1,3,5-Triazin-2-amine, 4-methoxy-6-(trifluoromethyl)-

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian germ cell study: cytogenicity / chromosome aberration

Type of information:

experimental study

Adequacy of study:

other information

Study period:

1998

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Data source

Reference

Reference 1

Reference Type:

other: Draft Renewal Assessment Report under Regulation (EC) 1107/2009

Title:

Draft Renewal Assessment Report under Regulation (EC) 1107/2009 - Tritosulfuron

Year:

2018

Bibliographic source:

Draft Renewal Assessment Report under Regulation (EC) 1107/2009

Reference 2

Reference Type:

study report

Title:

Unnamed

Year:

1998

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.12 (Mutagenicity - In Vivo Mammalian Erythrocyte Micronucleus Test)

Principles of method if other than guideline:

According to the current OECD TG 474 (2014), intraperitoneal injection is generally not recommended. However, this way of exposure was used in the present study, since it was one of the recommended and routinely used administration routes in studies performed in accordance with the previous guideline OECD 474 (1997 and 1983). Nevertheless, since it was demonstrated that the test item was bioavailable, this deviation does not affect the validity of the study.
Additionally, at least 4000 PCE per animal should be scored for the incidence of micronucleated immature erythrocytes according to OECD TG 474 (2014). However, in the current study, only 2000 PCE per animal were scored, since this was required by the previous guideline OECD 474 (1997). Nevertheless, for the 48-hour exposure experiment, the required number of PCEs was scored (2 x 2000 PCE/animal) in order to verify the results obtained.

GLP compliance:

yes

Type of assay:

mammalian bone marrow chromosome aberration test

Test material

Test material information

Constituent 1

Reference substance name:

4-methoxy-6-(trifluoromethyl)-1,3,5-triazin-2-amine

EC Number:

610-962-9

Cas Number:

5311-05-7

Molecular formula:

C5H5F3N4O

IUPAC Name:

4-methoxy-6-(trifluoromethyl)-1,3,5-triazin-2-amine

Test animals

Species:

mouse

Strain:

NMRI

Sex:

male

Administration / exposure

Route of administration:

intraperitoneal

Results and discussion

Any other information on results incl. tables

Tables are attached separately

Applicant's summary and conclusion

Conclusions:

According to the results of the study, test item is not cytotoxic in mammalian germ cell.

Executive summary:

Clastogenic/aneugenic activity of tritosulfuron metabolite test item was tested in vivo in NMRI mice. The maximum dose was selected based on severe toxicity, including mortality seen after intraperitoneal injection of 50, 100 and 500 mg/kg bw of the test item. After 24 hrs no increase in micronuclei formation was observed under study conditions. 48 hrs after administration of AMTT the increase in micronucleated PCE was reported compared to the concurrent control. However, the increase was within the HCD range for solvent control. The exposure of bone marrow is indirectly demonstrated by clinical signs observed in pretoxicity studies after single exposure to 12.5 and 25 mg/kg bw (reduction in spontaneous activity, eyelid closure, apathy abdominal position). Additionally, a study on kinetics in mice was performed, directly demonstrating the exposure of bone marrow to AMTT.
AMTT did not induce the formation of micronucleus in vivo under study conditions. The study was performed according to OECD 474 (1997) and principles of GLP. Despite deviations (intraperitoneal application, 2000 PCE scored per animals) the study is acceptable.