Registration Dossier

Toxicological information

Carcinogenicity

Currently viewing:

Administrative data

Description of key information

No evidence of carcinogenicity was seen in NCI screening studies in the rat and mouse.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion
Dose descriptor:
NOAEL
2 250 mg/kg bw/day

Additional information

The carcinogenicity of urea was investigated in NCI 12 -month screening studies in the rat and mouse (Fleischman et al, 1980). No evidence of carcinogenicity or toxicity was seen in either study at the very high dose level of 45000 ppm (4.5% in the diet).

F344 rats (50/sex/group) were exposed to urea in the diet at concentrations of 4500, 9000 or 45000 ppm for 12 months. Five animals/sex/group were sacrificed at the end of the 365-day exposure period and a comprehensive list of tissues was investigated histopathologically; interim deaths were similarly investigated. All remaining animals were sacrificed after the 4-month recovery period and investigated histopathologically. There were no signs of toxicity. A significant linear trend in the incidence of interstitial cell tumours was noted in male rats. The incidence was 21/50 in controls, 27/48, 25/48 and 35/50 in the low, intermediate and high dose groups respectively. The authors do not consider this finding to be of biological significance as the background incidence of this tumour type is noted to be up to 100% in F344 rats.

Using default conversion factors, the dose level of 45000 ppm is calculated to be equivalent to approximately 2250 mg/kg bw/d in the rat and 6750 mg/kg bw/d in the mouse.

B6C3F1 mice (50/sex/group) were exposed to urea in the diet at concentrations of 4500, 9000 or 45000 ppm for 12 months. Five animals/sex/group were sacrificed at the end of the 365-day exposure period and a comprehensive list of tissues was investigated histopathologically; interim deaths were similarly investigated. All remaining animals were sacrificed after the 4-month recovery period and investigated histopathologically. There were no signs of toxicity. A significantly increased incidence of haematopoietic tumours (malignant lymphoma) was seen in female rats in the mid-dose group. The incidence of this finding was 10 -92 in controls; 7/43, 10/38 and 9/50 in low, mid and high dose group animals, respectively. There is no relationship to treatment in the absence of a dose-response relationship.

Justification for classification or non-classification

No classification is proposed for carcinogenicity. There is no evidence from animal studies that urea is carcinogenic. The physiological role of urea and level of production by the human body indicates that the substance is not carcinogenic.