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Toxicological information

Carcinogenicity

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Description of key information

According to column 2 of REACH Annex X, information requirement 8.9.1, a carcinogenicity study does not need to be conducted if the substance is classified as a germ cell mutagen category 1A or 1B. Since the registereed substance is reasonably known to be mutagenic category 1B, it is considered justified to omit testing for this endpoint. Additionally, the substance is already classified as carcinogens category 1B. Further testing for carcinogenicity is neither considered necessary nor considered to be an expedient or responsible use of animals.

Please refer to the document ‘Consideration of the long term toxicity of Distillates (shale oil)’, as included in section 13, for further information.

Supporting data (as considered in a weight of evidence approach):

RIVM (Rat Study on benzo[a]pyrene)

This study demonstrated the carcinogenic potential of the test material in a variety of organs when administered by gavage to rats. Major target organs were liver, forestomach and epidermal structures, of which the liver is considered the most relevant for human risk assessment in terms of pathogenesis and sensitivity.

RIVM (Mouse study on benzo[a]pyrene)

Target tissues for carcinogenicity in mice exposed to benzo[a]pyrene via the diet were the forestomach, oesophagus and tongue. No clear treatment-related induction of liver tumours was found.

IARC Monograph of high-temperature crude shale oils, low-temperature crude shale-oils, fractions of high-temperature shale-oil, crude shale-oil distillation fractions, shale-oil bitumens and commercial blends of shale-oils

There is sufficient evidence for the carcinogenicity in experimental animals of high-temperature crude shale oils, low-temperature crude shale-oils, fractions of high-temperature shale-oil, crude shale-oil distillation fractions, shale-oil bitumens and commercial blends of shale-oils.

There is limited evidence for the carcinogenicity in experimental animals of raw oil shale, spent oil shale and a residue of shale-oil distillation.

There is sufficient evidence that shale-oils are carcinogenic in humans.

Key value for chemical safety assessment

Additional information

According to column 2 of REACH Annex X, information requirement 8.9.1, a carcinogenicity study does not need to be conducted if the substance is classified as a germ cell mutagen category 1A or 1B. Since the registereed substance is reasonably known to be mutagenic category 1B, it is considered justified to omit testing for this endpoint. Additionally, the substance is already classified as carcinogens category 1B. Further testing for carcinogenicity is neither considered necessary nor considered to be an expedient or responsible use of animals.

Please refer to the document ‘Consideration of the long term toxicity of Distillates (shale oil)’, as included in section 13, for further information.

Supporting data (as considered in a weight of evidence approach)

RIVM (Rat Study on benzo[a]pyrene)

A study was conducted to provide an estimation of the cancer risks associated with the actually experienced daily exposure to dietary PAH in the Netherlands. Benzo[a]pyrene was considered to be a representative indicator of PAH. This carcinogenicity study in rats orally exposed to benzo[a]pyrene, was considered to adequately represent the carcinogenic fraction of PAH.

During the study, groups of 52 animals per sex, per dose, received doses of test material, by oral gavage, for 5 days a week over a period of 104 weeks . The animals were observed daily and their behaviour and clinical signs were examined. Body weights, food and water consumption was measured at least weekly. Following the end of the exposure period the animals were sacrificed and were subjected to macroscopic examination, additionally tissue samples were processed for further histopathological investigation.

Findings from the study clearly showed benzo[a]pyrene to be a potent carcinogen upon chronic oral administration. Tumours were induced at multiple sites in both sexes of rats, i.e. liver, forestomach, auditory canal, oral cavity, skin, and intestines, and additionally the kidney in males, and the mammary and oesophagus in females. The most potent carcinogenic effects of benzo[a]pyrene under the present conditions were observed in the liver and forestomach, both organs with a low spontaneous incidence in this rat strain. The lowest dose level associated with a significantly inceased tumour response is 10 mg/kg bw/day for females and 3 mg/kg bw/day for males.

RIVM (Mouse study on benzo[a]pyrene)

The report includes (as an Annex) a summary of findings from mouse diet studies which were conducted at NCTR (Culp et al., 1994 and 1998). The NCTR project incorporates a chronic oral carcinogenicity study with B[a]P.

During the study, groups of 48 female 5-week old B6C3F1 mice were administered via the diet B[a]P (5, 25, and 100 ppm; calculated daily intake of 0.6, 3, 12 B[a]P in mg/kg bw, corrected for reductions in food consumption)

for 24 months. Two additional groups of 48 mice served as controls, i.e. one was fed the standard diet, the other received standard diet that had been treated with aceton in a manner identical to the B[a]P diets (Solvent control).

With respect to B[a]P, at the highest dose tested a decrease in body weight was observed from week 50 onwards, most probably due to effects secondary to tumour-development in the upper digestive tract. B[a]P induces in these female B6C3F1 mice tumours in the epithelial layer of the tongue, the esophagus, and the forestomach. Also, increased incidences of sarcomas and of tumours in the squamous cell of the larynx were observed. B[a]P treatment did not induce tumours in the liver and lung, nor hemangiosarcomas or histiocytic sarcomas.

In conclusion, the target tissues for carcinogenicity in mice exposed to benzo[a]pyrene via the diet were the forestomach, oesophagus and tongue. No clear treatment-related induction of liver tumours was found.

IARC Monograph of high-temperature crude shale oils, low-temperature crude shale-oils, fractions of high-temperature shale-oil, crude shale-oil distillation fractions, shale-oil bitumens and commercial blends of shale-oils

There is sufficient evidence for the carcinogenicity in experimental animals of high-temperature crude shale oils, low-temperature crude shale-oils, fractions of high-temperature shale-oil, crude shale-oil distillation fractions, shale-oil bitumens and commercial blends of shale-oils.

There is limited evidence for the carcinogenicity in experimental animals of raw oil shale, spent oil shale and a residue of shale-oil distillation.

There is sufficient evidence that shale-oils are carcinogenic in humans.

Justification for classification or non-classification

The substance is classified as a carcinogen (category 1B) in consideration of the presence of polyaromatic hydrocarbons (PAHs) analysed in the substance at a level greater than the generic cut-off limits for classification for carcinogenicity. PAHs are widely acknowledged to possess CMR properties. The harmonised classification of the PAH substance benzo[a]pyrene is applied to this substance as it has been established that this substance is considered to be representative of the PAHs contained within the registered substance. Furthermore, the hazard of benzo[a]pyrene is well established in light of the wealth of toxicological data that are available on the substance.

Please refer to the document ‘Consideration of the long term toxicity of Distillates (shale oil)’, as included in section 13, for further information.