Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

Two reverse mutation assays covering bacterial strains TA97, TA98, TA100, TA1535, TA1537 and TA1538 did not produce any evidence of mutation with and without metabolic activation up to the maximum dose which did not cause significant cell toxicity. 2-butoxyethanol, a read across substance for 2 -(2-butoxyethoxy)ethanol, does not increase the rate of reverse mutations in the E coli baterial strain WP2uvrA. (See attached document in Chapter 13 of lead registrant dossier for full justification for read across.)

An in vitro cytogenicity assay using CHO cells with and without metabolic activation produced no evidence of cytogenic properties when tested at doses up to those that cause cytotoxicity. An in vitro forward gene mutation assay at the HGPRT locus of CHO cells did not elicit a positive response when tested up to the maximum recommended dose of 5000ul/ml with and without metabolic activation. A rat hepatocyte unscheduled DNA synthesis assaydid not induce any activity when tested at doses up to a level that caused overt cytotoxicity.

In an in vitro mammalian gene mutation study which examined the genotoxic potential of 2 -(2 -butoxyethoxy)ethanol using the the L5178Y TK+/- mouse lymphoma test, ambiguous results were obtained in the absence of metabolic activation. Mutation frequencies up to 4.5x those of the solvent control were seen. Thee result was considered ambigous because of the associated toxicity seen at the higher doses, the lack of biological plausibility, the weakness of the response when expressed on a molar basis relative to positive controls and the fact that the result was clearly negative in the presence of metabolic activation. This study was also in contrast to the clear negative result obtained in the CHO line mutation response reported above.

In an in vivo mouse micronucleus test that used 3 post treatment sampling times, 2 -(2 -butoxyethoxy)ethanol did not increase the incidence of micronucleated polychromatic erythrocytes in either sex when tested up to a single maximum tolerated dose of 3300mg/kg.

The mutagenic potential was also examined using an in vivo Drosophilia sex linked recessive lethal assay using both a feeding and an injection route of exposure. No increase in recessive lethal mutations was observed using either condition.

The lack of any response in vivo and the lack of any response in the in vitro studies apart from the outlying ambiguous result in vitro in ML cells leads to the conclusion of a lack of genotoxic potential for this substance.


Short description of key information:
IN VITRO
Reverse mutation in bacteria, with and without metabolic activation (Ames): negative
Reverse mutation in bacteria, with and without metabolic activation (Ames): negative
Cytogenicity assay, CHO cells with and without metabolic activation: negative
Gene mutation assay, HGPRT locus of CHO cells with and without metabolic activation: negative
Gene mutation study, L5178Y TK+/- ML. without metabolic activation: ambigous. with metabolic activation: negative
Rat UDS assay, negative
IN VIVO
Mouse micronucleus assay. negative
Drosophilia sex linked recessive lethal assay. negative

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

No evidence of mutagenicity sufficient to warrant classification under either directive 67/548 or regulation 1272/2008.