Methyl O-(4-amino-3,5-dichloro-6-fluoropyridin-2-yloxy)acetate

Endpoint summary

Additional information

A series of in vitro mutagenicity tests and one in vivo mutagenicity test have been conducted on Fluroxypyr acid and these are summarised in the following table.

 

Table 1: Summary of genotoxicity studies with Fluroxypyr acid

Test system	Test object	Conc. of Fluroxypyr*	Batch and purity of Fluroxypyr	Positive controls	Results	Reference
Ames	S. typhimuriumTA 98, 100, 1535, 1537 and 1538	10 - 10,000 µg/plate	Lot 140-75-8  >98%	-naphthyl-amine, Neutral red, 2-AAF, 2-AA	Negative (+/- S9 mix)	Hossack et al., 1979
In vitro CHO chromosome aberration	Chinese hamster ovary cells	62.5 - 1000 µg/plate	Lot 433T-1282-7 98.2%	CPA, 4-nitroquinoline N-oxide	Negative (+/- S9 mix)	Holmstrom & Mc Gregor, 1983a
In vitro unscheduled DNA synthesis	Human embryonic lung cells (Flow 2002)	1 - 4000 µg/mL	Lot 433T-1282-7 98.2%	EMS CPA	Negative	Mc Gregor & Riach, 1983a
In vitro CHO/ HGPRT	Chinese hamster ovary cells (CHO-K1, CCL 61)	500 - 2000 µg/mL	Lot433T-1282-7 98.2%	EMS, DMN	Negative (+/- S9 mix)	Davis, 1983
In vitro mouse lymphoma	L5178Y with heterozygous, TK locus	33.3 - 3333.3 µg/mL	Lot 433T-1282-7 98.2%	EMS, 2-AAF	Positive (+/- S9 mix)	Mc Gregor & Riach, 1983b
In vivo chromosome aberration in Chinese hamsters	Femoral bone marrow cells	Five daily gavage doses of 73 - 735 mg/kg	Lot 433T-1282-7 98.2%	CPA	Negative	Holmstrom & Mc Gregor, 1983a

* The carrier was DMSO in all in vitro tests and 0.5% aqueous SCMC in the in vivo test

The only positive result obtained with Fluroxypyr acid was mutation of the thymidine kinase (TK) locus from the heterozygous TK+/- to the homozygous TK-/- condition in in vitro cultured L5178Y mouse lymphoma cells. In accordance with the evaluation criteria specified in the report, results did not indicate a significant response although the mutation frequency at the highest valid concentration of 1000 µg/ml was marginally increased (<2-fold) in the presence of S9 metabolic activation. These data indicated that any potential unequivocal response would only occur between 1000 and 3000 µg/ml; the second phase therefore employed concentrations in the range 800 - 2400 µg/ml. Results indicated weak mutagenic responses in both the presence and absence of S9-mix. The positive results were subsequently reproduced in another independent investigation, which also looked at the effect of pH on the response, as pH and osmolality changes are known to produce positive results in this type of assay. These results showed that the mutagenic activity of Fluroxypyr could be substantially reduced by maintaining pH around neutrality during the exposure period suggesting that activity is due to an ionised form of Fluroxypyr or its interaction with the test medium.

Short description of key information:
see Discussion

Endpoint Conclusion:

Justification for classification or non-classification

In conclusion, a positive result was obtained in one of five in vitro mutagenicity tests. It is likely that this represents a false positive result. All other tests, including those that, like the mouse lymphoma test, are capable of detecting point mutations, were negative. In addition, as indicated in the next section of this document 7.7. Fluroxypyr is not carcinogenic in animals at toxic and limit dosages.