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Toxicological information

Carcinogenicity

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Description of key information

The mutagenicity studies and the oral rat study on liver tumour initiating and promoting activity were used to assess the carcinogenicity of AHTN. The result is that AHTN has no carcinogenic potential.

AHTN is demonstrated to be not genotoxic. There are no indications from repeated dose toxicity studies, which could be used to judge the carcinogenic potential. It has been shown that AHTN has no liver tumour initiating and promoting activity in rats exposed to human-relevant doses.

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 study available

Carcinogenicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

ATHN has been tested for liver tumour initiating and promotingactivity in rats exposed to human-relevant doses. Female and male juvenile Wistar rats (5 weeks old at start) were exposed to AHTN (300μg/kg bw day) dissolved in isopropylmyristate alone or to single intraperitoneal dose of diethylnitrosamine (DEN) (100 mg/kg bw day) for 90 days.

 

After the exposure period, the liver was removed and examined by light microscopy. An immunohistochemical analysis was performed. The presence of placental glutathione Stransferase (GST-P)-positive hepatic lesions was also assessed.

Male animals exposed to AHTN either alone or in combination with DEN showed a similar number of GST-P-positive single hepatocytes compared to the control group. GST-P-positive mini-foci and foci were not observed.

 

In female rats there was no difference in the number of GST-P-positive single hepatocytes and mini-foci between the AHTN-exposed rats and the untreated animals.

The female rats that were exposed to AHTN either alone or in combination with DEN, GST-P-positive foci could not be observed or appeared to be similar in number to that in untreated rats.

It can be concluded that under the conditions in this study, AHTN lacks initiaton and promotion of liver tumor and it does not lead to hepatotoxicity.

Justification for classification or non-classification

Based on the available information classification for carcinogenicity is not warranted in accordance with EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation No. 1272/2008.