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Carcinogenicity

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Description of key information

Studies were available to access the carcinogenic potential of Diuron. The NOAEL for carcinogenic effects was between 1.0 and 10 mg/kg bw/d for males and 1.7 and 17 mg/kg kg/d for females.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion
Dose descriptor:
NOAEL
1 mg/kg bw/day

Additional information

The carcinogenic potential of Diuron was tested in a reliable 2-year carcinogenicity study in rats conducted according to EPA 83-1 guideline (comparable to OECD 453) (Schmidt, 1985).

Wistar rats were randomly assigned to 4 groups of 50 males and 50 females each. Ten additional males and females per group were included for interim sacrifice at 12 months. Three groups were administered 25, 250, or 2500 ppm of Diuron in the feed. This equates to nominal concentrations of 0, 1.0, 10 and 111 mg/kg bw/d in males; and 0, 1.7, 17 and 203 mg/kg bw/d in females. Overall, a low mortality rate unrelated to dosing was observed.

At the 24-month examination, non-neoplastic findings related to Diuron were fibrosis of the spleen, which occurred secondary to blood effects, in males at 250 and 2500 ppm and in females at 2500 ppm. Moreover, activated bone marrow in the top dose animals was observed. Upon morphometric analysis of spleens, sex-specific variations were noted.All animals treated with Diuron showed increased incidences of urothelial hyperplasia, which can be considered a pre-neoplastic lesion.

Malignant neoplasias of the urothelial bladder epithelium were increased in animals of the top dose group. 33 of 49 males showed transitional carcinoma sometimes accompanied by hornification or differentiation from squamous epithelial carcinoma and females transitional epithelial carcinoma (11 out of 50). At lower dose levels, maximum incidences of 2% for these lesions were found as compared to 67% and 22% for males and females at top dose. Urinary bladder papilloma were increased in males (6%) at 2500 ppm compared to 0% in other groups. In females 0 - 4% was found in all groups. One transitional epithelial papilloma and two transitional epithelial carcinomas of the renal pelvis were found in males at 2500 ppm in association with urothelial changes. With regard to urothelial lesions the no-effect level was between 25 and 250 ppm. However, all females revealed alterations of blood parameters. The NOAEL was 25 ppm actual Diuron for male rats, equal to 1 mg/kg bw/day, no NOAEL could be set for females. (Schmidt, 1985).

Based on the increased incidence of urothelial hyperplasia in all treated rats and the increased incidence of malignant neoplasias of the urothelial bladder epithelium at the top dose, Diuron therefore needs to be classified according to the criteria of Directives 67/548/EEC (DSD) and 1272/2008/EC (CLP).

In mice, the carcinogenic potential of Diuron was also tested in a 2-year combined chronic toxicity and carcinogenicity study conducted according to OECD 453 (Eiben, 1990).

NMRI mice (4 groups of 60 males and 60 females) were used in the study. Three dosed groups received 25, 250 or 2500 ppm of Diuron in the feed and a control group received un-medicated feed. The study was conducted for 24 months with an interim sacrifice after 12 months on 10 animals per sex and per group. The highest dose did not produce clinical symptoms or show effects on mortality and food consumption. Also no indications for an increased number of benign and malignant tumours were observed but in the high-dosage female group an increase in epithelial hyperplasias of the bladder, oedemas and thickening of the urinary bladder mucosa must be related to treatment with Diuron. That’s why the NOAEL was set to 50.8 mg/kg bw/d in males and 77.5 mg/kg bw/d in female animals (equivalent to 250 ppm). (Eiben, 1990).

Based on hyperplasia in the bladder epithelium and increased mammary gland adenocarcinoma in mice, Diuron therefore needs to be classified according to the criteria of Directives 67/548/EEC (DSD) and 1272/2008/EC (CLP).


Carcinogenicity: via oral route (target organ): urogenital: urinary bladder

Justification for classification or non-classification

Based on the available data on carcinogenicity Diuron needs to be classified:

DSD: Cat 3: R40

CLP: Category 2 carcinogen