Choline hydrogen carbonate

Endpoint summary

Description of key information

- Choline chloride, dermal application, rabbit, skin of the back and ear, 20 h duration and observation after 24 h and 8 d: not irritating
- Sodium bicarbonate, dermal application, rabbit, 24 h duration, occlusive and semi-occlusive: not irritating
Eye irritation:
- Choline chloride rabbit, 50mm³ of the eye, 1 h, 24 h and 8 d: not irritating (slight irritation after 1h, completely reversible)
- Sodium bicarbonate, 0.1 mL of solid, up to 7 d observation: slightly irritating (mechanical, not relevant for Choline bicarbonate)

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

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

Adequacy of study:

key study

Study period:

1963

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: well documented study result on read-across substance Choline chloride, which meets basic scientific principles

Qualifier:

no guideline followed

Principles of method if other than guideline:

A Choline chloride solution (undiluted) was adminstered to rabbit skin for 20 hours.

GLP compliance:

not specified

Species:

rabbit

Strain:

not specified

Details on test animals or test system and environmental conditions:

The substance was administered dermally to rabbit skin (back) for 20 hours.
The substance was administered dermally to rabbit ears for 20 hours.

Type of coverage:

not specified

Preparation of test site:

not specified

Vehicle:

unchanged (no vehicle)

Controls:

other: the untreated skin served as a control

Amount / concentration applied:

no data

Duration of treatment / exposure:

20 hours

Observation period:

24 hours and 8 days after the application for 20 h

Number of animals:

no data

Irritation parameter:

other:

Basis:

mean

Time point:

other: 24 hours and 8 days after application

Score:

ca. 0

Reversibility:

fully reversible

Remarks on result:

other: ambigous slight redness was observed on the back of the animals

Irritation parameter:

other:

Basis:

mean

Time point:

other: 24 hours and 8 days after application

Score:

0

Remarks on result:

other: no irritation was found on the ears after 20 hour applications

Irritant / corrosive response data:

ambigous slight redness of the skin was observed after a 20 hours application and a 24 hour / 8 days observation period.

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: other: EU-GHS

Conclusions:

The study was considered to be of high quality (reliability Klimisch 2). The substance did not show a significant irritation after a single dermal application to rabbit skin for 20 h. The substance is not considered to be irritating to the skin.

Executive summary:

The skin irritation potential of the read-across substance Choline chloride was investigated in rabbits (BASF, 1963). The test substance was administered to the back or to the ears for 20 hours and the resulting effects were evaluated. After 24 -hours an ambigous slight reddening of the skin of the back, or for the ears after 24 hours and also after 8 days no changes of the skin of any animal were observed. The test item can be regarded as not irritating to the skin.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

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

Adequacy of study:

key study

Study period:

1963

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: well documented study result on read-across substance Choline chloride, which meets basic scientific principles

Qualifier:

no guideline followed

Principles of method if other than guideline:

A Choline chloride solution (undiluted) was adminstered to rabbit eyes for 20 hours.

GLP compliance:

not specified

Species:

rabbit

Strain:

not specified

Details on test animals or tissues and environmental conditions:

The substance was administered to rabbit eyes for 20 hours.

Vehicle:

unchanged (no vehicle)

Controls:

other: the untreated eye served as a control

Amount / concentration applied:

no data

Duration of treatment / exposure:

1 h, 24 h, 8 days

Observation period (in vivo):

1 h, 24 h, 8 days

Number of animals or in vitro replicates:

no data

Details on study design:

the test item was applied unchanged to an area of 1 * 50 mm³ of the rabbit eye

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 1 h

Score:

> 0

Reversibility:

fully reversible within: 24 hours

Remarks on result:

other: slight reddening was observed after 1 hour

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 24 hours

Score:

0

Reversibility:

other: not applicable

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 8 days

Score:

0

Reversibility:

other: not applicable

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: other: EU-GHS

Conclusions:

The study was considered to be of high quality (reliability Klimisch 2). The substance did not show a significant irritation after a single ocular application to the rabbit eye for 20 h. The substance is not considered to be irritating to the eyes.

Executive summary:

The eye irritation potential of the read-across substance Choline chloride was investigated in rabbits (BASF, 1963). The test substance was administered to the rabbit eye and the resulting effects were evaluated. After 1-hours a slight reddening was noted, which was fully reversible as after 24 hours and after 8 days no findings were reported. The test item can be regarded as not irritating to the eye.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

There are four studies available to assess the irritating potential of choline bicarbonate, either to the skin or to the eyes:

 

BASF, 1966, skin irritation, key study on Choline chloride:

The skin irritation potential of the read-across substance Choline chloride was investigated in rabbits (BASF, 1963). The test substance was administered to the back or to the ears for 20 hours and the resulting effects were evaluated. After 24-hours an ambiguous slight reddening of the skin of the back, or for the ears after 24 hours and also after 8 days no changes of the skin of any animal were observed.The study was considered to be of good quality (reliability Klimisch 2). The substance did not show a significant irritation after a single dermal application to rabbit skin for 20 h, so the substance is not considered to be irritating to the skin and hence, choline bicarbonate does not need to be classified.

 

IJT, 1987, skin irritation, supporting study on Sodium bicarbonate:

In a peer-reviewed assessment report, classified as Klimisch 2, on the read-across substance Sodium bicarbonate, two studies were cited. Hence, the results are considered as reliable and sufficient to support the data provided in the Key study. In both studies, 0.5 g Sodium bicarbonate was applied for 24 h on the abraded and non-abraded skin of six rabbits, covered with a gauze patch (study 1) or occlusively (study 2), with a 48 h (study 1) or 72 h (study 2) post-observation period. In study 1, none of the animals had signs of skin irritation, in study 2, it was concluded that the test substance was not a primary irritant. So, NaHCO3 does not need to be classified as skin irritant and, taking into account the available data from the key study, choline bicarbonate does not need to be classified according to Regulation 1272/2008/EC, too.

 

BASF, 1963, eye irritation, key study on Choline chloride:

The eye irritation potential of the read-across substance Choline chloride was investigated in rabbits (BASF, 1963). The test substance was administered to the rabbit eye and the resulting effects were evaluated. After 1-hours a slight reddening was noted, which was fully reversible as after 24 hours and after 8 days no findings were reported.The study was considered to be of good quality (reliability Klimisch 2). The substance did not show a significant irritation after a single ocular application to the rabbit eye for 20 h.Hence, Choline chloride can be regarded as not irritating to the eye, and so, Choline bicarbonate does not need to be classified, too.

 

Murphy, 1982, eye irritation, supporting study on Sodium bicarbonate:

In a primary eye irritation study similar to OECD 405 (Klimisch 2), 0.1 mL of solid NaHCO3 was instilled into the conjunctival sac of one eye of New Zealand albino rabbits for 30s (washout) and also without wash-out. Animals were then observed for 7 days. Irritation was scored by the method of Draize.

Sodium bicarbonate (in solid form) did not induce corneal opacity in all animals but produced conjunctivitis which lasted through day 7 in all animals tested; however, iritis was not reported. In this study, the solid read-across substance Sodium bicarbonate is only slightly irritating to the rabbit eye, which is rather attributed to mechanical but chemical irritation: The instillation of the solid compound is generally very likely to overestimate the actual irritating potential of a compound due to mechanical irritation. It can be reasonably concluded that the observed slightly irritating effect of Sodium bicarbonate in the rabbit eye is only due to mechanical and not chemical irritation and is hence not transferrable to Choline bicarbonate as it is only distributed as aqueous solution. Hence, it can be concluded that Choline bicarbonate, which is distributed as aqueous solution, is not an eye irritant and does consequently not need to be classified according Regulation 1272/2008/EC.

 

In summary, no irritation study on either skin or eye is available for Choline bicarbonate. However, due to its ionic structure, the low logPow (estimated to be approx. -3.77 to -2.25) and high water solubility (> 750 g/L), a complete dissociation into the organic cation choline and inorganic anion bicarbonate can be taken as a given. So, it is scientifically justified to cover this endpoint with data from individual test results gained for either the cation or anion in combination with corresponding inert counterions. Based on the structure of the available ions, i.e. choline, sodium, bicarbonate or chloride, no synergistic or antagonistic effects are to be expected for the irritating potential of the complete molecule. Hence, the results obtained in all four above mentioned studies can be transferred without modification to choline bicarbonate and further testing can be omitted due to animal welfare.

In all four available studies, the test item did not trigger classification, neither according to Directive 67/548/EEC nor Regulation 1272/2008/EC. The only slight irritating effect was observed in the supporting study on eye irritation on the solid Sodium bicarbonate. Since this effect however is expected to be caused by mechanical rather than chemical irritation, and is so not relevant for Choline bicarbonate which is only distributed as aqueous solution, the outcome of all studies is considered to be negative and Choline bicarbonate does consequently not need to be classified, neither as skin nor eye irritant, neither according to Directive 67/548/EEC nor Regulation 1272/2008/EC.

 

Event though there is no human data available on the hazards of Choline bicarbonate for skin or eye irritation, there is no reason to assume that the lack of irritating effects is not relevant for humans, as no inter-species differences in the mode of action of the compound were identified.

In conclusion, the available information is of good quality, sufficient to cover both skin and eye irritation endpoints, no datagaps were identified and the tonnage-driven data requirements under REACH are fully met.

Justification for selection of skin irritation / corrosion endpoint:
The test item has higher structural similarities to the registered substance, both available studies were assessed with Klimisch 2 and have a negative outcome, i.e. no irritating effects were determined.

Justification for selection of eye irritation endpoint:
The test item has higher structural similarities to the registered substance, both available studies were assessed with Klimisch 2 and have a negative outcome, i.e. no irritating effects were determined.

Justification for classification or non-classification

In all four available studies, the test item did not trigger classification, neither according to Directive 67/548/EEC nor Regulation 1272/2008/EC. The only slight irritating effect was observed in the supporting study on eye irritation on the solid Sodium bicarbonate. Since this effect however is expected to be caused by mechanical rather than chemical irritation, and is so not relevant for Choline bicarbonate which is only distributed as aqueous solution, the outcome of all studies is considered to be negative and Choline bicarbonate does consequently not need to be classified, neither as skin nor eye irritant, neither according to Directive 67/548/EEC nor Regulation 1272/2008/EC.