Potassium formate

Endpoint summary

Description of key information

Potassium formate is of low acute toxicity (LD50, mouse > 5000 mg/kg). Inhalation and dermal data are lacking but can be read across (dermal LD50 >2000 mg/kg bw; LC50 >0.83 mg/L [corrected for formula weight]) from sodium formate (cf. data below) because differences between the two alkali metals are considered to be negligible. 
Sodium formate data: the acute oral and dermal toxicity is low (LD50 values in rodents >2000 mg/kg).  Inhalation is not considered to represent a relevant route of exposure, because formate salts are solids with a very low vapour pressure. Consequently only few inhalation studies are available. The maximal attainable dust concentration of 0.67 mg sodium formate/L (rats, 4 hours) produced no signs of toxicity. The LC50 was therefore >0.67 mg/L in the sole available inhalation study.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Refer to remarks.

Remarks:

Summary with tables and figures of a pre-guideline study. Meets generally accepted scientific standards, well documented and acceptable for assessment. This report was submitted to the MAK commission of the Deutsche Forschungsgemeinschaft (DFG) assessing hazardous materials.

Principles of method if other than guideline:

Pre-guideline study. LD50 determination was presumably conducted similar to the method used in OECD guideline 401.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

- Name of test material (as cited in study report): Kaliumformiat, or K-Formiat

Species:

mouse

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

no data

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

no data

Doses:

Applied doses not specified

No. of animals per sex per dose:

Total number of animals: 50

Control animals:

not specified

Sex:

not specified

Dose descriptor:

LD50

Effect level:

5 500 mg/kg bw

95% CL:

5 000 - 6 000

Table: oral LD50 of formic acid and its salts in the mouse:

 

 

Substance	LD50 (mg/kg bw)	LD50range (mg/kg bw)	LD50,formate (mg/kg bw)#	No of animals
Formic acid	1100	1000-1200	1076	55
Na-formate	11200	9600-12800	7410	45
K-formate	5500	5000-6000	2950	50
NH4-formate	2250	2050-2460	1610	50
Ca-formate	1920	1280 -2560	1330	45

 

# = calculated proportion of formate anion of the LD₅₀dose.

Thus, the order of oral toxicity in mice was  formic acid  >  Ca, NH4, K salts  >  sodium formate.

 

Interpretation of results:

GHS criteria not met

Conclusions:

The oral LD50 of potassium formate was 5500 mg/kg bw in mice. The oral toxicity of formic acid and its salts depended largely on the presence of H-ions, not on the presence of formate. Therefore formic acid was more toxic than the salts.

Executive summary:

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 LD₅₀ values and elucidate the mode of action. Potassium formate was tested in a total of 50 mice. The oral LD₅₀was 5500 (range 5000 to 6000) mg/kg bw in 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 (low reliability of 4 is assigned for formal reasons) and is used in a Weight of Evidence approach.

 

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Remarks:

Secondary source (ECB IUCLID 2000). The full report was not available for review.

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

not specified

Limit test:

no

Specific details on test material used for the study:

Assumingly Sodium Formate.

Species:

rat

Dose descriptor:

LD50

Effect level:

> 3 000 mg/kg bw

Interpretation of results:

study cannot be used for classification

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other:

Remarks:

Summary with tables and figures of a pre-guideline study. Meets generally accepted scientific standards, well documented and acceptable for assessment. This report was submitted to the MAK commission of the Deutsche Forschungsgemeinschaft (DFG) assessing hazardous materials.

Principles of method if other than guideline:

Pre-guideline study. LD50 determination was presumably conducted similar to the method used in OECD guideline 401.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

- Name of test material (as cited in study report): Na-Formiat

Species:

mouse

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

no data

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

no data

Doses:

Applied doses not specified

No. of animals per sex per dose:

Total number of animals: 45

Control animals:

not specified

Sex:

not specified

Dose descriptor:

LD50

Effect level:

11 200 mg/kg bw

95% CL:

9 600 - 12 800

Table: oral LD50 of formic acid and its salts in the mouse:

 

 

Substance	LD50 (mg/kg bw)	LD50range (mg/kg bw)	LD50,formate (mg/kg bw)#	No of animals
Formic acid	1100	1000-1200	1076	55
Na-formate	11200	9600-12800	7410	45
K-formate	5500	5000-6000	2950	50
NH4-formate	2250	2050-2460	1610	50
Ca-formate	1920	1280-1330	1330	45

 

# = calculated proportion of formate anion of the LD₅₀dose.

Thus, the order of oral toxicity in mice was  formic acid  >  Ca, NH4, K salts  >  sodium formate.

 

Interpretation of results:

GHS criteria not met

Conclusions:

The oral LD50 of sodium formate was approx. 11200 mg/kg bw in mice. The oral toxicity of formic acid and its salts depended largely on the presence of H-ions, not on the presence of formate. Therefore formic acid was more toxic than the salts.

Executive summary:

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 LD₅₀ values and elucidate the mode of action. Sodium formate was tested in a total of 45 mice. The oral LD₅₀was 11200 mg/kg bw (range: 9600-12800) in 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 (low reliability of 4 is assigned for formal reasons) and is used in a Weight of Evidence approach.

 

Reference 4

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Remarks:

Secondary source (ECB IUCLID 2000). The full report was not available for review.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

Assumingly Sodium Formate.

Species:

mouse

Strain:

C57BL

No. of animals per sex per dose:

12

Dose descriptor:

LD50

Effect level:

3 700 - 4 700 mg/kg bw

Mice fed with a folic acid supplemented diet showed a slightly higher LD50 (4700 mg/kg) than mice fed a diet
without folic acid supplements (LD50 3700 mg/kg).

Interpretation of results:

study cannot be used for classification

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

Only one concentration level tested. Large discrepancy between nominal and measured concentration (0.67 mg/L vs. 10 mg/L target concentration).

Qualifier:

according to guideline

Guideline:

EPA OTS 798.1150 (Acute inhalation toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

- Name of test material (as cited in study report): C-1261 (Sodium Formate)
- Substance type: white powder
- Physical state: solid
- Analytical purity: 99% active ingredient

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: males 9 weeks, females 10 weeks
- Weight at study initiation: mean weights: males 337 g; females 235 g
- Fasting period before study: no data
- Housing: individually
- Diet: ad libitum; standard laboratory diet
- Water: ad libitum
- Acclimation period: 15 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): slightly higher than the desired range of 20-24°C
- Humidity (%): 40-60
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: day 1 To: day 15

Route of administration:

inhalation: dust

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

0.67 mg/l

No. of animals per sex per dose:

5

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations: daily; weighing: on days days 1, 2, 3, 5, 8, and 15
- Necropsy of survivors performed: yes

Statistics:

not required

Sex:

male/female

Dose descriptor:

LC0

Effect level:

> 0.67 mg/L air

Exp. duration:

4 h

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 0.67 mg/L air

Exp. duration:

4 h

Mortality:

There were no deaths during the exposure or the 14-day observation period. 

Clinical signs:

other: Adverse clinical sighs were minimal and consisted of decreased activity and eyes partly or fully closed during the exposure, and lacrimation and nasal discharge but generally fully recovered within a week. 

Body weight:

There was a slight and transient reduction in body weight gain following the exposure but all animals continued to gain weight a few days after the exposure period (cf. section: Any other information on results)

Gross pathology:

No findings that could be related to treatment.

Other findings:

Atmosphere
The chamber temperature was 25 degrees and the relative humidity ranges for 17% to 6% with the lower values in the latter part of the study (considered as a result of the dessicant activity of fine particles of sodium formate). Chamber concentration of test material was measured at nine intervals during the study and ranged from 0.5 to 0.86 mg/L.

 

Mean terminal body weights (grams); 4-hour exposure, 0.67 mg/L

 

Day	Females	Males
1	235	337
2	230	333
5	236	344
8	244	365
15	255	414

 

 

Interpretation of results:

GHS criteria not met

Conclusions:

The acute inhalation LC50 is greater than 0.67 mg/L. This was the highest practicable concentration whch could be acheived. No mortality was seen at this dose.

Executive summary:

In an acute inhalation toxicity test, 5 Sprague Dawley rats of either sex were exposed to an atmosphere containing ground sodium formate dust (4hours 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 effect 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.

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

830 mg/m³ air

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

- Name of test material (as cited in study report): sodium formate
- Substance type: salt
- Physical state: solid
- Analytical purity: 100%
- Lot/batch No.: 1292066

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd, Füllinsdorf, Switzerland
- Age at study initiation: males 8-10 weeks, females 12-14 weeks
- Weight at study initiation: means: males 269 g; females 222 g
- Housing: single housing in Macrolon, type III cages
- Diet: complete diet from Kliba, Basel, Switzerland, ad libitum
- Water: ad libitum
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Vehicle:

CMC (carboxymethyl cellulose)

Details on dermal exposure:

TEST SITE
- Area of exposure: approx. 40 cm²
- % coverage: 10
- Type of wrap if used: gauze and adhesive fleece (Fixomull stretch)


REMOVAL OF TEST SUBSTANCE
- Washing (if done): warm water
- Time after start of exposure: 24 hours


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mgsodium formate/kg bw; 2.02 mL/kg bw
- Concentration (if solution): 99%
- Constant volume or concentration used: yes
- For solids, paste formed: yes


VEHICLE
- Amount(s) applied (volume or weight with unit): 20 µL/kg bw
- Concentration (if solution): 1%

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
-- Signs and symptoms: at least daily
-- Body weight: determined before application (day 0), and weekly thereafter

- Necropsy of survivors performed: yes

Statistics:

Probit analysis or a binominal test, depending on the results

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

There was no mortality in male (0/5) or female rats (0/5).

Clinical signs:

other: There were no systemic clinical signs in male or female rats at any time. Specifically, there were no local skin reactions in male or female rats at any time.

Gross pathology:

No findings in organs of males and females.

Interpretation of results:

GHS criteria not met

Conclusions:

The acute dermal LD50 was therefore >2000 mg/kg bw in male and female Wistar rats.

Executive summary:

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 LD₅₀was > 2000 mg/kg bw (BASF AG, 2007).

 

The study is considered to be fully valid and acceptable for assessment.

 

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

Only few acute toxicity data are available for potassium formate. An oral LD50 value in mice is available (>5000 mg/kg bw), 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 two alkali metals 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 potassium formate. Regarding inhalation, this exposure route is not considered as being relevant for any of the formate salts.

Acute oral toxicity:

Potassium formate: 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. Potassium formate was tested in a total of 50 mice. The oral LD₅₀ was 5500 mg/kg bw in mice. The acute oral toxicity was therefore low (Malorny, 1969).

 

Sodium formate: There are several independent sources which demonstrate that the acute oral toxicity in rodents is very low.

First, 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. Sodium formate was tested in a total of 45 mice. The oral LD₅₀ was 11200 mg/kg bw in 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 (though a low reliability of 4 is assigned for formal reasons) and is used in a Weight of Evidence approach.

Further, the LD₅₀ was reported to be >3000 mg/kg bw in rats (Huels, 1989) and mice (Smith, 1982).

Overall, it is concluded that the acute oral LD₅₀ of potassium formate in rats and mice is >2000 mg/kg bw.

Acute inhalation toxicity:

Potassium formate: 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 (equivalent to 0.83 mg potassium formate/L). 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 potassium formate LC₅₀ is considered to be >0.83 mg/L in rats.

Acute dermal toxicity:

Potassium formate: 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 potassium LD₅₀is considered to be >2000 mg/kg bw in rats.

Justification for classification or non-classification

Acute oral toxicity:

Classification criteria of regulations 67/548 EC and 1272/2008/EC are not met.

Acute inhalation toxicity:

Insufficent data for classification. The acute inhalation LC₅₀ is expected to be greater than 0.83 mg/L for a 4-hour inhalation exposure in rats. The inhalation route is not considered to represent a relevant route of exposure.

Acute dermal toxicity:

Classification criteria of regulations 67/548 EC and 1272/2008/EC are not met.