Potassium carbonate

Endpoint summary

Description of key information

Reliable acute toxicity data are available for the oral, dermal and inhalation route. The oral LD50 (rat) is > 2000 mg/kg bw or in the range of 2000 mg/kg bw and the oral LD50 (mice) is 2570 +/- 142 mg/kg bw, the dermal LD50 (rat) is > 2000 mg/kg and the 4.5 h LC50 (rat) is > 4.96 ± 1.14 mg/L. Local irritation reactions to the alkaline salt at the site of application are theoretically possible and have been actually seen around the mouth, the forelimbs and the eyes but not in the deeper respiratory tract in an acute inhalation study, the skin in the acute dermal toxicity study and in one acute oral study at the stomach and intestines after gavage application of lethal dose levels >/= 2000 mg/kg bw. 

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:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

no

Remarks:

prior to GLP settings

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Sulzfeld, Germany
- Age at study initiation: 4 - 7 weeks
- Weight at study initiation: male 105 - 125 g; female 105 - 120 g
- Fasting period before study: over night fasted
- Housing: individual in makrolon cages on bedding
- Diet: ad libitum, R 4 rat laboratory chow, Ssniff Versuchtier-Diäten GmbH, 4770 Soest/ Westfalen
- Water : ad libitum, tap water
- Acclimation period: 2 days


ENVIRONMENTAL CONDITIONS
- Temperature: 20 - 23 °C
- Humidity: 40 - 70 %
- Air changes (per hr): 10 per hour
- Photoperiod (hrs dark / hrs light): 12 hour dark/light cycle

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 100.0 mg/mL in aqua destillata

MAXIMUM DOSE VOLUME APPLIED: 20 mL/kg bw

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes

- Clinical examination was performed 15 and 30 minutes, 1, 2, and 4 hours following dosing and once daily thereafter.

- Body weight measurements: on the day prior to application (study day -1),
at the day of application (study day 0) and on day 7 and 14 after application.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

0/10 animals died

Clinical signs:

other: piloerection during the first 30 minutes after application in all animals

Gross pathology:

no macroscopic findings at necropsy

Other findings:

no data

Interpretation of results:

GHS criteria not met

Conclusions:

On the basis of the results obtained after a single oral administration, the oral LD50 of the test article "potash calc." was determined to be > 2000 mg/kg bw. No significant clinical signs, effects on body weight or gross pathological findings were observed.

Executive summary:

In an acute oral toxicity study (limit test, equivalent to now deleted OECD guideline 401), 5 male and 5 female, fasted Sprague-Dawley rats were given a single oral dose of 2000 mg/kg bw of test substance “potash calc.” and observed for 14 days.

Oral LD₅₀ Males and Females > 2000  mg/kg bw

No mortality occurred in this limit test. Except of piloerection during the first 30 minutes after application in all animals, there were no treatment related clinical signs, necropsy findings or changes in body weight.         

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

no

Remarks:

prior to GLP settings

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Sulzfeld, Germany
- Age at study initiation: 4 - 7 weeks
- Weight at study initiation: male 95 - 120 g; female 100 - 115 g
- Fasting period before study: over night fasted
- Housing: individual in makrolon cages on bedding
- Diet: ad libitum, R 4 rat laboratory chow, Ssniff Versuchtier-Diäten GmbH, 4770 Soest/ Westfalen
- Water: ad libitum, tap water
- Acclimation period: 6 days


ENVIRONMENTAL CONDITIONS
- Temperature: 20 - 23 °C
- Humidity: 40 - 70 %
- Air changes (per hr): 10 per hour
- Photoperiod (hrs dark / hrs light): 12 hour dark/light cycle

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 100.0 mg/mL in aqua destillata

MAXIMUM DOSE VOLUME APPLIED: 20 mL/kg bw

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes

- Clinical examination was performed 15 and 30 minutes, 1, 2, and 4 hours following dosing and once daily thereafter.

- Body weight measurements: on the day prior to application (study day -1),
at the day of application (study day 0) and on day 7 and 14 after application.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

0/10 animals died

Clinical signs:

other: piloerection during the first 30 minutes after application in all animals

Gross pathology:

no macroscopic findings at necropsy

Interpretation of results:

GHS criteria not met

Conclusions:

On the basis of the results obtained after a single oral administration, the oral LD50 of the test article "potash hydrate" was determined to be > 2000 mg/kg bw. No significant clinical signs, effects on body weight or gross pathological findings were observed.

Executive summary:

In an acute oral toxicity study (limit test, equivalent to now deleted OECD guideline 401), 5 male and 5 female, fasted Sprague-Dawley rats were given a single oral dose of 2000 mg/kg bw of test substance “potash hydrate” and observed for 14 days.

Oral LD₅₀ Males and Females > 2000  mg/kg bw

No mortality occurred in this limit test. Except of piloerection during the first 30 minutes after application in all animals, there were no treatment related clinical signs, necropsy findings or changes in body weight gains.         

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:

comparable to guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

other: US EPA Pesticide Assessment Guidelines, Subdivision F, Hazard Evaluation: Human and Domestic Animals, November 1984, Acute Exposure, Inhalation

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hilltop Lab Animals, Scottdale, PA
- Age at study initiation: no data in study summary
- Weight at study initiation: 200 - 223 g
- Fasting period before no data in study summary
- Housing: no data in study summary
- Diet (e.g. ad libitum): no data in study summary
- Water (e.g. ad libitum): no data in study summary
- Acclimation period: no data in study summary


ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data in study summary
- Humidity (%): no data in study summary
- Air changes (per hr): no data in study summary
- Photoperiod (hrs dark / hrs light): no data in study summary

Route of administration:

inhalation: dust

Type of inhalation exposure:

not specified

Details on inhalation exposure:

Prior to aerosolization, the test substance was ground for 24 hours in a ball mill.
Chamber concentration and the particle size distribution of the aerosolized test substance were determined periodically during the exposure period.

The gravimetric chamber concentration was 4 .96 ± 1.14 mg/L with approximately 3 % of the particles below 1 µm and 38 % below
3 µm. The mass median aerodynamic diameter was approximately 3.6 µm.

Particle size distribution was measured by the Andersen Cascade Impactor.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

gravimetric

Duration of exposure:

4.5 h

Concentrations:

4 .96 ± 1.14 mg/L gravimetric chamber concentration

No. of animals per sex per dose:

5 animals per sex/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: no data in study summary
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 4.96 mg/L air (analytical)

Exp. duration:

4.5 h

Remarks on result:

other: SD

Remarks:

4 .96 ± 1.14 mg/L

Mortality:

No mortalities occurred as a result of exposure.

Clinical signs:

other: In-chamber animal observations were limited due to the accumulation of test substance on the walls of the exposure chamber. During the first hour of exposure decreased activity, irregular respiration, hunched posture and lethargy were noted. Upon chamber

Body weight:

All rats gained weight over the 14-day observation period.

Gross pathology:

Gross necropsy findings at terminal sacrifice were generally unremarkable. Apart from red lung discoloration consistent with euthanasia by CO2 inhalation, all tissues and organs appeared normal.

Interpretation of results:

GHS criteria not met

Conclusions:

On the basis of the results obtained after an inhalation exposure of 4.5 h, the LC50 of the test article " Biocode # 5654" was determined to be > 4 .96 ± 1.14 mg/L.

Executive summary:

In an acute inhalation toxicity study performed according to the US EPA Pesticide Assessment Guidelines, Subdivision F, Hazard Evaluation: Human and Domestic Animals, November 1984, Acute Exposure, Inhalation, 5 male and 5 female Sprague-Dawley rats were exposed by inhalation route to aerosolized test article “Biocode # 5654” for 4.5 hours. Test substance was aerosolized after being ground in a ball mill for 24 hours. The gravimetric chamber concentration was 4 .96 ± 1.14 mg/L with approximately 3 % of the particles below 1 µm and 38 % below 3 µm. The mass median aerodynamic diameter (MMAD) was approximately 3.6 µm. Animals were observed for 14 days.

LC₅₀ Combined:  > 4 .96 ± 1.14mg/L air (analytical)

 

No animal died in this study. During the first hour of exposure decreased activity, irregular respiration, hunched posture and lethargy were noted. Within 24 hours the irritative nature of the test substance became evident. Dermal necrosis and corneal opacity were noted in all animals. Damage was most severe around the mouth and on the forelimbs. Aside from these conditions, most animals recovered by day 6. There were no substance related gross necropsy findings at terminal sacrifice.

In this limit test the determined LC₅₀ is > 4 .96 ± 1.14 mg/L air (analytical). As no animal died, it is considered to be appropriate not to classify the substance for acute inhalation toxicity according to CLP, EU GHS (Regulation (EC) No 1272/2008).

EU GHS limit values for acute inhalation toxicity are 1.0 < category 4 ≥ 5.0 mg/L for dust/mist. Furthermore the exposure time was slight increased (4.5 h) when compared with the EU GHS requirement of 4 hours inhalation exposure.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

4 960 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:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

other: US EPA Pesticide Assessment Guidelines, Subdivision F, Hazard Evaluation: Human and Domestic Animals, November 1984, Acute Exposure, Dermal Toxicity

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Davidson's Mill Farm, S. Brunswick, New Jersey
- Age at study initiation: no data in study summary
- Weight at study initiation: no data in study summary
- Fasting period before study: no data in study summary
- Housing: no data in study summary
- Diet (e.g. ad libitum): no data in study summary
- Water (e.g. ad libitum): no data in study summary
- Acclimation period: no data in study summary


ENVIRONMENTAL CONDITIONS
no data in study summary

Type of coverage:

occlusive

Vehicle:

water

Details on dermal exposure:

TEST SITE
- Area of exposure: no data in study summary
- % coverage: no data in study summary
- Type of wrap if used: no data in study summary


REMOVAL OF TEST SUBSTANCE
- Washing (if done): wiped clean of any residual material
- Time after start of exposure: 24 hours


2000 mg/kg bw of the test substance was moistened with distilled water and applied to intact dose sites.

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The rabbits were observed on several occasions and at least once daily.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Remarks on result:

other: no animal died

Mortality:

All animals survived.

Clinical signs:

other: One male exhibited a reduction in food consumption on days 11-12. Apart from the dermal irritation at the dose site of all animals, there were no other signs of gross toxicity, adverse pharmacologic effects or abnormal behavior.

Gross pathology:

Gross necropsy findings at terminal sacrifice were unremarkable. All tissues and organs appeared normal.

Interpretation of results:

GHS criteria not met

Conclusions:

On the basis of the results obtained after a single dermal administration, the oral LD50 of the test article "Biocide #5654, Potassium Carbonate"
was determined to be > 2000 mg/kg bw. All animals survivied. No significant clinical signs, effects on body weight or gross pathological findings were observed apart from dermal irritation at the dose site of all animals.

Executive summary:

In an acute dermal toxicity study performed according to the US EPA Pesticide Assessment Guidelines, Subdivision F, Hazard Evaluation: Human and Domestic Animals, November 1984, Acute Exposure, Dermal Toxicity, 5 male and 5 female young adult New Zealand With rabbits were dermally exposed to the test article "Biocide #5654, Potassium Carbonate" moistened in distilled water for 24 hours at a dose of  2000 mg/kg bw.  Animals then were observed for 14 days.

 

Dermal LD₅₀ Combined:  > 2000 mg/kg bw

 

No animal died in this limit test.       

 

No significant clinical signs or effects on body weight were observed, apart from dermal irritation at the dose site of all animals. There were no treatment related gross necropsy findings at terminal sacrifice. All tissues and organs appeared normal.

 

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

Acute toxicity data are available for the oral, dermal and inhalation route.

Potassium carbonate in its crystalline modifications hydrate and anhydrate was tested for acute toxicity in studies similar to OECD guideline 401 in male and female Sprague-Dawley rats. The LD50 for both potassium carbonate modifications was > 2000 mg/kg bw. Both studies have been performed as limit tests with a single dose of 2000 mg/kg bw. No animal died, body weight gain was not affected and no pathological findings were seen at necropsy in none of the studies. No treatment related clinical signs were observed, except of piloerection during the first 30 minutes after application in all animals (Study director, 1984 a, b).

In a reliable supporting study (Study director, 1998) performed with potassium carbonate according to OECD Guideline 401 in male and female Sprague-Dawley rats, a LD50 of 1983 (95% C.I.: 1769 to 2222) mg/kg bw was determined. Males received single doses of 1183, 2000, and 2600 mg/kg bw, females were only treated with 2000 mg/kg bw. In the dose groups 1183, 2000, and 2600 mg/kg bw 0/5, 5/10 (3 males and 2 females), and 5/5 animals died, respectively. The factor between the dose levels is not the same: the factor between the low dose and the mid dose is higher than between the mid dose and the high dose. Therefore, this choice dose levels will influence the calculation of the LD50 value in a negative way.  Time of death was within 2 days after treatment, first cases were observed 4 hours after dosing in the highest dose group. Animals died, showed marked signs of stomach and intestine corrosion (erosions, congestion and hemorrhages). No macroscopic abnormalities were seen in surviving animals at study termination, except of one animal of the 2000 mg/kg bw group with necrosis, ulcer, and thickened walls of stomach and decreased size of spleen. Sedation or hypoactivity, piloerection and hunched posture were observed in animals treated at the various dose levels, starting 30 minutes to 4 hours after administration. These changes were accompanied by shallow breathing and/or diarrhea in the animals treated at doses of 2000 mg/kg bw or higher. Recovery was archived by days 3-10 after dosing in the surviving animals of the various dose groups.

Slight decrease in body weight or stasis of growth was found in some animals of the various groups mainly at the day 3 weighing. Differences in test conditions to the studies Study director (1984 a,b) consisted in a higher body weight of experimental animals (200 to 284 g compared to 95 to 125 g) and lower application volume (10 ml/kg bw aqueous solution compared to 20 ml/kg bw, which is the more common dose volume for aqueous test substance formulations).

Therefore, the animals died in the study, were dosed with a larger absolute dose and a higher concentrated aqueous formulation than the animals in the studies Study director (1984 a,b), which showed almost no response to the application of a comparable dose per kg bw.

Most probably, gastrointestinal activity of potassium carbonate seen in the study Study director (1998) is due to the alkalinity of the specific compound formulation, not sufficiently neutralized by the stomach acid.

 

Smyth et al. (1969) have published a LD50 for potassium carbonate of 1870 (95% C.I.: 1340-2600) mg/kg bw determined in male Carworth-Wistar rats. Purity of the test substance, mortality, symptoms, and pathological findings were not reported and thus reliability 4 is assigned.

 

In a publication in russian (Babaian et al., 1989), acute oral studies in rats and mice with potassium carbonate has been reported. From the abstract LD50-values of 2980 +/- 142 and 2570 +/- 142 mg/kg bw for rat and mice, respectively, can be derived.

 

In an acute inhalation toxicity study performed according to the US EPA/FIRA Guideline 5 male and 5 female Sprague-Dawley rats were exposed by inhalation route to aerosolized potassium carbonate for 4.5 hours at a chamber concentration of 4 .96 ± 1.14 mg/L. Test substance was aerosolized after being ground in a ball mill for 24 hours. Mass median aerodynamic diameter (MMAD) of the particles in the atmosphere was 3.6 µm. Animals were observed for 14 days. The LC50 was determined to be > 4 .96 ± 1.14 mg/L air (analytical).

No animal died in this study. During the first hour of exposure decreased activity, irregular respiration, hunched posture and lethargy were noted. Within 24 hours the irritative nature of the test substance became evident.Marked skin reactionsand corneal opacity were noted in all animals. Impact was most severe around the mouth and on the forelimbs. Aside from these conditions most animals recovered by day 6. There were no substance related gross necropsy findings at terminal sacrifice.

 

In an acute dermal toxicity study performed according to the US EPA/FIFRA Guideline, 5 male and 5 female young adult New Zealand With rabbits were dermally exposed to potassium carbonate moistened in distilled water for 24 hours at a dose of 2000 mg/kg bw. Animals then were observed for 14 days. The dermal LD50 was determined to be > 2000 mg/kg bw. No animal died in this limit test.

No significant clinical signs or effects on body weight were observed, apart from dermal irritation at the dose site of all animals. There were no treatment related gross necropsy findings at terminal sacrifice. All tissues and organs appeared normal.

 

Conclusion

The oral LD50 (rat) is > 2000 mg/kg bw or in the range of 2000 mg/kg bw and the oral LD50 (mice) is 2570 +/- 142 mg/kg bw. Absence of intrinsic toxic properties of potassium carbonate by oral exposure of humans is generally taken for granted, which is proved by its long-standing safe use in food and pharmaceuticals and its GRAS (generally recognized as safe) status in the USA.

The dermal LD50 (rat) is > 2000 mg/kg and the 4.5 h LC50 (rat) is > 4.96 ± 1.14 mg/L. Beside irritating effects to skin there was no evidence for an intrinsic toxic property after dermal or inhalative exposure. In the acute inhalation study, irritating effects were pronounced around the mouth, the forelimbs and the eyes, whereas considerable clinical symptoms and necropsy findings of respiratory irritation were missing.

 

Justification for classification or non-classification

There is no evidence on an intrinsic acute toxic activity of potassium carbonate after oral, dermal or inhalation exposure.

The LD₅₀ value for the dermal route was determined to be > 2000 mg/kg bw and the oral LD₅₀ values determined in reliable studies were > 2000 mg/kg bw or in the range of 2000 mg/kg bw. The minor lower deviation of the upper limit-value for classification seen in one reliable supporting oral study (actual LD₅₀ of 1987 mg/kg bw) is judged as not relevant in view of a serious health risk to humans and does not substantiate a classification, as the divergence from the results of the other reliable acute oral toxicity tests most probably arised from the dose preparationand the questionable statistical evaluation of the test results as discussed above.

 

In a limit test via inhalation route, the determined LC₅₀ was > 4 .96 ± 1.14 mg/L air (analytical). EU GHS limit values for acute inhalation toxicity are 1.0 < category 4 ≥ 5.0 mg/L for dust/mist. However, as no animal died and furthermore the exposure time was slightly increased (4.5 h) when compared with the EU GHS requirement of 4 hours inhalation exposure, the test result is considered to be adequate not to classify the substance for acute inhalation toxicity according to CLP, EU GHS (Regulation (EC) No 1272/2008).

According to GHS Regulation (EC) No 1272/2008, a classification for acute toxicity of potassium carbonate is not required and labelling is not necessary.