Urea phosphate

Carcinogenicity

Description of key information

Urea phopshate dissociated directly into urea and phosphoric acid in aqueous environment. No evidence of carcinogenicity was seen in NCI screening studies in the rat and mouse with urea. In addition, urea phosphate is considered not genotoxic and thus no further studies are considered necessary.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion

Dose descriptor:

NOAEL

2 250 mg/kg bw/day

Justification for classification or non-classification

Based on the available data, urea phosphate does not have to be classified for carcinogenicity according to Directive 67/548/EEC and the CLP Regulation.

Additional information

Urea phopshate dissociated directly into urea and phosphoric acid in aqueous environment.

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.

As phosphoric acid is not genotoxic, no further carcinogenicity testing is considered necessary.