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Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline, GLP study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report Date:
2014

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
GLP compliance:
yes
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
Triisotridecyl phosphite
Lankromark LE571
Batch: W024077 (3284/047)
Analytical purity: 98%

Test animals

Species:
mouse
Strain:
CD-1
Sex:
male/female
Details on test animals and environmental conditions:
The animals were 7 to 8 weeks old on day one of dosing. The females were nulliparous and not pregnant. Male weights: 32-37 g; Female weights: 23-34 g; at the start of the study.TEST ANIMALS- Source:- Age at study initiation: 7 to 8 weeks old on day one of dosing- Weight at study initiation: Males: 32-37 g; Female weights: 23-34 g- Assigned to test groups randomly: yes- Housing: Group (5 animals of same sex per cage)- Acclimation period: 8 daysENVIRONMENTAL CONDITIONS- Temperature (°C): 20 - 23°C- Humidity (%): 65 - 67 %- Air changes (per hr): Minimum 15 air changes per hour.- Photoperiod (hrs dark / hrs light): 12 h artificial light (06:00 - 18:00 h) and 12 h darkness

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
vegetable oil
Details on exposure:
2000 mg/kg bw of TiTDP was given in vegetable oil via oral gavage for two consecutive days.
Duration of treatment / exposure:
2 days
Frequency of treatment:
once daily
Doses / concentrations
Remarks:
Doses / Concentrations:2000 mg/kg bwBasis:actual ingested
No. of animals per sex per dose:
5
Control animals:
yes, concurrent vehicle
Positive control(s):
Mitomycin-C, 1 mg/kg bw was used as a positive, concurrent, control

Examinations

Tissues and cell types examined:
Femoral bone marrow
Details of tissue and slide preparation:
SAMPLING TIMES: Vehicle control and treated groups (18 - 24 h after last treatment); Positive control (24 h after last treatment)
Evaluation criteria:
per Test Guideline

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
no effects
Vehicle controls validity:
valid
Positive controls validity:
valid
Additional information on results:
RESULTS OF DEFINITIVE STUDY- Induction of micronuclei (for Micronucleus assay): No- Ratio of PCE/NCE (for Micronucleus assay): P/E ratio was 12.40% lower in treated male animals and 1.18% higher in treated female animals than in their respective vehicle control animals. These differences were not considered to be biologically significant.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negativeBased on the results of the study, it is concluded that TiTDP does not have micronucleus induction potential in male and female mice.
Executive summary:

In a reliable OECD 474 Guideline GLP study, TiTDP did not cause micronucleus induction in male and female mice when administered at a limit dose of 2000 mg/kg bw by gavage for two consecutive days.

Note

An in vivo study was conducted due to concerns about the hydrolytic instability of the test substance in the in vitro test system.  Also, this test is preferred still amongst some non-EU regulatory agencies and this particular study was done for non-REACH purposes as well.