Registration Dossier

Administrative data

Description of key information

There is no evidence for a skin sensitising potential of Fatty acids, C18 unsatd., mono and diester with triethanolamine , di-Me sulfate-quaternized based on a weight of evidence including information from OECD 406 guideline studies (Buehler test / Guinea pig maximisation test) with the partially unsaturated TEA-Esterquat and oleic acid-based TEA-Esterquat.

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
Study period:
1992-06-18 to 1992-07-12
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
May 12, 1981
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
A valid GPMT conducted according to guideline is available, which is reliable without restrictions and adequate for classification and labelling purposes. Potency estimation is not mandatory when existing guideline and GLP conforming data are available, which were conducted before the new annex of the REACH Regulation entered into force. Moreover, no indication for skin sensitisation was observed in this study, thus, no dose response information is needed. For this reason and for reasons of animal welfare no additional LLNA was conducted.
Species:
guinea pig
Strain:
other: Pirbright white Bor:DHPW (SPF)
Sex:
male/female
Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
intradermal injection: 5 % in aqua ad inject
topical application: 25 % in aqua ad inject
Day(s)/duration:
intradermal: day 0 / epicutaneous: 7 days after intradermal for 48 h
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:
10% in aqua ad inject.
Day(s)/duration:
day 21 / 24 h exposure
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
20 (10 male, 10 female)
Details on study design:
RANGE FINDING TESTS:
- Intradermal injection:
The test article was diluted with aqua ad inject. and Freund's complete adjuvant (FCA; Sigma, 8024 Deisenhofen) to give a final concentration of 5 %.
Two animals were employed for the concentration tested, skin reactions were recorded 48 h after treatment.

- Dermal Application:
The test article was used undiluted. A closed patch exposure was effected by means of an occlusive bandage. Since this maximum concentration proved irritating, lower concentrations (75, 50, 25, 10 %) were tested. Ten animals were employed and skin reactions were recorded 48 h post applicationem.

MAIN STUDY
A. INDUCTION EXPOSURE (day 0)
- First stage -an area of 4 x 6 cm over the shoulders was clipped short with electric clippers and cleaned with 70 % (v/v) ethanol. Three pairs of intradermal injections were then made symmetrically in two rows on either side of the spine:
-- Test group:
1. 0.1 ml FCA 50 % (w/w) diluted in aqua ad inject.
2. 0.1 ml test article diluted in aqua ad inject (final concentration: 5 %)
3. 0.1 ml test article diluted in FCA /aqua ad inject (final concentration: 5 %)
-- Control group:
1. 0.1 ml FCA 50 % (w/w) diluted in aqua ad inject
2. 0.1 ml aqua ad inject. (undiluted)
3. 0.1 ml aqua ad inject 50 % (w/w) diluted in FCA

-- Second stage (day 7)
- 7 days after the intradermal injections the dermal application was initiated subsequent to reclipping of the area 24 hours before application of the test article at the highest concentration producing mild to moderate irritation, i.e. (25 % in aqua ad. inject). The test article was spread in a thick layer [to saturation] over a 4 x 5 cm patch (filter paper). The latter was firmly secured over the previous injection sites by an occlusive dressing for 48 h.
Control animals received a patch loaded with the vehicle alone.

B. CHALLENGE EXPOSURE (day 21)
Both control and test animals were subjected to a challenge exposure 14 days after the second stage of induction. The challenge test was performed on a 5 x 5 cm clipped and shaved area on each flank. The maximal non-irritating concentration of the test article (10 % in aqua ad iniect.) was applied to the left flank and the vehicle to the right using the patch technique described. In each case the duration of exposure was 24 h under an occlusive dressing. 24 and 48 h after patch removal, allergic responses were evaluated on a numerical scale according to Draize.

GRADING SYSTEM
Dermal reactions graded for erythema and edema according to grading scale:
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

No edema: 0
Very slight edema (barely perceptible): 1
Slight edema (edges well defined by raising): 2
Moderate edema (raised approx 1 mm): 3
Severe edema (raised > 1 mm; beyond area of exposure): 4
Positive control substance(s):
yes
Remarks:
2,4 dinitrochlorobenzene (extreme sensitizer) and benzocaine (moderate sensitizer) are tested periodically. The last test with an acceptable level of response to each of these substances was performed in April 1992.
Positive control results:
2,4 dinitrochlorobenzene (extreme sensitizer) and benzocaine (moderate sensitizer) are tested periodically. The last test with an acceptable level of response to each of these substances was performed in April 1992.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
10 %
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
10 %
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
10 %
No. with + reactions:
0
Total no. in group:
20
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
10 %
No. with + reactions:
0
Total no. in group:
20
Reading:
other: periodically tested
Group:
positive control
Remarks on result:
positive indication of skin sensitisation

RESULTS

Pilot study (range finding):

- Intradermal: No specific findings were observed.

- Dermal:

-- 100, 75 and 50 %: Partly well-defined erythema and slight oedema with induration of the treated areas were observed.

-- 25 %: Slight to well-defined erythema were observed.

-- 10 %: No skin reactions were observed, highest non-irritant concentration.

Main study:

Signs of irritation during induction:

At a concentration of 25 % slight to well-defined erythema and oedema were observed.

Challenge (conc. of test substance: 10 %, left flank) : The sensitization rate at 24 h and at 48 h was 0 %.

No reactions observed in control and test animals at 24 or 48h.

Interpretation of results:
GHS criteria not met
Conclusions:
The test article "partially unsaturated TEA-Esterquat" is considered to be a non-sensitizer in this study.
Executive summary:

In a dermal sensitization study according to OECD Guideline 406, May, 12 1981 with partially unsaturated TEA-Esterquat (a.i. 90 %, in isopropanol 10 %) diluted in water young adult Pirbright white guinea pigs (10 male, 10 female) were tested using the MAXIMIZATION TEST method.

Intradermal induction was performed with a 5 % test substance concentration. After dermal induction with 25 % solution of test substance, slight to well defined erythema and oedema was observed. None of the animals of the test group or control group showed any positive skin reactions after challenge treatment with a non-irritating test article concentration of 10 % in water. The sensitization rate at 24 h and at 48 h was 0 %.

The test article is considered to be a non-sensitizer in this study. 

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1993-10-13 to 1993-11-20
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
July 17, 1992
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of study:
Buehler test
Justification for non-LLNA method:
A valid Buehler test conducted according to guideline is available, which is reliable without restrictions and adequate for classification and labelling purposes. Potency estimation is not mandatory when existing guideline and GLP conforming data are available, which were conducted before the new annex of the REACH Regulation entered into force. Moreover, no indication for skin sensitisation was observed in this study, thus, no dose response information is needed. For this reason and for reasons of animal welfare no additional LLNA was conducted.
Species:
guinea pig
Strain:
other: Pirbright white Bor: DHPW (SPF)
Sex:
male/female
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
25% (1st and 2nd exposure) and 10% (3rd exposure)
Day(s)/duration:
once weekly for a total of three 6-h exposures
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:
10 %
Day(s)/duration:
2 weeks after induction, 6 h exposure
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
study group 20 (10 male, 10 female)
control group 10 (5 male, 5 female)
Details on study design:
RANGE FINDING TESTS:
- The test was conducted in two males and two females using Hill-Top Chambers (Hill Top, Cincinnati, USA) secured with rubber dental dam (4D Rubber Co., Ltd.,UK), the test article was applied in concentrations of 100%, 50%, 25% and 10% to discrete areas of clipped skin on the back of the animals (two concentrations per animal). The animals were then immobilized in metal restrainers for 6 h, after which time the patches were removed and the animals returned to their cages. Skin reactions were recorded 24 h and 48 h after patch removal.

MAIN STUDY
A. INDUCTION EXPOSURE
The induction procedure was performed in both the test and the control group. The test article was applied at a concentration of 25% (first and second exposure) and 10% (third exposure) to an area of clipped skin in the left anterior quadrant of the back of each test animal, whilst the control animals were subjected to an exposure with the vehicle at the same site. Method of application and duration of exposure were the same as in the pilot study. The treated skin site of each animal was evaluated 24 h after patch removal to detect dermal irritation. This procedure was repeated on the same site once weekly for a total of three 6-h exposures.

On the basis of the results of the range finding the concentrations of 25% and 10% of the test article were considered to ie suitable for induction exposure and challange exposure, respectively. Because of mmoderate irritation after the second induction exposure the concentration used for the third induction procedure was reduced to 10%.

After the last induction exposure all animals remained untreated for 2 weeks prior to challenge.

B. CHALLENGE EXPOSURE
Both test and control groups were subjected to a challenge exposure with the test article and the vehicle. The test article was applied in a concentration of 10% to a clipped area of skin in the right posterior quadrant of the back and the vehicle was applied in the right anterior quadrant of each animal. Method of application and duration of exposure were the same as in the pilot study. Approximately 21 h after patch removal and 3 h before the first evaluation the skin area was cleared of hair by reclipping. The evaluation of the skin was performed 24 h and 48 h after the end of the exposure period in order to detect possible allergic responses.
Positive control substance(s):
yes
Remarks:
The reaction to the positive control substance 2-mercaptobenzotbiazole is tested periodically. The last test with an acceptable level of response (extreme sensitizer) to this substance at the concentration of 15% in peanut oil was performed in November 19
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
10 %
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
10 %
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
10 %
No. with + reactions:
0
Total no. in group:
10
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
10 %
No. with + reactions:
0
Total no. in group:
10
Reading:
other: periodically tested
Group:
positive control
Remarks on result:
positive indication of skin sensitisation

RESULTS

Pilot study (range finding):

- 100 %: moderate to severe erythema (score 3), moderate oedema (score 2)

- 50 %: well-defined and moderate to severe erythema (scores 2 and 3), very slight to slight oedema (scores 1 and 2)

- 25 %: very slight erythema (score 1), no or very slight oedema (scores 0 and 1)

- 10 %: no skin reactions

Main study:

The sensitization rate at 24 h and at 48 h was 0 %.

Interpretation of results:
GHS criteria not met
Conclusions:
In this study, the test substance partially unsaturated TEA-Esterquat is considered to be a non-sensitizer.
Executive summary:

In a dermal sensitization study according to OECD Guideline 406, Juli 17, 1992 with partially unsaturated TEA-Esterquat (a.i. 90%) in water young adult Pirbright white guinea pig (10 male, 10 female) were tested using the BUEHLER method.

The sensitization rate at 24 h and at 48 h was 0 %

In this study, the test substance partially unsaturated TEA-Esterquat is considered to be a non-sensitizer. 

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
2004-01-13 to 2004-02-20
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
July 17, 1992
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
Version / remarks:
July 30, 1996
GLP compliance:
yes (incl. certificate)
Type of study:
Buehler test
Justification for non-LLNA method:
A valid Buehler test conducted according to guideline is available, which is reliable without restrictions and adequate for classification and labelling purposes. Potency estimation is not mandatory when existing guideline and GLP conforming data are available, which were conducted before the new annex of the REACH Regulation entered into force. Moreover, no indication for skin sensitisation was observed in this study, thus, no dose response information is needed. For this reason and for reasons of animal welfare no additional LLNA was conducted.
Species:
guinea pig
Strain:
other: Ibm: GOHI; SPF-quality (Himalayan spotted)
Sex:
male
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
25%, three times at intervals of one week, 6 h exposure
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:
1%
Day(s)/duration:
14 d after induction, 6 h exposure
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
Total of 38 animals
8 – preliminary screen
10 – main test control
20 – main test treatment
Details on study design:
PRELIMINARY STUDY AND DOSE RANGE FINDING
Left and right cranial and caudal flanks: 1. test: 50, 25, 15, 10; 2. test: 5, 3, 1 and 0.3% (w/w) 50% of test item was applied in a 25 mm Hill top chamber with a spatula.
25, 15, 10, 5, 3, 1 and 0.3% of test items were applied at 0.5 ml in a 25 mm Hill top chamber.
Application for 6h under fully occluded conditions. The application sites were assessed for erythema and oedema approx. 24 and 48 h after removal of the patches.

INDUCTION
25% (minimally irritating); left cranial and caudal flanks; topical application of aqueous solution for 6h, three times at intervals of one week. Skin grading 24h following patch
removal

CHALLENGE
1% (non-irritating); left cranial and caudal flanks; 14d after the last induction exposure, application of the challenge patch on the shaved skin for 6h; skin evaluations 24 and 48h after patch removal

GRADING SYSTEM
Dermal reactions graded for erythema, edema and other clinical changes in skin condition according to grading scale:
No visible change: 0
Discrete or patchy erythema: 1
Moderated and confluent erythema: 2
Intense erythema and swelling: 3
Positive control substance(s):
yes
Remarks:
Alpha-Hexylcinnamaldehyde
Positive control results:
Result: 20/20 (24 h reading) and 17/20 (48 h reading) test animals were observed with descrete/patchy to moderate/confluent erythema after the challenge treatment with the highest tested non-irritating concentration of Alpha-Hexylcinnamaldehyde at 5 % in PEG 300. No skin effect was observed in the control group.
Conclusion: In this study, 100 % (24 h reading) of the animals of the test group were observed with skin reactions after challenge treatment performed with the highest tested non-irritating concentration of Alpha-Hexylcinnamaldehyde at 5 % in PEG 300.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
1 % in purfified wate
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
1 % in purified water
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
1 % in purified water
No. with + reactions:
0
Total no. in group:
10
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
1 % in purfied water
No. with + reactions:
0
Total no. in group:
10
Reading:
other: periodically tested
Group:
positive control
Remarks on result:
positive indication of skin sensitisation

PRELIMINARY STUDY AND DOSE RANGE FINDING

Concentration for induction: 25% (minimally irritating).

Concentration for challenge:1% (highest non‐irritating dose)

SKIN EFFECTS IN INDUCTION

19/20 (first induction), 20/20 (second and third induction): discrete/patchy to moderate/confluent erythema

0/10 control group: no reactions

SKIN EFFECTS IN CHALLENGE

No skin reaction observed in the control and test animals treated with the test item at 1% in purified water.

Interpretation of results:
GHS criteria not met
Conclusions:
In this study, the test substance partially unsaturated TEA-Esterquat is considered to be a non-sensitizer.
Executive summary:

In a dermal sensitization study according to OECD Guideline 406, July, 17, 1992 with partially unsaturated TEA-Esterquat (a.i. 90 % in approx. 10 % isopropanol) diluted in purified water 20 male young adult Himalayan spotted guinea pigs were tested using the Bühler test method.

The sensitization rate at 24 h and at 48 h was 0 %

In this study, the test substance partially unsaturated TEA-Esterquat is considered to be a non-sensitizer. 

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1994-02-01 to 1994-03-17
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
July 17, 1992
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
Version / remarks:
December 29, 1992
Principles of method if other than guideline:
Minor deviation: timing of second challenge at 3 % no clear.
GLP compliance:
yes
Type of study:
Buehler test
Justification for non-LLNA method:
A valid Buehler test conducted according to guideline is available, which is reliable with restrictions and adequate for classification and labelling purposes. Potency estimation is not mandatory when existing guideline and GLP conforming data are available, which were conducted before the new annex of the REACH Regulation entered into force. Moreover, no indication for skin sensitisation was observed in this study, thus, no dose response information is needed. For this reason and for reasons of animal welfare no additional LLNA was conducted.
Species:
guinea pig
Strain:
Pirbright-Hartley
Sex:
female
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
12.5%
Day(s)/duration:
3 times at intervals of one week, 6 h exposure
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
1st challenge: 3 %
2nd challenge: 3 % and 1 %
Day(s)/duration:
14 d (1st challenge) and 21 d (2nd challenge) after last induction exposure; 6 h exposure
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
3 – preliminary study (for induction)
5 – dose finding (for challenge)
10 ‐ control
20 – treated
Details on study design:
PRELIMINARY STUDY AND DOSE FINDING
Preliminary (for induction): left flank: 3, 6, 12.5, 25%
Topical application 0.5 g/plaster (4-6 cm2) aqueous solution (‘viscous to pasty’) for 6h under fully occluded conditions.
Result: Minimally irritating concentration at 12.5%

Dose finding (for challenge): 6, 8, 10, 12%
Topical application 0.5 g/plaster (4-6 cm2) aqueous solution for 6h under fully occluded conditions.

INDUCTION
12.5% (minimally irritating), left cranial flank
Topical application 0.5 g/plaster (4-6 cm2) aqueous solution (‘viscous to pasty’) for 6h under fully occluded conditions, three times at intervals of one week. Skin grading 1 and 24h following patch removal after 3rd induction

CHALLENGE
3% (1st challenge, left and right caudal flanks); 1 % (2nd challenge, left and right caudal flanks); 3% (2nd challenge , right caudal flank only)
14 and 21 days after beginning of last induction (3rd), application of the challenge patch on the shaved skin for 6h; skin evaluation 24, 48 and 72h after patch removal

GRADING SYSTEM
Dermal reactions graded for erythema and edema according to grading scale:
- No reaction: 0
- Partial or slight erythema: 1 (add. grade)
- Weak erythema: 1
- Moderated and diffuse erythema and/or edema: 2
- Strong erythema and/or edema: 3
Positive control substance(s):
not specified
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
3 %
No. with + reactions:
0
Total no. in group:
10
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
3 %
No. with + reactions:
3
Total no. in group:
10
Clinical observations:
grande 1 left and/or right flank
Reading:
1st reading
Hours after challenge:
72
Group:
negative control
Dose level:
3 %
No. with + reactions:
1
Total no. in group:
10
Clinical observations:
grade 1 right flank
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
3 %
No. with + reactions:
5
Total no. in group:
20
Clinical observations:
grade 1 right and/or left flank
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
3 %
No. with + reactions:
11
Total no. in group:
20
Clinical observations:
grade 1 right and/or left flank
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
72
Group:
test group
Dose level:
3 %
No. with + reactions:
1
Total no. in group:
20
Clinical observations:
grade 1 left flank
Remarks on result:
no indication of skin sensitisation
Reading:
rechallenge
Hours after challenge:
24
Group:
negative control
Dose level:
3 %
No. with + reactions:
1
Total no. in group:
10
Clinical observations:
grade 1
Reading:
rechallenge
Hours after challenge:
48
Group:
negative control
Dose level:
3 %
No. with + reactions:
3
Total no. in group:
10
Clinical observations:
grade 1
Reading:
rechallenge
Hours after challenge:
72
Group:
negative control
Dose level:
3 %
No. with + reactions:
0
Total no. in group:
10
Reading:
rechallenge
Hours after challenge:
24
Group:
test group
Dose level:
3 %
No. with + reactions:
5
Total no. in group:
20
Clinical observations:
grade 1, only right flank tested
Remarks on result:
positive indication of skin sensitisation
Reading:
rechallenge
Hours after challenge:
48
Group:
test group
Dose level:
3 %
No. with + reactions:
9
Total no. in group:
20
Clinical observations:
grade 1, only right flank tested
Remarks on result:
positive indication of skin sensitisation
Reading:
rechallenge
Hours after challenge:
72
Group:
test group
Dose level:
3 %
No. with + reactions:
3
Total no. in group:
20
Clinical observations:
grade 1, only right flank tested
Remarks on result:
positive indication of skin sensitisation
Reading:
rechallenge
Hours after challenge:
24
Group:
negative control
Dose level:
1 %
No. with + reactions:
0
Total no. in group:
10
Reading:
rechallenge
Hours after challenge:
48
Group:
negative control
Dose level:
1 %
No. with + reactions:
0
Total no. in group:
10
Reading:
rechallenge
Hours after challenge:
72
Group:
negative control
Dose level:
1 %
No. with + reactions:
0
Total no. in group:
10
Reading:
rechallenge
Hours after challenge:
24
Group:
test group
Dose level:
1 %
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Reading:
rechallenge
Hours after challenge:
48
Group:
test group
Dose level:
1 %
No. with + reactions:
3
Total no. in group:
20
Clinical observations:
grade 1, only left flank
Remarks on result:
positive indication of skin sensitisation
Reading:
rechallenge
Hours after challenge:
72
Group:
test group
Dose level:
1 %
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Group:
positive control
Remarks on result:
other: not specified

PRELIMINARY STUDY

- Minimally irritating concentration at 12.5%

DOSE FINDING

- The result of the dose finding study was a significantly increased irritative sensitivity of the animals therefore concentration for challenge: 3%

Evaluation of dermal effects after challenge with 3 %, re-challenge with 3 and 1 % test substance dilutions in dest. water:

Treatment group:

Animal/

hours

challenge 3 %

re-challenge 1 %

re-challenge 3 %

left flank

right flank

left flank

right flank

right flank

24

48

72

24

48

72

24

48

72

24

48

72

24

48

72

19

0

0

0

1

1

0

0

0

0

0

0

0

0

0

0

20

0

0

0

0

0

0

0

0

0

0

0

0

1

1

0

21

0

0

0

0

1

0

0

0

0

0

0

0

1

1#

0

22

0

1

0

0

0

0

0

0

0

0

0

0

0

0

0

23

1

0

0

1

0

0

0

1

0

0

0

0

0

1

1

24

0

0

0

0

0

0

0

0

0

0

0

0

1

0

0

25

0

1

0

0

0

0

0

0

0

0

0

0

1

0#

0

26

0

0

0

0

1

0

0

0

0

0

0

0

0

0

0

27

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

28

1

1

0

0

0

0

0

0

0

0

0

0

0

0

0

29

0

0

0

0

0

0

0

1

0

0

0

0

0

1

1

30

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

31

1

1

0

1

1

0

0

0

0

0

0

0

0

1

0

32

0

0

0

0

0

0

0

0

0

0

0

0

0

1

0

33

0

0

0

0

1

0

0

0

0

0

0

0

0

0

0#

34

0

0

0

0

0

0

0

1

0

0

0

0

0

0

0

35

0

1

0

0

1

0

0

0

0

0

0

0

0

0

0

36

0

1

0

0

1

0

0

0

0

0

0

0

1

1

1

37

1

0

0

1

0

0

0

0

0

0

0

0

0

0

0

38

0

1

0

0

1

1

0

0

0

0

0

0

0

1

0

# scratch

 

Negative control animals:

 

Animal/

hours

challenge 3 %

re-challenge 1 %

re-challenge 3 %

left flank

right flank

left flank

right flank

 

 

 

24

48

72

24

48

72

24

48

72

24

48

72

24

48

72

4

0

0

0

0

0

0

0

0

0

0

0

0

1

1

0

5

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

6

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

7

0

1

0

0

1

0

0

0

0

0

0

0

0

0

0

8

0

0

0

0

1

1

0

0

0

0

0

0

0

1

0

9

0

0

0

0

0

0

0

0

0

0

0

0

1

0

0

10

0

0

0

0

0

0

0

0

0

0

0

0

0

1

0

11

0

1

0

0

0

0

0

0

0

0

0

0

0

0#

0

12

0

0

0

0

0

0

0

0

0

0

0

0

0

0#

0

13

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

# scratch

Interpretation of results:
study cannot be used for classification
Remarks:
ambiguous due to inconsistent pattern
Conclusions:
No conclusion in the report. The study results were evaluated to be ambiguous, due to the partly inconsistent pattern and in most cases rapid fading of response at challenge and re-challenge with 3 % test substance concentration in test and control animals.
Executive summary:

In a dermal sensitization study according to OECD Guideline 406, July, 17, 1992 with the “partially unsaturated TEA-Esterquat” (a.i. 77 % in isopropanole) diluted in water 20 female young adult Pirbright-Hartley guinea pigs were tested using the Bühler test method.

For Induction a mild to moderate irritating concentration of 12.5 % was used. Challenge was performed with a 3 % dilution on the left and right flank. Grade 1 reactions were observed in 25, 55 and 5 % of test animals on right/ and or left flank at the 24, 48 and 72 hour reading, respectively. In 30 % of negative control animals as well a grade 1 reaction was observed at the 48 hour reading on left and/or right flank and in 10 % on the right flank at 72 hours. At re-challenge on the right flank with the same concentration grade 1 reaction was observed in 25, 45 and 15 % of test animals at 24, 48 and 72 hours, respectively. 20 and 30 % of control animals showed grade 1 reactions at 24 and 48 hours. 72 hours after application no effects were observed.

Re-challenge with 1 % revealed no reactions in negative control animals and no reactions on right flank of test animals. Grade 1 response was seen in 3/20 animals at the 48 hours reading, on the left flank. No reactions were observed at the 24 and 72 hour readings in test animals.

Considering only reactions with a clean control group and values of right flank as recommended by the OECD guideline 406 the results of the re-challenge with 1 % are negative with a sensitisation rate of 0 %. However, positive reactions have been observed at re-challenge with 1 % on the left flank, but only at one time point and with grade 1 in 3 animals. A partly inconsistent pattern and in most cases rapid fading of response was observed at challenge and re-challenge with 3 % test substance concentration in test and control animals.

In conclusion the study results were evaluated to be ambiguous.

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1994-03-22 to 1994-05-13
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
July 17, 1992
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
Version / remarks:
December 29, 1992
GLP compliance:
yes
Type of study:
Buehler test
Justification for non-LLNA method:
A valid Buehler test conducted according to guideline is available, which is reliable with restrictions and adequate for classification and labelling purposes. Potency estimation is not mandatory when existing guideline and GLP conforming data are available, which were conducted before the new annex of the REACH Regulation entered into force. Moreover, no indication for skin sensitisation was observed in this study, thus, no dose response information is needed. For this reason and for reasons of animal welfare no additional LLNA was conducted.
Species:
guinea pig
Strain:
Pirbright-Hartley
Sex:
female
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
1st induction: 60 %
2nd induction: 50 %
3rd induction: 25 %
Day(s)/duration:
3 times at interval of one week, 6 h exposure
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
1st challenge: 10 %
2nd challenge: 3 %
Day(s)/duration:
14 day (1st challenge) and 21 days (2nd challenge) after last induction; 6 h exposure
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
3 – preliminary study (for induction)
10 ‐ control
5 – dose finding (for challenge)
20 – treated
Details on study design:
PRELIMINARY STUDY AND DOSE RANGE FINDING
Preliminary (for induction):
Left flank: 6, 12.5, 25, 50%
Right flank: 50, 60, 80, 100%
Appearance: < 6% liquid; 12.5-25% viscous; >50% high viscous
Topical application 0.5 g/plaster (4-6 cm2) aqueous solution (‘viscous to pasty’) for 6h under fully occluded conditions

Dose range (for challenge): 5, 10, 20, 25%
One week prior to challenge in 5 control animals already treated with vehicle.

MAIN STUDY
INDUCTION
1st induction: 60%, left cranial flank
2nd induction: 50%, left cranial flank
3rd induction: 25%, another left skin area behind
(Lowering the concentration by means of experience.)
Control: vehicle was applied to the left cranial flanks
Topical application 0.5 g/plaster (4-6 cm2) aqueous solution (‘viscous to pasty’) for 6h under fully occluded conditions, three times at intervals of one
week. Skin grading 1 and 24h following patch removal for each induction period

CHALLENGE
10% (1st challenge, right and left caudal flanks); 3% (re-challenge; right and left caudal flanks)
14 and 21 days after beginning of last induction, application of the challenge patch on the shaved skin for 6h; skin evaluations 24, 48 and 72h after patch removal

GRADING SYSTEM
Dermal reactions graded for erythema and edema by blind reading according to grading scale:
- No reaction: 0
- Slight erythema: 0+ (add. grade)
- Weak erythema and/or edema: 1
- Moderated and diffuse erythema and/or edema: 2
- Strong erythema and/or edema: 3
Positive control substance(s):
not specified
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
10 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
right and left caudal flanks
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
10 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
right and left caudal flanks
Reading:
1st reading
Hours after challenge:
72
Group:
negative control
Dose level:
10 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
right and left caudal flanks
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
10 %
No. with + reactions:
5
Total no. in group:
20
Clinical observations:
animals with positive response on both flanks, irrespective of severity
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
10 %
No. with + reactions:
11
Total no. in group:
20
Clinical observations:
animals with positive response on both flanks, irrespective of severity
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
72
Group:
test group
Dose level:
10 %
No. with + reactions:
3
Total no. in group:
20
Clinical observations:
animals with positive response on both flanks, irrespective of severity
Remarks on result:
positive indication of skin sensitisation
Reading:
rechallenge
Hours after challenge:
24
Group:
negative control
Dose level:
3 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
right and left caudal flanks
Reading:
rechallenge
Hours after challenge:
48
Group:
negative control
Dose level:
3 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
right and left caudal flanks
Reading:
rechallenge
Hours after challenge:
72
Group:
negative control
Dose level:
3 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
right and left caudal flanks
Reading:
rechallenge
Hours after challenge:
24
Group:
test group
Dose level:
3 %
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
animals with positive response on both flanks, irrespective of severity
Remarks on result:
no indication of skin sensitisation
Reading:
rechallenge
Hours after challenge:
48
Group:
test group
Dose level:
3 %
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
animals with positive response on both flanks, irrespective of severity
Remarks on result:
no indication of skin sensitisation
Reading:
rechallenge
Hours after challenge:
72
Group:
test group
Dose level:
3 %
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
animals with positive response on both flanks, irrespective of severity
Remarks on result:
no indication of skin sensitisation
Group:
positive control
Remarks on result:
other: not specified

PRELIMINARY STUDY AND DOSE RANGE FINDING

- Minimally irritating concentration at 60%

-10% concentration for challenge (maximum non‐irritating dose)

Evaluation of dermal effects after challenge with 10 % and re-challenge with 3 % test substance dilutions in dest. water:

Treatment group

Animal/

hours

challenge 10 %

re-challenge 3 %

left flank

right flank

left flank

right flank

24

48

72

144

24

48

72

144

24

48

72

24

48

72

19

0+

1

0+

 

1

1

0+

e

0+

0+

0+

0

0

0

20

0

0

0

 

0

0

0

 

0

0

0

0

0

0

21

0

0

0

 

0

0+

0

 

0

0

0

0

0

0

22

1

1

0+

e

0

0+

0

 

0+

0+

0

0

0

0

23

0

0

0

 

0

0

0

 

0

0

0

0

0

0

24

1

1

1

 

0

1

1

e

0

0

0

0

0

0

25

0

0+

0

 

0

0+

0

 

0

0

0

0

0

0

26

0

0+

0

 

0

0+

0

 

0

0

0

0

0

0

27

1

1

0+

 

0+

0+

0

 

0

0

0

0

0

0

28

0

0+

0

 

0+

0

0

 

0

0

0

0

0

0

29

0

0

0

 

0

0

0

 

0

0

0

0

0

0

30

1

1

1

e

0+

0+

0+

 

0

0

0

0

0

0

31

0

0

0

 

0+

0+

0

 

0

0

0

0

0

0

32

1

0+

0

 

0+

0+

0+

 

0

0

0

0

0

0

33

0

0+

0

 

0

0

0

 

0

0

0

0

0

0

34

0

0

0

 

1

1

1

e

0

0

0

1

0+

1

35

0+

1

0+

 

1

1

0+

 

0

0

0

0

0

0

36

0

0

0

 

0

0

0

 

0

0

0

0

0

0

37

0

0+

0

 

0

0+

0

 

0

0

0

0

0

0

38

0

0+

0

 

0+

1

0+

e

0

0

0

0

0

0

 

e = eschar; e =strong eschar

An additional score 0+ for slight erythema was added by the study authors.

 

For evaluation a response was considered positive, when a reaction on both flanks was observed, irrespective of severity. 

 

All readings for negative control group were zero.

Interpretation of results:
GHS criteria not met
Conclusions:
In this study, partially unsaturated TEA-Esterquat (a.i. 90 %) is not a dermal sensitizer.

Executive summary:

In a dermal sensitization study according to OECD Guideline 406, July, 17, 1992 with partially unsaturated TEA-Esterquat (a.i. 90 %) diluted in purified water 20 female young adult Pirbright-Hartley guinea pigs were tested using the Bühler test method.

Dermal induction was performed at concentrations of 60, 50 and 25 %, due to severity of response the concentration has to be decreased.

At challenge with 10 % test substance on the left and right flank, responses of slight erythema (score 0+, added by the study authors) and weak erythema/edema (score 1) were observed. No response was observed in negative control animals. For evaluation a response was considered positive, when a reaction on both flanks was observed, irrespective of severity. The resulting response rates were 25, 55 and 15 % at the 24, 48 and 72 hour readings, respectively. A consistent response over a period of 2 readings in minimum and a response on the contra lateral flank was observed in 35 % (7/20) of test animals. Re-challenge was performed with a 3 % dilution of the test substance on the left and right flank. Only responses on one flank were observed in 3 animals, most of them with a 0+ score. No reactions were observed in control animals. Due to the failure of response on the contra lateral flank the re-challenge was considered to be negative.

In this study, partially unsaturated TEA-Esterquat is not a dermal sensitizer.

.

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1997-03-20 to 1997-05-30
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
17th July 1992
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
Version / remarks:
29 th Dec 1992
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
A valid GPMT conducted according to guideline is available, which is reliable without restrictions and adequate for classification and labelling purposes. Potency estimation is not mandatory when existing guideline and GLP conforming data are available, which were conducted before the new annex of the REACH Regulation entered into force. Moreover, no indication for skin sensitisation was observed in this study, thus, no dose response information is needed. For this reason and for reasons of animal welfare no additional LLNA was conducted.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
Induction:
interdermal: 1 % test substance
dermal: 20 % test substance
Day(s)/duration:
dermal epicutaneous induction 7 d afer intradermal; 48 h exposure
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
Challenge: 1 % test substance
re-challenge: 1 % test substance
Day(s)/duration:
day 21 / day 28; 24 h exposure
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
Total of 55 animals (28 males and 27 females)
15 – preliminary study (2 animals for intradermal; 13 for topical)
20 – main study treatment group (10 males, 10 females)
10 – main study control (5 males, 5 females)
10 – main study reserve control for 2nd challenge
Route of administration intradermal and topical at induction; topical at challenge
Details on study design:
PRELIMINARY STUDY
A. Topical application
Irritation assessment following 24h occlusive exposure to test material at 100, 80, 60, 40, 20, 10, 5, 3, 1 and 0.5%; skin assessment 24 and 48h after removal of test substance.
Result: 20% was highest concentration to cause mild to moderate skin irritation. This concentration was selected for topical induction. No alterations were observed with 1% and 0.5%; 1% was selected for challenge.

B. Intradermal
0.1 ml of test substance at 0, 0.25, 0.5, 1, 3 and 5 % applied intradermally, both in physiological saline and in an emulsion made up of Freund’s Complete Adjuvant and physiological saline. Assessments made 24, 48 and 72h and 6 and 8 days post-administration Result: 1% in both vehicles (physiological saline and FCA) selected for intradermal induction.

MAIN STUDY
A. INDUCTION EXPOSURE
Day 0: Treatment group:
− Injection 1: 1:1 mixture (v/v) FCA/physiological saline
− Injection 2: 1% Tetranyl CO/40 in physiological saline
− Injection 3: 1% Tetranyl CO/40 in a 1:1 mixture (v/v) FCA/physiological saline
Control group:
- Injection 1: 1:1 mixture (v/v) FCA/physiological saline
- Injection 2: physiological saline
- Injection 3: 50 % (v/v) formulation of physiological saline in a 1:1 mixture (v/v) FCA/physiological saline

Day 7: Treatment group:
Region, free of fur, was treated topically with a 2 x 4 cm patch of filter paper, fully loaded with a 20% solution of Tetranyl CO/40 in bi-distilled water. Patch was covered by an occlusice bandage and left in place for 48 hours.
Control group:
Only vehicle was applied.

After removal of patches, test aereas were washed with warm water.


B. CHALLENGE EXPOSURE
Day 21: Left flank of all animals, including controls, treated topically with 0.5 ml of 1% test substance for 24h under an occlusive patch. 0.5 ml of vehicle alone applied to right flank.
Day 28: 2nd challenge. Test substance applied at 1% in bidest water to right flank and vehicle to left flank

GRADING SYSTEM
Dermal reactions graded for erythema and edema by blind reading according to grading scale:
No reaction: 0
Mild redness: 1
Moderate erythema: 2
Severe erythema with or without edema: 3
Positive control substance(s):
yes
Remarks:
2-Mercaptobenzothiazole
Positive control results:
The evaluation of the cutaneous alterations recorded in the treatment group, 24 and 48 h after the end of the exposure to the administered substance revealed that 10 of the 20 animals in the treatment group showed a reaction attributable to a sensibilisation process. the data are comparable to those obtained by Magnusson and Kligman (1969), for the assay with the substance Mercaptobenzothiazole
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
1 % test substance
No. with + reactions:
3
Total no. in group:
19
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
1 % test substance
No. with + reactions:
3
Total no. in group:
19
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
1 % test substance
No. with + reactions:
1
Total no. in group:
10
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
1 % test substance
No. with + reactions:
0
Total no. in group:
10
Reading:
rechallenge
Hours after challenge:
24
Group:
test group
Dose level:
1 % test substance
No. with + reactions:
0
Total no. in group:
19
Remarks on result:
no indication of skin sensitisation
Reading:
rechallenge
Hours after challenge:
48
Group:
test group
Dose level:
1 % test substance
No. with + reactions:
0
Total no. in group:
19
Remarks on result:
no indication of skin sensitisation
Reading:
rechallenge
Hours after challenge:
24
Group:
negative control
Dose level:
1 % test substance
No. with + reactions:
0
Total no. in group:
10
Reading:
rechallenge
Hours after challenge:
48
Group:
negative control
Dose level:
1 % test substance
No. with + reactions:
0
Total no. in group:
10
Group:
positive control
Remarks on result:
positive indication of skin sensitisation

Preliminary Study

Topical application:

Result: 20% was highest concentration to cause mild to moderate skin irritation. This concentration was selected for topical induction. No alterations were observed with 1% and 0.5%; 1% was selected for challenge.

Intradermal injections:

Result: 1% in both vehicles (physiological saline and FCA) selected for intradermal induction

Main Study

Mortality:

One male, belonging to the treatment group, was found dead during the induction phase. But the death of this animal did not influence the results of the assay as the minimum number of animals required for the treatment group in assays in which Freud´s Complete Adjuvant is used during the induction phase is 10.

Grades:

1st challenge:

− Grade 1 reaction in 3/19 (15%) animals at 24 and 48h

− reactions in 1/10 (10 %) animals of control group at 24 h reading no effects at 48 h reading

2nd challenge:

- No effects in test or control group

Interpretation of results:
GHS criteria not met
Conclusions:
The test substance oleic acid-based TEA-Esterquat can be classified as a non-sensitiser to the guinea pig under the conditions of this study.

Executive summary:

In a dermal sensitization study with oleic acid-based TEA-Esterquat in bidest. water, young adult male and female Dunkin-Hartley guinea pigs were tested using the method of Magnusson and Kligman according to OECD guideline 406. Positive control material was 2-Mercaptobenzothiazole.

 In this study, the test substance oleic acid-based TEA-Esterquat produced a sensitisation rate of 15 % (3/19) at the first challenge and a sensitisation rate of 0 (0/20) at re-challenge at a concentration of 1 % and is considered to be a non-sensitizer.

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:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The hypothesis for this analogue approach is that target and source substances, being different compounds, have similar (eco) toxicological properties based on structural similarity with common functional groups; a quaternized ethanolamine moiety, one to three ester groups with a typical UVCB distribution with long-chain fatty acids of natural origin.
Furthermore identical precursors (triethanolamine, long-chain fatty acids, dimethyl sulphate) are used for manufacturing. Therefore common breakdown products via physical and biological processes, which result in structurally similar chemicals, are evident.
For further information refer to general justification for read-across attached to chapter 13 of this IUCLID file.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
See general justification for read-across attached to chapter 13 of this IUCLID file.

3. ANALOGUE APPROACH JUSTIFICATION
See general justification for read-across attached to chapter 13 of this IUCLID file.

4. DATA MATRIX
See general justification for read-across attached to chapter 13 of this IUCLID file.
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Reason / purpose:
read-across: supporting information
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
1-10% in several studies
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
1-10% in several studies
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
other: all readings
Group:
negative control
Dose level:
Controls from different studies
Remarks on result:
other: valid
Key result
Reading:
other: all readings
Group:
positive control
Dose level:
Positive controls from different studies
Remarks on result:
other: valid
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

No experimental data are available for the assessment of sensitizing potential of the target substanceFatty acids, C18 unsatd., mono and diester with triethanolamine , di-Me sulfate-quaternized. However, reliable relevant data are available for the closely related source substances partially unsaturated TEA-Esterquat and oleic acid-based TEA-Esterquat. 

Summary

Two Buehler tests with the source substance partially unsaturated TEA-Esterquat were negative, one was judged as ambiguous due to an inconsistent response pattern and in most cases rapid fading of responses at challenge and re-challenge in test and control animals. In one further Buehler test the source substance partially unsaturated TEA-Esterquat was identified as weak sensitiser. Furthermore, two Guinea Pig Maximisation Tests, one conducted with partially unsaturated TEA-Esterquat, the other with oleic acid-based TEA-Esterquat are available, which were both negative.

A weight of evidence approach is used for evaluation. There is no indication from the available specifications to link the weak positive findings in the Buehler studies to differences in the degree of saturation of the underlying alkyl chain in partially unsaturated TEA-Esterquat.

The interpretation of results for those studies which were evaluated to be positive for skin sensitisation were complicated through the occurrence of a partly inconsistent pattern and in most cases rapid fading of response. Evaluation of response was hampered due to irritation and the absence of a clean negative control. Considering the studies with clean negative controls, proper performed induction with 100% test substance or mild to moderate irritating concentrations, there was no (0%) evidence for a skin sensitisation potential.

 

Studies in detail

In a dermal sensitization study with oleic acid-based TEA-Esterquat in bidest. water, young adult male and female Dunkin-Hartley guinea pigs were tested using the method of Magnusson and Kligman according to OECD guideline 406. Positive control material was 2-Mercaptobenzothiazole.

 In this study, the test substance oleic acid-based TEA-Esterquat produced a sensitisation rate of 15 % (3/19) at the first challenge and a sensitisation rate of 0 (0/20) at re-challenge at a concentration of 1 % and is considered to be a non-sensitizer.

 

In a dermal sensitization study according to OECD Guideline 406, May, 12 1981 with partially unsaturated TEA-Esterquat (a.i. 90 %, in isopropanol 10 %) diluted in water young adult Pirbright white guinea pigs (10 male, 10 female) were tested using the MAXIMIZATION TEST method.

Intradermal induction was performed with a 5 % test substance concentration. After dermal induction with 25 % solution of test substance, slight to well defined erythema and oedema was observed. None of the animals of the test group or control group showed any positive skin reactions after challenge treatment with a non-irritating test article concentration of 10 % in water. The sensitization rate at 24 h and at 48 h was 0 %. The test item is considered to be a non-sensitizer in this study.  

 

In a dermal sensitization study according to OECD Guideline 406, July 17, 1992 with partially unsaturated TEA-Esterquat (a.i. 90%) in water young adult Pirbright white guinea pig (10 male, 10 female) were tested using the BUEHLER method.

The sensitization rate at 24 h and at 48 h was 0 %. In this study, the test substance partially unsaturated TEA-Esterquat is considered to be a non-sensitizer. 

 

In a dermal sensitization study according to OECD Guideline 406, July, 17, 1992 with partially unsaturated TEA-Esterquat (a.i. 90 % in approx. 10 % isopropanol) diluted in purified water 20 male young adult Himalayan spotted guinea pigs were tested using the Bühler test method.

The sensitization rate at 24 h and at 48 h was 0 %. In this study, partially unsaturated TEA-Esterquat is considered to be a non-sensitizer. 

 

In a dermal sensitization study according to OECD Guideline 406, July, 17, 1992 with partially unsaturated TEA-Esterquat (a.i. 77 % in isopropanol) diluted in water 20 female young adult Pirbright-Hartley guinea pigs were tested using the Bühler test method.

For Induction a mild to moderate irritating concentration of 12.5 % was used. Challenge was performed with a 3 % dilution on the left and right flank. Grade 1 reactions were observed in 25, 55 and 5 % of test animals on right/ and or left flank at the 24, 48 and 72 hour reading, respectively. In 30 % of negative control animals as well a grade 1 reaction was observed at the 48 hour reading on left and/or right flank and in 10 % on the right flank at 72 hours. At re-challenge on the right flank with the same concentration grade 1 reaction was observed in 25, 45 and 15 % of test animals at 24, 48 and 72 hours, respectively. 20 and 30 % of control animals showed grade 1 reactions at 24 and 48 hours. 72 hours after application no effects were observed.

Re-challenge with 1 % revealed no reactions in negative control animals and no reactions on right flank of test animals. Grade 1 response was seen in 3/20 animals at the 48 hours reading, on the left flank. No reactions were observed at the 24 and 72 hour readings in test animals.

Considering only reactions with a clean control group and values of right flank as recommended by the OECD guideline 406 the results of the re-challenge with 1 % are negative with a sensitisation rate of 0 %. However, positive reactions have been observed at re-challenge with 1 % on the left flank, but only at one time point and with grade 1 in 3 animals. A partly inconsistent pattern and in most cases rapid fading of response was observed at challenge and re-challenge with 3 % test substance concentration in test and control animals. In conclusion the study results were evaluated to be ambiguous.

 

In a dermal sensitization study according to OECD Guideline 406, July, 17, 1992 with partially unsaturated TEA-Esterquat (a.i. 90 %) diluted in purified water 20 female young adult Pirbright-Hartley guinea pigs were tested using the Bühler test method.

Dermal induction was performed at concentrations of 60, 50 and 25 %, due to severity of response the concentration has to be decreased.

At challenge with 10 % test substance on the left and right flank, responses of slight erythema (score 0+, added by the study authors) and weak erythema/edema (score 1) were observed. No response was observed in negative control animals. For evaluation a response was considered positive, when a reaction on both flanks was observed, irrespective of severity. The resulting response rates were 25, 55 and 15 % at the 24, 48 and 72 hour readings, respectively. A consistent response over a period of 2 readings in minimum and a response on the contra lateral flank was observed in 35 % (7/20) of test animals. Re-challenge was performed with a 3 % dilution of the test substance on the left and right flank. Only responses on one flank were observed in 3 animals, most of them with a 0+ score. No reactions were observed in control animals. Due to the failure of response on the contra lateral flank the re-challenge was considered to be negative.

In conclusion there is evidence for a weak sensitisation potential of partially unsaturated TEA-Esterquat in this study.

Justification for read-across

The read-across is built on the hypothesis that target and source substances, being different compounds, have similartoxicologicalproperties based on structural similaritywith common functional groups.

A detailed justification for read-across is attached to chapter 13 of the IUCLID file.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

There is no information available for respiratory sensitisation. Therefore, there is a data gap in this respect. However, the data gap cannot be fulfilled with experimental data, since there is no internationally accepted animal or in vitro model for respiratory sensitisation. In case human data for respiratory sensitisation emerges, this will be taken into account.

Justification for classification or non-classification

Based on the available data,Fatty acids, C18 unsatd., mono and diester with triethanolamine , di-Me sulfate-quaternizeddoes not need to be classified as skin sensitizer according the criteria of CLP, EU GHS (Regulation (EC) No 1272/2008).