2,6-xylidine

Endpoint summary

Additional information

Test method	Test organism	Purity	Dose range (µg/plate)	Result w/wo metabolic activation	Reference
Ames test	S.typhimurium; TA 98, 100	>99 %	500-4000	+?/-	Kugler-Steinmeier et al.(1989)
Ames test	S.typhimurium; TA 100, 1537, 98	97 %	121-1815	-/-	Zimmer et al. (1980)
Ames test	S.typhimurium; TA 1535, 1537	97 %	3.6-3600	-/-	Florin et al. (1980)
Ames test	S.typhimurium TA 97, 98, 100, 102	nd	nd	+?/-	Kimmel et al. (1986)
Ames test	S.typhimurium; TA 100	99 %	1-1000	-/-	Hartman et al. (1979)
Ames test	S.typhimurium; TA 97, 98, 100, 1535, 1537	nd	10-3333	+?/-	Zeiger et al.(1988)
SCE test	CHO cell line WB 1	nd	33-1510	+/+	Galloway et al. (1987)
Chromosome aberration	CHO cell line WB 1	nd	900-1400	+/+	Galloway et al. (1987)
Mouse lymphoma test	L5178 lymphoma cells	nd	nd	+/+	Rudd et al. (1983)

Short description of key information:
Gene mutation in bacteria
A number of studies were done by different authors to investigate the mutagenic capacity of the test substance in bacteria. In the Ames test for 2,6-xylidine only a weak mutagenic effect, or no effect at all was found. An overview of the results is given in the table below.

Gene mutation in mammalian cells
Actually, there is no information available

Cytogenicity in mammalian cells
In mammalian cells 2,6-xylidine was investigated in a Sister chromatoid exchange assay and a chromosome aberration assay both in the CHO cell line WB1. In both assays the test substance showed positive effects with or without metabolic activation (Galloway, et al.).

Other studies
Actually, there is no information available.

Cytogenicity in vivo
2,6-xylidine gave negative results in the in vivo micronucleus test in mice following oral administration. 2,6-xylidine was given either once in doses of up to 350 mg/kg (Parton et al., 1988) or one to three times (at daily intervals) in doses of up to 375 mg/kg (Parton et al., 1990). In both studies no cytotoxic effects on the bone marrow were observed (PCE/NCE ratio). 2,6-xylidine induced no genetic effect in the recessive-lethal test with Drosophila melanogaster (Zimmering et al., 1989). 2,6-Xylidine brought about no DNA repair (UDS) in the hepatic cells of rats following oral administration of doses up to 850 mg/kg in vivo (Mirsalis et al., 1989). Oral application of 200 mg/kg 2,6-xylidine (Seiler, 1977) to male mice had no effect on the testicular DNS synthesis. Covalent binding of 2,6-xylidine to the DNA of hepatic cells and epithelial cells of the nasal cavity was examined in male rats 24 hours after i.p. application of 14C-2,6-xylidine. The binding index was calculated at 0.6, or was below the sensitivity limit of the method. However, pretreatment with non-labelled 2,6-xylidine for nine days (oral administration of 262.5 mg/kg once daily) led to a significant increase in the binding index to 41.9 for tissue ...

Endpoint Conclusion:

Justification for classification or non-classification

With respect to mutagenicity there are negative (Ames with rat and also hamster S-9 mix which is more effective in activation of aromatic amines (2), DNA damage and repair) and positive (SCE, chromosome aberration, mouse lymphoma) in vitro tests, yet all in vivo tests (SLRL in Drosophila mel., micronucleus test, UDS test, host-mediated assay) were negative. DNA binding in pretreated rats (9 days with 262.5 mg/kg/d cold material) after i.p. administration was found in liver (slight, CBI 7 .9) and nasal turbinates (moderate, CBI 41.9), whereas a single application was negative; thus, only after massive repeated application of the test substance DNA binding occurred.

 

A classification with respect to mutagenicity is not warranted according to EU and GHS classification criteria.