Potassium carbonate

Endpoint summary

Description of key information

Potassium carbonate has an intrinsic  irritating activity.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

other: FDA, Appraisal of the Safety of Chemicals in Food, Drugs and Cosmetics, 1959

Principles of method if other than guideline:

Test substance was applied to two sites per animal, on an abraded and an intact site, and held under occlusive dressing for 24 hours

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: H. Fortkamp, 4540 Lengerich
- Age at study initiation: 11 -17 weeks, male
- Weight at study initiation: 2.60 - 2.98 kg
- Housing: individual in screen bottom cages
- Diet: ad libitum, Ssniff K, laboratory rabbit chow (Ssniff Versuchstier-Diäten GmbH, 4770 Soest/ Westfalen, Germany)
- Water: tap water, ad libitum
- Acclimation period: 6 days


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

Type of coverage:

occlusive

Preparation of test site:

other: shaved, one site abraded, one site intact

Vehicle:

physiological saline

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 mg test substance per application site (as delivered by the sponsor), moistened with physiological saline

Duration of treatment / exposure:

24 hours

Observation period:

72 hours

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm
- % coverage: trunk
- Type of wrap if used: occlusive

The dorsal area of the trunk of six rabbits was clipped one day before treatment with an electric clipper (Aesulap Favorita II).
Before start of treatment the right sites of each animal were scarified to induce a lesion of stratum corneum, without cause of bleeding or injury of the dermis.
A portion of 500 mg test substance was moistened with physiological saline and applied to each of the test sites, one abraded and one intact per animal and covered with a 2.5 x 2.5 cm gauze patch.
The gauze patch was secured with a self-adhesive, occlusive dressing. After 24 hours the coverings were removed and remaining test substance was wiped off with a disposal paper. Animals were examined for signs of erythema and edema one to two hours, and 48 hours after patch removal.

SCORING SYSTEM: as stipulated by Draize (1959)

Irritation parameter:

erythema score

Remarks:

intact skin

Basis:

animal: 1-6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: no reading at 48 h

Irritation parameter:

edema score

Remarks:

intact skin

Basis:

animal: 1-6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: no reading at 48 h

Irritant / corrosive response data:

Intact skin: sites were free of erythema and edema at both readings 24 and 72 hours after substance application (= 1 and 48 hour(s) after patch removal).
Abraded skin: a dark brown discoloration with moderate red edges (score 4) was observed at the 24 and 72 hours readings (= 1 and 48 hour(s) after patch removal) in all animals. These findings were interpreted by the study authors as necrosis, and were accompanied by slight edema (score 2) at the 24 hours reading.

Irritation parameter results

Irritation parameter	Basis	Mean score		Remarks
		24 hr	72 hr
edema	animal: #1, #2, #3, #4, #5, #6	0	0	intact skin
erythema	animal: #1, #2, #3, #4, #5, #6	0	0	intact skin
edema	animal: #1, #2, #3, #4, #5, #6	2	0	abraded skin
erythema	animal: #1, #2, #3, #4, #5, #6	4	4	abraded skin

Intact skin: all readings were 0.

Abraded skin: 24 hours reading (= 1 hour after patch removal): erythema Score 4 in 6/6 animals; edema score 2 in 6/6 animals

72 hours reading (= 48 hours after patch removal): erythema Score 4 in 6/6 animals; edema score 0 in 6/6 animals

Average skin irritation index (Primary Dermal Irritation Index (PDII), maximal possible index of 8) calculated by the study authors: 2.5. Effects on intact and abraded skin were included in the index calculation.

Based on this Index the test item was considered to be a moderate skin irritant by the study authors.

Scheme for interpretation of results used by the study authors:

Primary Skin Irritation Score (PDII)

0 : non irritant

> 0.- 2: mild irritant

> 2 - 5: moderate irritant

> 5: severe irritant

Interpretation of results:

GHS criteria not met

Conclusions:

Classification is based on erythema/eschar and oedema of intact skin calculated as mean scores following grading at 1 and 48 hour(s) after removal of the test material, in consideration of reversibility.
According to CLP, EU GHS (Regulation (EC) No 1272/2008) "potash hydrate" is classified as non skin irritant.

Executive summary:

In a primary dermal irritation study according to FDA, Appraisal of the Safety of Chemicals in Food, Drugs and Cosmetics, 1959, six New Zealand White rabbits were dermally exposed to 500 mg of test substance “potash hydrate” per test site. The substance was administered for 24 hours to abraded and intact shaved body surface areas of 2.5 cm² each under occlusive conditions. Animals then were observed for further 48 hours. Irritation was scored by the method stipulated by Draize 1959 one to two hours, and 48 hours after patch removal (= 24 and 72 hours readings).

The intact skin sites were free of erythema and edema at both readings 24 and 72 hours after substance application.

According to the skin irritation/corrosion test guidelines EU Method B.4 and OECD TG 404 stipulated in COUNCIL REGULATION (EC) No 440/2008, only intact skin should be treated. Therefore, reactions of abraded skin are not included in the classification given above.

In this study, test substance "potash hydrate" is not a dermal irritant.

No classification for acute dermal irritation/corrosion is justified for "potash hydrate" according to the following regulations:

• EU-GHS, Regulation (EC) No 1272/2008 (CLP)

• OECD GHS, (2nd rev. edition, UN, 2007)

Reference 2

Endpoint:

skin irritation: in vivo

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: FDA, Appraisal of the Safety of Chemicals in Food, Drugs and Cosmetics, 1959

Principles of method if other than guideline:

Test substance applied to two sites per animal, on an abraded and an intact site, and held under occlusive dressing for 24 hours.

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: H. Fortkamp, 4540 Lengerich
- Age at study initiation: 11 -17 weeks, male
- Weight at study initiation: 2.58 - 2.94 kg
- Housing: individual in screen bottom cages
- Diet: ad libitum, Ssniff K, laboratory rabbit chow (Ssniff Versuchstier-Diäten GmbH, 4770 Soest/ Westfalen, Germany)
- Water: tap water, ad libitum
- Acclimation period: 6 days


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

Type of coverage:

occlusive

Preparation of test site:

other: shaved, one site abraded, one site intact

Vehicle:

physiological saline

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 mg test substance per application site (as delivered by the sponsor), moistened with physiological saline

Duration of treatment / exposure:

24 hours

Observation period:

72 hours

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm
- % coverage: trunk
- Type of wrap if used: occlusive

The dorsal area of the trunk of six rabbits was clipped one day before treatment with an electric clipper (Aesulap Favorita II).
Before start of treatment the right sites of each animal were scarified to induce a lesion of stratum corneum, without cause of bleeding or injury of the dermis.
A portion of 500 mg test substance was moistened with physiological saline and applied to each of the test sites, one abraded and one intact per animal and covered with a 2.5 x 2.5 cm gauze patch.
The gauze patch was secured with a self-adhesive, occlusive dressing. After 24 hours the coverings were removed and remaining test substance was wiped off with a disposal paper. Animals were examined for signs of erythema and edema one to two hours, and 48 hours after patch removal.

SCORING SYSTEM: as stipulated by Draize (1959)

Irritation parameter:

erythema score

Remarks:

intact skin

Basis:

animal: 1-6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: no reading at 48 h

Irritation parameter:

edema score

Remarks:

intact skin

Basis:

animal: 1-6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: no reading at 48 h

Irritant / corrosive response data:

Intact skin: sites were free of erythema and edema at both readings 24 and 72 hours after substance application (= 1 and 48 hour(s) after patch removal).
Abraded skin: a dark brown discoloration with moderate red edges (score 4) was observed at the 24 and 72 hours readings (= 1 and 48 hour(s) after patch removal) in all animals. These findings were interpreted by the study authors as necroses, and were accompanied by slight edema (score 2) at the 24 hours reading.

Irritation parameter results

Irritation parameter	Basis	Mean score		Remarks
		24 hr	72 hr
edema	animal: #1, #2, #3, #4, #5, #6	0	0	intact skin
erythema	animal: #1, #2, #3, #4, #5, #6	0	0	intact skin
edema	animal: #1, #2, #3, #4, #5, #6	2	0	abraded skin
erythema	animal: #1, #2, #3, #4, #5, #6	4	4	abraded skin

Intact skin: all readings were 0.

Abraded skin: 24 hours reading (= 1 hour after patch removal): erythema Score 4 in 6/6 animals; edema score 2 in 6/6 animals

72 hours reading (= 48 hours after patch removal): erythema Score 4 in 6/6 animals; edema score 0 in 6/6 animals

Average skin irritation index (Primary Dermal Irritation Index (PDII), maximal possible index of 8) calculated by the study authors: 2.5.

Effects on intact and abraded skin were included in the index calculation.

Based on this Index the test item was considered to be a moderate skin irritant by the study authors.

Scheme for interpretation of results used by the study authors:

Primary Skin Irritation Score (PDII)

0 : non irritant

> 0.- 2: mild irritant

> 2 - 5: moderate irritant

> 5: severe irritant

Interpretation of results:

GHS criteria not met

Conclusions:

Classification is based on erythema/eschar and oedema of intact skin calculated as mean scores following grading at 1 and 48 hour(s) after removal of the test material, in consideration of reversibility.
According to CLP, EU GHS (Regulation (EC) No 1272/2008) "potash-calc." is classified as non skin irritant.

Executive summary:

In a primary dermal irritation study according to FDA, Appraisal of the Safety of Chemicals in Food, Drugs and Cosmetics, 1959, six New Zealand White rabbits were dermally exposed to 500 mg of test substance “potash-calc.” per test site. The substance was administered for 24 hours to abraded and intact shaved body surface areas of 2.5 cm² each under occlusive conditions. Animals then were observed for further 48 hours. Irritation was scored by the method stipulated by Draize 1959 one to two hours, and 48 hours after patch removal (= 24 and 72 hours readings).

The intact skin sites were free of erythema and edema at both readings 24 and 72 hours after substance application.

According to the skin irritation/corrosion test guidelines EU Method B.4 and OECD TG 404 stipulated in COUNCIL REGULATION (EC) No 440/2008, only intact skin should be treated. Therefore, reactions of abraded skin are not included in the classification given above.

No classification for acute dermal irritation/corrosion is justified for "potash-calc." according to the following regulations:

• EU-GHS, Regulation (EC) No 1272/2008 (CLP)

• OECD GHS, (2nd rev. edition, UN, 2007)

Reference 3

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1993-01-22 to 1993-01-30

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, Skin Irritation

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Davidson's Mill Farm, S. Brunswick, NJ, USA
- Age at study initiation: no data in study summary
- Weight at study initiation: no data in study summary
- 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: animals were acclimated, no further 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

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

water

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 mg test substance per application site (as delivered by the sponsor), moistened with distilled water

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure: 6 cm²
- % coverage: scapular to the lumbar region
- Type of wrap if used: semi-occlusive

A sample of Biocode #5654, Lot #1244Ml was received from the sponsor on January 20, 1993. The sample was moistened with distilled water prior to
application and applied to the skin of six rabbits.
Six healthy New Zealand Albino rabbits were acclimated to the test environment and then clipped free of hair from the scapular to the lumbar region. One 6 cm2 intact site on each rabbit was treated with 0.5 grams of the test substance. The sites were covered with a semiocclusive dressing for approximately 4 hours at which time the patches were removed and the sites were wiped clean. The sites were scored for erythema and edema at 1, 24, 48 and 72 hours after patch removal.

SCORING SYSTEM: most probably Draize (no data in available study summary)

Irritation parameter:

erythema score

Basis:

animal: #1

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

erythema score

Basis:

animal: #2, #3, #4, #5, #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal: #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

edema score

Basis:

animal: #2, #3, #4, #5, #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

One hour after patch removal all animals exhibited very slight to well-defined erythema and 2 rabbits had very slight to slight edema. The incidence and severity of irritation decreased with time. Very slight erythema and edema was noted at only one site at 24 hours. By 72 hours all treated sites were free from all dermal irritation.

Other effects:

All animals appeared active and healthy. Apart from skin irritation, there were no signs of gross toxicity, adverse pharmacologic effects or abnormal behaviour.

Interpretation of results:

GHS criteria not met

Conclusions:

Classification is based on erythema/eschar and oedema of intact skin calculated as mean scores following grading at 24, 48 and 72 hours after removal of the test material, in consideration of reversibility.
According to CLP, EU GHS (Regulation (EC) No 1272/2008) test substance "Biocode #5654" ( Potassium Carbonate) is classified as non skin irritant.

Executive summary:

In a primary dermal irritation study according to US EPA Pesticide Assessment Guidelines, Subdivision F, Hazard Evaluation: Human and Domestic Animals, November 1984, Acute Exposure, Skin Irritation, six New Zealand White rabbits were dermally exposed to 500 mg of test substance "Biocode #5654" ( Potassium Carbonate) per test site. The substance was administered for 4 hours to intact shaved body surface areas of 6 cm² each under semiocclusive conditions. Animals then were observed for further 72 hours. Irritation was scored by the method of Draize for erythema and edema at 1, 24, 48 and 72 hours after patch removal.

One hour after patch removal all animals exhibited very slight to well-defined erythema and 2 rabbits had very slight to slight edema. The incidence and severity of irritation decreased with time. Very slight erythema and edema was noted at only one site at 24 hours. By 72 hours all treated sites were free from all dermal irritation.

All animals appeared active and healthy. Apart from skin irritation, there were no signs of gross toxicity, adverse pharmacologic effects or abnormal behaviour.

In this study, test substance "Biocode #5654" ( Potassium Carbonate) is not a dermal irritant.

No classification for acute dermal irritation/corrosion is justified for "Biocode #5654" ( Potassium Carbonate)

according to the following regulations:

• EU-GHS, Regulation (EC) No 1272/2008 (CLP)

• OECD GHS, (2nd rev. edition, UN, 2007)

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

2010-05-07 to 2010-08-03

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying Ocular Corrosives and Severe Irritants)

Version / remarks:

07 September 2009

Deviations:

no

Principles of method if other than guideline:

In this assay the quantitative measurements of changes in corneal opacity and permeability with an opacitometer and a visible light spectrophotometer are used to evaluate the potential irritancy of a test substance. The two endpoints corneal opacity and permeability are combined to give a final in vitro irritation score (IVIS) related to five categories of irritancy: non irritant, mild, moderate, severe/ corrosive (INVITTOX Protocol No. 127, 2009). As discussed above alkaline substances increase the measured opacity which would lead to an over predictive rating in the case of potash.

GLP compliance:

yes

Species:

cattle

Details on test animals or tissues and environmental conditions:

Isolated corneas from the eyes of cows and bulls with the age of 24-30 month and free of macroscopically visible defects.
Supplier: Slaughterhouse "Klaus Grandits"; A-2860 Kichschlag, Austria

Vehicle:

water

Controls:

yes, concurrent positive control

yes, concurrent negative control

Amount / concentration applied:

Experiment I: 50%, 20%, 10% and 5%
Experiment II: 3%, 1%, 0.1% and 0.03%

Duration of treatment / exposure:

4 hours

Observation period (in vivo):

5.5 hours (duration of treatment plus post exposure time)

Number of animals or in vitro replicates:

3 isolated corneas per concentration

Details on study design:

Fresh isolated and quality checked corneas were mounted in cornea holders and the initial opacity was determined. After equilibration 750 µl of the test substance preparation were topically administered to 3 isolated bovine corneas to the epithelial surfaces for 4 hours and final opacity was measured. Then 1 ml of a fluorescein solution was added on the epithelial site and permeability was measured after 90 minutes.
In each experiment two groups of 3 corneas each served as positive and negative controls. Both control substances (negative control: sterile aqua dest., positive control: 20 % imidazole) were administered under identical conditions as the test substance.

Finally the IVIS (In Vitro Irritancy Score) was calculated as follows:
IVIS = mean opacity value + (15 x mean permeability)

The opacity and mean permeability values were corrected for background opacity and the negative control permeability values. The mean opacity value results from subtraction of final opacity from initial opacity.

A substance that induces an IVIS>/= 55.1 is defined as ocular corrosive or severe irritant.

Irritation parameter:

in vitro irritation score

Run / experiment:

Potassium carbonate 50%

Value:

118.3

Negative controls validity:

valid

Positive controls validity:

valid

Irritation parameter:

in vitro irritation score

Run / experiment:

Potassium carbonate 20%

Value:

97

Negative controls validity:

valid

Positive controls validity:

valid

Irritation parameter:

in vitro irritation score

Run / experiment:

Potassium carbonate 10%

Value:

98

Negative controls validity:

valid

Positive controls validity:

valid

Irritation parameter:

in vitro irritation score

Run / experiment:

Potassium carbonate 5%

Value:

160.7

Negative controls validity:

valid

Positive controls validity:

valid

Irritation parameter:

in vitro irritation score

Run / experiment:

Potassium carbonate 3.0 %

Value:

72.1

Negative controls validity:

valid

Positive controls validity:

valid

Irritation parameter:

in vitro irritation score

Run / experiment:

Potassium carbonate 1%

Value:

57.4

Negative controls validity:

valid

Positive controls validity:

valid

Irritation parameter:

in vitro irritation score

Run / experiment:

Potassium carbonate 0.3%

Value:

6.1

Negative controls validity:

valid

Positive controls validity:

valid

Irritation parameter:

in vitro irritation score

Run / experiment:

Potassium carbonate 0.1%

Value:

3.6

Negative controls validity:

valid

Positive controls validity:

valid

Irritation parameter:

in vitro irritation score

Run / experiment:

Potassium carbonate 0.03%

Value:

1.9

Negative controls validity:

valid

Positive controls validity:

valid

Other effects / acceptance of results:

IVIS of the negative control was 6.5 in experiment I and 3.3 in experiment II and for the positive control 111.8 (experiment I) and 105.8 (experiment II), thus demonstrating the validity of experiments.

Test Results

 

Test Concentration	IVIS	in vitro Rating	Classification
Potassium carbonate 3.0 %	72,1	corrosive	Eye Irritation Cat. 1, H319
Potassium carbonate 1.0 %	47,7	moderate eye irritant	no prediction can be made
Potassium carbonate 0.3 %	6,0	mild eye irritant	no prediction can be made
Potassium carbonate 0.1 %	3,6	mild eye irritant	no prediction can be made
Potassium carbonate 0.03 %	1,9	non eye irritant	no classification

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

In conclusion, the results of the performed BCOP test are considered to support the rating of potassium carbonate as severe irritant, but not as corrosive.

Executive summary:

For animal welfare reasons no additional animal tests have been performed to set specific concentration limits. Instead the specific concentration limits could be established with an alternative approach by using the BCOP assay.

 

Proposed specific concentration limits for the endpoint eye irritation:

C ≥ 3 % :        Eye irritation cat.2, H319 - Causes serious eye irritation

 

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

other: FDA, Appraisal of the Safety of Chemicals in Food, Drugs and Cosmetics, 1959

Principles of method if other than guideline:

Draize Test

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: H. Fortkamp, 4540 Lengerich
- Age at study initiation: 11 -17 weeks, male
- Weight at study initiation: 2.51 - 3.30 kg
- Housing: individual in screen bottom cages
- Diet: ad libitum, Ssniff K, laboratory rabbit chow (Ssniff Versuchstier-Diäten GmbH, 4770 Soest/ Westfalen, Germany) ad libitum
- Water: tap water, ad libitum
- Acclimation period: 7 days


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

Vehicle:

unchanged (no vehicle)

Controls:

other: The untreated eye served as control

Amount / concentration applied:

undiluted
Amount applied: 0.1 mL

Duration of treatment / exposure:

eyes were not rinsed.

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

6

Details on study design:

The animals were treated with the test article as delivered by the spnsor, which was instilled into the conjunctival sac of the left eye after gently pulling the lower lid away from the eyeball. The lid was then gently held together for about one to two seconds, afterwards animals were returned to their cages.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM:
- as stipulated by Draize 1959 and guideline for acute eye irritation of US Interagency Regulatory Liaison Group (IRLG) Testing Standards and Guidelines Work Group (January 1981)

READINGS:
- 1 hour, 1, 2, 3, 4 and 7 days after instillation of test substance

TOOL USED TO ASSESS SCORE:
- 24 hours before treatment eyes were examined for lesions after application of fluorescein 0.15 %.

Irritation parameter:

cornea opacity score

Basis:

animal: 1, 2, 4, 5

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 7 d (= end of observation period)

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #6

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 7 d (= end of observation period)

Irritation parameter:

iris score

Basis:

animal: 1, 2, 4, 5, 6

Time point:

24/48/72 h

Score:

>= 1 - <= 1.33

Max. score:

2

Reversibility:

not fully reversible within: 7 d (= end of observation period)

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

animal: 1-6

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

not fully reversible within: 7 d (= end of observation period)

Irritation parameter:

chemosis score

Basis:

animal: 1, 2, 4, 6

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 7 d (= end of observation period)

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 7 d (= end of observation period)

Irritation parameter:

chemosis score

Basis:

animal #5

Time point:

24/48/72 h

Score:

2.67

Max. score:

4

Reversibility:

not fully reversible within: 7 d (= end of observation period)

Irritant / corrosive response data:

Moderate to serious effects on cornea, iris and conjunctiva were observed but no clear proof that this is not reversible after 21 days was obtained.
For details refer to "remarks on results".

Potash Eye Irritation mean values

Time point after treatment	Mean Values
	Cornea score opacity	Iris score	Conjunctiviae score
			redness	chemosis
1 hour	2	0	3	4
1day	2	0,8	3	3
2 days	2	0,8	3	3,5
3 days	2	1,5	3	3,5
4 days	2	1,4	3	3,2
7 days	2,8	1	3	2,8

Remark: no observations was made after 7 days

 

Scoring system

Score	Cornea score opacity	Iris score	Conjunctiviae score
			redness	chemosis
1	no opacity	normal	no redness	no swelling
2	single, slight opacity	morphologic changes	slight redness	slight swelling
3	diffuse opacity	tissue destruction	clear redness	clear swelling
4	distinct opacity	n.a.	strong redness	strong swelling

n.a. = not applicable

Mean Total Scores (MTS) according to Kay and Calandra were calculated and used for classification by the study authors:

1h: MTS = 48.0

1d: MTS = 50.5

2d: MTS = 51.2

3d: MTS = 61.2

4d: MTS = >/= 68.8

7d: MTS = >/= 74.3

Maximum Mean Total Score (MMTS) possible: 110)

Based on these mean scores, the test item was considered to be seriously irritating by the study authors.

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

Classification is based on effects on the cornea, iris and conjunctiva calculated as mean scores following grading at 24, 48 and 72 hours after instillation of the test material. The observation time did not extend beyond 7 days, therefore the reversibility of the effects could not be evaluated. As conclusion from this study, there are indications of severe eye irritation but no clear proof that this is not reversible over 21 days.

Executive summary:

In a primary eye irritation study according to FDA (Appraisal of the Safety of Chemicals in Food, Drugs and Cosmetics, 1959), the moistened test substance “potash-hydrate” was instilled into the conjunctival sac of 6 male New Zealand White rabbits. The eyes were not rinsed after substance application. Animals then were observed for 7 days. Irritation was scored by the method of Draize.

One hour after the application of the test item clear irritation of the eyes was observed. All animals showed conjunctival redness (mean score 3) and chemosis (mean score 4), accompanied by moderate secretion (score 2) and all but one animals a moderate corneal opacity. In addition, 5/6 animals developed an iritis. By the end of the observation period of seven days, effects decreased or remained as it. At day 7, all animals showed still moderate conjunctival redness and slight to marked chemosis, accompanied by secretion (score 1, 2 or 3). Corneal pannus formation was present in two animals. Five of the six animals had still an opacity of the cornea of different occurence (score 0, 1, 4).

The observation time did not extend beyond 7 days, even though eye responses were still present at this time, since the test protocol followed did not demand a longer observation period at the time the study was performed.

The mean scores of observed chemosis and iris effects decreased within the observation period of seven days. The monitored changes on conjunctivial redness stayed unchanged during the study period and the corneal opacity worsened slightly. Nevertheless, no clear proof that the observed effects are not reversible after 21 days has been obtained.

Reference 3

Endpoint:

eye irritation: in vivo

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: FDA, Appraisal of the Safety of Chemicals in Food, Drugs and Cosmetics, 1959

Principles of method if other than guideline:

Draize Test

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: H. Fortkamp, 4540 Lengerich
- Age at study initiation: 11 -17 weeks, male
- Weight at study initiation: 2.57 - 2.85 kg
- Housing: individual in screen bottom cages
- Diet: ad libitum, Ssniff K, laboratory rabbit chow (Ssniff Versuchstier-Diäten GmbH, 4770 Soest/ Westfalen, Germany) ad libitum
- Water: tap water, ad libitum
- Acclimation period: 7 days


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

Vehicle:

unchanged (no vehicle)

Controls:

other: The untreated eye served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
- Concentration (if solution): instilled undiluted in the original state as delivered by the sponsor

Duration of treatment / exposure:

eyes were not rinsed.

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

6

Details on study design:

The animals were treated with the test article (as delivered by the sponsor), which was instilled into the conjunctival sac of the left eye after gently pulling the lower lid away from the eyeball. The lid was then gently held together for about one to two seconds, afterwards animals were returned to their cages.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM:
- as stipulated by Draize 1959 and guideline for acute eye irritation of US Interagency Regulatory Liaison Group (IRLG) Testing Standards and Guidelines Work Group (January 1981)

READINGS:
- 1 hour, 1, 2, 3, 4 and 7 days after instillation of test substance

TOOL USED TO ASSESS SCORE:
- 24 hours before treatment eyes were examined for lesions after application of fluorescein 0.15 %.

Irritation parameter:

cornea opacity score

Basis:

animal: 1, 2, 6

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 7 d (=end of observation period)

Irritation parameter:

cornea opacity score

Basis:

animal: 3, 4

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 7 d (= end of observation period)

Irritation parameter:

cornea opacity score

Basis:

animal #5

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 d

Irritation parameter:

iris score

Basis:

animal: 1-6

Time point:

24/48/72 h

Score:

1.33

Max. score:

2

Reversibility:

not fully reversible within: 7 d (= end of observation period)

Remarks:

fully reversible for 50% of the animals

Irritation parameter:

conjunctivae score

Basis:

animal: 1-6

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

not fully reversible within: 7 d (= end of observation period)

Irritation parameter:

chemosis score

Basis:

animal: 1-6

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 7 d (= end of observation period)

Irritant / corrosive response data:

Moderate to serious effects on cornea, iris and conjunctiva were observed, but no clear proof that this is not reversible after 21 days was obtained.

Potash Eye Irritation mean values

Time point after treatment	Mean Values
	Cornea score opacity	Iris score	Conjunctiviae score
			redness	chemosis
1 hour	2,2	2	3	4
1day	2,2	2	3	4
2 days	2,2	2	3	4
3 days	2,2	2	3	4
4 days	1,8	1,7	3	3
7 days	1,8	0,5	2,3	1,8

Remark: no observations was made after 7 days

 

Scoring system

Score	Cornea score opacity	Iris score	Conjunctiviae score
			redness	chemosis
1	no opacity	normal	no redness	no swelling
2	single, slight opacity	morphologic changes	slight redness	slight swelling
3	diffuse opacity	tissue destruction	clear redness	clear swelling
4	distinct opacity	n.a.	strong redness	strong swelling

n.a. = not applicable

Mean Total Scores (MTS) according to Kay and Calandra were calculated and used for classification by the study authors:

1h: MTS = 56.3

1d: MTS = 60.5

2d: MTS = 65.5

3d: MTS = 70.5

4d: MTS = 57.8

7d: MTS = 49.8

Maximum Mean Total Score (MMTS) possible: 110)

Based on these mean scores, the test item was considered to be seriously irritating by the study authors.

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

Classification is based on effects on the cornea, iris and conjunctiva calculated as mean scores following grading at 24, 48 and 72 hours after instillation of the test material. The observation time did not extend beyond 7 days, therefore the reversibility of the effects could not be evaluated. As conclusion from this study, there are indications of severe eye irritation but no clear proof that this is not reversible over 21 days.

Executive summary:

In a primary eye irritation study according to FDA (Appraisal of the Safety of Chemicals in Food, Drugs and Cosmetics, 1959), the moistened test substance "potash-calc." was instilled into the conjunctival sac of 6 male New Zealand White rabbits. The eyes were not rinsed after substance application. Animals then were observed for 7 days. Irritation was scored by the method of Draize.

One hour after the application of the test item clear irritation of the eyes was observed. All animals showed conjunctival redness (mean score 3) and chemosis (mean score 4), accompanied by moderate secretion (score 2) and corneal opacity. In addition all animals developed an iritis. For all observed effects the mean scores decreased within the observation period of seven days. At day 7, all animals showed still slight to moderate conjunctival redness and slight to distinct chemosis, accompanied by secretion (score 1 or 3) in all but one animal. Corneal pannus formation was present in 2/6 animals. Five of the six animals had still an opacity of the cornea of different occurance (score 1 - 3). The iritis was completely reversible in 3/6 animals and had decreased in the other 3 animals to score 1 by day 7.

The observation time did not extend beyond 7 days, even though eye responses were still present at this time, since the test protocol followed did not demand a longer observation period at the time the study was performed. A decrease in severity of some effects was observed until study termination on day 7. No clear proof that the observed effects are not reversible after 21 days has been obtained.

Reference 4

Endpoint:

eye irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Justification for type of information:

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
This read-across hypothesis is based on transformation of the target and source substances to common compounds (scenario 1 of the Read-Across Assessment Framework (RAAF), ECHA, March 2017 - transformation to common compounds). The target substance potassium carbonate as well as the source substances potassium hydrogencarbonate and potassium chloride dissociate in aqueous media to potassium and the respective anion.

For further details, please refer to the Justification for Read-Across attached in Iuclid Chapter 13.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Please refer to the Justification for Read-Across attached in Iuclid Chapter 13.

3. ANALOGUE APPROACH JUSTIFICATION
Please refer to the Justification for Read-Across attached in Iuclid Chapter 13.

4. DATA MATRIX
Please refer to the Justification for Read-Across attached in Iuclid Chapter 13.

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

according to guideline

Guideline:

other: EPA 16 CFR 1500.42

Deviations:

yes

Remarks:

not reported

Species:

rabbit

Strain:

New Zealand White

Vehicle:

unchanged (no vehicle)

Controls:

other: the untreated eye served as control

Amount / concentration applied:

undiluted
Amount applied: 0.1 ml

Observation period (in vivo):

14 days

Details on study design:

The animal`s eye was treated with 0.1 ml of the test article, the untreated eye served as control.

REMOVAL OF TEST SUBSTANCE
Animal group 1 (three animals): rinsed after 4 sec.
Animal group 2(six animals): not rinsed

SCORING SYSTEM:
- as stipulated by Draize

READINGS:
- 1,2,3, 4,7,10 and 14 days after instillation of test substance

TOOL USED TO ASSESS SCORE:
- A fluorescein wash

Remarks on result:

other: results from non-irritating to highly irritating were reported

Remarks:

no detailed results reported

Irritant / corrosive response data:

results from non-irritating to highly irritating were reported in the different studies

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

No detailed information according experimental results is available. On the basis of existing data, sodium carbonate monohydrate is irritating to the eye.
Since soda ash and potash are such similar substances it can be concluded by read across that the argumentation used for soda ash classification also can be used for potash.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Additional information

Reliable animal studies on skin and eye irritation are available for both crystalline modifications of potassium carbonate, hydrate and anhydrate. In addition, human data on eye and skin effects from accidental exposures and an in vitro test on eye irritation are available. Both modifications caused serious irritation when applied in crystalline form to the eyes of rabbits. If applied in moistened crystalline form to scarified skin of rabbits it generated moderate irritations. However, both crystalline forms were not irritating to the intact skin of rabbits, even not after occluded application for 24 hours. In accidental exposures, potassium carbonate induced slight to moderate skin and serious eye irritation which healed under medical treatment completely without permanent damages. The result of an in vitro BCOP-test indicates a serious irritating activity of potassium carbonate to eyes.

According to Regulation (EC) No 1272/2008 primary emphasis shall be placed upon existing human experience and animal testing data.

Considerable clinical symptoms and necropsy findings of respiratory irritation were missing in an acute inhalation study in which the animals were exposed to approximately 5 mg potassium carbonate dust/L for 4.5 h, even though a high amount of the dust was of respirable size. Local reversible respiratory tract irritation reactions have been seen in a sub acute inhalation study, performed with an aqueous scrubbing solution (pH 9.9) containing potassium carbonate as ingredient. Nevertheless, the irritation potential of the scrubbing solution was considered to be caused by the other ingredients as well. In conclusion, under exposure and use conditions potassium carbonate most likely dissociates and develops an alkaline potential- for example in the case of contact with humid mucous membranes or wet skin or if used as aqueous solution - an irritating (to skin) to seriously (to eyes) irritating activity has to be taken into account.

In all three available eye irritation tests, the substance has been applied as a solid. The B5 method states: «The eyes of the test animals should not be washed for at least 24 hours following instillation of the test substance, except for solids ... If the solid test substance has not been removed from the eye of the test animal by physiological mechanisms at the first observation time point of 1 hour after treatment, the eye may be rinsed with saline or distilled water». Therefore, the mechanical friction most possible have added an effect to the observed irritation.

The assessment of irritation data is further supported by read across to the similar substance soda ash (Na₂CO₃) for which a Hera Risk Assessment, a SIDS dossier and an official classification is available. A justification for read-across is attached to iuclid section 13.

The available eye irritation tests for sodium carbonate revealed different results. Studies using a dose of 0.1 ml sodium carbonate monohydrate and sodium carbonate (anhydrous) resulted in a classification of irritating. However, based on a study with a dose of 0.1 g sodium carbonate it was not classified as an ocular irritant. Based on the overall results sodium carbonate is considered as irritating to the eyes. Some of the available eye irritation studies are summarized in the OECD HPV file available on the UNEP website. By evaluating the results it should be considered, that the used scoring system in the U.S. gives results significantly different from the scoring system used for EU classification in the CLP Regulation. For this reason, the irritation estimation drawn from this study cannot be used as such for CLP classification, without raw data re-assessment with the EU scoring system.

Study observation period was 7 days for potash (in the case of soda ash 7 or 14 days), but not 21 days as required by the today’s EU classification rules. For soda ash, some animals showed reversibility of effects at 14 days already, however, data are not sufficient to draw conclusions. For potash, the picture is somehow similar but more scattered. Individual animals showed a decrease of the effects whereas in few animals the effects stayed unchanged until day seven. As conclusion from these studies, there are indications of serious eye irritation but no clear proof that this is not reversible after 21 days. Finally, it should also be realized that sodium and potassium carbonate has been manufactured for more than 100 years and has been used in very high tonnages (consumer, professional and industrial uses), while the human experience does not indicate that irreversible effects on the eyes do occur. Furthermore, for sodium carbonate, the OECD HPV dossier, based on the same studies as cited above, concluded that the substance was irritating to the eyes and not highly irritating. This dossier was approved by many EU member states.

Since soda ash and potash are such similar substances it can be concluded by read across that the argumentation used for soda ash classification also can be used for potash.

The following information is taken into account for any hazard / risk assessment:

Potassium carbonate has an intrinsic irritating activity.

Justification for classification or non-classification

Irritation

Potassium carbonate has an intrinsic irritating activity and has to be labelled accordingly. Based on animal and human data on eye effects and on read across data and argumentations for sodium carbonate, a labelling Cat. 2 is required according to Regulation (EC) No 1272/2008, respectively. In spite of the fact, that potassium carbonate did not cause any irritation on intact skin within the reported animal tests a classification as skin irritant has been considered as a prudent approach. Therefore, for skin effects a labelling with Cat. 2 are ascertained. As consequence of the available data from inhalation studies a labelling with H335 has been deliberated, too.

The activity of potassium carbonate is solely based on alkalinity. In mixtures, the acid reserve of the additional compounds of the mixtures may compensate the alkalinity of potassium carbonate and thus its irritancy. Therefore, with reference to CLP Regulation (EC) No 1272/2008, Annex I, 3.2.3.1.2, for classification of potassium carbonate in mixtures it is justified to take the acid reserve of the mixture into account.

Corrosivity

Potassium carbonate shows indications of intrinsic irritating activity. Serious eye irritation caused by potassium carbonate is documented; however, no clear proof that it is not reversible after 21 days is given due to study design. Furthermore, data from accidental exposure to humans indicate a slight irritation potential to skin and a serious irritation potential to the eyes. In animal studies no irritation potential for intact skin has been documented. The irritating activity of potassium carbonate is solely based on alkalinity. In mixtures, the acid reserve of the additional compounds may compensate the alkalinity of potassium carbonate and herewith its irritancy.

These considerations are supported by read-across to the related substance sodium carbonate (soda ash) for which a Hera Risk Assessment, a SIDS dossier and an official classification is available. In these documents the irritating nature of sodium carbonate is described.

Overall, based on animal and human data regarding eye effects and on read across to the related substance sodium carbonate, according to Regulation (EC) No 1272/2008 classification with eye irritant Cat. 2 in combination with H319 (warning), respectively, is required. For reasons of precaution an additional classification as skin irritant Cat. 2 and as respiratory tract irritant with STOT SE 3 / H335 is ascertained.