tumors were the consequence of a process that does not occur in humans, and, therefore, are not relevant to human risk assessment. The mouse liver tumors may have been the consequence of a hormonal imbalance although there is no direct evidence that that was the case. Nevertheless, the absence of such tumors in female rats or of male rats or mice brings into question the direct relevance of these tumors to humans. The overall no adverse effect level was 292 ppm (or approximately 1400 mg/m³). However, if the kidney and liver tumors are discounted as not being relevant to humans, the overall NOAEL is 2056 ppm or approximately 10,000 mg/m³. 

Justification for selection of carcinogenicity via inhalation route endpoint:

well conducted chronic inhalation study with many follow-up mechanistic studies

Justification for selection of carcinogenicity via dermal route endpoint:

The incidence of skin tumours was similar to control group animals.