Registration Dossier

Administrative data

Description of key information

A 26/38-week initiation-promotion carcinogenicity study with 1,4-benzenediamine, N,N’-mixed Ph and tolyl derivs.  at 1900 ppm in the food (or ca. >100 mg/kg bw/day) did not reveal initiating activity nor clear evidence of promoting activity towards the liver and urinary bladder when compared and combined with control compounds.    

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

There was a key study for carcinogenicity assessment, which was designed as a 26/38-week initiation-promotion study in male Fisher 344 rats (Iatropoulos, 1997). The study was conducted according to GLP and while conventional testing for carcinogenicity employs a 2 year chronic exposure design, the methodology employed in this study is was considered to be a scientifically-sound approach to study the carcinogenicity of chemicals for liver and urinary bladder. The test compound 1,4-benzenediamine, N,N’-mixed Ph and tolyl derivs. administered via the diet at 1900 ppm (corresponding to >100 mg/kg bw/day) was tested in combination with and compared to ‘initiators’ and ‘promoters’ for liver (diethylnitrosamine and phenobarbital, respectively) and urinary bladder (butylhydroxybutylnitrosamine and nitrilotriacetate, respectively). Animals were sacrificed at weeks 26 & 38 with complete gross examinations. There were no adverse clinical findings during the study, whereas body weights were slightly suppressed in all but one test group compared to controls. Findings for organs included increased liver and kidney weights in groups dosed with initiator and test chemical above control values and reference groups with initiator only. 1,4-Benzenediamine, N,N’-mixed Ph and tolyl derivs. clearly lacked any evidence of initiating activity towards the liver and bladder. Promotional activity was not evident as the various indices were virtually unchanged from groups that were treated with known initiators alone. This was supported by lack of PCNA findings in the study.

Overall, the test chemical did not display characteristics in this study expected of carcinogenic chemicals. Similar results were seen at the 26 and 38-week sacrifice period.

Justification for classification or non-classification

In accordance to Directive 67/548/EEC (Dangerous Substances Directive) and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008, classification of 1,4-Benzenediamine, N,N'-mixed Ph and tolyl derivs. for carcinogenicity is not warranted based on the available test data, as the available rat study did not display characteristics expected of carcinogenic chemicals.