fatty acid chloride, C12, reaction product with sodium glutamate and sodium hydroxide

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation, other

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

Justification for read-across is provided in chapter 13 as separate statement

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

assessment report

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1994

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

adopted May 12th 1981; updated July 17th, 1992

GLP compliance:

yes

Type of study:

Buehler test

Justification for non-LLNA method:

The study was performed prior to the establishment of LLNA.

Specific details on test material used for the study:

purity given in the report: 22% in water
pH in water: 5.8 (10g/l)

Species:

guinea pig

Strain:

Pirbright-Hartley

Sex:

female

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

Concentration / amount:

100% / 0.5 ml

Day(s)/duration:

6 h

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

Remarks:

The challenge treatment was performed 14 days after the induction treatment.

Concentration / amount:

100% / 0.5 ml

Day(s)/duration:

6 h

No. of animals per dose:

6 used for determination of non-irritating concentration
10 used for control
20 used for test material treatment

Details on study design:

Doses tested for the determination of non-irritating concentration: 100% test material, 50% test material in water, 10% test material; 0.5 ml was applied to skin usiing 2 x 2 cm patch; occlusive for 6 hours; irritation score reading at 24hours after removal of patch.

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

0%

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

no effect

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

100%

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

no effect

Remarks on result:

no indication of skin sensitisation

Interpretation of results:

GHS criteria not met

Conclusions:

Sodium N-cocoyl glutamate was investigated for its skin isensitization property according to the Guideline OECD 406 (Buehler method). It is not skin sensitizing.

Executive summary:

Sodium N-cocoyl glutamate was investigated for its skin sensitization property according to the OECD 406 (Buehler method). 0.5 ml of the test material wasoccusively applied to the clipped skin of guinea pigs for 6 hours as induction and challenge treatment. None of the twenty treated animals responded. Sodium N-cocoyl glutamate is not skin sensitizing.

Cross-reference 2

Reason / purpose for cross-reference:

assessment report

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

2008

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

The study was performed prior to the establishment of LLNA.

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

male

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland GmbH
- Age at study initiation: 5-6 weeks
- Weight at study initiation: 282 – 388 g
- Housing: Individually in Makrolon type-4 cages with standard softwood bedding
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3418 guinea pig breeding / maintenance diet, ad libidum
- Water (e.g. ad libitum): Community tap water from Füllinsdorf, ad libitum.
- Acclimation period: 2008-09-18 to 2008-10-13


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

Route:

intradermal

Vehicle:

water

Concentration / amount:

5 % / 0.1 ml

Adequacy of induction:

highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically

Route:

epicutaneous, occlusive

Vehicle:

water

Concentration / amount:

50% /0.3 ml

Day(s)/duration:

24h

Adequacy of induction:

highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically

Route:

epicutaneous, occlusive

Vehicle:

water

Concentration / amount:

5% /0.2 mL

Day(s)/duration:

24h

Adequacy of challenge:

highest non-irritant concentration

No. of animals per dose:

5 control animals (males)
10 treated animals (males)

Details on study design:

RANGE FINDING TESTS:
A: Intradermal injections:
Four intradermal injections (0.1 mL/site) of a 1:1 (v/v) mixture of Freund's Complete Adjuvant/physiological saline (day 1) (shaved neck of one guinea pig)
Five days later: Four intradermal injections (0.1 mL/site) at concentrations of H = 15 %, I = 10 % and J = 5 % of the test item in purified water (clipped flank of the same guinea pig)
Dermal reactions assessed 24 hrs later.

B: Epidermal applications:
Four intradermal injections (0.1 mL/site) of a 1:1 (v/v) mixture of Freund's Complete Adjuvant/physiological saline (day 1) (shaved necks of two guinea pigs)
Five days later: Epidermal application with the test item at K = 15 %, L = 10 %, M = 5 % and N = 3 % in purified water (shaved flanks of the same two guinea pigs)
Dermal reactions assessed 24 and 48 hrs after removal of the bandage.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal / epicutaneously)
- Exposure period: injected / 48 h occlusive
- Site: scapular region (clipped free of hair)
- Frequency of applications: 1 / 1
- Duration: 0 - 8 days
- Concentrations:
1st application: 5% intradermal; 2nd application: 50% epicutaneous

B.
CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 22
-Exposure period: 24 hrs
- Site: left flank (test item); right flank: vehicle (clipped free of hair)
- Concentrations: 5% occlusive epicutaneous
- Evaluation (hr after challenge): 24 and 48 hrs

Positive control substance(s):

yes

Remarks:

ALPHA-HEXYLCINNAMALDEHYDE

Positive control results:

Discrete/patchy to moderate/confluent erythema with or without scaling was observed in nine out of ten test animals at the 24- and 48-hour reading after the challenge treatment with ALPHA-HEXYLCINNAMALDEHYDE at 1 % in PEG 300 (left shoulder). Five test animals showed discrete/patchy erythema at the 24-hour reading after treatment with ALPHAHEXYLCINNAMALDEHYDE at 0.1 % in PEG 300 (left flank). No skin effect was observed in the control group.
Based on the above mentioned findings in an adjuvant sensitization test (M&K-test) in guinea pigs and in accordance to Commission Directive 2001/59/EC, ALPHAHEXYLCINNAMALDEHYDE has to be classified and labelled as a skin sensitizer.

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

5%

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

none

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

5 %

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

none

Remarks on result:

no indication of skin sensitisation

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

0

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

none

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: none.

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

0

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

none

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: none.

Skin reactions in the intradermal pretest
Animal No.	Concentration (%)	Reactions
671, male	75	Moderate and confluent erythema Oedema and necrosis
	50	Moderate and confluent erythema Oedema and necrosis
	25	Moderate and confluent erythema Oedema and necrosis
689, male	15	Moderate and confluent erythema Necrosis
	10	Moderate and confluent erythema Necrosis
	5	Discrete/patch erythema

Skin reactions in the intradermal pretest
Animal No.	Concentration (%)	Reactions after removal of badange
		24h	28h
672, male	100	Intense erythema and swelling; Fissures	Moderate and confluent erythema; Scaling
	75	Intense erythema and swelling; Fissure	Moderate and confluent erythema; Scaling
	50	Moderate and confluent erythema	Moderate and confluent erythema; Scaling
	25	Discrete/patchy erythema	No visible change
673, male	100	Intense erythema and swelling; Fissures	Moderate and confluent erythema; Scaling
	75	Intense erythema and swelling; Fissures	Moderate and confluent erythema; Scaling
	50	Discrete/patchy erythema	No visible change
	25	Discrete/patchy erythema	Discrete/patchy erythema
690, male	15	Discrete/patchy erythema	No visible change
	10	No visible change	No visible change
	5	No visible change	No visible change
	3	No visible change	No visible change
691, male	15	Discrete/patchy erythema	No visible change
	10	Discrete/patchy erythema	No visible change
	5	No visible change	No visible change
	3	No visible change	No visible change

Skin reactions after epidermal induction of with test item treated animals
Animal No.	Reactions after removal of badange
	24h	28h
679	Discrete/patchy erythema	Discrete/patchy erythema
680	Discrete/patchy erythema	Discrete/patchy erythema
681	Discrete/patchy erythema	No visible change
682	Discrete/patchy erythema	Discrete/patchy erythema
683	Discrete/patchy erythema	Discrete/patchy erythema
684	Discrete/patchy erythema	Discrete/patchy erythema
685	Discrete/patchy erythema	No visible change
686	Discrete/patchy erythema	Discrete/patchy erythema
687	Moderate and confluent erythema	Discrete/patchy erythema
688	Discrete/patchy erythema	Discrete/patchy erythema

Skin reactions after epidermal challenge of with test item treated animals
Animal No.	Reactions after removal of badange
	24h	28h
679	No visible change	No visible change
680	No visible change	No visible change
681	No visible change	No visible change
682	No visible change	No visible change
683	No visible change	No visible change
684	No visible change	No visible change
685	No visible change	No visible change
686	No visible change	No visible change
687	No visible change	No visible change
688	No visible change	No visible change

Interpretation of results:

GHS criteria not met

Conclusions:

Sodium N-cocoyl glycinate was investigated for its skin isensitization property according to the Guideline OECD 406 (M&K). It is not skin sensitizing.

Executive summary:

Sodium N-cocoyl glycinate was investigated for its skin sensitization property according to the OECD 406 (M&K). As for induction, ten male guinea pigs were treated intradermally at concentration of 5% in water and one week later epidermally at concentration of 50 % in water. Five control animals were treated with vehicle only. Two weeks after the epidermal induction, all animals were epidermally challenged at concentration of 5%. None of the animals responded. Sodium N-cocoyl glycinate is not skin sensitizing.

Materials and methods

Test material

Test material information

Constituent 1

Reference substance name:

fatty acid chloride, C12, reaction product with sodium glutamate and sodium hydroxide

EC Number:

947-842-3

IUPAC Name:

fatty acid chloride, C12, reaction product with sodium glutamate and sodium hydroxide

Test material form:

solid: particulate/powder

Results and discussion

In vivo (non-LLNA)

Results

Results 1

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

5%

No. with + reactions:

0

Total no. in group:

5

Results 2

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

5%

No. with + reactions:

0

Total no. in group:

5

Results 3

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

0

No. with + reactions:

0

Total no. in group:

10

Results 4

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

0

No. with + reactions:

0

Total no. in group:

10

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The skin sensitization property of the registration substance sodium N-lauroyl glutamate is derived based on the read-across to Sodium N-cocoyl glutamate and Sodium N-cocoyl glycinate. No skin isensitizing property can be reliably derived.

Executive summary:

The skin sensitisation property of the registration substance, sodium N-lauroyl glutamate, is derived based on the read-across to sodium N-cocoyl glutamate and sodium N-cocoyl glycinate.

The registration substance and the read-across sources are amides of fatty acids and amino acids and can be characterized as "N-fatty acyl amino acids", of which endogeous occurence and metabolism are known. Based on the comparable chemical structure, comparable phys-chem data and expected comparable metabolism, these compound are likely exhibit comparable toxicity profiles.

Sodium N-cocoyl glutamate was investigated for its skin sensitization property according to the OECD 406 (Buehler method). 0.5 ml of the test material wasoccusively applied to the clipped skin of guinea pigs for 6 hours as induction and challenge treatment. None of the twenty treated animals responded. Sodium N-cocoyl glutamate is not skin sensitizing.

Sodium N-cocoyl glycinate was investigated for its skin sensitization property according to the OECD 406 (M&K). As for induction, ten male guinea pigs were treated intradermally at concentration of 5% in water and one week later epidermally at concentration of 50 % in water. Five control animals were treated with vehicle only. Two weeks after the epidermal induction, all animals were epidermally challenged at concentration of 5%. None of the animals responded. Sodium N-cocoyl glycinate is not skin sensitizing.

Likewise, the registration substance, sodium N-lauroyl glutamate is considered as not skin sensitizing.