Formic acid, manufacture of, by-products from

Carcinogenicity

Description of key information

Data are avaialable for formates

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

708 mg/kg bw/day

Study duration:

chronic

Species:

rat

Quality of whole database:

Klimisch score = 1. Modern study compliant with current test guidelines and GLP

Carcinogenicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Carcinogenicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Potassium diformate (1:2) did not show potential for carcinogenicity in two long-term rodent feeding studies. This result can be extrapolated to formic acid. No carcinogenic potential is predicted for trimethylopropane or pentaerythritol or their corresponding esters. Due to the lack of carcinogenic associated with its components,the reaction mass of 2,2-bis(formyloxymethyl)propane-1,3-diyl diformate and formic acidis not predicted to have any carcinogenic potential.On this basis, the substance does not meet the criteria for classification for carcinogenicity according to Regulation 1272/2008/EC.

Additional information

The reaction mass of 2,2-bis(formyloxymethyl)propane-1,3-diyl diformate and formic acid consists of formic acid, propylidynetrimethanol-esters and pentaerythritol-esters. The toxicity of the propylidynetrimethanol-esters and pentaerythritol-esters is predicted to be comparable to propylidynetrimethanol and pentaerythritol respectively. Due to the corrosivity of formic acid, carcinogenicity studies using this substance are scientifically unjustified. The carcinogenic potential of formic acid has been determined by read-across to studies on the formate salts. Data from carcinogenicity studies using formate salts and the assessment of the carcinogenic potential of propylidynetrimethanol and pentaerythritol are considered appropriate to meet the REACH Annex VII-X data requirements for the reaction mass of 2,2-bis(formyloxymethyl)propane-1,3-diyl diformate and formic acid.

Formic acid

Due to the corrosivity of formic acid, studies requiring repeated oral dose testing are not justified for scientific reasons and on animal welfare grounds. Formate salts have been used in studies requiring repeated oral dosing. NOAEL values obtained in such studies may be used to calculate the NOAEL for the formate anion which may be read across to formic acid, taking into account stoichiometry and formula weights. Read-across to the findings from carcinogenicity studies using potassium formate is considered appropriate to determine the carcinogenic potential of the formate ion, and hence formic acid.

 

There are two combined chronic oral feeding toxicity and oncogenicity studies using potassium diformate (1:2). These tests include the combined 104-week chronic toxicity and oncogenicity rat study (50 Crl: HanWist(Glx: BRL) BR rats/sex/concentration at concentrations of 0, 50, 400, and 2000 mg/kg bw/day (BASF, 2002a) and the combined oral feed 80-week chronic toxicity and oncogenicity mouse study (51 Crl: CD-1 (ICR) BR mice/sex/concentration at concentrations of 0, 50, 400, and 2000 mg/kg bw per day; BASF, 2002b). The pattern of mortality did not indicate any treatment-related effect in either the rat or mouse. The spectrum of tumours was generally consistent with that expected in rats or mice of these strains. There were no tumours of unusual nature or incidence indicative of specific target organ carcinogenicity in the stomach or any other tissue at any concentration level in any species or sex. The NOAEL for carcinogenicity was 2000 mgpotassium diformate/kg bw/day in both sexes. This dose is equivalent to 708 mgformic acid/kg bw/day, or1415 mgformate anion/kg bw/day.

 

Potassium diformate (1:2) did not show potential for carcinogenicity in two long-term rodent feeding studies. This result can be extrapolated to formic acid

 

Propylidynetrimethanol & pentaerythritol

There are no studies available which have investigated the carcinogenic potential of propylidynetrimethanol or pentaerythritol. These substances did not show mutagenic activity in genotoxicity studies and (histo) pathological alterations indicative for a potential carcinogenic effect were not observed in the available repeated dose toxicity studies. No testing has therefore been triggered according to Annex X of Regulation(EC) No. 1907/2006. Similarly, a lack of carcinogenic potential is predicted for the corresponding esters.

The reaction mass of 2,2-bis(formyloxymethyl)propane-1,3-diyl diformate and formic acid

Based on the available evidence its component substances, the reaction mass of 2,2-bis(formyloxymethyl)propane-1,3-diyl diformate and formic acid is not expected to have any carcinogenic potential.

Justification for selection of carcinogenicity via oral route endpoint:
The reaction mass of 2,2-bis(formyloxymethyl)propane-1,3-diyl diformate and formic acid consists of formic acid, propylidynetrimethanol-esters and pentaerythritol-esters. Data from carcinogenicity studies using formate salts and the assessment of the carcinogenic potential of propylidynetrimethanol and pentaerythritol is considered appropriate to meet the REACH Annex VII-X data requirements for the reaction mass of 2,2-bis(formyloxymethyl)propane-1,3-diyl diformate and formic acid.