Calcium diformate

Endpoint summary

Description of key information

Calcium diformate is of low acute toxicity (LD50, rat > 2000 mg/kg). Inhalation and dermal data are lacking but can be read across (dermal LD50 >2000 mg/kg bw; LC50 >0.64 mg/L [corrected for formula weight]) from sodium formate, because toxicological properties are deemed to depend on the formate anion whereas contributions of the metal cations are considered to be minor important.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Dose descriptor:

LC50

Value:

0.64 mg/m³ air

Acute toxicity: via dermal route

Endpoint conclusion

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

Only oral acute toxicity data are available for calcium diformate whereas inhalation and dermal data are lacking. A read across from sodium formate can be made because sodium and potassium formate are expected to behave very similar, and differences between the metals ions are considered to be negligible. Thus, water solubility, physical state (solid) and a very low vapour pressure, and low acute oral toxicity are in common. Very low dermal absorption and the absence of irritating properties are confirmed for sodium formate and expected for calcium diformate. Regarding inhalation, this exposure route is not considered as being relevant for any of the formate salts.

Acute oral toxicity:

The acute oral toxicity of calcium diformate (1000, 2000, 3100, 3500, 3800, 4000 mg/kg bw; dissolved in water, oral gavage) was examined in male Wistar rats (10 per dose). The method was similar to OECD test guideline 401, observation period was 14 days.  There were no clinical signs or mortality in animals at 1000 mg/kg bw. Mortality, sedation, increased diuresis, and reduced general state were noted in the dose groups at 2000 mg/kg bw and above. The LD₅₀ was 3050 (95% confidence range 2540 – 3390) mg/kg bw (Bayer, 1978). The study is considered to be of low reliability (3, i.e. invalid) because of the very poor study report. The LD₅₀ value does, however, indicate low oral toxicity and may be used in a weight of evidence approach for assessment.

The acute oral toxicity of calcium diformate (2000, 2520, 3180, 3980, 5000 mg/kg bw; dissolved in water, oral gavage) was examined in male and female Wistar rats (5/sex/dose). The method was similar to OECD test guideline 401, the observation period was 14 days. Mortality was noted in the dose groups at 2000 mg/kg bw and above.The LD₅₀was 2560 mg/kg bw in rats (Degussa, 1979). The study is considered to be of low reliability (4) because of the study report is not yet available The calculated LD₅₀ value does, however, indicate low oral toxicity and may be used in a weight of evidence approach for assessment.

 

The acute oral toxicity of formic acid and several of its salts was examined in male and female mice in a pre-guideline study. The aim was to establish LD₅₀values and elucidate the mode of action. Calcium diformate was tested in a total of 45 mice. The oral LD₅₀ was 1920 mg/kg bw (range: 1280-2560) in male and female mice. The acute oral toxicity was therefore low (Malorny, 1969).  This pre-guideline publication reviews the results of a variety of studies including metabolism and excretion, acute and repeated toxicity, and toxicity to reproduction. These results were used in the course of an early MAK-assessment. Though formal requirements for modern studies are not met, the published results are valuable for the assessment of formic acid and its salts. The study is considered to be valid, but secondary information with limited documentation, and useful in a Weight of Evidence approach.    

A lower LD₅₀ of 1210 mg/kg bw that was reportedly obtained with rats (Union Carbide, 1968) was not taken into consideration because no details are known on this study, and because sufficient data on calcium formate and other formate salts exist.

Overall, there is evidence that the acute oral LD₅₀of calcium diformate in rats is >2000 mg/kg bw.

Acute inhalation toxicity:

Calcium diformate: no data

Sodium formate: sodium formate is a solid, inhalation is therefore not considered to represent a relevant route of exposure. However, an acute inhalation study is available as follows.

In an acute inhalation toxicity test, 5 Sprague Dawley rats of either sex were exposed to an atmosphere containing ground sodium formate dust (4 hours whole body exposure). The study was conducted according to the US EPA guideline EPA OTS 798.1150 (similar to OECD guideline 403) and under GLP conditions. The target concentration was 10 mg/L, the observation period 14 days.

 

The mean gravimetric particle concentration was 0.67 mg/L under the conditions of this study. The average mass median aerodynamic diameter was 5.4 µm with an average geometric standard deviation of 2.4 µm. There were no mortalities. Signs of treatment were minimal and included nasal discharge and lacrimation after treatment with recovery within one week, and a transient reduction of body weight gain. No treatment-related changes were seen at the terminal necropsy (Biodynamics, 1990).

 

Overall, exposure of rats to the highest practical aerosol concentration of test material, with a large portion in the respirable range, was not

associated with adverse effects other than eye and nasal irritation. The acute inhalation LC₅₀is greater than 0.67 mg/L for a 4-hour inhalation exposure. The study provides useful information, though inhalation is not considered to represent a relevant route of exposure for a solid like sodium formate.

 

Conclusion: the 4-hour calcium diformate LC₅₀ is considered to be >0.64 mg/L in rats.

Acute dermal toxicity:

Calcium diformate: no data

Sodium formate: in an OECD TG 402 study Wistar rats (5/sex) were administered sodium formate on the fur-clipped dorsal skin at 2000 mg/kg bw under semi-occlusive conditions for 24 hours and observed for 14 days. The study was conducted under GLP conditions. No mortality or clinical signs of toxicity, skin reactions and no effects on body weights were seen, and no changes were seen in any organs during necropsy. The LD₅₀ was >2000 mg/kg bw (BASF AG, 2007).

Conclusion: the dermal calcium diformate LD₅₀is considered to be >2000 mg/kg bw in rats.

Justification for classification or non-classification

No classification. Criteria of regulations 67/548/EC and 1272/2008/EC are not met.