Potassium formate

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian germ cell study: gene mutation

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Data source

Reference

Reference Type:

publication

Title:

Formaldehyde-induced mutations in Drosophila melanogaster in dependence of the presence of acids.

Author:

Stumm-Tegethoff BFA

Year:

1969

Bibliographic source:

Theor Appl Genetics 39, 330-334.

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 477 (Genetic Toxicology: Sex-linked Recessive Lethal Test in Drosophila melanogaster)

Version / remarks:

Exceeds guideline study in that the effect of the pH value was clearly elucidated

GLP compliance:

no

Type of assay:

Drosophila SLRL assay

Test material

Test material information

Constituent 1

Reference substance name:

Sodium formate

EC Number:

205-488-0

EC Name:

Sodium formate

Cas Number:

141-53-7

Molecular formula:

CHO2Na

IUPAC Name:

sodium formate

Details on test material:

- Name of test materials (as cited in study report): Formic acid
Sodium formate; produced by neutralization of 0.1% formic acid with glycine-NaOH buffer (feeding experiment)

Specific details on test material used for the study:

- Name of test materials (as cited in study report): Formic acid
Sodium formate; produced by neutralization of 0.1% formic acid with glycine-NaOH buffer (feeding experiment)

Test animals

Species:

Drosophila melanogaster

Strain:

other: Oregon-K

Sex:

male

Details on test animals or test system and environmental conditions:

Environment: 24°C

Administration / exposure

Route of administration:

oral: feed

Vehicle:

- Vehicle(s)/solvent(s) used: feed was used to allow dosing of both the liquid acid and the solid sodium formate salt

Details on exposure:

Oregon-K strain of Drosophila melanogaster were treated using dosed feed with 0.1 % formic acid, or sodium formate produced by neutralization of 0.1% formic acid with glycine-NaOH buffer.
Vapor phase exposure: Males were exposed 24 h in specially designed bottles containing 5 ml of the test substance. The flies themselves were kept in small glass tubes which were closed with gauze on the lower end and with cotton wool on the upper end.
Larval feeding experiment: A nutrient containing agar, brewer's yeast, corn meal, sucrose and water was prepared, autoclaved, cooled and supplemented with the chemicals to be tested. Females were allowed to lay eggs for 24 to 48 h and were then discarded. Males, which spent their whole larval life on the medium, were collected 24 h after emergence and mated individually to 2 females. The pH of the feed varied between 4.2 to 5.6, depending on the added reagent.
Matings: the Muller-5 technique was used to test for sex-linked lethals. About 50 males were individually crossed with one or two virgins. Every three days the males were transferred to fresh virgins in order to produce three successive broods.

Duration of treatment / exposure:

entire larval stage

Doses / concentrations

Dose / conc.:

0.1 other: % as formic acid

No. of animals per sex per dose:

About 50 treated males were mated with M-5 virgins and every third day the males were transferred to two fresh virgins in order to produce three successive broods

Examinations

Statistics:

Statistical evaluation included the chi-square test, the rank correlation method of Kendall (1955), or a special test for mutation frequency of Stevens (1942).

Results and discussion

Test results

Sex:

male

Genotoxicity:

negative

Any other information on results incl. tables

1) Vapor experiment
Exposure to 0.1% Formic Acid (FA) significantly (p<0.001) increased the  

number of mutations compared to controls.
=========================================================
                               Brood
           1st            2nd          3rd       total
---------------------------------------------------------
         n     %        n     %      n     %      n     % 
---------------------------------------------------------
FA     1068  1.12     1130  1.42    850  1.41   3048  1.31 

Historical control                              2584  0.15
=========================================================
n = number of chromosomes tested
% = percentage of sex-linked lethals found                                                    

2) Larval feeding experiments
Exposure to 0.1% Formic Acid (FA) increased the number of mutations 

without gaining statistical significance between broods or compared to 

controls.
===========================================================
                               Brood
           1st            2nd          3rd       total
-----------------------------------------------------------
         n     %        n     %      n     %      n     % 
-----------------------------------------------------------
FA      786  1.15      522  1.34    671   0.88   1879  1.11
NaF                    544  0.38

Historical control                               2584  0.15
===========================================================
n = number of chromosomes tested
% = percentage of sex-linked lethals found 
NaF = Formic acid, neutralized to pH = 7.5 using a 0.1 M glycine-NaOH buffer.                                                  

The sodium formate (NaF; produced from formic acid by neutralization) sex-linked lethal was not different from the control. 

Formic acid results of the feeding study were also stated as not being significantly different from control.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative

Executive summary:

Formic acid was tested for genetic toxicity in a multigenerational test in Drosophila melanogaster similar to the OECD Guideline No. 477 (Genetic Toxicology: Sex-linked Recessive Lethal Test in Drosophila melanogaster). Following exposure to 0.1% formic acid vapour, the number of mutants was significantly increased compared to historical controls (p<0.001).

An increase was also seen with 0.1% formic acid in a subsequent feeding experiment, but without gaining statistical significance.  Sodium formate (produced by neutralization of formic acid) at the same molar concentration in the feed was negative in the Drosophila SLRL test. The authors concluded that the mutations observed with formic acid were related to the acidic pH, rather than to the acid or the formate molecule itself (Stumm-Tegethoff, 1969).

Conclusion:

Formic acid and sodium formate did not induce mutations in the Drosophila SLRL test in vivo.

This result can be read across to other formate salts including potassium formate.