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Diss Factsheets

Administrative data

Description of key information

The results obtained in this study indicate that LAE does not elicit a sensitisation response in the guinea pig, though no reaction was observed at challenge test.

The test substance had not produced any sensitization rate and therefore it can be classified as non-sensitizer.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From June 8, 2000 to February 2, 2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
A guideline study with GLP.
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
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The study was performed before the entry into force of REACH Regulation.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Nossan S.r.l., Correzzana (MI), Italy
- Age at study initiation: 4 to 5 weeks
- Weight at study initiation: 300-350 g
- Housing: in groups of up to 5 animals, in stainless steel cages measuring 48 x 63 x 41 cm with a grid floor
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 24°C
- Humidity (%): 45 to 65%.
- Photoperiod (hrs dark / hrs light): artificial cycle of 12 hours light/12 hours dark

IN-LIFE DATES: From: May 2, 2000 To: May 25, 2000
Route:
intradermal
Vehicle:
water
Concentration / amount:
0.1 %
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
20%
Day(s)/duration:
48 hours
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
5%
Day(s)/duration:
24 hours
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
Number of animals in test group: 10
Number of animals in negative control group: 5
Details on study design:
RANGE FINDING TESTS:
- Intradermal injection tolerance test: Two animals were selected from those available. Six sites were selected on each animal and these injected intradermally with 0.1 ml single concentration of the test item. The 2 animals were treated with the substance at concentrations of 50%, 20%, 10%, 5%, 1% and 0.5% in sterile water. The treated sites were examined 5 days later for any signs of reaction to treatment. Observed irritation was recorded using the Draize scoring scale (below) and any response not covered by the scoring scale was separately described.
- Topical application tolerance test: Five animals were selected from those available and each of them injected intradermally at the prepared site with two injections, each of 0.1 ml, of emulsified Freund's complete adjuvant. Seven days later, the flanks of each animal were clipped free of hair and dosed with 2 concentrations of the test item, 1 on either flank. All animals were treated in this manner such that a total of 5 concentrations of the test item (50%, 20%, 10% 5% and 1% in sterile water). Within the group, each concentration was duplicated. The adhesive dressings and gauze patches were removed after 24 hours contact with the skin.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2: Intradermal injectionand topical application
- Exposure period: 7 days intradermal injection; 48 hours topical application
- Test group: 1 test group of 10 animals
- Control group: 5 animals
- Site: scapular region
- Frequency of applications: Intradermal injection (day 0); topical application (day 8)
- Duration: 21 days
- Concentrations: 0.1% intradermal injection; 20% topical application

B. CHALLENGE EXPOSURE
- No. of exposures: Challenge exposure topical application (1)
- Day(s) of challenge: 2
- Exposure period: 24 hours
- Test group: 1 test group of 10 animals
- Control group: 5 animals
- Site: flanks
- Concentrations: 5%
- Evaluation (hr after challenge): 3, 24 and 48 hours
Positive control substance(s):
yes
Remarks:
(mercaptobenzothiazole)
Positive control results:
70% response in test group and 0% response in control group at challenge. Incidence at challenge is acceptable. Test system is regarded as valid.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
5 %
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:
test chemical
Dose level:
5 %
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:
negative control
Dose level:
0 %
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
5 %
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
0
Remarks on result:
not measured/tested
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
0
Remarks on result:
not measured/tested

Maximum concentration not causing irritating effects in preliminary test: 5 %

Signs of irritation during induction:


Intradermal injection: Well defined erythema was apparent following administration of Freund's complete adjuvant, the vehicle or the test substance mixed with Freund's complete adjuvant.  Slight reaction was seen in five animals at both sites treated with the test substance.  No reaction was observed at those sites following 48 hours topical exposure to test item or vehicle alone.

Topical application: No reaction was observed around the injection sites of animals following topical exposure to the test substance or the vehicle alone.

Evidence of sensitisation of each challenge concentration:
No response was observed in any animal.

Other observations:
Changes in bodyweight of animals during the study period were generally similar in animals from both the test and control groups.

Table 1. Details on main study Challenge individual results:

Dermal response
Vehicle Test item  
Group function

Animal

Sex

24 h

48 h

24 h

48 h
CONTROL 221 Female

0

0

0

0

223

0

0

0

0

225

0

0

0

0

227

0

0

0

0

229

0

0

0

0

TEST

231

0

0

0

0

233

0

0

0

0

235

0

0

0

0

237

0

0

0

0

239

0

0

0

0

241

0

0

0

0

243

0

0

0

0

245

0

0

0

0

247

0

0

0

0

249

0

0

0

0

Erythema and Eschar Formation Value

No erythema

0

Very slight erythema (barely perceptible)

1

Well-defined erythema

2

Moderate to severe erythema

3

Severe erythema (beet redness) to slight eschar formation

(injuries in depth)

4

Oedema Formation

No oedema

0

Very slight oedema (barely perceptible)

1

Slight oedema (edges of area well-defined by definite raising)

2

Moderate oedema (raised approximately 1 millimetre)

3

Severe oedema (raised more than 1 millimetre and extending beyond the area of exposure)

4
Interpretation of results:
GHS criteria not met
Conclusions:
The results obtained in this study indicate that LAE does not elicit a sensitisation reponse in the guinea pig, as no reaction was observed at challenge.
Executive summary:

The study was performed according to OECD 406 guideline and in agreement with those of B.6 detailed in Commision Directive 96/54/EEC.

The results obtained in this study indicate that LAE does not elicit a sensitisation response in the guinea pig, there being no reaction observed at challenge. LAE is not sensitising to skin and has not to be classified for skin sensitisation.

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From to September 15, 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
A guideline study with GLP.
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 before the entry into force of REACH Regulation.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Hall Limited, Burton-on-Trent, Staffordshire, UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 379-441 g
- Housing: individually or in pairs in solid-floor polypropylene cages furnished with woodflakes
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-21 ºC
- Humidity (%): 47-73%
- Air changes (per hr): 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours continous light and 12 hours of darkness

IN-LIFE DATES: From: June 27, 1995 To: July 31, 1995
Route:
intradermal
Vehicle:
water
Remarks:
distilled
Concentration / amount:
1 %
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
50% v/v
Day(s)/duration:
48 hours
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
50 and 25 % v/v
Day(s)/duration:
24 hours
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
10 animals for the main study and 5 for control
Details on study design:
RANGE FINDING TESTS:
- Selection of Concentration for Intradermal Induction: Two concentrations of test material were investigated (1 % and 5% w/v in distilled water) and evaluated in a total of two guinea pigs. The highest concentration that caused only mild to moderate skin irritation, and which was well tolerated systemically, was selected for the intradermal induction stage of the main study.
- Selection of Concentration for Topical Induction: Two guinea pigs (intradermally injected with Freund's Complete Adjuvant eleven days earlier) were treated with the undiluted test material and three preparations of the test material (75%, 50% and 25% v/v in distilled water). The highest concentration producing only mild to moderate dermal irritation was selected for the topical induction stage of the main study.
- Selection of Concentration for Topical Challenge: Four preparations of the test material (50%, 25%, 10% and 5% v/v in distilled water) were evaluated in two guinea pigs (different from the previous study) under occlusive dressings for an exposure period of 24 hours. The highest non-irritant concentration of the test material and one lower concentration were selected for the topical challenge stage of the main study.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures:2: Intradermal and topical induction.
- Exposure period: 7 days intradermal injection; 48 hours topical application
- Test group: 1 test group of 10 animals
- Control group: 5 animals
- Site: shoulder region
- Frequency of applications: Intradermal injection (day 0); topical application (day 8)
- Duration: 21 days
- Concentrations: 1 w/v% in distilled water for intradermal injection; 50% v/v in distilled water for topical application

B. CHALLENGE EXPOSURE
- No. of exposures: Challenge exposure topical application (1)
- Day(s) of challenge: 2
- Exposure period: 24 hours
- Test group: 1 test group of 10 animals
- Control group: 5 animals
- Site: both flanks
- Concentrations: 50% and 25% v/v in distilled water
- Evaluation (hr after challenge): 3, 24 and 48 hours
Positive control substance(s):
yes
Remarks:
(positive control data from several substances: November 1993 to November 1994)
Positive control results:
Results from the positive control data (November 1993 to November 1994) are within the expected range.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
50% v/v
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:
test chemical
Dose level:
50% v/v
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% v/v
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:
test chemical
Dose level:
25% v/v
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:
negative control
Dose level:
50% v/v
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
50% v/v
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
25% v/v
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
25% v/v
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
100% and 75% in araches oil
No. with + reactions:
7
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Remarks:
alpha-hexylcinnamaldehyde Tech. 85%
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
25% in 95% aqueous ethanol
No. with + reactions:
8
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Remarks:
2-Mercaptobenzothiazole
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
10% and 5% in 80%aqueous ethanol
No. with + reactions:
7
Total no. in group:
18
Remarks on result:
positive indication of skin sensitisation
Remarks:
Ethyl 4-aminobenzoate 98%
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.1% and 0.05% in arachis oil
No. with + reactions:
9
Total no. in group:
9
Remarks on result:
positive indication of skin sensitisation
Remarks:
2,4-Dinitrochlorobenzene

Table 1. Individual skin reaction in test and control animals at Challenge:

24 h

48 h

50%

25%

50%

25%

Group function

Animal

Sex

Er*

Oe*

Er*

Oe*

Er*

Oe*

Er*

Oe*

TEST

1

Male

0

0

0

0

0

0

0

0

2

0

0

0

0

0

0

0

0

3

0

0

0

0

0

0

0

0

4

0

0

0

0

0

0

0

0

5

0

0

0

0

0

0

0

0

6

0

0

0

0

0

0

0

0

7

0

0

0

0

0

0

0

0

8

0

0

0

0

0

0

0

0

9

0

0

0

0

0

0

0

0

10

0

0

0

0

0

0

0

0

CONTROL

11

0

0

0

0

0

0

0

0

12

0

0

0

0

0

0

0

0

13

0

0

0

0

0

0

0

0

14

0

0

0

0

0

0

0

0

15

0

0

0

0

0

0

0

0

Er=Erythema
Oe=Oedema

 * Draize J.H., (1977) "Dermal and Eye Toxicity Tests" In: Principles and Procedures for Evaluating the Toxicity of Household Substances, National Academy of Sciences, Washington D.C. p.31

Erythema and Eschar Formation Value

No erythema

0

Very slight erythema (barely perceptible)

1

Well-defined erythema

2

Moderate to severe erythema

3

Severe erythema (beet redness) to slight eschar formation

(injuries in depth)

4

Oedema Formation

No oedema

0

Very slight oedema (barely perceptible)

1

Slight oedema (edges of area well-defined by definite raising)

2

Moderate oedema (raised approximately 1 millimetre)

3

Severe oedema (raised more than 1 millimetre and extending beyond the area of exposure)

4
Interpretation of results:
GHS criteria not met
Conclusions:
The test substance has not produced any sensitisation rate and is classified as non-sensitizer.
Executive summary:

A study was performed to assess the contact sensitisation potential of Nα-Lauroyl-L-arginine ethyl ester monohydrochloride (LAE) in the albino guinea pig. The study was performed in compliance with the OECD Guidelines for Testing of Chemicals No. 406 "Skin Sensitisation" (adopted 17 July 1992) and Method B6 of Commission Directive 92/69/EEC (which constitutes Annex Vof Council Directive 67/548/EEC).

Ten test and five control animals were used for the main study.

Based on the results of sighting tests, the concentrations of test material for the induction and challenge phases were selected as follows:

 

Intradermal Induction                                 :     1 % w/v in distilled water

Topical Induction                                         :     50% v/v in distilled water

Topical Challenge                                       :     50% and 25% v/v in distilled water

The test material produced a 0% (0/10) sensitisation rate and was classified as a non-sensitiser to guinea pig skin.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Two studies were performed to assess the contact sensitisation potential of the test material LAE in compliance with the recommendations of the OECD Guidelines for the Testing of ChemicalsNo. 406 "Skin Sensitisation" (adopted 17 July 1992) and Method B6 of Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 67/548/EEC).

Results of both studies assure a 0% sensitisation rate classifying LAE as a non-sensitiser to guinea pig skin. The test material did not meet the criteria for classification as a sensitiser according to EU labelling regulations.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Observations and results obtained under the Guidelines mentioned above show that dehydrated Nα-Lauroyl-L-arginine ethyl ester monohydrochloride (LAE) has no sensitisation response effects.