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Description of key information

The conclusion is drawn based on weight-of-evidence. QSAR predictions of the major and minor components were done, which did not result in structural alerts for skin sensitising properties. Two GPMTs are available: one performed with the registered substance and one performed with a substance analogue. Both tests did not show sensitising properties of the test substances.

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:
(Q)SAR
Adequacy of study:
weight of evidence
Study period:
September - October 2011
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
accepted calculation method
Justification for type of information:
The objective of this study was to obtain predictions on the skin sensitisation of the 4 representative potential C12-alkyl derivatives present in the substance with the DEREK NEXUS programme.
Principles of method if other than guideline:
The objective of this study was to obtain predictions on the skin sensitisation of the 4 representative potential C12-alkyl derivatives present in the substance with the DEREK NEXUS programme. In this assessment version 2.0.0 of DEREK NEXUS was used. DEREK NEXUS is a knowledge-based system that contains over 700 toxicity alerts based on the presence of substructures. The system contains more than 50 alerts specific to skin sensitization. The rules are based on the presence of specific substructures, or chemical classes related to potential mechanisms for skin sensitization.
GLP compliance:
no
Key result
Remarks on result:
no indication of skin sensitisation
Remarks:
For all 4 representative potential C12-alkyl derivatives present in the substance, DEREK NEXUS did not find any substructures in its database that fired an alert for sensitisation potential.

For all 4 representative potential C12-alkyl derivatives present in the substance, DEREK NEXUS did not find any substructures in its database that fired an alert for sensitisation potential.

Interpretation of results:
GHS criteria not met
Conclusions:
The objective of this study was to obtain predictions on the skin sensitisation of 4 representative potential C12-alkyl derivatives present in the substance (monoamphoacetate A and B, and diamphoacetate A and B) with the DEREK NEXUS programme. In this assessment version 2.0.0 of DEREK NEXUS was used. DEREK NEXUS is a knowledge-based system that contains over 700 toxicity alerts based on the presence of substructures. The system contains more than 50 alerts specific to skin sensitization. The rules are based on the presence of specific substructures, or chemical classes related to potential mechanisms for skin sensitization. For all 4 representative potential C12-alkyl derivatives present in the substance, DEREK NEXUS did not find any substructures in its database that fired an alert for sensitisation potential.
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Study period:
October 2011
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
accepted calculation method
Justification for type of information:
The objective of this study was to obtain predictions on the skin sensitisation of potential minor constituents (by-products) present in the substance with the DEREK NEXUS programme.
Principles of method if other than guideline:
The objective of this study was to obtain predictions on the skin sensitisation of potential minor constituents (by-products) present in the substance with the DEREK NEXUS programme. In this assessment version 2.0.0 of DEREK NEXUS was used. DEREK NEXUS is a knowledge-based system that contains over 700 toxicity alerts based on the presence of substructures. The system contains more than 50 alerts specific to skin sensitization. The rules are based on the presence of specific substructures, or chemical classes related to potential mechanisms for skin sensitization.
GLP compliance:
no
Remarks on result:
no indication of skin sensitisation
Remarks:
For all 3 investigated potential minor constituents (by-products) present in the substance, DEREK NEXUS did not find any substructures in its database that fired an alert for sensitisation potential.

For all 3 investigated potential minor constituents (by-products) present in the substance, DEREK NEXUS did not find any substructures in its database that fired an alert for sensitisation potential.

Interpretation of results:
GHS criteria not met
Conclusions:
The objective of this study was to obtain predictions on the skin sensitisation of 3 potential minor constituents (by-products) present in the substance with the DEREK NEXUS programme. In this assessment version 2.0.0 of DEREK NEXUS was used. DEREK NEXUS is a knowledge-based system that contains over 700 toxicity alerts based on the presence of substructures. The system contains more than 50 alerts specific to skin sensitization. The rules are based on the presence of specific substructures, or chemical classes related to potential mechanisms for skin sensitization. For all 3 investigated potential minor constituents (by-products) present in the substance, DEREK NEXUS did not find any substructures in its database that fired an alert for sensitisation potential.
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
The rationale to read across the data is attached in Section 13.
Reason / purpose:
read-across source
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
1 % (solid content approx. 0.394%)
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 1 % (solid content approx. 0.394%). No with. + reactions: 0.0. Total no. in groups: 10.0.
Key result
Reading:
2nd reading
Hours after challenge:
72
Group:
test group
Dose level:
1 % (solid content approx. 0.394%)
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: test group. Dose level: 1 % (solid content approx. 0.394%). No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
1 % (solid content approx. 0.394%)
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 1 % (solid content approx. 0.394%). No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
2nd reading
Hours after challenge:
72
Group:
negative control
Dose level:
1 % (solid content approx. 0.394%)
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: negative control. Dose level: 1 % (solid content approx. 0.394%). No with. + reactions: 0.0. Total no. in groups: 5.0.
Group:
positive control
Remarks on result:
not measured/tested
Interpretation of results:
GHS criteria not met
Conclusions:
In this adjuvant type guinea pig test method for skin sensitisation conducted with REWOTERIC AM C according to OECD 406 and GLP, positive reactions in 0 of the 20 animals (0%) were observed during challenge. Therefore, based on the results of this study the substance shall not be classified as a skin sensitiser in accordance with the CLP Regulation. This result is read across to the registered substance.
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
February 5, 1990 - March 13, 1990
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Justification for type of information:
The study was conducted before in chemico/ in vitro methods were developed.

Study conducted comparable to OECD 406 and GLP. Deviations: - no data provided about the latest reliability check (however because skin reactions were observed at challenge, the model seemed to be responsive) - the choice for the intradermal induction exposure was based on the minimal irritating exposure in the range finding test, while it should have been the highest exposure to cause mild-to-moderate skin irritation
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
no data about the latest reliability check; the choice for the intradermal induction exposure was based on the minimal irritating exposure in the range finding test, while it should have been the highest exposure to cause mild-to-moderate skin irritation
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The test substance was tested positive in an LLNA test (Sire, 2006). The test substance is a surfactant with irritating effects. As both properties are described in scientific literature as confounding factors for false positives, the LLNA result is considered inconclusive and an alternative test to the LLNA was thus needed.
Species:
guinea pig
Strain:
other: Pirbright white
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Fa. Winkelmann, Borchen, Germany
- Age at study initiation: no data
- Weight at study initiation: Main study: ca. 390 g (average)
- Housing:
Test group: 6 groups with 3 per cage and 1 group with 2 per cage (Makrolon Type IV)
Control group: 2 groups with 3 per cage and 2 groups with 2 per cage
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): ca. 20-25 °C
- Humidity (%): ca. 45-70%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hrs/12 hrs

IN-LIFE DATES: From: February 12, 1990 To: March 9, 1990
Route:
intradermal and epicutaneous
Vehicle:
physiological saline
Concentration / amount:
See section "Details on study design"
Route:
epicutaneous, occlusive
Vehicle:
physiological saline
Concentration / amount:
See section "Details on study design"
No. of animals per dose:
Test animals: 20 (7 groups)
Control animals: 10 (4 groups)
Details on study design:
RANGE FINDING TESTS

6 animals were used in total for these tests

For the intradermal induction exposure:
- Concentrations: 0.5; 1; 2 and 3%
- Amount: 0.1 mL
- Scoring: the skin reactions were scored 24 and 48 hours after application
- Result (see also the attached background material): the lowest, the 0.5% concentration, showed to be minimal irritating and was used for the main test (although the highest exposure to cause mild-to-moderate skin irritation should have been choosen)

For the epicutaneous induction and challenge exposure (occlusive):
- Concentrations: (1) 30; 50 and 70% and (2) 10; 30 and 50%
- Amount: 0.1 g
- Scoring: the skin reactions were scored 24 and 48 hours after patch removal
- Exposure period: 48 hours (occlusive)
- Result (see also the attached background material): as at the 24 hours reading in the 1st experiment crusts were observed in almost all animals, the experiment was performed analogue on the other flank (left) with slightly lower concentrations. In this experiment it was shown that 50% can be considered a concentation causing minimal irritation, to use in the main test. As in the second experiment no irritating effects were observed at 10 and 30%, but irritating effects were observed at 30% in the 1st experiment, 20% was chosen as the non-irritating challenge concentration to use in the main test.

MAIN STUDY

Test animals: 20 (7 groups)
Control animals: 10 (4 groups)

A. INDUCTION EXPOSURE
- No. of exposures: 2
1) Intradermal injections on day 0:
- Concentration: 0.5% in physiol. saline
- Site: shoulder/back
Three pairs of intradermal injections:
1) 0.1 mL: FCA (50% in physiol. Saline)
2) 0.1 mL: 0.5% of the substance in physiol. saline
3) 0.1 mL: 50% with 0.5% of the substance in physiol. Saline + 50% FCA (50% in physiol. Saline)
-Readings: scores were rated 1 hour and 24 hours after injection
2)Topical application on day 7:
- Concentration: 50% in physiol. Saline
- Amount: 0.5 g (control animals: 0.5 mL of physiol. Saline)
- Area: approximately 6 cm^2
- Exposure period: 48 hours (occlusive)
- Readings: scores were rated 1 hour and 24 hours after patch removal
B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day of challenge: day 21 (14 days after the start of the 2nd induction)
- Exposure period: 24 hours (occlusive)
- Site: one flank, not specified which
- Concentration: 20% in physiol. saline
- Amount: 0.1 g
- Readings: scores were rated 24 and 48 hours after patch removal
Challenge controls:
Not applicable
Positive control substance(s):
not specified
Positive control results:
No data
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
20% (solid content approx. 7%)
No. with + reactions:
5
Total no. in group:
20
Clinical observations:
No data
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 20% (solid content approx. 7%). No with. + reactions: 5.0. Total no. in groups: 20.0. Clinical observations: No data.
Key result
Reading:
2nd reading
Hours after challenge:
72
Group:
test group
Dose level:
20% (solid content approx. 7%)
No. with + reactions:
4
Total no. in group:
20
Clinical observations:
No data
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: test group. Dose level: 20% (solid content approx. 7%). No with. + reactions: 4.0. Total no. in groups: 20.0. Clinical observations: No data.
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
20% (solid content approx. 7%)
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No data
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 20% (solid content approx. 7%). No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No data.
Reading:
2nd reading
Hours after challenge:
72
Group:
negative control
Dose level:
20% (solid content approx. 7%)
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No data
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: negative control. Dose level: 20% (solid content approx. 7%). No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No data.
Group:
positive control
Remarks on result:
not measured/tested

Animal No. / Animal Group No.

Intradermal induction

 

With 0.5% of the test material (solid content approximately 0.18%)

Epicutaneous induction

 

With 50% of the test material (solid content approximately 17.5%)

Challenge exposure

 

With 20% of the test material (solid content approximately 7%)

Scoring after 1 hour

Scoring after 24 hours

Scoring 1 hour after patch removal

Scoring 24 hours after patch removal

Scoring 24 hours after patch removal

Scoring 48 hours after patch removal

1/1

0

0

1

1

0

0

2/1

0

0

2

2

0

0

3/1

0

0

1

1

1

0

1/2

0

0

2

1

0

0

2/2

0

0

2

1

0

0

3/2

0

0

1

1

0

0

1/3

0

0

1

2

1

1

2/3

0

1

2

1

2

3/3

0

0

1

2

0

0

1/4

0

0

2

1

0

0

2/4

0

0

1

2

0

0

3/4

0

0

1

1

0

0

1/5

0

0

2

2

0

0

2/5

0

0

2

2

0

0

3/5

0

1

1

0

0

1/6

0

0

2

2

0

0

2/6

0

2

1

0

0

3/6

0

0

2

2

1

1

1/7

0

0

1

1

0

0

2/7

0

0

1

1

1

2; crust forming

- See the attached background material for the results of the Range finding tests

Other information:

- No mortalities

- No significant difference between the average body weight of the control and test animals during the study

Interpretation of results:
GHS criteria not met
Conclusions:
In this adjuvant type guinea pig test method for skin sensitisation conducted comparable to OECD 406 and GLP, positive reactions in 5 of the 20 animals (25%) were observed during challenge. Therefore, based on the results of this study the substance is not classified as a skin sensitiser in accordance with the CLP Regulation.
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1998-04-20 to 1998-08-03
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
The tes was conducted before in chemico/ in vitro methods were developed.
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
adopted by the Council on July 17, 1992 (reported Paris, April 29, 1993)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
Version / remarks:
Juli 30, 1996
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The test substance was tested positive in an LLNA test (Sire, 2006). The test substance is a surfactant with irritating effects. As both properties are described in scientific literature as confounding factors for false positives, the LLNA result is considered inconclusive and an alternative test to the LLNA was thus needed.
Species:
guinea pig
Strain:
other: Ibm: GOHI; SPF-quality guinea pigs (synonym: Himalayan spotted)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: BRL, Biological Research Laboratories Ltd. Wölferstrasse 4, CH-4414 Füllinsdorf / Switzerland
- Age at study initiation: 4 - 6 weeks
- Weight at study initiation: pretest groups: 304-358 g, control and test group: 309-399 g
- Housing: Individually in Makrolon type-4 cages with standard softwood bedding (“Lignocel”, Schill AG, CH-41 32 Muttenz).
- Diet: ad libitum, standard laboratory guinea pig diet Nafag Ecosan 845 25W4, batch nos. 112/97 and 122/97
- Water: ad libitum, Community tap water from Füllinsdorf, once weekly additional supply of ascorbic acid (approx. 1 g/l) via the drinking water was provided.
- Acclimation period: One week for the control and test group under test conditions after health examination. No acclimatization for the animals
of the pretests. Only animals without any visible signs of illness were used.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24°C
- Humidity (%): 38-61 % (mean values: 40-58 %)
- Air changes (per hr): 10-15
- Photoperiod: 12-hour light, 12-hour dark cycle. Music was played during the light period.
Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
induction:
- intradermal: 5 %
- epidermal: 75 %
challenge: 1 %
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
induction:
- intradermal: 5 %
- epidermal: 75 %
challenge: 1 %
No. of animals per dose:
test group: 10
control group: 5
Details on study design:
TEST ARTICLE PREPARATION
The test article and vehicle were placed into a glass beaker on a tared Mettler PM 460 balance and a weight by weight dilution was prepared. Homogeneity of the test article in a suitable vehicle (bi-distilled water) was maintained during treatment using a magnetic stirrer. The preparations were
made immediately prior to each dosing.

RANGE FINDING TESTS:
- Intradermal Injection:
Four intradermal injections (0.1 ml/site) of a 1: 1 (v/v) mixture of Freund’s Complete Adjuvant/physiological saline were made into the shaved neck of one guinea pig. One week later intradermal injections (0.1 ml/site) were made into the clipped flank of the same guinea pig at concentrations of 5, 3 and 1 % of the test article in bi-distilled water. The resulting dermal reactions were assessed 24 hours later. For intradermal induction application in the main study a 5 % test article concentration was selected.

- Dermal Application:
Four intradermal injections (0.1 ml/site) of a 1: 1 (v/v) mixture of Freund’s Complete Adjuvant/physiological saline were made into the shaved neck of two guinea pigs. One week later both flanks of each of the guinea pigs were clipped and shaved just prior to the application. Thereafter 4 patches of filter paper (2 x 2 cm) were saturated with the test article at A = 100 %, B = 75 %, C = 50 % and D = 25 % in bi-distilled water and applied to the clipped and shaved flanks. The volume of test article applied was approximately 0.2 ml. The patches were covered by a strip of aluminum foil and firmly secured by elastic plaster wrapped around the trunk and covered with impervious adhesive tape. This procedure ensured the intensive contact of the test article. The dressings were removed after an exposure period of 24 hours.
Approximately 21 hours after removal of the dressing the application site was depilated with an approved depilatory cream (VEET Cream, Reckitt & Colman AG, CH-4123 Allschwil) to clean the application site, so that possible erythema reactions were clearly visible at that time.
The depilatory cream was placed on the patch sites and surrounding areas, and left on for 3-5 minutes. It was then thoroughly washed off with a stream of warm, running water. The animals were then dried with a disposable towel, and returned to their cages.
The reaction sites were assessed 24 and 48 hours after removal of the bandage for erythema and oedema on a numerical basis according to Draize.

After the above epidermal pretest the highest non-irritating concentration could not be determined. Therefore, a second epidermal pretest was performed in the same manner using two additional guinea pigs and the concentrations of A = 15 %, B = 10 %, C = 5 % and D = 1 % in bi-distilled water.

The concentration selected for the induction period and challenge procedure was 75 % and 1 %, respectively.

MAIN STUDY
A. INDUCTION EXPOSURE
- First stage (intradermal injections): An area of dorsal skin from the scapular region (approximately 6 x 8 cm) was clipped free of hair. Three pairs of intradermal injections (0.1 ml/site) were made at the border of a 4 x 6 cm area in the clipped region as follows:
-- Test group:
1) 1: 1 (v/v) mixture of Freund’s Complete Adjuvant and physiological saline.
2) The test article, diluted to 5 % with bi-distilled water.
3) The test article diluted to 5 % by emulsion in a 1: 1 (v/v) mixture of Freund’s Complete Adjuvant and physiological saline.
-- Control group:
1) 1: 1 (v/v) mixture of Freund’s Complete Adjuvant and physiological saline.
2) Bi-distilled water
3) 1: 1 (w/w) mixture of bi-distilled water in a 1: 1 (v/v) mixture of Freund’s Complete Adjuvant and physiological saline.

-- Second stage (epidermal applications): One week after the injections, the scapular area (approximately 6 x 8 cm) was again clipped and shaved free of hair prior to the application. A 2 x 4 cm patch of filter paper was saturated with the test article (75 % in bi-distilled water) and placed between the injection sites of the test animals. The volume of test article applied was approximately 0.3 ml. The patch was covered with aluminum foil and firmly secured by an elastic plaster wrapped around the trunk of the animal and secured with impervious adhesive tape. The dressings were left in place for 48 hours. The epidermal application procedure described ensured intensive contact of the test article.

The guinea pigs of the control group were treated as described above with bi-distilled water only.

Reaction sites were assessed for erythema and oedema 24 and 48 hours after removal of the dressing, using the numerical grading system according to Draize.

B. CHALLENGE EXPOSURE
The test and control guinea pigs were challenged two weeks after the epidermal induction application. The test and control guinea pigs were treated in the same way.

Hair was clipped and shaved from a 5 x 5 cm area on the left and right flank of each guinea pig just prior to the application. Two patches (2 x 2 cm) of filter paper were saturated with the highest non-irritating concentration of 1 % (left flank) and the vehicle only (bi-distilled water applied to the right flank) using the same method as for the epidermal application. The volume of test article applied was approximately 0.2 ml. The dressings were left in place for 24 hours.

Approximately 21 hours after removal of the dressing the test sites treated with the test article were depilated as described in the epidermal pretest.

Approximately 24 and 48 hours after the removal of the dressing the application sites were assessed for erythema and oedema using the numerical scoring system according to Draize. The readings were made under artificial fluorescent light (daylight spectrum).
Challenge controls:
Not applicable
Positive control substance(s):
yes
Remarks:
2-MERCAPTOBENZOTHIAZOLE tested periodically (RCC project 902068) from 27-OCT-1997 to 04-DEC-1997
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
1 % (solid content approx. 0.394%)
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 1 % (solid content approx. 0.394%). No with. + reactions: 0.0. Total no. in groups: 10.0.
Key result
Reading:
2nd reading
Hours after challenge:
72
Group:
test group
Dose level:
1 % (solid content approx. 0.394%)
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: test group. Dose level: 1 % (solid content approx. 0.394%). No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
1 % (solid content approx. 0.394%)
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 1 % (solid content approx. 0.394%). No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
2nd reading
Hours after challenge:
72
Group:
negative control
Dose level:
1 % (solid content approx. 0.394%)
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: negative control. Dose level: 1 % (solid content approx. 0.394%). No with. + reactions: 0.0. Total no. in groups: 5.0.
Group:
positive control
Remarks on result:
not measured/tested

RESULTS:

SKIN EFFECTS AFTER INTRADERMAL INDUCTION -PERFORMED ON TEST DAY 1

- The expected and common findings were observed in the control and test group after intradermal application of FCA in physiological saline and with/without the test article; the intradermal applications were observed with erythema, oedema, necrotizing dermatitis, encrustation and exfoliation of encrustation.

SKIN EFFECTS AFTER EPIDERMAL INDUCTION - PERFORMED ON TEST DAY 8

-CONTROL GROUP: No erythematous or oedematous reaction was observed in the animals treated with bi-distilled water only.

-TEST GROUP: Slight to well-defined erythematous reactions were observed in all test animals treated with the test article at 75 % in bi-distilled water.

SKIN EFFECTS AFTER THE CHALLENGE - PERFORMED ON TEST DAY 22

-CONTROL AND TEST GROUP: No skin reactions were observed in the animals either when treated with bi-distilled water only or when treated with the test article at 1 % in bi-distilled water.

VIABILITY / MORTALITY / MACROSCOPIC FINDINGS

- As there were no deaths during the course of the treatment period no necropsies were performed.

CLINICAL SIGNS, SYSTEMIC

- No symptoms of systemic toxicity were observed in the animals.

BODY WEIGHTS

- The body weight of the animals was within the range commonly recorded for animals of this strain and age.

Interpretation of results:
GHS criteria not met
Conclusions:
In this adjuvant type guinea pig test method for skin sensitisation conducted according to OECD 406 and GLP, positive reactions in 0 of the 20 animals (0%) were observed during challenge. Therefore, based on the results of this study the substance shall not be classified as a skin sensitiser in accordance with the CLP Regulation.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Local Lymph Node Assay (LLNA)

An aqueous solution of the substance (containing approx. 37%) was found to induce proliferation of lymphocytes in the murine Local Lymph Node Assay at a concentration of 50% (v/v) only (SI = 3.44). This may be a false-positive result, taking into account:

- that significant irritation was observed starting from this concentration, as shown by an increase in ear thickness (11.34% at the 50% concentration and ≥56% at 100% in the preliminary test)

- that the proliferation response was only marginally increased above the cut-off level (SI of 3), indicating a weak response in the presence of irritation

- that there have been several literature publications, reporting apparent false positive results from the LLNA for certain groups of chemicals, including surfactants (as also recognized in the OECD Guideline revised in 2010). Based on these publications it is considered justified to not conclude on the sensitisation potential of a surfactant only on the LLNA result (when more information is available)

As it is not clear whether a false-positive result was obtained and there is more information available, it is not considered justified to conclude on the sensitizing potential of this substance only on the results of this LLNA study. Therefore the conclusion of this study is assessed to be inconclusive.

Guinea Pig Maximization Test (GPMT)

In an adjuvant type guinea pig test method for skin sensitisation conducted similar to OECD 406 and GLP, positive reactions in 5 of the 20 animals (25%) were observed during challenge. Although a deviation of the study was to base the choice for the intradermal induction exposure on the minimal irritating exposure instead of on the highest exposure to cause mild-to-moderate skin irritation, the concentrations selected for the other phases of the study (topic applications for the induction and challenge phases) were in compliance with the guidelines. Based on the results of this study the substance does not need to be classified for skin sensitising in accordance with the CLP Regulation.

Human Repeated Insult Patch Test (HRIPT)

Under the conditions of a human repeated insult (occlusive) patch test procedure, a 0.5% aqueous dilution of the aqueous solution of the substance (at 0.15%) did not induce clinically significant skin irritation nor show any evidence of induced allergic contact dermatitis in human subjects. This concentration is likely representative of in-use conditions for most consumer formulations.

DEREK assessments

Predictions on the skin sensitisation potential of the 4 representative potential C12-alkyl derivatives and of 3 potential minor constituents (by-products) present in the substance were obtained with the DEREK NEXUS programme. In this assessment version 2.0.0 of DEREK NEXUS was used. DEREK NEXUS is a knowledge-based system that contains over 700 toxicity alerts based on the presence of substructures. The system contains more than 50 alerts specific to skin sensitization. The rules are based on the presence of specific substructures, or chemical classes related to potential mechanisms for skin sensitization. For all 7 investigated structures (potentially) present in the substance, DEREK NEXUS did not find any substructures in its database that fired an alert for sensitisation potential.

Additional supporting considerations

The main potential surfactant structures present did not trigger any structural alerts in a second sensitization assessment model, ToxTree v.2.1.0, i.e. no alert for nucleophilic aromatic substitution, Schiff Base formation, Michael acceptor, acyl transfer agents, or nucleophilic aliphatic substitution.

Despite a long history of use in consumer products, there are only rare occurrences of in-use sensitization reports with surfactants in general, and with alkylamphoacetates more specifically.

Read across data

In an adjuvant type guinea pig test method for skin sensitisation conducted according to OECD 406 and GLP, positive reactions in 0 of the 20 animals (0%) were observed during challenge with an aqueous solution of the read across substance AMPHOACETATES C8-C18 (common name). See also the document with the read across rationale, attached in Section 13.

Conclusion

Based on a weight-of-evidence approach it is considered justified to conclude that the substance has a low potential to cause skin sensitisation in humans.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Skin sensitisation

Based on a weight-of-evidence approach, the substance is considered to be not classified for skin sensitisation in accordance with the CLP Regulation.

Respiratory sensitisation

Due to the lack of data, the substance is not classified. In addition, given the physical-chemical properties of the substance and its use pattern, a potential for causing respiratory sensitisation is unlikely.