Registration Dossier

Toxicological information

Carcinogenicity

Currently viewing:

Administrative data

Description of key information

Not carcinogenic

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
348 mg/kg bw/day
Study duration:
chronic
Species:
rat
System:
urinary
Organ:
bladder

Carcinogenicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Carcinogenicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The carcinogenic potential of the substance was evaluated using a read-across approach using two structural analogues, as detailed in the Justification for the Use of Read-Across presented in Section 13 of this IUCLID Registration Dossier.

The carcinogenic potential of the substance was evaluated in an experimental study on Source Chemical 06 (SC06). Groups of 80 male and 80 female Charles River CD rats were administered 0, 2000, 8000, 30,000 and 40,000 ppm test item via feed for a period of 104 weeks (2 years)

The NOAEL for chronic and carcinogenic effects is set at 8000 ppm (equivalent to 348 mg/kg bw/day among males and 450 mg/kg bw/day among females) per day based on calculi, hyperplasia and inflammation of the urinary bladder. Transitional cell papilloma and carcinoma are also observed in urinary bladder of the high‐dose males group.

Secondly, the capacity of the substance to induce neoplasia in rodents was evaluated in an experimental study on Source Chemical 01 (SC01) on both rats and mice. 50 male Fischer 344 rats per group were administered doses of 0, 100 and 200 mg/kg bw per day, 50 female rats were administered 0, 50 and 100 mg/kg bw per day, and, in a second study, 50 male and 50 female B6C3F1 mice per group were administered doses of 0, 100 and 200 mg/kg bw per day, by oral gavage for a total of 103 weeks.

Findings included slightly changed body weights of male mice and rats, increased mortality among male mice and rats, fatty metamorphosis of liver among female mice, hepatocellular adenomas among female mice, pneumonia (lung disease and lung tumours) among rats, and cataracts among rats. Even though no NOAEL could be determined, the effects recorded on the animals are not considered relevant to humans.

Justification for classification or non-classification

According to Annex I, 3.6.2.1, of the REACH Regulation, for the purpose of classification for carcinogenicity, substances are allocated to one of two categories based on strength of evidence and additional considerations (weight of evidence). In certain instances, route-specific classification may be warranted, if it can be conclusively proved that no other route of exposure exhibits the hazard. Although toxicity to the urinary bladder is evident at the higher doses tested, there is no evidence of carcinogenicity in any of the studies identified and using a weight of evidence approach. Therefore, the substance is not classified as a carcinogen according to the CLP Regulation (EC) no. 1272/2008.