Disodium Capryloyl Glutamate

Endpoint summary

Description of key information

Evaluation of skin sensitisation

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Reference 1

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Remarks:

Hypoallergenicity test

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

From November 10, 2000 to November 17, 2000

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Qualifier:

according to guideline

Guideline:

other: Hypoallergenicity (T12C)

Version / remarks:

See Principles of method if other than guideline

Deviations:

no

Principles of method if other than guideline:

Hypoallerginicity (T12C):
The method consists in an occlusive application of the test substance by means of Finn Chambers (alluminium cells of some 20 microlitres volume) on 20 selected subjects’ back or forearm, for 48 hours. After the removal of the occlusion, the cutaneous reactions induced by the product are evaluated. These evaluations are performed 24 and 48 hours later.
The repeated control of the treated areas allows us to trace the presence and/or the activity in elicitation of cutaneous reactions of common allergens.
- The method consists in an occlusive application of 48h. The test substance was put in Finn Chambers (aluminium cells with a diameter of 8 mm, 50 mm2 area, volume of 20 microlitres), which were filled slightly more than half their volume. The cells were applied on the back or on the forearm of the subject, on healthy skin previously cleaned from sebum.
- The test substance was tested at 7% in S.A.L.

GLP compliance:

yes

Remarks:

and GCP

Type of study:

other: Test T12C: Hypoalergenicity

Justification for non-LLNA method:

Conducted before the requirement of LLNA method was implemented

Specific details on test material used for the study:

Appearance: liquid and transaprent

Species:

other: Human

Sex:

male/female

Details on test animals and environmental conditions:

- 20 subjects
- cleaned from sebum

No. of animals per dose:

Total of 20 persons

Details on study design:

Criteria for inclusion
Race: caucasian. Age: adults aged from 18 to 65 (the number of subjects aged between 55 and 65 must not be higher than 10% of the total). Sex: male and female. Health state: no pathologies either for the period immediately before or during the test. Knowledge of the italian language. Easily contactable.
Criteria for exclusion
Persons who cannot be included according to the criteria listed in Criteria for inclusion; Subjects undergone epicutaneous tests in the last four weeks or to sensitization tests in the last six months; Subjects using topical or systemic pharmaceutical treatments that may influence the test (ex. antihistaminics, cortisone); Pregnant and nursing women; Person showing either temporary or chronic cutaneous diseases; Subjects who usually expose or have recently exposed themselves to UV radiation.
Drop-out and Restrictions

Challenge controls:

Negative (empty cell) and vehicle controls

Positive control substance(s):

no

Key result

Reading:

other: after 24 and 48 hours

Group:

test chemical

Dose level:

7% in S.A.L. (active matter)

No. with + reactions:

0

Total no. in group:

0

Clinical observations:

no effects

Remarks on result:

no indication of skin sensitisation

Results recording:

48 hours after application the strips were removed and then, after 30 minutes, the occlusive cutaneous reaction was evaluated (T1). An evident redness after 30 minutes was a possible sign of irritation caused by the product. A second check was made 24 hours after the removal (T2) of the plaster strip and a third one 48 hours later (T3). There are 5 kinds of reactions (1 -5); ranging from "no erythema to "possibly exudation and infiltration".

Interpretation of the results:

- The first check does not enable a final assessment; however, it provides useful indications:

1) A positive reaction (+, ++, +++) disappearing within the some hours after the removal of the cells is not regarded as an allergic reaction and therefore it is not included in the final calculation of the data. However, such reactions will be reported, since they can be regarded as either irritant reactions or a sign of moderate sensitivity of the subject to one or more components of the product.

2) A doubtful reaction (slightly visible +/-), which disappears within 24 hours after the removal of the cells is not included in the calculation.

- The checks made at successive times enabled identification of positive allergic reactions. The allergenic potential of the product is expressed as a percentage of allergic reactions and is evaluated considering: the number of reactions observed severity, type and duration of such reactions. On the basis of the data reported in literature, the presence/activity of common allergens in the product can be related to the percentage of the allergic reactions observed (from "no reaction" to "maximum").

Results:

The number of total allergic reactions and the percenrage of allergic reactions = 0.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the study conditions, the substance was considered to be non-sensitizing to human skin.

Executive summary:

A supporting study was conducted to determine the skin sensitizing potential of the substance according to the Method T12C "Hypoallergenicity", in compliance with GLP. The method consisted of an occlusive application of the test substance (7% in S.A.L.) for 48 h by means of Finn Chambers (alluminium cells of 20 microlitres volume) on 20 selected subjects back or forearm. After the removal of the occlusion, the cutaneous reactions induced by the product were evaluated. These evaluations were performed 24 and 48 hours later. The checks made at successive times enabled identification of positive allergic reactions. The allergenic potential of the product was expressed as a percentage of allergic reactions and was evaluated considering the number of reactions observed, severity, type (from "no erythema to "possibly exudation and infiltration") and duration of such reactions. On the basis of the data reported in literature, the presence/activity of common allergens in the product can be related to the percentage of the allergic reactions observed (from "no reaction" to "maximum"). The number of total allergic reactions and the percenrage of allergic reactions were 0. Under the study conditions, the substance was considered to be non-sensitizing to human skin (Sirigu, 2000).

Reference 2

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Remarks:

Buehler test

Type of information:

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

Adequacy of study:

weight of evidence

Study period:

From May 07, 2001 to August 08, 2001

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

RA Study

Justification for type of information:

Refer to the section 13 of IUCLID dataset for details on the read across justification. The skin sensitisation study with the read across substance is considered sufficient to fulfil the information requirements as further explained in the provided endpoint summary.

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

no

GLP compliance:

yes

Type of study:

Buehler test

Justification for non-LLNA method:

Conducted before the requirementof LLNA method was implemented

Species:

guinea pig

Strain:

Himalayan

Remarks:

spotted

Sex:

male

Details on test animals and environmental conditions:

Test animals
- Source: RCC Ltd, Biotechnology & Animal Breeding Division, Wolferstrasse 4, CH-4414 Fullinsdorf / Switzerland
- Age at study initiation: 4-6 weeks
- Weight at study initiation: 290-418g
- Housing: Makrolon type-4 cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: one week

Environmental conditions
- Temperature (°C): 22 ±3
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12h/12h

Route:

epicutaneous, occlusive

Vehicle:

water

Remarks:

Bi-distilled

Concentration / amount:

Induction: 100% (substamce was apllied undiluted)
Challenge: 50% diluted in water
Rechallenge: 25%, 50% diluted in water

Day(s)/duration:

6 hours once a week for 3 weeks

Route:

epicutaneous, occlusive

Vehicle:

water

Remarks:

Bi-distilled

Concentration / amount:

Induction: 100% (substamce was apllied undiluted)
Challenge: 50% diluted in water
Rechallenge: 25%, 50% diluted in water

Day(s)/duration:

6 hours

No. of animals per dose:

Test group: 20 animals
Control group: 10 animals

Details on study design:

- Irritation screening test:
An irritation screening test was performed to determine the minimal irritating concentration used in the induction period and the highest non-irritating concentration used for the challenge. Four different concentrations (5%, 25%, 50%, 100% diluted with bi-distilled water) were used on each animal for a 6-hour exposure period. 4 guinea pigs were used. Application sites were assessed after 24 and 48 hours.
The most representative concentration to stimulate a state of immune hypersensitivity was 100% used in the induction phase and a concentration of 50% was used in the challenge as the highest non-irritating concentration.

- Main study:
1. Induction
The fur was clipped from the left shoulder of each test animal and the patches applied, over a period of 3 weeks. The animals were treated with the test substance applied undiluted. Each animal received one patch per week which remained in place for approximately 6 hours each. The repeated application was performed at the same site. The interval between exposure was one week. The control animals remained untreated. After the last induction exposure the test animals were left untreated for 2 weeks before the challenge. The skin responses were graded 24 hours after the patches had been removed. Any gross skin reactions were recorded without depilation.

2. Challenge- performed on test day 29
The animals previously exposed during the induction period (i.e. test group) as well as the previously untreated control animals were challenged two weeks after the last induction exposure using the test substance at 50% in bi-distilled water. The fur was clipped from the left posterior quadrant of the side and back of the animals. The exposure period was 6 hours on a naive skin site. The responses were graded at 24 and 48 hours after the patches had been removed.

3. Second challenge
The test group was rechallenged 14 days following primary challenge. All animals in the test group were included in the rechallenge. The test substance was applied on the right cranial flank at 50% in bi-distilled water and on the the right caudal flank at 25% in bi-distilled water.

The grading method used for irritation screen, induction and challenge was identical. The scoring system was performed by visual assessment of erythema, oedema and other clinical changes in skin conditions. They were assessed as follows:
0 = no visible change
1 = discrete or patchy erythema
2 = moderate and confluent erythema
3 = intense erythema and swelling
Grading of all animals was done by positioning each animal under true-light (Philips TLD 36W/84 or Osram 36W/31 830).

Challenge controls:

During induction the control animals remained untreated. At the challenge the controls were treated the same as the test group. Only the test group was challenged a second time

Positive control substance(s):

yes

Remarks:

2-Mercaptobenzothiazole

Positive control results:

Five out of 10 test animals were observed with discrete/patchy erythema at the 24-hour reading and moderate/confluent erythema was observed at the 48-hour reading in all ten test animals after the challenge treatment with the highest tested non-irritating concentration of 2-Mercaptobenzothiazole at 0.03 % in mineral oil. No skin reactions were observed in the control group.

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

0%

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

0%

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

25%

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

25%

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

positive control

Dose level:

0.03%

No. with + reactions:

5

Total no. in group:

10

Remarks on result:

positive indication of skin sensitisation

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

positive control

Dose level:

0.03%

No. with + reactions:

10

Total no. in group:

10

Remarks on result:

positive indication of skin sensitisation

Interpretation of results:

other: CLP criteria are not met

Conclusions:

Under the study conditions, the substance was not sensitizing to Guinea pig skin.

Executive summary:

A study was conducted to determine the in vivo skin sensitisation potential of the substance according to OECD Guideline 406, in compliance with GLP. The experiment was performed on male Guinea pigs. For the induction phase, the undiluted test substance was used. During challenge, 12 out of 20 animals reacted with distinct erythema. Therefore, a purified/diluted sample (25%) was prepared for the re-challenge procedure. During the re-challenge with the purified sample, no skin reactions were observed after 24 and 48 h in any animal. Under the study conditions, the substance was not sensitizing to Guinea pig skin (RCC Ltd, 2001).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

In vivo:

 

A study was conducted to determine the in vivo skin sensitisation potential of the read-across substance L-glutamic acid, N-coco acyl derivs., monosodium salts according to OECD Guideline 406, in compliance with GLP. The experiment was performed on male Guinea pigs. For the induction phase, the undiluted test substance was used. During challenge, 12 out of 20 animals reacted with distinct erythema. Therefore, a purified/diluted sample (25%) was prepared for the re-challenge procedure. During the re-challenge with the purified sample, no skin reactions were observed after 24 and 48 h in any animal. Under the study conditions, the substance was not sensitizing to Guinea pig skin (RCC Ltd, 2001).

 

A supporting study was conducted to determine the skin sensitizing potential of the substance according to the Method T12C "Hypoallergenicity", in compliance with GLP. The method consisted of an occlusive application of the test substance (7% in S.A.L.) for 48 h by means of Finn Chambers (alluminium cells of 20 microlitres volume) on 20 selected subjects back or forearm. After the removal of the occlusion, the cutaneous reactions induced by the product were evaluated. These evaluations were performed 24 and 48 hours later. The checks made at successive times enabled identification of positive allergic reactions. The allergenic potential of the product was expressed as a percentage of allergic reactions and was evaluated considering the number of reactions observed, severity, type (from "no erythema to "possibly exudation and infiltration") and duration of such reactions. On the basis of the data reported in literature, the presence/activity of common allergens in the product can be related to the percentage of the allergic reactions observed (from "no reaction" to "maximum"). The number of total allergic reactions and the percenrage of allergic reactions were 0. Under the study conditions, the substance was considered to be non-sensitizing to human skin (Sirigu, 2000).

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the in vivo skin sensitisation study with the read-across substance L-glutamic acid, N-coco acyl derivs., monosodium salts and a supporting study with the substance, no classification for skin sensitisation is warranted according to EU CLP (1272/2008) criteria.