Urea, reaction products with formaldehyde and glyoxal

Endpoint summary

Additional information

In vitro studies:

The test material (analytical purity: 93.4 %) was not mutagenic in an Ames test according to OECD TG 471 in compliance with GLP in Salmonella typhimurium strains TA98, TA100, TA1535, TA1537 and Escherichia coli strain WP2 uvrA, both in the presence and in the absence of S-9 mix from Aroclor 1254 induced rats, when tested up to 5500 µg/plate (BASF SE 2010). A weak bacteriotoxic effect was occasionally observed depending on the strain and test conditions at 5500 µg/plate.

Supportingly, the test material (analytical purity: 75% in aqueous solvent) was negative in an Ames test with S. typhimurium strain TA102 when tested up to 10000 µg/plate with and without metabolic activation (BASF AG 1992). In this test, the uncommon tester strain was used because it is known to be sensitive to formaldehyde, the presumptively causative agent when released from the test substance.

In contrast, in a study of Zeiger et al. (1987), the test material (analytical purity 41.4%) was positive in S. typhimurium strain TA 100 with S9-mix only at > 3000 µg/plate in water, but not when diluted with DMSO. It is unclear why the test conducted with DMSO was negative in contrast to that with water since the test substance itself (41.4% in water) and the test medium contains appreciable amounts of water. Because the tests with the two solvents were performed in different laboratories (as described in Zeiger et al., 1987), it is difficult to discern whether the variable results were due to the tests being conducted in different laboratories or the use of different solvents. It is also not known whether the test concentrations listed were corrected for test material purity.

 

The test item (analytical purity: 93.4%) did not induce gene mutations at the HPRT locus in V79 cells in an in vitro mammalian cell gene mutation test according to OECD TG 476 in compliance with GLP when tested with and without metabolic activation (BASF SE 2010).

 

In vivo studies:

The test material (analytical purity: 73%) has been tested in an in vivo micronucleus assay according to OECD TG 474 in compliance with GLP (BG Chemie 1995). NMRI mice were exposed to 500, 1000 and 2000 mg/kg of the test substance which was administered by gavage. No toxic effects and no genotoxicity were observed in this study.

Furthermore, Foureman et al. (1994) reported that the test item (analytical purity: 41.4%) was not genotoxic in several in vivo tests in Drosophila melanogaster that were conducted according to the NTP standard protocol (reciprocal translocation assay, SLRL test with feeding of the test material, and a SLRL test with injection of the test material).

Short description of key information:
In vitro:
Ames test: negative
HPRT test: negative

In vivo:
Micronucleus test in mice (oral, gavage): negative

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

GHS classification according to Annex I 1272/2008 CLP (EU GHS):

no classification warranted.

If the formaldehyde content is at or above 1 % classification and labelling with Muta. 2, H341 is warranted.