Potassium hydrogencarbonate

Eye irritation

Administrative data

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:

other: Test procedure according to national (US) standards comparable to international guidelines

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1984

Report date:

1984

Materials and methods

Test guideline

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

Test material

Test material information

Constituent 1

Reference substance name:

Potassium hydrogencarbonate

EC Number:

206-059-0

EC Name:

Potassium hydrogencarbonate

Cas Number:

298-14-6

Molecular formula:

CH2O3.K

IUPAC Name:

potassium hydrogen carbonate

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: not reported
- Age at study initiation: not reported
- Weight at study initiation: 2.55 - 3.33 kg
- Housing: not reported
- Diet: ad libitum, Ssniff K, laboratory rabbit chow (Ssniff Versuchstier-Diäten GmbH, 4770 Soest/ Westfalen, Germany)
- Water: tap water, ad libitum
- Acclimation period: not reported


ENVIRONMENTAL CONDITIONS
- Temperature (°C): not reported
- Humidity (%): not reported
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): not reported

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: 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 male rabbits

Details on study design:

The animals were treated with 0.1 ml of the test article, 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 %.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal: #1, #2, #3, #4, #5, #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 2

Irritation parameter:

iris score

Basis:

animal: #1, #2, #3, #4, #5, #6

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 3

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 3 days

Results 4

Irritation parameter:

conjunctivae score

Basis:

animal: #2, #6

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

not fully reversible within: 7 day in one animal

Remarks on result:

other: no observation beyond 7 days, clear tendency to reversibility from day 4 onward

Results 5

Irritation parameter:

conjunctivae score

Basis:

animal: #3, #4

Time point:

24/48/72 h

Score:

1.67

Max. score:

3

Reversibility:

not fully reversible within: 7 day in one animal

Remarks on result:

other: no observation beyond 7 days, clear tendency to reversibility from day 3 onward

Results 6

Irritation parameter:

conjunctivae score

Basis:

animal #5

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 7 days

Results 7

Irritation parameter:

chemosis score

Basis:

animal: #1, #4

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 2 days

Results 8

Irritation parameter:

chemosis score

Basis:

animal: #3, #6

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 4 days

Results 9

Irritation parameter:

chemosis score

Basis:

animal #5

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 3 days

Results 10

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 4 days

Irritant / corrosive response data:

No effects on iris were observed. 1/6 animals showed a transient corneal opacity score 1 one hour after substance application. Mild or moderate conjunctival redness and discharge and moderate or severe chemosis were observed in all animals at the first scoring one hour after substance instillation (conjuncival redness score 1 in 2/6 and score 2 in 4/6 animals, chemosis score 2 score in 5/6 and score 3 in 1/6 animals, discharge score 1 in 5/6 and score 2 in 1/6 animals). A tendency to reversibility was seen from scoring at day 1 onward. All animals were free of corneal opacity one day after treatment. Conjunctival redness was fully reversible in 4/6 animals and almost reversible in the remaining 2/6 animals within the observation period of 7 days. Chemosis and discharge were fully reversible in all animals at day 4.

Any other information on results incl. tables

rritant/corrosive response data for each animal at each observation time

Score at time point / Reversibility	Cornea		Iris	Conjunctivae	Chemosis	Discharge
	Max. score: 4	Area affected	Max. score: 2	Max. score: 3	Max. score: 4	Max.score: 3
1 hour	1/0/0/0/0/0	4/0/0/0/0/0	0/0/0/0/0/0	2/2/2/2/1/1	2/3/2/2/2/2	1/1/1/1/1/2
Day 1 (24 hours)	0/0/0/0/0/0	0/0/0/0/0/0	0/0/0/0/0/0	1/2/2/2/1/2	1/2/1/1/2/2	0/1/1/0/1/1
Day 2 (48 hours)	0/0/0/0/0/0	0/0/0/0/0/0	0/0/0/0/0/0	1/2/2/2/1/2	0/2/1/0/2/1	0/1/1/0/1/1
Day 3 (72 hours)	0/0/0/0/0/0	0/0/0/0/0/0	0/0/0/0/0/0	0/2/1/1/1/2	0/2/1/0/0/0	0/0/1/0/0/0
Day 4	0/0/0/0/0/0	0/0/0/0/0/0	0/0/0/0/0/0	0/1/1/1/1/1	0/0/0/0/0/0	0/0/0/0/0/0
Day 7	0/0/0/0/0/0	0/0/0/0/0/0	0/0/0/0/0/0	0/1/1/0/0/0	0/0/0/0/0/0	0/0/0/0/0/0
Average 24h, 48h, 72h	0/0/0/0/0/0	0/0/0/0/0/0	0/0/0/0/0/0	0.67/2/1.67/1.67/1/2	0.33/2/1/0.33/1.33/1	0/0.67/1/0/0.67/0.67
Reversibility #	c		c	n*	c	c

#  Reversibility: c. = completely reversible; n.c.= not completely reversible; n. = not reversible

* The observation time did not extend beyond 7 days, even through slight eye responses were still present at that time, therefore, the reversibility of the eye effects cannot be proved. However, ocular lesions showed a clear tendency of reversibility. At study termination, reversibility was complete in 4/6 animals and almost complete in the remaining 2/6 animals. Therefore, a full reversibility in all animals is very likely if the observation period would have been extended to 21days, as required according to recent guidelines.

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

1h: MTS = 13.3

1d: MTS = 7.7

2d: MTS = 6.7

3d: MTS = 3.7

4d: MTS = 1.7

7d: MTS = 0.7

Maximum Mean Total Score (MMTS) possible: 110)

Based on these mean scores, according to the classification scheme of Kay and Calandra the test item was considered to be mild irritating (class 4 of maximum possible 8) by the study authors.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Judgment 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, in consideration of reversibility.
Test substance induced neither substantial corneal opacity nor iritis. Mean values of eye response at 24, 48 and 72 h for conjunctival redness and chemosis were less than those triggering a classification according to CLP Regulation (EC) No 1272/2008 and reversibility of effects can be assumed. Therefore, no classification for serious eye damage/eye irritation is justified for test substance "Kaliumbikarbonat" (potassium hydrogencarbonate) according to Regulation (EC) No 1272/2008.

Executive summary:

In a primary eye irritation study according to FDA (Appraisal of the Safety of Chemicals in Food, Drugs and Cosmetics, 1959), 0.1 ml of test substance "Kaliumbikarbonat" (potassium hydrogencarbonate) 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. No effects on iris were observed. 1/6 animals showed a transient corneal opacity score 1 one hour after substance application. Mild or moderate conjunctival redness and discharge and moderate or severe chemosis were observed in all animals at the first scoring one hour after substance instillation (conjuncival redness score 1 in 2/6 and score 2 in 4/6 animals, chemosis score 2 score in 5/6 and score 3 in 1/6 animals, discharge score 1 in 5/6 and score 2 in 1/6 animals). A tendency to reversibility was seen from scoring at day 1 onward. All animals were free of corneal opacity one day after treatment. Conjunctival redness was fully reversible in 4/6 animals and almost reversible in the remaining 2/6 animals within the observation period of 7 days. Chemosis and discharge were fully reversible in all animals at day 4. The observation time did not extend beyond 7 days, even through slight eye responses were still present at that time. Sinve, ocular lesions showed a clear tendency of reversibility, there are no indications that these effects would not be reversible after 21 days. At study termination, reversibility was complete in 4/6 animals and almost complete in the remaining 2/6 animals. Therefore, a full reversibility in all animals is very likely if the observation period would have been extended to 21days, as required according to recent guidelines. Test substance induced neither substantial corneal opacity nor iritis. Mean values of eye response at 24, 48 and 72 h for conjunctival redness and chemosis were less than those triggering a classification according to CLP Regulation (EC) No 1272/2008. Study was terminated at study day 7 before ocular lesions fully reversed in all animals. However, fully reversibility can be assumed. Therefore, the test substance “Kaliumbikarbonat” (potassium hydrogencarbonate) was considered not irritating.

According to the eye irritation/corrosion test guidelines EU Method B.5 and OECD TG 405 stipulated in COUNCIL REGULATION (EC) No 440/2008, observation to full reversibility or 21 days is claimed. This is not fulfilled by this study, since study was terminated before eye effects completely reversed in all animals.However, complete reversibility can be assumed from healing process.

No classification for serious eye damage/eye irritation is justified for "Kaliumbikarbonat" (potassium hydrogencarbonate) according to the following regulations:

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

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