Registration Dossier

Administrative data

Description of key information

Urea is of very low acute toxicity by all routes investigated.  The acute oral LD50 of urea is reported to be 14.3-15.0 g/kg bw in the rat and 11.5-13.0 g/kg bw in the mouse.  The acute subcutaneous LD50 is reported to be 8.2-9.4 g/kg bw in the rat and 9.2-10.7 g/kg bw in the mouse.  The acute intravenous LD50 of urea is reported to be 5.3-5.4 g/kg bw in the rat and 4.6-5.2 g/kg bw in the mouse.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50
14 300 mg/kg bw

Additional information

Acute oral toxicity

Urea is of very low acute oral toxicity in the rat and mouse. Sato et al (1977) report LD50 values of 14.3 (12.9 -15.9) and 15.0 (13.4 -16.8) g/kg bw in male and female rats; LD50 values of 11.5 (10.6 -12.5) and 13.0 (11.0 -15.4) g/kg bw in the mouse. Urea is of generally low acute oral toxicity in most species but higher toxicity is noted in ruminants due to the generation of ammonia by gastric flora. Stiles et al (1970) report an LDlo of approximately 600 mg/kg bw in cattle.

Acute dermal toxicity

No data are available: a waiver is proposed for this endpoint. Urea is demonstrated to be of very low acute toxicity by the oral, subcutaneous and intravenous routes in the rat and mouse. Testing for acute dermal toxicity is not justified on scientific grounds and for reasons of animal welfare. Specifically, the very low toxicity of urea by the subcutaneous and intravenous routes indicates that dermal toxicity would also be very low, even assuming rapid and total dermal penetration.

Acute inhalation toxicity

No data are available: a waiver is proposed for this endpoint. The substance is a non-volatile solid and is produced as crystals with a particle size of >100 µm. There is therefore no potential for inhalation exposure. In addition, the substance has been demonstrated to be of very low toxicity by other routes of exposure. Testing for acute inhalation toxicity is therefore not justified on scientific grounds or based on exposure considerations.

Acute toxicity by other routes of exposure

Urea is also of very low acute toxicity by the subcutaneous route. Sato et al (1977) report LD50 values of 9.4 (8.2 -10.8) and 8.2 (7.1 -9.5) g/kg bw in male and female rats and LD50 values of 9.2 (8.6 -9.8) and 10.7 (9.5 -12.1) g/kg bw in male and female mice. It is notable that the subcutaneous LD50 values are greatly in excess of the limit dose for acute dermal toxicity testing.

Urea is of very low toxicity following intravenous administration. Sato et al (1977) report LD50 values of 5.4 (4.9 -5.9) and 5.3 (4.8 -5.7) g/kg bw in male and female rats and LD50 values of 4.6 (4.3 -4.9) and 5.2 (4.8 -5.6) g/kg bw in male and female mice, respectively.

Justification for classification or non-classification

Urea is of inherently very low toxicity by all routes investigated. No data are available for the inhalation route, however low toxicity can also be predicted for this route. No classification is proposed for acute toxicity according to CLP.