Reaction mass of glycerol, glycerol 1-formate, glycerol 2-formate, glycerol 1,2-diformate, glycerol 1,3-diformate and glycerol triformate

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

This endpoint study record is part of a Weight of Evidence approach comprising of read-across from three studies for one analogue source substance. The results of the read-across studies agree as to the potential for genetic toxicity and are sufficient to fulfil the information requirements as further explained in the provided genetic toxicity endpoint summary.

Data source

Reference

Reference Type:

publication

Title:

SIDS Initial Assessment Report for SIAM 26: Formic Acid and Formates

Author:

OECD SIDS

Year:

2008

Bibliographic source:

OECD SIDS (2008). SIDS Initial Assessment Report for SIAM 26: Formic Acid and Formates. Paris, 15-18 April 2008

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

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

GLP compliance:

not specified

Type of assay:

mammalian erythrocyte micronucleus test

Test material

Test material information

Constituent 1

Reference substance name:

Potassium formate(1:2)

EC Number:

243-934-6

EC Name:

Potassium formate(1:2)

Cas Number:

20642-05-1

Molecular formula:

CH2O2.1/2K

IUPAC Name:

potassium formate(1:2)

Details on test material:

Test substance: Potassium diformate

Specific details on test material used for the study:

Reported as: Potassium hydrogen diformate (KHFo)

Test animals

Species:

rat

Strain:

not specified

Sex:

male/female

Administration / exposure

Route of administration:

intravenous

Vehicle:

Yes: not specified

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

12.5 mg/kg bw/day (nominal)

Doses / concentrations 2

Dose / conc.:

25 mg/kg bw/day (nominal)

Doses / concentrations 3

Dose / conc.:

50 mg/kg bw/day (nominal)

No. of animals per sex per dose:

five male and five female rats

Positive control(s):

Yes: not specified

Examinations

Tissues and cell types examined:

Bone marrow blood cells were prepared at 24 and 48 hours post treatment and examined for micronucleated polychromatic erythrocytes.

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

yes

Remarks:

The PCE/NCE ratio was reduced at the highest concentration compared to vehicle controls, indicating toxicity to the bone marrow

Vehicle controls validity:

valid

Positive controls validity:

valid

Additional information on results:

A decrease in the PCE/NCE ratio was observed when compared to the vehicle control. The group mean frequencies of micronucleated PCE at the 24-hour sampling time were comparable between the treatment and control groups. At the 48-hour sampling time there was an overall statistically significant trend. However, the authors noted that all group mean micronucleus frequencies were within the historical negative control range and, compared to the vehicle group, the increase was not statistically significant. It was concluded that KHFo did not increase the percentage of micronuclei in an in vivo rat bone marrow micronucleus test.

Applicant's summary and conclusion

Conclusions:

KHFo did not increase the percentage of micronuclei in an in vivo rat bone marrow micronucleus test.

Executive summary:

The analogue source substance SS4 did not increase percent of micronuclei in an in vivo rat bone marrow micronucleus test performed in accordance with OECD Test Guideline 474 when tested at doses of up to 50 mg/kg bw. In this study, rats (5/sex) were intravenously administered SS4 and bone marrow blood cells were prepared at 24 and 48 hours post treatment and examined for micronucleated polychromatic erythrocytes. A decrease in the PCE/NCE ratio was observed when compared to the vehicle control. The group mean frequencies of micronucleated PCE at the 24-hour sampling time were comparable between the treatment and control groups. At the 48-hour sampling time there was an overall statistically significant trend. However, the authors noted that all group mean micronucleus frequencies were within the historical negative control range and, compared to the vehicle group, the increase was not statistically significant. It was concluded that KHFo did not increase the percentage of micronuclei in an in vivo rat bone marrow micronucleus test.