Reaction products of 1H-Imidazole-1-ethanol, 4,5-dihydro-, 2-(C7 odd-numbered alkyl) derivs. and sodium hydroxide and chloroacetic acid

Endpoint summary

Description of key information

- Skin irritation: based on the results of 2 distinct in vivo studies in rabbits (using aqueous solutions with a concentration of 15% or 49% solid content, respectively), the registered substance is not irritating to the skin.

- Eye irritation: based on the results of 2 distinct in vivo studies in rabbits (using aqueous solutions with a concentration of 15% or 49% solid content, respectively), the registered substance is not irritating to the eyes.

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:

weight of evidence

Study period:

1999

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Remarks:

Study in accordance with US FHSA/CPSC design, 16 CFR 1500 for Skin Irritation testing

Qualifier:

according to guideline

Guideline:

other: FHSA/CPSC Design, 16 CFR 1500 for Skin Irritation testing

Principles of method if other than guideline:

Occlusive 24h application of 0.5 mL of test item to unabraded and abraded skin sites of each rabbit and skin examination at 24 and 72h after application

GLP compliance:

yes

Specific details on test material used for the study:

Trade name: Mackam 2CY-75
Purity: 15% solids (active and impurities)
Chemical active ingredient: Disodium caprylo amphoacetate
CAS No.: 68608-64-0
Batch No.: L-48049

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Kuiper Rabbitry, Gary, Indiana
- Age at study initiation: 8 to 10 weeks
- Weight at study initiation: not specified
- Housing: individually in stainless steel cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 4 days

ENVIRONMENTAL CONDITIONS
- Temperature, humidity and light controlled rooms (no details provided)

IN-LIFE DATES: Not detailed

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.5 mL per site to unabraded and abraded skin sites

Duration of treatment / exposure:

24 hours

Observation period:

Skin reactions graded at 24 and 72 hours after application

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure: approximately 1'' square
- % coverage: 100 (2-layer gauze patch secured with non-irritation porous adhesive tape)
- Type of wrap if used: entire site covered wth 4 mil plastic wrap and secured with more adhesive tape

REMOVAL OF TEST SUBSTANCE
- At the end of the 24-hour contact period, excess material was removed from the sites

OBSERVATION TIME POINTS
- 24 and 72 hours after application

SCORING SYSTEM:
- Method of calculation: Draize Scoring System

Irritation parameter:

edema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0.5

Reversibility:

not specified

Remarks on result:

other: Abraded skin

Irritation parameter:

edema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Reversibility:

not specified

Remarks on result:

other: Unabraded skin

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0.5

Reversibility:

not specified

Remarks on result:

other: Abraded skin

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0.5

Reversibility:

not specified

Remarks on result:

other: Unabraded skin

Irritation parameter:

edema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0.5

Reversibility:

not specified

Remarks on result:

other: Abraded skin

Irritation parameter:

edema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0.5

Reversibility:

not specified

Remarks on result:

other: Unabraded skin

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

1

Reversibility:

not specified

Remarks on result:

other: Abraded skin

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0.5

Reversibility:

not specified

Remarks on result:

other: Unabraded skin

Irritation parameter:

edema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Reversibility:

not specified

Remarks on result:

other: Abraded skin

Irritation parameter:

edema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Reversibility:

not specified

Remarks on result:

other: Unabraded skin

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0.5

Reversibility:

not specified

Remarks on result:

other: Abraded skin

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Reversibility:

not specified

Remarks on result:

other: Unabraded skin

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.5

Reversibility:

not specified

Remarks on result:

other: Abraded skin

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.5

Reversibility:

not specified

Remarks on result:

other: Unabraded skin

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Reversibility:

not specified

Remarks on result:

other: Abraded skin

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.5

Reversibility:

not specified

Remarks on result:

other: Unabraded skin

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Reversibility:

not specified

Remarks on result:

other: Abraded skin

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Reversibility:

not specified

Remarks on result:

other: Unabraded skin

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.5

Reversibility:

not specified

Remarks on result:

other: Abraded skin

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.5

Reversibility:

not specified

Remarks on result:

other: Unabraded skin

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Reversibility:

not specified

Remarks on result:

other: Abraded skin

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Reversibility:

not specified

Remarks on result:

other: Unabraded skin

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Reversibility:

not specified

Remarks on result:

other: Abraded skin

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Reversibility:

not specified

Remarks on result:

other: Unabraded skin

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 24/72h

Score:

ca. 1

Max. score:

2

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

See details in Table below

Rabbit	Erythema/Eschar (unabraded skin)				Edema (unabraded skin)				Erythema/Eschar (abraded skin)				Edema (abraded skin)				Reversibility
	24h	48h	72h	Mean	24h	48h	72h	Mean	24h	48h	72h	Mean	24h	48h	72h	Mean
512	1	N/A	1	1.0	2	N/A	0	1.0	1	N/A	1	1.0	2	N/A	0	1.0	N/A
513	1	N/A	0	0.5	0	N/A	0	0.0	1	N/A	0	0.5	0	N/A	0	0.0	N/A
514	1	N/A	0	0.5	1	N/A	0	0.5	1	N/A	1	1.0	1	N/A	0	0.5	N/A
515	0	N/A	0	0.0	0	N/A	0	0.0	1	N/A	0	0.5	0	N/A	0	0.0	N/A
516	1	N/A	0	0.5	1	N/A	0	0.5	1	N/A	1	1.0	1	N/A	0	0.5	N/A
517	1	N/A	0	0.5	0	N/A	0	0.0	1	N/A	0	0.5	1	N/A	0	0.5	N/A
N/A Not assessed

Interpretation of results:

GHS criteria not met

Conclusions:

Not a skin irritant based on in vivo testing

Executive summary:

Disodium caprylo amphodiacetate, as Mackam 2CY-75, 15% solids, was tested for its skin irritation potential in New-Zealand White rabbits. The test article was applied as such at a dose of 0.5 mL to unabraded and abraded skin sites on a clipped area of each of 6 rabbits. The test sites were occluded and the test material remained on the skin for a 24-hour contact period. The application sites were graded for indications of skin reactions (erythema and/or edema) using the Draize Scoring System at 24 and 72 hours after sample application.

No significant skin reactions occurred over the observation period.

Under the conditions of the experiment, the primary dermal irritation score was 1.0, indicating that disodium caprylo amphoacetate, as Mackam 2CY-75, 15% solids, is not irritating to the skin.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1978

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Remarks:

Only two-page summary report available

Qualifier:

no guideline followed

Principles of method if other than guideline:

Determine the degree of skin irritation by the test material when applied to the clipped intact and abraded skin of rabbits

GLP compliance:

no

Specific details on test material used for the study:

Trade name: Miranol J2M Conc
Purity: not specified
Typical solid content (active + impurities) for the commercial product: 49%
Chemical active ingredient: Disodium caprylo amphoacetate
CAS No.: 68608-64-0
Batch No.: 4349D78

Species:

rabbit

Strain:

other: albino (strain not specified)

Details on test animals or test system and environmental conditions:

No details provided

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.5 mL per site to unabraded and abraded skin sites

Duration of treatment / exposure:

24 hours

Observation period:

Skin reactions graded at 24 and 72 hours after application

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 10% of total body area
- % coverage: patch area was covered with Webril patches
- Type of wrap if used: entire experimental area sealed with Blenderm Surgical Tape

REMOVAL OF TEST SUBSTANCE
Not specified

OBSERVATION TIME POINTS
- 24 and 72 hours after application

SCORING SYSTEM:
- Method of calculation: Draize Scoring System

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Reversibility:

not specified

Remarks on result:

other: Abraded skin

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Reversibility:

not specified

Remarks on result:

other: Unabraded skin

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.5

Reversibility:

not specified

Remarks on result:

other: Abraded skin

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.5

Reversibility:

not specified

Remarks on result:

other: Unabraded skin

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 24/72h

Score:

ca. 2

Max. score:

2

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

See details in Table below

Erythema/Eschar (unabraded skin)

Edema (unabraded skin)

Erythema/Eschar (abraded skin)

Edema (abraded skin)

Reversibility

24h

48h

72h

Mean

24h

48h

72h

Mean

24h

48h

72h

Mean

24h

48h

72h

Mean

1

N/A

0

0.5

0

N/A

0

0.0

1

N/A

0

0.5

0

N/A

0

0.0

N/A

N/A Not assessed

Interpretation of results:

GHS criteria not met

Conclusions:

Not a skin irritant based on in vivo testing

Executive summary:

Disodium caprylo amphodiacetate, as Miranol J2M Conc, was tested for its skin irritation potential in albino rabbits. The test article was applied as such at a dose of 0.5 mL to unabraded and abraded skin sites on a clipped area of each of 3 rabbits. The test sites were occluded and the test material remained on the skin for a 24-hour contact period. The application sites were graded for indications of skin reactions (erythema and/or edema) using the Draize Scoring System at 24 and 72 hours after sample application.

No significant skin reactions occurred over the observation period.

Under the conditions of the experiment, the primary dermal irritation score was 2.0, indicating that disodium caprylo amphoacetate, as Miranol J2M Conc, is not irritating to the skin.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1999

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Remarks:

Study in accordance with US FHSA/CPSC design, 16 CFR 1500 for Eye Irritation testing

Qualifier:

according to guideline

Guideline:

other: US FHSA/CPSC design, 16 CFR 1500 for Eye Irritation testing

Principles of method if other than guideline:

Instillation of 0.1 mL of test item in one eye of each rabbit and eye examination at 24, 48 and 72h after instillation

GLP compliance:

yes

Specific details on test material used for the study:

Trade name: Mackam 2CY-75
Purity: 15% solids (active and impurities)
Chemical active ingredient: Disodium caprylo amphoacetate
CAS No.: 68608-64-0
Batch No.: L-48049

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Kuiper Rabbitry, Gary, Indiana
- Age at study initiation: 8 to 10 weeks
- Weight at study initiation: not specified
- Housing: individually in stainless steel cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 4 days

ENVIRONMENTAL CONDITIONS
- Temperature, humidity and light controlled rooms (no details provided)

IN-LIFE DATES: Not detailed

Vehicle:

unchanged (no vehicle)

Controls:

other: contralateral eye served as untreated control for each rabbit

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): 15% solid content

Duration of treatment / exposure:

Single instillation

Observation period (in vivo):

72 hours

Duration of post- treatment incubation (in vitro):

Not applicable

Number of animals or in vitro replicates:

6

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: no

SCORING SYSTEM: Draize Scoring System

TOOL USED TO ASSESS SCORE: visual examination

Irritation parameter:

conjunctivae score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0.3

Reversibility:

fully reversible within: 48h

Irritation parameter:

conjunctivae score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Reversibility:

not specified

Irritation parameter:

conjunctivae score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0.3

Reversibility:

fully reversible within: 48h

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.3

Reversibility:

fully reversible within: 48h

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Reversibility:

not specified

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Reversibility:

not specified

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

mean

Score:

0.3

Max. score:

1

Reversibility:

fully reversible within: 48h

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Rabbit	Cornea				Iris				Conjunctival redness				Conjunctival chemosis				Reversibility
	24h	48h	72h	Mean	24h	48h	72h	Mean	24h	48h	72h	Mean	24h	48h	72h	Mean
548	0	0	0	0.0	0	0	0	0.0	0	0	0	0.0	0	0	0	0.0	N/A
549	0	0	0	0.0	0	0	0	0.0	0	0	0	0.0	0	0	0	0.0	N/A
550	0	0	0	0.0	0	0	0	0.0	1	0	0	0.3	0	0	0	0.0	Yes
551	0	0	0	0.0	0	0	0	0.0	1	0	0	0.3	0	0	0	0.0	Yes
552	0	0	0	0.0	0	0	0	0.0	0	0	0	0.0	0	0	0	0.0	N/A
553	0	0	0	0.0	0	0	0	0.0	1	0	0	0.3	0	0	0	0.0	Yes
N/A Not applicable

Interpretation of results:

GHS criteria not met

Remarks:

Conjunctival redness individual mean scores remained below 2 (GHS threshold for classification)

Conclusions:

Not an eye irritant based on in vivo testing

Executive summary:

Disodium caprylo amphodiacetate, as Mackam 2CY-75, 15% solids, was tested for its eye irritation potential in New-Zealand White rabbits. The test article was insitllated as such at a dose of 0.1 mL in one eye of each of 6 rabbits, the contralateral eye serving as an untreated control. The treated eyes were graded for indications of irritation (cornea, iris, conjunctival redness and conjunctival chemosis) using the Draize Scoring System at 24, 48 and 72 hours after sample instillation.

No significant ocular reactions occurred over the observation period, except slight conjunctival redness at 24h in 3 out of 6 rabbits with full reversibility.

Under the conditions of the experiment, disodium caprylo amphoacetate, as Mackam 2CY-75, 15% solids, was not irritating to the eyes.

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1999

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Remarks:

Only short summary report available

Qualifier:

no guideline followed

Principles of method if other than guideline:

Instillation of 0.1 mL of test item in one eye of each rabbit and eye examination on days 1, 2, 3, 4 and 7 after instillation

GLP compliance:

no

Specific details on test material used for the study:

Trade name: Miranol J2M Conc
Purity: not specified
Typical solid content (active + impurities) for the commercial product: 49%
Chemical active ingredient: Disodium caprylo amphoacetate
CAS No.: 68608-64-0
Batch No.: 4349D78

Species:

rabbit

Strain:

other: albino (strain not specified)

Details on test animals or tissues and environmental conditions:

No details provided

Vehicle:

unchanged (no vehicle)

Controls:

other: contralateral eye served as untreated control for each rabbit

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): 49% solid content (typical for this commercial product)

Duration of treatment / exposure:

Single instillation

Observation period (in vivo):

7 days

Duration of post- treatment incubation (in vitro):

Not applicable

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: no

SCORING SYSTEM: Draize Scoring System

TOOL USED TO ASSESS SCORE: visual examination

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.7

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Reversibility:

fully reversible within: 7 days

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

mean

Score:

>= 1 - <= 1.7

Max. score:

2

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of weak irritation

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

>= 0.7 - <= 1.7

Max. score:

3

Reversibility:

fully reversible within: 72h

Remarks on result:

probability of weak irritation

Rabbit	Cornea						Iris						Conjunctival redness						Conjunctival chemosis						Reversibility
	Day 1	Day 2	Day 3	Day 4	Day 7	Mean Days 1 -3	Day 1	Day 2	Day 3	Day 4	Day 7	Mean Days 1 -3	Day 1	Day 2	Day 3	Day 4	Day 7	Mean Days 1 -3	Day 1	Day 2	Day 3	Day 4	Day 7	Mean Days 1 -3
1	0	0	0	0	0	0.0	0	0	0	0	0	0.0	1	1	1	1	0	1.0	1	1	0	0	0	0.7	Yes
2	0	0	0	0	0	0.0	0	0	0	0	0	0.0	2	2	1	1	0	1.7	3	2	0	0	0	1.7	Yes
3	0	0	0	0	0	0.0	0	0	0	0	0	0.0	2	1	1	1	0	1.3	2	1	0	0	0	1.0	Yes

Interpretation of results:

GHS criteria not met

Remarks:

Conjunctival redness and chemosis individual mean scores remained below 2 (GHS threshold for classification)

Conclusions:

Not an eye irritant based on in vivo testing

Executive summary:

Disodium caprylo amphodiacetate, as Miranol J2M Conc, was tested for its eye irritation potential in New-Zealand White rabbits. The test article was instillated as such at a dose of 0.1 mL in one eye of each of 3 rabbits, the contralateral eye serving as an untreated control. The treated eyes were graded for indications of irritation (cornea, iris, conjunctival redness and conjunctival chemosis) using the Draize Scoring System on Days 1, 2, 3, 4 and 7 after sample instillation.

No significant ocular reactions occurred over the observation period, except slight conjunctival redness in all 3 rabbits with full reversibility within 7 days, and slight conjunctival chemosis in all 3 rabbits with full reversibility within 72h.

Under the conditions of the experiment, disodium caprylo amphoacetate, as Miranol J2M Conc, was not irritating to the eyes.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the experimental results and the 2017 CESIO recommendations for CAS 68608-64-0, no classification according to CLP or UN-GHS criteria is warranted for skin or eye irritation.