N,N'-bis(1,4-dimethylpentyl)-p-phenylenediamine

Carcinogenicity

Description of key information

The carcinogenic potential of 77PD was evaluated in an early and limited chronic feeding study in rats (Monsanto Co. 1978). The survival rate of treated animals was comparable to control animals. A decrease in body weight and body weight gain was noted in the highest dose group (300 ppm, ca. 22.5 mg/kg bw/day) throughout the study. No treatment-related alterations were observed in hematology, clinical chemistry and urinalyses. Neither gross lesions nor histological alterations related to test substance treatment were noted in animals sacrificed at study termination. The histological lesions noted were those of naturally occurring diseases and were present in test and control animals with similar incidence and relative severity. Microscopic evaluations of suspected neoplasms among all sacrificed and all animals that died during the study showed no differences between test and control rats as to the organ system involved and type or classification of neoplasms. The spectrum of neoplasms observed was comparable to the historical control data.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion

Dose descriptor:

NOAEL

22.5 mg/kg bw/day

Justification for classification or non-classification

No classification is required according to the classification criteria 67/548/EWG and regulation no. 1272/2008 (GHS).

Additional information

Carcinogenicity: oral

The carcinogenic potential of 77PD was evaluated in an early limited chronic feeding study (Monsanto Co. 1978). Groups of albino rats were feed (50 per dose and sex) with 0, 30, 100 or 300 ppm test substance in the diet. Body weights were recorded on the first day of the test, weekly for 13 weeks, and monthly thereafter. Food consumption was recorded at weekly intervals for 13 weeks and a monthly interval thereafter. Routine checks for mortalities and moribund animals were conducted daily during the investigation. Clinical signs and were recorded as noted during the daily mortality checks during months 1 through 17; these observations were recorded once per month for month 18 through 22 and twice per month for months 23 and 24. Haematology, clinical chemistry and urinalyses were done on all remaining animals at study termination. In addition, blood and urine samples were collected individually from 10 rats of each sex from the control and 300 ppm group at 3, 6, 12, 18, and 24 months of testing. Complete gross necropsies were conducted on all animals found dead, on all animals sacrificed in extremis and on all remaining animals at 24 months of testing. Microscopic examinations were conducted on some animals found dead, selected animals sacrificed in extremis, and on all surviving animals of the control and 300 ppm groups at 24 months of testing.

Survival among treated animals was similar to that among the control animals. However, an increase in mortality among control and test animal occurred 17 months of testing because of a severe respiratory infection. All animals received tetracycline hydrochloride treatment for a 2-week period (30 g/kg of diet). No clinical signs were noted. A slight reduction in body weights and body weight gains were noted for males and females treated with 300 ppm throughout the study (for more details see chapter repeated dose toxicity). Body weights of animals fed 100 ppm were statistically reduced only during the initial 7 weeks of testing; whereas in the following weeks the body weights were comparable to control. Animals of the lowest dose group (30 ppm) had body weights comparable to control during the whole study. Food consumption of animals from the 100 ppm and 300 ppm treatment groups was reduced during the first weeks of testing. The food intake of these animals was similar to the control during subsequent weeks. The food intake of low dose group animals was comparable to control. No treatment-related effects were noted in hematology, clinical chemistry and urinalyses; neither gross lesions nor histological alterations related to test substance treatment were noted in animals sacrificed at study termination (for more details see chapter repeated dose toxicity). The histological lesions noted were those of naturally occurring diseases and were present in test and control animals with similar incidence and relative severity. In addition, microscopic evaluations of suspected neoplasms among all sacrificed and all animals that died during the study were conducted. No differences were noted between test and control rats as to the organ system involved, type or classification of neoplasms. The spectrum of neoplasms observed was comparable to the historical control data.