Sodium formate

Endpoint summary

Description of key information

Studies of acute oral, dermal and inhalation toxicity are available for sodium formate.

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:

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

Key result

Dose descriptor:

LD50

Effect level:

>= 3 700 - <= 4 700 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 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

Conclusions:

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).

Executive summary:

In a non-standard study, mice fed with a folic acid supplemented diet showed a slightly higher LD50 (4700 mg/kg bw) than mice fed a diet without folic acid supplements (LD50 3700 mg/kg bw).

Reference 2

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:

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

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:

GHS criteria not met

Conclusions:

The acute oral LD50 of sodium formate in the rat is reported to be >3000 mg/kg bw.

Executive summary:

In a scondary source, the acute oral LD50 of sodium formate in the rat is reported to be >3000 mg/kg bw.

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 -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 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 LD50 was 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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Three different reports are in the mouse and rat are available. Studies are of limited quality individually but note very low acute oral toxicity for sodium formate.

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:

comparable to 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 was found to be greater than 0.67 mg/L for a 4-hour inhalation exposure.

Executive summary:

In an acute inhalation toxicity test, five 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 LC50 is greater than 0.67 mg/L for a 4-hour inhalation exposure.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

670 mg/m³ air

Quality of whole database:

A single guideline-compliant study is available for sodium formate

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

Key result

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 of sodium formate was >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 LD50 was > 2000 mg/kg bw (BASF AG, 2007). 

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

A single guideline-compliant study is available for sodium formate

Additional information

Acute oral toxicity

There are several independent sources which, individually are not of high quality but can be used as weight of evidence to 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 LD50 values 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 (Malorny, 1969). A second 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 were 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 in rats was reported to be >3000 mg/kg bw in two other studies (Smith, 1982; Huels, 1989).  Overall, it is concluded that the acute oral LD50 of sodium formate in rats and mice is >2000 mg/kg bw; sodium formate does not therefore require classification for acute oral toxicity according to CLP.

 

Acute inhalation toxicity

In an acute inhalation toxicity study, five 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 LC50 is >0.67 mg/L for a 4-hour inhalation exposure. Sodium formate does not therefore require classification for acute inhalation toxicity according to CLP.

Acute dermal toxicity

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). Sodium formate does not therefore require classification for acute dermal toxicity according to CLP.

Justification for classification or non-classification

Studies of acute oral, dermal and inhalation toxicity are available for sodium formate and demonstrate low toxcity by all routes. Based on the results of the available studies, sodium formate does not require classification for acute toxicity according to the CLP Regulation.