diuron (ISO); 3-(3,4-dichlorophenyl)-1,1-dimethylurea

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Dose descriptor:

NOAEL

14.8 mg/kg bw/day

Additional information

A reliable two-generation study in rats was conducted according EPA 83 -4, thus in compliance with OECD 416 (Cook, 1990). Four groups of Wistar rats (30 males and 30 females per group) recieved Diuron at 0, 10, 250 or 1750 ppm in the diet for 73 days prior to mating, then during the mating period and finally during pregnancy and weaning. The first (F1) generation received Diuron during growth into adulthood, mating, pregnancy, and until weaning of the second generation.

There were no changes compared to control in body weight, food consumption, body weight gains and food efficiencies at dosage groups up to 250 ppm in P1- and F1-animals during pre-mating, mating and post-mating phases. Final body weights, weight gains and overall food consumption of P1/F1 males and females in the 1750 ppm groups were significantly lower than their respective controls.

No compound-related clinical signs or mortality were detected in the P1/F1 generations. There were no compound related effects apparent in the mating index, fertility index, or gestation length in either the P1 or F1 parental generations. There were no compound-related effects on litter size or survival in either the F1 or F2 generations pups. Pups weights (males and females) were decreased in both generations in the 1750 ppm dose group. Maternal weights were also decreased at this dietary level of Diuron. Relative testis in P1/F1 males in the 1750 ppm groups were increased, but this effect was due to the reduced body weights and was judged not be a compound related effect. The increased incidence of large spleen in the female F1 1750 ppm group correlated microscopically with congestion. It was concluded by the authors that the enlarged spleens were due to incomplete exsanguination at necropsy, however, enlarged spleen is a commonly noted sign following Diuron-treatment. Under the conditions of this study, the NOAEL is 250 ppm (equals 14.8 to 22.1 mg/kg bw/day) for both adults and their offspring.

Short description of key information:
A NOAEL of 250 ppm (equals 14.8 to to 22.1 mg/kg bw/day) for both generations was identified from the study.

Effects on developmental toxicity

Description of key information

Studies were available to access the developmental/teratogenicity of Diuron. A NOAEL for maternal was 10 mg/kg bw/day in rabbits and 16 mg/kg bw/day in rats, while the NOAEL for offspring was 80 mg/kg bw/day in rats. In rabbits, up to and including the highest dose tested, no effects were observed.

Effect on developmental toxicity: via oral route

Dose descriptor:

NOAEL

80 mg/kg bw/day

Additional information

The developmental toxicity potential of Diuron was test in a reliable prenatal developmental toxicity study equivalent or similar to OECD 414 inwhite rabbits (Dearlove, 1986b).After artificial insemination (=day 0 of presumed gestation) with spermatozoa from bucks of the same source and strain, the 25 females per group received oral doses of 0 (vehicle), 2, 10, and 50 mg Diuron /kg bw/d on days 7 through 19 of presumed gestation.Overall, a statistically significant decreasing average daily food consumption and body weight gain was observed for the top dose on days 13 to 20, resulting in significant weight loss to day 20, so that the NOAEL of maternal toxic effects is set 10 mg/kg bw/d. In contrast, Diuron did not adversely affect the development of the offspring at the top dose. Therefore the NOAEL of embryotoxic / teratogenic effects is assessed to 50 mg/kg bw/d. (Dearlove1986b).

The developmental toxicity potential of Diuron was also tested in a prenatal developmental toxicity study equivalent or similar to OECD 414 in Crl: COBS (SD) BR stain rats. Female rats received oral doses of 0, 16, 80, and 400 mg/kg bw Diuron once daily on days 6 through 15 presumed gestation. As the administration of 80 mg/kg/d and higher caused significantly reduced feed consumption and loss of body weight during the period of treatment the NOAEL for maternal toxic effects is determined to be 16 mg/kg bw/d. For foetuses average body weights were significantly decreased for the high dosage group litters and skeletal alterations and delayed ossifications were observed. That`s why the NOAEL of embryotoxic/ teratogenic effects is set to 80 mg/kg bw/d. (Dearlove, 1986a).

Justification for classification or non-classification

The available data on toxicity to reproduction is conclusive but not sufficient for classification according to directives DSD (67/548/EEC) or CLP (1272/2008/EC).