Registration Dossier

Administrative data

Description of key information

Data from various species (including human volunteers) indicate that urea is not irritating to intact skin.   
The results of a guideline-compliant eye irritation study would trigger classification as an eye irritant, however medical surveillance data collected over several decades showed no adverse effects after direct contact with urea.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

Skin irritation

Frosch & Kligman (1977) (cited in WHO/JECFA evaluation) exposed human volunteers to three daily applications of urea (dissolved in water) at concentrations of between 7.5 -30%; applications were made to intact and scarified skin. On abraded skin, slight irritation was seen with 7.5% urea; marked irritation was seen with 30% urea. No effects were seen on intact skin. In a study by Lashmar et al (1989) application of 10% urea for 24 hours induced no discernible change in the histological appearance of the skin. No evidence of skin irritation was seen in a modern guideline study (Hooiveld, 2003).

It is notable that skin creams, commonly containing urea at concentrations of between 5 -10% but also at concentrations of up to 25% and higher are widely used for the treatment of dry/irritant skin conditions, therefore it can be predicted that urea is not a skin irritant. Urea is also naturally present in the stratum corneum at a level of approximately 1%. It is also notable that no signs of local irritation were noted in 28 -day and 25 -week repeated dose dermal toxicity studies in the rat (Sato et al, 1977)

Eye irritation

Urea was found to be a mild eye irritant in a guideline-compliant study (Kirsch & Kersebohm, 1988), which would not require a classification according to DSD, however require a classification according to CLP.

Medical surveillance data of 10 urea producing facilities were collected, which showed no cases of eye irritation or related adverse eye effects resulting from exposure to urea. (Borealis Agrolinz Melamine, 2013).

Justification for classification or non-classification

Skin irritation:

No classification is proposed. There is no evidence from animal studies or from human experience that urea is a skin irritant.

Eye irritation:

No classification is proposed. Although formally a classification as eye irritant would be required according to CLP, medical surveillance data show no adverse effects on eyes following direct contact.