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Toxicological information

Carcinogenicity

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Description of key information

No human data are available, and no carcinogenicity studies in laboratory animals have been conducted with MCCPs.
The available data indicates that MCCPs would not be genotoxic carcinogens. Significant increases in the incidences of liver (in males and females) and thyroid (in females only) tumours were seen in laboratory animals administered a C12 chlorinated paraffin (60% chlorinated) by gavage at 125 mg/kg bw/day and above (in mice) and 312 mg/kg bw/day and above (in rats), 5 days/week, for 2 years, and of kidney tumours in male rats at 312 mg/kg bw/day.
Clear modes of action were indicated for the liver and thyroid tumours, and these tumours are considered to be of little or no relevance to human health. The underlying mechanism for the kidney tumours has not been fully elucidated. However, recent mechanistic evidence shows that alpha2u-binding is probably the primary mechanism for kidney tumour formation induced by this SCCP in male rats, and the available evidence strongly suggests that the underlying mechanism would not be relevant to humans. Therefore, SCCPs, and by analogy MCCPs, should be considered not to pose a carcinogenic hazard to humans

Key value for chemical safety assessment

Additional information

No human data are available, and no carcinogenicity studies in laboratory animals have been conducted with C14-17 chlorinated paraffins. Given the similarities between MCCPs and C10-13 chlorinated paraffins (SCCPs) in physicochemical properties and in the results obtained in relation to other toxicological endpoints, particularly the effects seen on the liver, thyroid and kidneys on repeated exposure, it is reasonable to assume that the carcinogenic potential of MCCPs will be similar, at least in qualitative terms, to that of SCCPs.

The available genotoxicity data on SCCPs, MCCPs, and LCCPs (C18-30 chlorinated paraffins), and consideration of their generally unreactive nature, indicates that chlorinated paraffins are not mutagenic and do not directly interact with DNA. Consequently, it can be concluded that MCCPs will not induce tumours by a genotoxic route.

From animal cancer bioassays, conducted as part of the US National Toxicology Program, significant increases in the incidence of hepatic tumours in males and females and tumours of the thyroid gland in females only were seen in B6C3F1mice (50 sex/group) administered a C12 chlorinated paraffin (60% chlorinated) by stomach tube at 125 mg/kg bw/day and above, 5 days/week, for 2 years (NTP, 1986). In Fischer-344 rats (50 sex/group) exposed, 5 days/week, for 2 years to the same C12 chlorinated paraffin (60% chlorinated) by gavage, there were statistically significant increases in hepatic tumours in males and females and thyroid tumours in females at 312 mg/kg bw/day and above, and of renal tumours in males at 312 mg/kg bw/day (but not at 625 mg/kg bw/day; the highest tested dose) (NTP, 1986).

 

From the available evidence, clear modes of action were indicated for the liver and thyroid tumours, namely chronic tissue damage caused by peroxisome proliferation in the case of the liver, and for the thyroid, long-term hormonal stimulation. The liver and thyroid tumours are considered to be of little or no relevance to human health. The underlying mechanism for the kidney tumours has not been fully elucidated. However, there is recent mechanistic evidence to show that alpha2u-binding is probably the primary mechanism for kidney tumour formation induced by this SCCP in male rats and the available evidence strongly suggests that the underlying mechanism would not be relevant to humans. Therefore, overall, SCCPs, and by analogy MCCPs, should be considered not to pose a carcinogenic hazard to humans (EU, 2008).

 

In 2004, an EC Group of Specialised Experts in the fields of Carcinogenicity, Mutagenicity and Reprotoxicity agreed that there were still data gaps leading to uncertainty about the relevance of these male rat kidney tumours for humans. Some experts argued that there were inconsistencies and contradictions in the mechanistic studies which might indicate that alternative mechanisms could not be excluded. The relation between the alpha2u mechanism and the kidney tumours was not adequately established in this case. The Specialised Experts agreed that a read-across from SCCPs to MCCPs was not justified for carcinogenicity, and consequently MCCPs could not be classified for this endpoint. They noted the absence of animal tumour data for MCCPs, the toxicological differences seen between SCCPs and LCCPs, and the heterogenous nature of all these compounds (EU, 2008).

 

Hence, based on the opinion of the Specialised Experts, read-across from SCCPs to MCCPs for this endpoint is not appropriate in terms of classification. Taking into account all the other existing data on MCCPs, specifically the lack of genotoxic activity and the kidney toxicity seen in repeated dose toxicity studies in rats (increased weight at 222 mg/kg bw/day and ‘chronic nephritis’ and tubular pigmentation at 625 mg/kg bw/day), it cannot be completely ruled out that this form of kidney toxicity might lead to cancer in male and female rats through a non-genotoxic mode of action, even though with the C12 chlorinated paraffin kidney tumours were seen in male rats only. Therefore, a risk characterisation for the carcinogenicity endpoint should be conducted using the same NOAEL of 23 mg/kg bw/day identified for repeated dose effects on the kidney (EU, 2008).

Justification for classification or non-classification

Under the EU CLP and DSD regulations, C14 -17 chlorinated paraffins would not be classified for human carcinogenicity based on the information described above.