1,3-dichloro-4-nitrobenzene

Carcinogenicity

Description of key information

2,4 -Dichloronitrobenzene revealed  carcinogenic activity by 2 -year feeding  in both rats and mice.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

BMDL10

12.3 mg/kg bw/day

Study duration:

chronic

Species:

other: rat and mouse

Justification for classification or non-classification

Due to the available data, 2,4 -DCNB has to be allocated to category 1B(H350) according to Regulation(EC)1272, 2008. According to Regulation (EC) 67548/EWG the substance is classified /labelled with Carc Cat 2; R 45 = may cause cancer.

Additional information

Carcinogenicity of 2,4 -dichloro-1 -nitrobenzene (2,4 -DCNB) was examined by dietary administration to F344/DuCrj rats and Crj:BDF1 mice of both sexes for 2 years. Dietary administration commenced when the animals were 6 weeks old. The dietary concentration of 2,4-DCNB was 0 (control), 750, 1,500 and 3,000 ppm (w/w) for male and female rats; 0, 750, 1,500 and 3,000 ppm for male mice; and 0, 1,500, 3,000 and 6,000 ppm for female mice. In rats, there was a dose-dependent and significant induction of renal cell adenomas and carcinomas in both sexes and of preputial glands adenomas in males. In all the 2,4-DCNB-fed groups of both sexes, the incidence of atypical tubular hyperplasia, a pre-neoplastic lesion in the kidney, in the proximal tubule was significantly increased. In mice, there was a dose-dependent and significant induction of hepatocellular adenomas, hepatocellular carcinomas, hepatoblastomas and peritoneal hemangiosarcomas in both sexes. The incidence of acidophilic hepatocellular foci was also significantly increased in female mice.

Thus, clear evidence of carcinogenic activity of 2,4 -DCNB by 2 -year feeding was demonstrated in both rats and mice.

Kano et al (2012) used a non-threshold approach to calculate the benchmark dose associated with 10 % risk over background (BMDL10). Based on the dose–response relationships between 2,4 -DCNB-intake and incidences of tumors obtained in the present study, a 95 % lower confidence limit of the BMDL10 was calculated using the linearized multistage model for total hepatic

tumors of male and female mice with US EPA’s benchmark dose software (Ver. 2.1.1) (US EPA 2009, Benchmark dose software version 2.1 user’s manual. 53 -BMDSRPT-0028, US EPA. Washington, DC ). The BMDL10 value for the endpoint of total hepatic tumors in male mice was 12.3 mg/kg per day and in female mice was 23.5 mg/kg per day.

Justification for selection of carcinogenicity via oral route endpoint:
No study was selected because there are carcingenicity studies available according to OECD Guideline 451 and under GLP conditions in rats and mice which are evaluated with Klimisch score 1
In both studies the compound elicited carcinogenic activity.

Carcinogenicity: via oral route (target organ): digestive: liver