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Diss Factsheets

Administrative data

Description of key information

Skin sensitisation (in vivo, OECD 406): not sensitising

Conclusion based on data with alcohols, C12-14, ethoxylated, sulfates, sodium salts (CAS No. 68891-38-3, EC No. 500-234-8).

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:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
GPMT
Deviations:
yes
Remarks:
No positive control included
GLP compliance:
no
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
A non-LLNA test is available that was performed prior to the current data requirements, stipulated in Regulation (EC) No 1907/2006. In accordance with the same Regulation, the data were included to avoid unnecessary testing.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
According to Guideline.
Route:
intradermal
Vehicle:
water
Concentration / amount:
Intradermal induction: 0.05%
Day(s)/duration:
single applications
Adequacy of induction:
not specified
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
Epicutaneous induction: 2.5 %
Adequacy of induction:
not specified
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
Challenge: 0.1 and 0.5%
Adequacy of challenge:
not specified
No. of animals per dose:
20 (test group)
10 (control gro
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.1%
No. with + reactions:
1
Total no. in group:
20
Clinical observations:
1 animal with erythema: localized reaction, restricted to a small area of the challenge site.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.5%
No. with + reactions:
6
Total no. in group:
20
Clinical observations:
2 animals with erythema, 4 animals with erythema, localized reaction restricted to a small area of the challenge site.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0.1%
No. with + reactions:
1
Total no. in group:
20
Clinical observations:
1 animal with erythema, localized reaction, restricted to a small area of the challenge site.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0.5%
No. with + reactions:
5
Total no. in group:
20
Clinical observations:
5 animals with erythema, localized reaction, restricted to a small area of the challenge site.
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
test chemical
Dose level:
0.1%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
none
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
test chemical
Dose level:
0.5%
No. with + reactions:
1
Total no. in group:
20
Clinical observations:
1 animal with erythema: localized reaction restricted to a small area of the challenge site.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0.5%
No. with + reactions:
2
Total no. in group:
10
Clinical observations:
2 animals with erythema: localized reaction restricted to a small area of the challenge site.
Remarks on result:
other: anterior site
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0.1%
No. with + reactions:
1
Total no. in group:
10
Clinical observations:
1 animals with erythema: localized reaction restricted to a small area of the challenge site.
Remarks on result:
other: posterior site
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0.5%
No. with + reactions:
2
Total no. in group:
10
Clinical observations:
2 animals with erythema: localised dermal reaction restricted to a small area of the challenge site.
Remarks on result:
other: anterior site
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0.1%
No. with + reactions:
1
Total no. in group:
10
Clinical observations:
1 animal with erythema: localised dermal reaction restricted to a small area of the challenge site.
Remarks on result:
other: posterior site
Reading:
rechallenge
Hours after challenge:
72
Group:
negative control
Dose level:
0.5%
No. with + reactions:
1
Total no. in group:
10
Clinical observations:
1 animal with erythema: localised dermal reaction restricted to a small area of the challenge site.
Remarks on result:
other: anterior site
Reading:
rechallenge
Hours after challenge:
72
Group:
negative control
Dose level:
0.1%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: posterior site
Group:
positive control
Remarks on result:
other: no information

 

Positive controls were not included.

Body weights were unaffected by treatment.

Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.
Conclusions:
In the present in vivo skin sensitisation guinea pig maximisation test, the test substance did not induce skin sensitising reactions in the tested animals. Local skin irritations were noted in a few cases, but the dermal reactions observed in the test animals were similar to those seen in animals of the control group. Therefore, it is concluded that in this test, the test substance did not produce any evidence of delayed contact hypersensitivity.
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
GPMT
Deviations:
yes
Remarks:
no occlusive dressing for challenge; 3 observations on 3 consecutive days; no positive control
GLP compliance:
not specified
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
A non-LLNA test is available that was performed prior to the current data requirements, stipulated in Regulation (EC) No 1907/2006. In accordance with the same Regulation, the data were included to avoid unnecessary testing.
Species:
guinea pig
Strain:
other: Pirbright white
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source:
- Females (if applicable) nulliparous and non-pregnant: [yes/no/not specified]
- Microbiological status of animals, when known:
- Age at study initiation:
- Weight at study initiation: mean: 567 g (treatment group); mean: 503 g (control group)
- Housing:
- Diet (e.g. ad libitum):
- Water (e.g. ad libitum):
- Acclimation period:
- Indication of any skin lesions:

ENVIRONMENTAL CONDITIONS
- Temperature (°C):
- Humidity (%):
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light):
- IN-LIFE DATES: From: To:
Route:
intradermal
Vehicle:
water
Concentration / amount:
Induction: 5% (based on 28% a.i.)
Day(s)/duration:
3 single injections in duplicates
Adequacy of induction:
not specified
No.:
#1
Route:
epicutaneous, open
Vehicle:
other: vaseline
Concentration / amount:
Challenge: 1% (based on 28% a.i.)
Day(s)/duration:
1 week after induction exposure duration: 48 h
Adequacy of challenge:
not specified
No.:
#2
Route:
epicutaneous, open
Vehicle:
other: vaseline
Concentration / amount:
Rechallenge: 1% (based on 28% a.i.)
Day(s)/duration:
2 weeks after challenge Exposure duration: 24 h
Adequacy of challenge:
not specified
No. of animals per dose:
20 (test group)
10 (control group)
Details on study design:
RANGE FINDING TESTS: not conducted

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 6 simultaneous exposures (3 injection schemes in duplicates)
- Test groups: treated groups only
- Site: skin area above the shoulders; size: 4 x 6 cm
- Frequency of applications: single
- Concentrations: 1) Freund's adjuvant, 0.1 mL; 2) test substance 5% in water, 0.1 mL; 3) mix of Freund's adjuvant with 5% test substance (1:1), 0.1 mL/kg

B. CHALLENGE EXPOSURE
- No. of exposures: 2 (1 challenge, 1 re-challenge)
- Day(s) of challenge: 1 week after induction (challenge); 2 weeks after challenge (rechallenge)
- Exposure period: 48 h (challenge); 24 h (rechallenge)
- Test groups: challenge, re-challenge
- Control group: re-challenge
- Site: ca. 2 x 4 cm of the area above the shoulders (covering the injection sites) for the challenge; 5 x 5 cm flank areas for the rechallenge
- Concentrations: 1% vaseline (challenge and rechallenge)
- Evaluation (hr after challenge): 24 hr

OTHER: In case the test substance is no skin irritant, the skin of the test animals is pre-treated 24 h prior to the Patch-test using 10% sodium lauryl sulfate in vaseline. The mixture is gently rubbed into the skin without the use of a bandage.
Positive control substance(s):
no
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
1%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
1%
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:
test chemical
Dose level:
1%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
erythema, oedema and necrosis in animals injected with Freund's adjuvant; some animals treated with test substance had erythema
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
1%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
erythema, oedema and necrosis in animals injected with Freund's adjuvant; some animals treated with test substance had erythema
Remarks on result:
no indication of skin sensitisation
Group:
positive control
Remarks on result:
other: no information
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.
Conclusions:
In the present in vivo skin sensitisation guinea pig maximization test, the substance did not induce any skin sensitising reactions when treated at a dose of 1%. Local skin irritations were noted predominantly as a response to treatment with Freund's adjuvant. Based on the results it is concluded that the test substance does not have skin sensitising potential.
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
GPMT
Deviations:
not specified
GLP compliance:
yes (incl. QA statement)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
A non-LLNA test is available that was performed prior to the current data requirements, stipulated in Regulation (EC) No 1907/2006. In accordance with the same Regulation, the data were included to avoid unnecessary testing.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Route:
intradermal
Vehicle:
unchanged (no vehicle)
Concentration / amount:
1) 0.1 mL Freund's Complete Adjuvant
2) 0.1 mL test substance (100%)
3) 0.1 mL Freund's Complete Adjuvant + test substance
Day(s)/duration:
single injections
Adequacy of induction:
not specified
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100%
Day(s)/duration:
7 days after injections Exposure duration: 48 h
Adequacy of induction:
not specified
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100% and 50% (solution in water)
Day(s)/duration:
14 days after induction Exposure duration: 24 h
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
20 (treatment group)
20 (control group)
Details on study design:
Observation time points: 24 h and 48 h after challenge
Positive control substance(s):
no
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
100%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
None
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
50%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
None
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
100%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
None
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
50%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
None
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
100%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
None
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
50%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
None
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
100%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
None
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
50%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
None
Remarks on result:
no indication of skin sensitisation
Group:
positive control
Remarks on result:
other: no information
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.
Conclusions:
In the present skin sensitisation guinea pig maximisation test, the test substance did not induce any skin sensitising reactions in treated animals. Therefore, it is concluded that the test substance is not a skin sensitiser.
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
22 May - 15 Jun 1989
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
GPMT
adopted in 1981
Deviations:
yes
Remarks:
24 and 48 h observation time points no positive control
GLP compliance:
not specified
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
A non-LLNA test is available that was performed prior to the current data requirements, stipulated in Regulation (EC) No 1907/2006. In accordance with the same Regulation, the data were included to avoid unnecessary testing.
Species:
guinea pig
Strain:
Dunkin-Hartley
Remarks:
Bor: DHPW
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: F. Winkelmann, Borchen, DE
- Females nulliparous and non-pregnant: not specified
- Age at study initiation: not reported
- Weight at study initiation: 325 g (tested animals); 324 g (control animals)
- Housing: 1-5 animals per Macrolon Type IV cage
- Diet: G4 guinea pig diet (Ssniff Spezialfutter GmbH, Soest, DE); ad libitum
- Water: tap water; ad libitum
- Acclimation period: 5 - 8 days
- Indication of any skin lesions: none

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 1
- Humidity (%): 60 ± 5
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Route:
intradermal
Vehicle:
water
Concentration / amount:
1) 0.1 mL mix of Freunds Complete Adjuvant (FCA) and demineralized water (1:1);
2) 0.1 mL of 0.1% test substance in demineralized water;
3) 0.1 mL of 0.1% test substance in a mixture of FCA and demineralized water (1:1)
Day(s)/duration:
single applications
Adequacy of induction:
not specified
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
challenge: 30%
Day(s)/duration:
1 week after induction exposure duration: 48 h
Adequacy of challenge:
not specified
No.:
#2
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
rechallenge: 10%
Day(s)/duration:
2 weeks after challenge exposure duration: 24 h
Adequacy of challenge:
not specified
No. of animals per dose:
20 (treated group)
10 (control group)
Details on study design:
RANGE FINDING TESTS: not conducted

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: a total of 6 injections (symmetrical, simultaneous)
- Exposure period: single injections
- Test groups: yes
- Control group: yes
- Site: 4 x 6 cm skin area above the shoulders
- Frequency of applications: once, simultaneously
- Duration: not applicable (single injections)
- Concentrations: 1) 0.1 mL mix of Freunds Complete Adjuvant (FCA) and demineralized water (1:1); 2) 0.1 mL of 0.1% test substance in demineralized water; 3) 0.1 mL of 0.1% test substance in a mixture of FCA and demineralized water (1:1)

B. CHALLENGE EXPOSURE
- No. of exposures: 2 (1 challenge, 1 rechallenge)
- Day(s) of challenge: 1 week after induction (challenge), 2 weeks after challenge (rechallenge)
- Exposure period: 48 h (challenge), 24 h (rechallenge)
- Test groups: yes
- Control group: yes
- Site: 2 x 4 cm above the shoulders (challenge); 2 x 2 cm flank area (rechallenge)
- Concentrations: 30% (challenge); 10% (rechallenge)
- Evaluation (hr after challenge): 24 and 48 h

OTHER: Animals were weighed before study start and once weekly.

SCORING CRITERIA
No erythema = 0
Slight erythema = 1
Clear and diffuse erythema = 2
Strong erythema with swelling = 3
Challenge controls:
Negative controls included, treated in the same way as treated animals but without the test substance.
Positive control substance(s):
no
Positive control results:
Not applicable.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
10%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
10%
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:
test chemical
Dose level:
10%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
none
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
10%
No. with + reactions:
1
Total no. in group:
20
Clinical observations:
One animal with slight eschar formation
Remarks on result:
no indication of skin sensitisation
Group:
positive control
Remarks on result:
other: no information

BODY WEIGHT

Body weight and body weight gain were unaffected and similar to the control group.

 

LOCAL SKIN REACTIONS

Induction: After intradermal injection with FCA only, the injection sites showed clear erythema, oedema and slight necrosis both in treated and control animals. For the combined injectinos with FCA and 0.1% test substance, strong erythema and clear oedema as well as strong necrosis were observed. For injections with 0.1% test substance only (without FCA), only slight erythema and oedema in treated animals were noted, whereas in the control animals injected with water only, slight erythema was observed.

Challenge: Both in treated and control animalls, strong and partly bloody infections in animals receiving FCA. In animals receiving water only, slight to clear erythema was observed. 24 h after patch removal, eschar formation was noted in animals treated with FCA.

Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.
Conclusions:
In the present in vivo skin sensitization guinea pig maximisation test, the test substance did not induce skin sensitizing reactions when treated at a concentration of 30%/10%. Local skin reactions were noted both in treated and control groups and were mainly attributable to FCA. Based on the results it is concluded that the test substance does not have skin sensitizing potential.
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
14 Dec 1988 - 19 Jan 1989
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
GPMT
Deviations:
not specified
GLP compliance:
not specified
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
A non-LLNA test is available that was performed prior to the current data requirements, stipulated in Regulation (EC) No 1907/2006. In accordance with the same Regulation, the data were included to avoid unnecessary testing.
Species:
guinea pig
Sex:
male/female
Route:
intradermal
Vehicle:
other: saline
Concentration / amount:
0.05 % (a.i.)
Day(s)/duration:
single injections
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
epicutaneous, occlusive
Vehicle:
other: saline
Concentration / amount:
10 % (a.i.)
Day(s)/duration:
6-7 days after intradermal injections Exposure duration: 48 h
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
other: saline
Concentration / amount:
25 % (a.i.)
Day(s)/duration:
14 days after induction Exposure duration: 24 h
Adequacy of challenge:
highest non-irritant concentration
No.:
#2
Route:
epicutaneous, occlusive
Vehicle:
other: saline
Concentration / amount:
25% (a.i.)
Day(s)/duration:
1 week after challenge #1
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
10 (treatment group)
4 (treated control group)
Positive control substance(s):
no
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
25%
No. with + reactions:
0
Total no. in group:
4
Clinical observations:
1 animal with very faint erythema (not usually confluent); score 0.5
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
25%
No. with + reactions:
0
Total no. in group:
4
Clinical observations:
None
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
25%
No. with + reactions:
4
Total no. in group:
10
Clinical observations:
4 animals with faint erythema (score 1) 1 animal with very faint erythema (score 0.5)
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
25%
No. with + reactions:
4
Total no. in group:
10
Clinical observations:
1 animal with moderate erythema (score 2) 3 animals with faint erythema (score 1) 2 animals with very faint erythema (score 0.5)
Remarks on result:
positive indication of skin sensitisation
Reading:
rechallenge
Hours after challenge:
24
Group:
negative control
Dose level:
25%
No. with + reactions:
0
Total no. in group:
4
Clinical observations:
2 animals with very faint erythema (score 0.5)
Remarks on result:
no indication of skin sensitisation
Reading:
rechallenge
Hours after challenge:
48
Group:
negative control
Dose level:
25%
No. with + reactions:
0
Total no. in group:
4
Clinical observations:
2 animals with very faint erythema (score 0.5)
Remarks on result:
no indication of skin sensitisation
Reading:
rechallenge
Hours after challenge:
24
Group:
test chemical
Dose level:
25%
No. with + reactions:
4
Total no. in group:
10
Clinical observations:
1 animal with moderate erythema (score 2) 3 animals with faint erythema (score 1) 1 animal with very faint erythema (score 0.5)
Remarks on result:
positive indication of skin sensitisation
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
25%
No. with + reactions:
4
Total no. in group:
10
Clinical observations:
1 animal with moderate erythema (score 2) 3 animals with faint erythema (score 1) 1 animal with very faint erytehma (score 0.5)
Remarks on result:
positive indication of skin sensitisation
Group:
positive control
Remarks on result:
other: no information
Interpretation of results:
other: Skin Sens. 1, H317. Classification according to Regulation (EC) No. 1272/2008 (CLP/EU GHS).
Conclusions:
In the present in vivo skin sensitisation guinea pig maximisation test, the test substance induced skin sensitising reactions in the treated animals with borderline results (4/10 animals in challenge and rechallenge, 40 % sensitization rate). Based on the results of this study, the test substance is concluded to be a skin sensitiser.
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
GPMT
adopted in 1981
Deviations:
not specified
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
A non-LLNA test is available that was performed prior to the current data requirements, stipulated in Regulation (EC) No 1907/2006. In accordance with the same Regulation, the data were included to avoid unnecessary testing.
Species:
guinea pig
Strain:
Pirbright-Hartley
Sex:
female
Route:
intradermal
Vehicle:
other: 0.9% NaCl solution
Concentration / amount:
5%
Day(s)/duration:
single injections
Adequacy of induction:
not specified
Route:
epicutaneous, occlusive
Vehicle:
other: 0.9% NaCl solution
Concentration / amount:
0.5%
Day(s)/duration:
48 h
Adequacy of induction:
not specified
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
other: 0.9% NaCl solution
Concentration / amount:
0.5%
Day(s)/duration:
24 h
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
10 (treatment group)
5 (control group)
Positive control substance(s):
no
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0.5% test substance in 0.9% NaCl solution
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
erythema and oedema
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0.5% test substance in 0.9% NaCl solution
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
erythema and oedema
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.5% test substance in 0.9% NaCl solution
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
erythema and oedema, more severe than in control group
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0.5% test substance in 0.9% NaCl solution
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
erythema and oedema, more severe than in control group
Remarks on result:
no indication of skin sensitisation
Group:
positive control
Remarks on result:
other: no information

Moderate erythema and severe oedema were noted for treated sites with Freund's Complete Adjuvant.

The reactions were more severe in test substance treated groups compared to controls.

Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.
Conclusions:
In the present in vivo skin sensitising guinea pig maximisation test, the test substance did not induce any skin sensitising reactions in the treated animals. Therefore, it is concluded that the test substance is not a skin sensitiser.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Skin sensitisation

Data on skin sensitisation are available for alcohols, C12-14, ethoxylated, sulfates, sodium salts (CAS No. 68891-38-3, EC No. 500-234-8) as well as several member substances of the Alkyl Ether Sulfates (AES) category.

 

Studies with alcohols, C12-14, ethoxylated, sulfates, sodium salts (CAS No. 68891-38-3, EC No. 500-234-8)

There are 6 studies on skin sensitisation, of which two have been summarised below.

A non-GLP study was performed with the substance according to the guinea pig maximisation test protocol described in OECD guideline 406 (Unger, 1986c). Twenty female guinea pigs were included in the test group, while 10 were included in the negative control. The test substance (70%) was suspended in water for the intradermal induction, and in distilled water for the topical induction and challenge phases, respectively. On Day 0 the intradermal induction was performed with 0.05% test substance. The topical induction started on Day 6 with a 2.5% concentration, lasting for 48 h under occlusive conditions. On Day 20 the animals of the test and negative control groups were challenged with 0.1% and 0.5% test substance for 24 h under occlusive conditions. Skin reactions were scored 24, 48 and 72 h after patch removal.

Following the challenge, mild erythema (score 1) was observed in 1/20 in the treatment group at the site treated with 0.1%, 24 and 48 h after patch removal. At the site treated with 0.5%, mild erythema (score 1) was observed in 6/20 animals at the 24-h reading time point. This persisted until the 48-h reading time point in 5/20 guinea pigs. Of these 5 animals, one still showed local skin irritation 72 h after patch removal. Most of the reactions were observed in a small area of the challenge site. In the negative control group, mild erythema (score 1) was observed in 1/10 at the site treated with 0.1%, 24 h after patch removal. At the site treated with 0.5%, 2/10 showed mild erythema (score 1) at the 24- and 48-h reading time point. The local skin effect persisted until 72 h after patch removal in 1/10 guinea pigs. No adverse effects on body weight were noted in any animals during the study period. A positive control group was not included in the study. The test substance showed no sensitising potential under the conditions of the study.

A study was performed with the substance according to the guinea pig maximisation test protocol described in OECD guideline 406 and under GLP conditions (BASF, 1989d). Ten female guinea pigs were included in the test group, while five were included in the negative control. The test substance (27%) was suspended in physiological saline for the intradermal induction, topical induction and challenge phases, respectively. On Day 1 the intradermal induction was performed with 5% test substance. The topical induction started on Day 9 with a 0.5% concentration, lasting for 48 h under occlusive conditions. On Day 22 the animals of the test and negative control groups were challenged with 0.5% test substance for 24 h under occlusive conditions. Skin reactions were scored 24 and 48 h after patch removal. The concentrations used in the main study were selected based on the results of a range-finding test with 9 animals.

Following the intradermal induction, skin irritation was noted at the test sites of all animals. The topical induction did not cause skin irritation in any negative control or test group animals. Following the challenge, no skin irritation was noted in any animal in the treatment and negative control group. No adverse systemic effects or body weight changes were noted in any animals during the study period. A positive control group was not included in the study. The test substance showed no sensitising potential under the conditions of the study.

Four additional in vivo studies are available, showing no skin sensitisation effects. These were performed with several different concentrations of alcohols, C12-14, ethoxylated, sulfates, sodium salts (CAS No. 68891-38-3, EC No. 500-234-8) and are evaluated below in the context of all available studies in the AES category.

 

Studies in the AES category

The available studies on skin sensitisation, including those performed with alcohols, C12-14, ethoxylated, sulfates, sodium salts (CAS No. 68891-38-3, EC No. 500-234-8), are summarised in Table 1 below:

 

Table 1: Database on skin sensitisation in the Alkyl Ether Sulfates (AES) category

CAS / EC Nos.

Substance

Study or Report No.

Study protocol (adopted in)

Concentration in test material [%]

Hazard conclusion

‘Linear’ subgroup

1471312-55-6 / 939-523-2

Alcohols, C8-10, ethoxylated, sulfates, sodium salts

121487

OECD 406 (GPMT)

98.7

Not sensitising

68585-34-2 / 500-223-8

Alcohols C10-16, ethoxylated (1-2,5 EO) sulphated, sodium salts

247/8409

Similar OECD 406 (GPMT)

Not reported

Not sensitising

4301

OECD 406 (GPMT)

10

Not sensitising

11182

Similar OECD 406 (GPMT)

Not reported

Not sensitising

11182

Similar OECD 406 (Buehler)

Not reported

Not sensitising

16604

Similar OECD 406 (Buehler)

31.4

Not sensitising

4309

Similar OECD 406 (GPMT)

Not reported

Sensitising

4303

Similar OECD 406 (GPMT)

Not reported

Sensitising

4289

Similar OECD 406 (GPMT)

Not reported

Sensitising

4304

Similar OECD 406 (GPMT)

Not reported

Sensitising

9731

Similar OECD 406 (Buehler)

Not reported

Sensitising

30449

Human data (HRIPT), Good clinical practices guideline 21 CFR parts 50 and 56

Not reported

Not sensitising

07-009A

Human data (HRIPT), Good clinical practices guideline 21 CFR parts 50 and 56

Not reported

Not sensitising

68891-38-3 / 500-234-8

Alcohols, C12-14, ethoxylated, sulfates, sodium salts

R770036

OECD 406 (GMPT)

28

Not sensitising

3170

OECD 406 (GPMT)

28

Not sensitising

861041D/UGF 19/SS

OECD 406 (GPMT)

70

Not sensitising

90/8507

Similar OECD 406 (GPMT)

Not reported

Not sensitising

89.0241

OECD 406 (GPMT)

27

Not sensitising

SM880964

Similar OECD 406 (GPMT)

27

Sensitising

174450-50-1 / 605-725-1

Alcohols C12-14 (even numbered), ethoxylated (< 2.5 EO), sulphated, triisopropanolamine salts

2399

OECD 406 (Buehler)

83.8

Not sensitising

‘Mixed branched & linear’ subgroup

160901-28-0 / 500-465-4

Alcohols, C9-11, branched and linear, ethoxylated, sulfates, sodium salts

221/7703

Similar OECD 406 (GPMT)

Not reported

Not sensitising

 

Evaluation of skin sensitisation as observed in studies

The available studies were performed with alcohols, C8-10, ethoxylated, sulfates, sodium salts (CAS No. 1471312-55-6, EC No. 939-523-2), alcohols C10-16, ethoxylated (1-2,5 EO) sulphated, sodium salts (CAS No. 68585-34-2, EC No. 500-223-8), alcohols, C12-14, ethoxylated, sulfates, sodium salts (CAS No. 68891-38-3, EC No. 500-234-8) and alcohols C12-14 (even numbered), ethoxylated (< 2.5 EO), sulphated, triisopropanolamine salts (CAS No. 174450-50-1, EC No. 605-725-1) from the ‘linear’ subgroup and with alcohols, C9-11, branched and linear, ethoxylated, sulfates, sodium salts (CAS No. 160901-28-0, EC No. 500-465-4) from the ‘mixed branched & linear’ subgroup. The concentration of the respective AES substances in the test material used in these studies varied from 10 - 98.7%, with water as the solvent in most test materials. For a number of studies no test material purity was reported. All in vivo animal studies followed the Buehler or GPMT protocol described in OECD guideline 406.

For a majority of the in vivo animal studies, no skin sensitising potential was reported. Mild to severe skin irritation effects (erythema and/or oedema) were observed following the epicutaneous and/or topical induction, and were absent following the challenge phase.

Two studies of high quality were available within the category and are summarised below.

A study was performed with alcohols, C8-10, ethoxylated, sulfates, sodium salts (CAS No. 1471312-55-6, EC No. 939-523-2) according to the guinea pig maximisation test protocol described in OECD guideline 406 and under GLP conditions (Z&S, 2013). Ten female guinea pigs were included in the test group. The pure test substance (98.7%) was suspended in physiological saline for the intradermal induction, and in vaseline for the topical induction and challenge phases, respectively. On Day 0 the intradermal induction was performed with 2.5% test substance. The topical induction started on Day 6 with a 1.5% suspension, lasting for 48 h under occlusive conditions. On Day 20 the animals of the test and negative control groups were challenged with 0.5% test substance for 24 h under occlusive conditions. Skin reactions were scored 24 and 48 h after patch removal. The concentrations used in the main study were selected based on the results of a range-finding test with 10 animals. In the positive control group, 5 female guinea pigs were treated according to the same protocol as the test group with mercaptobenzothiazole. The intradermal and topical induction concentrations were 2% and 25%, respectively, while the challenge was performed with a 15% suspension in vaseline.

Following the intradermal induction, skin irritation was noted at the test sites of all animals. The topical induction did not cause skin irritation in any negative control or test group animals. Following the challenge, no skin irritation was observed in the negative control and test group animals. No adverse systemic effects of the treatment or significant body weight changes were noted in any animals. The 5 animals in the negative control group did not show any skin reactions following the challenge, while 5/5 animals in the positive control group showed a positive indication of skin sensitisation, indicating the controls were valid. The test substance showed no sensitising potential under the study conditions.

The study with alcohols C12-14 (even numbered), ethoxylated (< 2.5 EO), sulphated, triisopropanolamine salts (CAS No. 174450-50-1, EC No. 605-725-1) was performed according to the Buehler protocol described in OECD guideline 406 and under GLP conditions. Twenty female guinea pigs were included in the test group and ten in the negative control group. The pure test substance (83.8%) was suspended in deionised water for the topical induction and challenge phases. On Day 0 the first topical induction was performed with 50% test substance, lasting for 6 h under occlusive conditions. The second and third topical induction was performed on Day 7 and 14, respectively, with a 50% concentration. On Day 28 the animals of the test and negative control groups were challenged with 25% test substance for 6 h under occlusive conditions. Skin reactions were scored 24 and 48 h after patch removal. The concentrations used in the main study were selected based on the results of a range-finding test with 6 animals.

The dermal treatment during the first induction phase led to scarcely detectable skin irritation in 2/20 animals, 24 h after patch removal. After the second induction phase, 14/20 animals exhibited slight to well-defined erythema in combination with slight oedema 24 h after patch removal. Before the treatment in the third induction phase, these 14 animals, after shearing, still exhibited scaling in the administration area. The test substance was administered to intact skin. 24 h after the second induction phase, the administration area exhibited scarcely detectable erythema and oedema in 4/20 animals, well-defined erythema and oedema in 5/20 animals and moderate erythema and oedema in 2/20 animals, in 1 animal combined with necrotic spots on the skin. The control animals treated with the vehicle did not show irritation on the treated skin at any reading time point during the three induction phases. The challenge treatment did not cause any cutaneous reactions in the negative control and test group animals in the form of erythema or oedema 24 and 48 h after patch removal. No adverse systemic effects of the treatment or significant body weight changes were noted in any animals. A reliability check was performed regularly with 2-mercaptobenzothiazole. The test substance showed no sensitising potential under the conditions of the study.

In the in vivo studies 4309, 4303, 4289, 4304 and 9731 performed with alcohols C10-16, ethoxylated (1-2,5 EO) sulphated, sodium salts (CAS No. 68585-34-2, EC No. 500-223-8), as well as study No. SM880964 performed with alcohols, C12-14, ethoxylated, sulfates, sodium salts (CAS No. 68891-38-3, EC No. 500-234-8), it was concluded that the test material caused skin sensitisation. However, for all these studies the information on the irritating skin effect following epicutaneous and/or topical induction was missing. In most studies for which this information was reported, the induction application caused skin irritation. Therefore, the skin effects observed following the challenge phase in these studies are likely to have been skin irritation, rather than skin sensitisation.

Two Human Repeated Insult Patch Tests (study No. 30449 and 07-009A) were performed with alcohols C10-16, ethoxylated (1-2,5 EO) sulphated, sodium salts (CAS No. 68585-34-2, EC No. 500-223-8). Some skin irritation was noted during the induction phases in a majority of the volunteers. Both studies concluded that the test substance showed no skin sensitising potential in the human volunteers.

Data on counter ions

There is experimental data on substances with the counter ions sodium (Na+) and triisopropanolamine (TIPA), showing negative results for skin sensitisation. This indicates that these counter ions will not have a skin sensitising potential.

Magnesium (Mg2+) and ammonium (NH4+) are both considered not to show a skin sensitising potential based on the available data (primarily on their salts).

For a detailed evaluation of a potential effect of the counter ions on the toxicological profiles of the AES member substances, please refer to the category justification attached to the category object.

 

Conclusion on skin sensitisation potential of substances in the AES category

The WoE analysis based on the in vivo studies and HIRPTs indicates that AES substances in general do not show a skin sensitising potential. The conclusion is fully supported by the OECD QSAR Toolbox profiling results. This applies to all AES substances in the category, whether they belong to the ‘linear’, ‘unsaturated’ or ‘mixed branched & linear’ subgroups and regardless of their counter ion. The outcome of this WoE evaluation is used for the hazard assessment and to conclude on classification and labelling of all AES substances in the category. This evaluation is considered sufficient for the hazard assessment and classification and labelling of the AES substances. For a detailed evaluation of the skin sensitising potential of the substances in the AES category, please refer to the category justification attached to the category object.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

The available data on skin sensitisation with alcohols, C12-14, ethoxylated, sulfates, sodium salts (CAS No. 68891-38-3, EC No. 500-234-8) do not meet the criteria for classification according to the CLP Regulation (EC) No. 1272/2008 and are therefore conclusive but not sufficient for classification.