Formic acid

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Dose descriptor:

NOAEL

676 mg/kg bw/day

Additional information

ORAL ROUTE

Formic acid was tested in a rat 2-generation study according to OECD test guideline No. 416 guideline and under GLP conditions. There was no effect on parental animals, reproduction parameters, or progeny at any dose level including 1000 mg/kg bw/day, the highest tested dose. The NOAEL values were therefore as follows:

NOAEL 1000 mg/kg bw/day for general systemic toxicity for F0 and F1 parental animals

NOAEL 1000 mg/kg bw/day for fertility and reproductive performance for the F0 and F1 parental rats

NOAEL 1000 mg/kg bw/day for developmental toxicity, in the F1 and F2 progeny.

 

1000 mg sodium formate would compare to 676 mg formic acid, the NOAEL values calculated for formic acid are therefore 676 mg formic acid/kg bw/day.

DERMAL ROUTE

Not applicable. Reasons: Formic acid is corrosive to the skin. Formate salts are not readily absorbed through the skin.

INHALATION ROUTE

In two OECD guideline No. 413 inhalation studies with formic acid conducted under GLP conditions, Fischer 344 rats and B6C3F1 mice (10 animals per sex and dose) were exposed to formic acid vapor at 0, 0.015, 0.030, 0.062, 0.122, or 0.244 mg/L (0, 8, 16, 32, 64, or 128 ppm; dose selection based on results of a range finding study) via whole-body inhalation 6 hours/day, 5 days/week for 13 weeks.

In addition to the parameters required for the subchronic studies, sperm motility and morphology was examined in both species at termination in all males, or estrous cycle of all females was examined during the last two weeks of exposure. Male and female reproductive organs were weighed and subjected to histopathology. Organ weights, histopathology, and reproductive organ function, i.e. sperm parameters and estrous cycle length, were not affected at the end of the 13 -week exposure period with the exception of the finding that In mice, sperm motility values were lower at all concentrations, but no dose-response relationship was seen and the values were within the range of historical controls.

Thus there were no findings that would indicate adverse effects of formic acid on male and female reproductive organs in the rat and mouse at any dose including the top dose (NOAEC = 128 ppm, i.e. 0.244 mg formic acid/L) in the rat and mouse 13-week inhalation studies (Thomson, 1992). In conclusion this indirectly demonstrates the absence of any reproductive toxicity via inhalative exposure and verifies the read across.

Short description of key information:
Oral: General remark: formate salts are generally used as test material, due to the corrosivity of formic acid. Not any reproductive toxicity was observed for Formic acid salts in a valid OECD 416 two generation study at the limit dose of 1000 mg/kg/day. This value may be used to calculate the NOAEL for formic acid, or the formate anion which may be used for read across to other salts. This result can be extrapolated to formic acid and other formate salts (Calculated reproduction NOAEL for formic acid: 667 mg/kg bw/day). Beyond this, there is no hint from inhalative repeated dose toxicity studies that formic acid is a reproductive toxicant via the inhalative route.

Effects on developmental toxicity

Description of key information

Developmental toxicity studies for sodium formate in rats and rabbits showed no effects on the developing fetuses with NOAEL values of 945 and 1000 mg/kg bw/day, respectively (Limit dose).  These data can be extrapolated to the related formates and to formic acid (with restrictions due to its corrosivity). No potential for any developmental toxicity is expected for formic acid therefore.

Effect on developmental toxicity: via oral route

Dose descriptor:

NOAEL

676 mg/kg bw/day

Additional information

Due to the corrosivity of formic acid, toxicity of the formate anion to reproduction was examined using formate salts. The respective NOAEL values obtained for the salts can be used to calculate NOAEL values for formic acid or other formate salts.

First study:       Wistar rats

In a developmental study, time-mated female rats (25/dose, OECD TG 414) were given NaFo (sodium formate) via oral gavage at 0, 59, 236, and 945 mg/kg bw/day during gestation days 6 to 19.  Maternal toxicity was not seen. Gestational parameters were not influenced and there were no effects on the developing fetuses. No malformations or skeletal variations were seen. The NOAEL for maternal and developmental toxicity was 945 mg sodium formate/kg bw/day, the highest dose tested.

 

Generally, formate salts are used as test material in studies requiring repeated dosing, due to the corrosivity of formic acid. NOAEL values obtained in such studies may be used to calculate the NOAEL for other salts or formic acid, taking into account stoichiometry and formula weights. For formic acid the calculation gives NOAEL values of 639 mg/kg bw/day for maternal toxicity, developmental toxicty, and teratogenicity.

Second study:   Himalayan rabbits

In a developmental toxicity study sodium formate was administered to 25 female Himalayan rabbits in water by gavage at dose levels of 0, 100, 300, and 1000 mg/kg bw/day from days 6 through 28 of gestation.

There were no treatment-related effects in mortality, clinical signs, body weight, food consumption,cesarean parameters, and terminal necropsy in the does. The maternal NOAEL is therefore 1000 mg sodium formate/kg bw/day.

There were no treatment-related effects in developmental parameters. Fetal weight at birth, sex distribution, placenta weight, pre- and postimplantation loss was not affected. There were no unusual or increased incidences of external, soft tissue or skeletal malformations attributable to the treatment. The developmental NOAEL is therefore 1000 sodium formate mg/kg bw/day. The NOAEL for teratogenicity is also 1000 sodium formate mg/kg bw/day, the highest dose tested.

 

The developmental toxicity studies in rats and rabbits are classified acceptable and are according to the guideline requirement for a developmental toxicity study (OECD 414).

 

In summary, the NOAEL values for sodium formate were as follows:

maternal toxicity:              NOAEL 1000 mg/kg bw/day

developmental toxicity:      NOAEL 1000 mg/kg bw/day

teratogenicity:                  NOAEL 1000 mg/kg bw/day

1000 mg sodium formate compare to 676 mg formic acid, the NOAEL values calculated for formic acid are therefore 676 mg formic acid/kb bw/day.

Justification for classification or non-classification

No classification because the criteria of regulations 67/547/EC and 1272/2008/EC are not met.