Potassium hydrogencarbonate

Endpoint summary

Description of key information

Reliable, adequate and relevant data from a Buehler sensitisation study according to US EPA/FIFRA Guideline in guinea pigs are available. There was no evidence for a skin sensitisation after challenge with 100 % of potassium hydrogencarbonate. The sensitisation rate was 0 %.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1993-01-21 to 1993-05-03

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Qualifier:

according to guideline

Guideline:

EPA OPP 81-6 (Skin Sensitisation)

Version / remarks:

US EPA Pesticide Assessment Guidelines, Subdivision F, Hazard Evaluation: Human and Domestic Animals, November 1984, Acute Exposure, Guinea Pig Sensitization (Buehler)

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

yes

Remarks:

only 10 instead of 20 animals in treatment group

GLP compliance:

yes

Type of study:

Buehler test

Justification for non-LLNA method:

A valid Buehler test conducted comparable to guideline with acceptable restrictions is available, which is reliable with restrictions and adequate for classification and labelling purposes. Potency estimation is not mandatory when existing guideline and GLP conforming data are available, which were conducted before the new annex of the REACH Regulation entered into force. Moreover, no indication for skin sensitisation was observed in this study, thus, no dose response information is needed. For this reason and for reasons of animal welfare no additional LLNA was conducted.

Species:

guinea pig

Strain:

Hartley

Sex:

not specified

Details on test animals and environmental conditions:

TEST ANIMALS
- Guinea pig strain Crl:(HA)BR
- Source: Charles River Laboratories, Inc., Hazleton Wisconsin facility at 3802 Packers Avenue, Madison, Wisconsin, USA
- Age at study initiation: young adult
- Weight at study initiation: 386 to 504 g
- Housing: individually housed in screen-bottom stainless steel cages
- Diet: ad libitum, Certified Guinea Pig ChoW® #5026, Purina Mills, Inc., USA
- Water: ad libitum
- Acclimation period: at least 7 days


ENVIRONMENTAL CONDITIONS
- Temperature: 19 to 24°C
- Humidity19 to 65% Relative Humidity
- Air changes (per hr): no data in study summary
- Photoperiod (hrs dark / hrs light): no data in study summary

Route:

epicutaneous, occlusive

Vehicle:

water

Concentration / amount:

Undiluted for induction and challenge. To enhance skin contact, the substance was moistened with deionized water.

Route:

epicutaneous, occlusive

Vehicle:

water

Concentration / amount:

Undiluted for induction and challenge. To enhance skin contact, the substance was moistened with deionized water.

No. of animals per dose:

irritation screening group: 4 animals
test group: 10 animals
negative control group: 10 animals
positive control group: 4 animals

Details on study design:

Irritation Screening Study
An irritation screening study using four animals was conducted to determine the irritation threshold of the test material. The test material was administered as a 0.2-g dose, moistened with deionized water and at concentrations of 25%, 50%, and 75% w/v in deionized water with each anima receiving two different concentrations of the test material. The appropriate test material concentrations, in the amount of 0.2 g or 0.4 mL, were applied to Hill Top Chamber® patches. The patches were then placed on two shaved sites on the right and left anterior quadrants of each animal, covered with an overlapping strip of dental dam, and overwrapped with Elastoplast® tape. The patches remained in place for 6 hours after which they were removed and the
sites were wiped with a wet disposable paper towel. The test sites were observed for erythema reactions at 24 and 48 hours after patch removal.

Definitive Study
Based on the results of the irritation screening study, the test material was administered as a 0.2-g dose (moistened with deionized water) for the induction phase and for the challenge application. All test and positive control mixtures used in the irritation screening or definitive phases of the study were stored at room temperature until administered.

- Induction Phase:
On the day of test material application, the hair was removed from the backs of each animal in the test and positive control groups with electric clippers. The test material was applied to each animal in the test group by placing 0.2 g (moistened with deionized water) of test material on an adhesive patch (Hill Top Chamber®, 25-mm diameter) and placing the patch on the induction site along the anterior left flank. The patch was covered with dental dam and overwrapped with Elastoplast® tape. The dressing remained in place for a period of 6 hours after which it was removed and the induction site wiped with a wet disposable paper towel.

The positive control material [0.3% w/v 2,4-dinitrochlorobenzene (DNCB) in 80% v/v ethanol in deionized water] was administered as a 0.4 mL dose to the positive control animals in the same manner used for the test material. The animals in the test and positive control groups received one application per week for 3 weeks for a total of three applications. Due to the strong irritation present in the induction site of the positive control animals, the third induction dose for these animals was applied to an induction site slightly posterior to the initial site.

The naive control animals were not treated during this phase of the study.

- Challenge Phase:
Two weeks following the administration of the third induction dose, a challenge dose of 0.2 g of test material was administered along the anterior right flank of the test group animals in the same manner as during the induction phase of the study.
At this time the 10 naive (previously untreated) control animals were also treated in the same manner with a challenge application of the test material.
The positive control material was administered at a concentration of 0.1% w/v in acetone. The method used for the positive control group was the same as that of the test group.

- Observations:
Approximately 3 hours before the 24-hour examination following the irritation screening and challenge applications, the test sites of the respective animals were depilated by applying Neet@ depilatory for approximately 20 minutes, which was then washed off with lukewarm water.
The respective application sites were examined and scored for erythema reactions according to the Buehler scoring scale at approximately 24 and
48 hours following the irritation screening, induction, and challenge applications.
Clinical observations were conducted daily throughout the study. Body weights on the definitive study animals were taken on Day 1, at weekly intervals throughout the study, and at termination of the experimental phase.

- Evaluation of Challenge Responses:
Determination of sensitization was based on reactions to the challenge dose. Grades of 1 or greater in the test animals may indicate evidence of sensitization, provided grades of less than 1 are seen in the naive control animals.

Challenge controls:

A naive control group of 10 animals was maintained under the same environmental conditions and treated with the test substance at challenge only.

Positive control substance(s):

yes

Remarks:

Dinitrochlorobenzene (DNCB)

Positive control results:

1/4 animals died within the induction phase. The surviving positive control animals were considered to have been sensitized because of the moderate dermal reactions they exhibited to the 0.1% w/v concentration of DNCB in acetone at challenge.
Historical data compiled at the test facility have indicated that a 0.1% w/v concentration of DNCB in acetone does not produce irritation or causes very slight irritation in previously untreated animals when treated in the same manner as for the challenge application.

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

100 %

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 100 % . No with. + reactions: 0.0. Total no. in groups: 10.0.

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

100 %

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 100 %. No with. + reactions: 0.0. Total no. in groups: 10.0.

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

100 %

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 100 %. No with. + reactions: 0.0. Total no. in groups: 10.0.

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

100 %

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 100 %. No with. + reactions: 0.0. Total no. in groups: 10.0.

Reading:

1st reading

Hours after challenge:

24

Group:

positive control

Dose level:

0.1% w/v DNCB in acetone

No. with + reactions:

4

Total no. in group:

4

Clinical Observations and Body Weights:

All animals appeared normal throughout the study with the exception of one positive control animal which appeared hypoactive and was hypothermic to touch on Day 8 and was found dead on Day 9. The gross necropsy of this animal revealed a dark-brown oral discharge, a dark-red focus area on the right median lobe of the liver, and a dark-red semi-solid surrounding the right median lobe of the liver.

There was no meaningful effect on body weight gain in surviving animals.

Dermal Reactions to Product Potassium Bicarbonate:

No dermal reactions were observed in the animals in the test group when administered the test material during the induction or challenge phase of the study.

None of the naive control animals reacted to the challenge application of the test material.

Positive Control (DNCB):

The surviving positive control animals were considered to have been sensitized because of the moderate dermal reactions they exhibited to the 0.1% w/v concentration of DNCB in acetone at challenge. Historical data compiled at HWI have indicated that a 0.1% w/v concentration of DNCB in acetone does not produce irritation or causes very slight irritation in previously untreated animals when treated in the same manner as for the challenge application.

Interpretation of results:

GHS criteria not met

Conclusions:

In this study, the test article "Potassium Bicarbonate" is not a dermal sensitizer.

Executive summary:

In a dermal sensitization study according to US EPA Pesticide Assessment Guidelines, Subdivision F, Hazard Evaluation: Human and Domestic Animals, November 1984, Acute Exposure, Guinea Pig Sensitization (Buehler) which is similar to OECD Guideline 406 (Skin Sensitisation) with the test article "Potassium Bicarbonate", young adult guinea pigs strain Crl:(HA)BR (10 test and 10 control animals) were tested using the method of Buehler. Positive control substance was Dinitrochlorobenzene (DNCB) with a sensitisation rate of 100 % (4 animals).

To enhance skin contact, the undiluted substance was moistened with deionized water for induction and challenge exposure. No irritation was noted at any of the test or negative control sites during the induction phase. After challenge exposure no skin reactions were observed in test or control animals at any observation time. Therefore the sensitisation rate was 0 %.

In this study, the test article "Potassium Bicarbonate" is not a dermal sensitizer.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

As expected, there is no evidence for a skin sensitisation from a Buehler sensitisation study. The abiotic dissociation of potassium hydrogencarbonate with tissue water results in the formation of potassium and carbonate ions. Potassium and carbonate ions are naturally occurring, effectively processed and regulated essential compounds in the body. K⁺ or HCO₃^- resulting from the ionisation (dissociation) of KHCO₃ will not influence the natural K⁺ or HCO₃^- level in the body due to the natural regulation mechanisms.and for this reason it is very unlikely that potassium hydrogencarbonate has an intrinsic sensitising activity. The absence of intrinsic toxic properties of potassium hydrogencarbonate is generally taken for granted, which is proved by its long-standing safe use in foodstuffs and pharmaceuticals with no limitations other than current good manufacturing practice and its GRAS (generally recognized as safe) status in the USA.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information:

No study available. However, based on the structure of potassium hydrogencarbonate, no sensitising effects to the respirators system are expected. The abiotic dissociation of potassium hydrogencarbonate with tissue water results in the formation of potassium and carbonate ions. Potassium and carbonate ions are naturally occurring, effectively processed and regulated essential compounds in the body and for this reason it is very unlikely that they could cause respiratory sensitisation. Absence of intrinsic toxic properties of potassium hydrogencarbonate is generally taken for granted, which is proved by its long-standing safe use in foodstuffs and pharmaceuticals with no limitations other than current good manufacturing practice and its GRAS (generally recognized as safe) status in the.

Justification for classification or non-classification

Reliable, adequate and relevant data from a Buehler study with guinea pigs indicate that potassium hydrogencarbonate does not induce skin sensitisation. Further on, based on the structure of potassium hydrogencarbonate, no sensitising effects are expected.

According to GHS Regulation (EC) No 1272/2008 potassium hydrogencarbonate is not classified as “sensitising” and labelling is not required.