Registration Dossier

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vivo

Description of key information
The guideline and non-guideline studies indicate that lactofen is neither genotoxic nor mutagenic.
Link to relevant study records
Reference
Endpoint:
genetic toxicity in vivo
Remarks:
Type of genotoxicity: other: in vivo: DNA binding assay and DNA covalent binding in mouse liver
Type of information:
other:
Adequacy of study:
supporting study
Study period:
2012
Rationale for reliability incl. deficiencies:
other: Short description on comprehensive studies available via the internet by US EPA and pubchem.ncbi.nlm.nih.gov
Principles of method if other than guideline:
short summary on different studies
Type of assay:
other: In vitro: Salmonella typhimurium/mammalian microsome mutagenicity assay, mammalian cytogenetic assay and unscheduled DNA synthesis,
Species:
other: short summary on different experiments
Strain:
not specified
Sex:
not specified
Route of administration:
other: in vitro / in vivo studies
Tissues and cell types examined:
see summary

The guideline and non-guideline studies indicate that lactofen is neither genotoxic nor mutagenic.

Conclusions:
Interpretation of results (migrated information): negative
Executive summary:

Executive summary is derived from the following internet links on 2012 -11 -09.

http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=62276#x321

http://www.epa.gov/iris/subst/0280.htm

References of individual studies:

PPG Industries. 1985b. MRID No. 00132883, 00150329. Available from EPA. Write to FOI, EPA, Washington, DC 20460.

• /GENOTOXICITY/ The guideline and non-guideline studies indicate that lactofen is neither genotoxic nor mutagenic. Equivocal (probably negative) results were observed in an in vivo DNA binding assay with radiolabeled lactofen. Salmonella typhimurium/mammalian microsome mutagenicity assay: negative with and without S-9. In vitro cytogenetic assay with Chinese hamster ovary (CHO) cells: negative for clastogenic effects with and without S-9. In vitro unscheduled DNA synthesis in primary mouse and rat hepatocytes: negative. In vivo DNA covalent binding in mouse liver: low level of binding (equivocal, probably negative).
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vivo:

The guidelien in vitro bacterial reverse mutation assay (OECD TG 471) indicated no evidence of mutagenic activity. According to a short summary on the lactfen data by US EPA the guideline and non-guideline studies indicate that lactofen is neither genotoxic nor mutagenic.

Lactofen was initially investigated using the Salmonella/microsome plate incorporation test for point mutagenic effects in doses of up to and including 5000 µg per plate on five Salmonella typhimurium L T2 mutants. These comprised the histidine-auxotrophic strains TA 1535, TA 100, TA 1537, TA 98 and TA 102. The independent repeat was performed as preincubation for 20 minutes at 37°C. Other conditions remained unchanged. Doses up to and including 1581 µg per plate did not cause any bacteriotoxic effects. Total bacteria counts remained unchanged and no inhibition of growth was observed. At 5000 µg per plate, the substance had only a weak, strain-specific bacteriotoxic effect. Due to the weakness of this effect this dose could nevertheless be used for assessment purposes. Substance precipitation occurred at the dose 5000 µg per plate.

Evidence of mutagenic activity of Lactofen was not seen. No biologically relevant increase in the mutant count, in comparison with the negative controls, was observed. The positive controls sodium azide, nitrofurantoin, 4-nitro-1,2-phenylene diamine, mitomycin C, cumene hydroperoxide and 2-aminoanthracene had a marked mutagenic effect, as was seen by a biologically relevant increase in mutant colonies compared to the corresponding negative controls. Therefore, Lactofen was negative without and with S9 mix in the plate incorporation as well as in the preincubation modification of the Salmonella/microsome test.

The following summary is taken from the EPA evaluation:

• /GENOTOXICITY/ The guideline and non-guideline studies indicate that lactofen is neither genotoxic nor mutagenic. Equivocal (probably negative) results were observed in an in vivo DNA binding assay with radiolabeled lactofen. Salmonella typhimurium/mammalian microsome mutagenicity assay: negative with and without S-9. In vitro cytogenetic assay with Chinese hamster ovary (CHO) cells: negative for clastogenic effects with and without S-9. In vitro unscheduled DNA synthesis in primary mouse and rat hepatocytes: negative. In vivo DNA covalent binding in mouse liver: low level of binding (equivocal, probably negative).

Justification for classification or non-classification

EPA evaluation indicates:"The guideline and non-guideline studies indicate that lactofen is neither genotoxic nor mutagenic."