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Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

in vitro
Ames negative (similar to OECD 471, CMA 1982)
Ames: negative (similar to OECD 471, Zeiger, 1985)
Mouse Lymphoma: negative (similar to OECD 476, McGregor 1988)
Mouse Lymphoma: negative (similar to OECD 476, CMA 1982)
CA: negative with S9, ambiguous without S9 (Galloway 1987)
SCE: negative without S9, ambiguous with S9 (similar to OECD 479, Galloway 1987)

in vivo
MNT, i.p.: negative (similar to OECD 474, Shelby 1993)
MNT, i.p.: negative (similar to OECD 474, CMA 1982)
Dominant lethal assay: negative (similar to OECD 478, Singh 1975)

Additional information

No mutations were found when Diethylhexyl adipate (DEHA) was incubated with TA-98, -100, -1535, - 1537, or -1538 Salmonella strains with and without metabolic activation at concentrations up to 150µl/plate, which corresponds to 139000µg/plate (CMA 1982; Zeiger et al. 1985). In addition, there was no evidence of mammalian cell mutation in mouse lymphoma assays conducted with and without metabolic activation (McGregor et al. 1998; CMA unpublished studies, 1982) up to 5000µg/mL. Cytotoxicity was observed in both assays and precipitation occured at and above 1000µg/mL. In a chromosome aberration assay an ambiguous result was obtained without S9, while in an SCE assay treatment in the presence of S9 led to ambiguous results (Galloway 1987). Since no clear positive result was obtained, the results are contradictory (ambiguous results only in the presence or absence of S9), and no hint for chromosome aberration was observed in two mouse lymphoma and several in vivo studies, DEHA is believed not to cause chromosome aberration in mammalian cells. Additionally, no unscheduled DNA synthesis was oberserved in primary rat hepatocytes (CMA, 1982, cited in OECD SIDS 2000).

Two independent mouse micronucleus assays were conducted without evidence of interaction with DNA even at a dose level of 5000 mg/kg (CMA , 1982 ; Shelby et al ., 1993). In a dominant-lethal study using mice, DEHA did not demonstrate decreases in litter size that might suggest adverse effects on spermatogenesis up to doses of close to 10000mg/kg (Singh et al ., 1975).

Justification for classification or non-classification

Based on the available data, classification as a genotoxic substance is not triggered according to EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.