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Diss Factsheets

Administrative data

Description of key information

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:
From March 19, 1991 to April 25, 1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of study:
Buehler test
Justification for non-LLNA method:
The study was conducted before the requirement for LLNA testing came into force.
Species:
guinea pig
Strain:
other: Pirbright white
Sex:
male/female
Details on test animals and environmental conditions:
Animals
Substrain: Bor: DHPW (SPF)
Source: Firma Winkelmann, Versuchstierzucht, Gartenstr. 27, 4799 Borchen
Acclimatisation period: at least 5 days
Animal selection: random
Animal identification: with colored markings; cage labelled with sex, date of study initiation, project no.
Weight range at study initiation: 307 - 400 g

Husbandry
Housing: collective housing up to a maximum of 5 animals per cage (Macrolon type IV)
Illumination: artificial lighting (120 lux) from 7.00 a.m. - 7.00 p.m.
Temperature: 22±3 °C
Relative humidity: 30 - 70 %
Measurement: with thermohygrometer twice daily
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
undiluted
Day(s)/duration:
6 hours
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
No.:
#20
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
58.2 % and 20.2 %
Day(s)/duration:
6 hours
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
Pilot study: 4 (two males and two females)
Main study: 20 animals (10 animals per treatment group)
Details on study design:
Pilot study (range finding):
A range finding test was conducted in two males and two females in order to determine the highest concentration of the test substance which did not produce excessive inflammation. Using Hill-Top Chambers (Hill Top, USA) secured with rubber dental dam (4D Rubber Co., Ltd., UK), the test substance was applied in four different concentrations to discrete areas of clipped skin on the back of each 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

Induction procedure:
Only test group was subject to an induction procedure. The test substance was applied undiluted to an area of clipped skin in the left anterior quadrant of the back of each animal. Method of application and duration of exposure were the same as in the pilot study. Dermal irritation was assessed 24 h after patch removal.
This procedure was repeated on the same site once weekly for a total of three 6-h exposures. After the last induction exposure all animals remained untreated for 2 weeks prior to challenge.

Challenge procedure:
Both test and control groups were subjected to a challenge exposure with the test substance. The latter was applied in concentrations of 58.23 % and 20.38 % to clipped areas of skin in the left posterior quadrant (58.23 %, induction area a) and in the right anterior quadrant (20.38 %, induction area b) of the back of each animal. Method of application and duration of exposure were the same as in the pilot study.
18 - 22 h after patch removal all animals were depilated with "Nair" roll-on (Carter Products, Inc., New York). Allergic responses were evaluated 24 h and 48 h after the end of the exposure period.
Challenge controls:
10 animals
Positive control substance(s):
yes
Remarks:
2.4 dinitrochlorobenzene (extreme sensitizer) and benzocaine (moderate sensitizer)
Positive control results:
The reaction to the positive control substances 2.4 dinitrochlorobenzene (extreme sensitizer) and benzocaine (moderate sensitizer) is tested periodically. The last test with an acceptable leval of response to each of these substances was perfonned in April, 1991.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
test substance 58.2% (a.i.)
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:
test chemical
Dose level:
test substance 20.2% (a.i.)
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 chemical
Dose level:
test substance 58.2 % (a.i.)
No. with + reactions:
3
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Remarks:
sensitisation rate 5 %
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
test substance 20.2 % (a.i.)
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Remarks:
sensitisation rate 0 %
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Remarks on result:
other: Positive controls have been periodically tested by CRO

Pilot study:

58.23 %: partly very faint, nonconfluent erythema

55, 40, 20.38 %: no skin reactions

Main study:

The Sensitization rate of induction area a: (58.23 % a.i.) 48 h was 5 %.

The Sensitization rate of induction area b: (20.38 % a.i.) 48 h was 0 %.

According to the OECD guideline for testing of chemicals (OECD 406, May 12, 1981), test substance 50.2 % may be classified as a weak sensitizer, and test substance 17.57 % may be classified as a non-sensitizer.

Interpretation of results:
GHS criteria not met
Conclusions:
Under the study conditions, test substance at 58.23% gave a positive response in 5% of the animals. There was no positive sensitisation response at treatment with the test substance at 20.38%.
Executive summary:

A study was conducted to determine the potential skin sensitising properties of the test substance in a solution at 58.23% (a.i.) and at 20.38% (a.i.) in the guinea pig sensitisation test (Buehler) according to OECD Guideline 406, in compliance with GLP. Twenty test and ten control animals were used. Initially a 6 h induction exposure to the test substance was performed in the test group once weekly for three weeks. Two weeks later both test and control groups were subjected to a single 6 h challenge exposure with the test substance. Allergic responses to the challenge procedure were evaluated 24 and 48 h after the challenge. Under the study conditions, test substance at 58.23% gave a positive response in 5% of the animals. There was no positive sensitisation response at treatment with the test substance at 20.38% (Kaufmann, 1999).

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
not specified
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The study was conducted before the requirement for LLNA testing came into force.
Species:
guinea pig
Strain:
Pirbright-Hartley
Details on test animals and environmental conditions:
Strain: Pirbright white
Substrain: Bor: DHPW (SPF)
Source: Firma Winkelmann, Versuchstierzucht, Gartenstr. 30, 4791 Borchen/Paderbom
Date of receipt: February 7, 1990
Acclimation period: at least 5 days
Animal selection: random
Animal identification: with color identification; cage labelled with the following information: sex, date of study initiation, IBR project no.
Weight range at study initiation: 321 - 399 g

Housing: collective housing up to a maximum of 5 animals per cage (Macrolon type IV)
Illumination: artificial lighting (120 lux) from 7 .00 a.m. - 7 .00 p.m.
Temperature: 18 ± 2 °C
Relative humidity: 50 - 85 %
Measurement: with thermohygrometer twice daily
Route:
epicutaneous, occlusive
Vehicle:
other: equal volumes of water and Freund's complete
Concentration / amount:
test substance 5 %
Day(s)/duration:
48 hours
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
No.:
#20
Route:
epicutaneous, occlusive
Vehicle:
other: equal volumes of water and Freund's complete
Concentration / amount:
test substance 10 %
Day(s)/duration:
48 hours
Adequacy of challenge:
highest non-irritant concentration
Details on study design:
Pilot study (range finding):

Intradermal injection
The test substance was diluted with equal volumes of water and Freund's complete adjuvant (FCA; Sigma, 8024 Deisenhofen) to give a final concentration of 5 %. If this concentration produced severe systemic toxicity, local necrosis or ulceration, it was reduced accordingly. Two animals were employed for each concentration tested, skin reactions being recorded 48 h after treatment.

Dermal application
Liquids were used at the highest concentration which did not produce excessive inflammation. A closed patch exposure was effected by means of an occlusive bandage. Two animals were employed for each concentration tested and skin reactions were recorded 48 h post applicationem.


Procedure of Main Study:

Induction procedure

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 alone (diluted 1:2 in water)
2. 0.1 mL test substance alone (in the appropriate concentration)
3. 0.1 mL test substance emulsified in FCA (in the appropriate concentration)

Control group:
1. 0.1 mL FCA alone (diluted 1:2 in water)
2. 0.1 mL vehicle alone (undiluted)
3. 0.1 mL vehicle alone (diluted 1: 2 with FCA)

Second stage
Second stage -7 days after the injections, the same area was clipped and cleaned again. The test substance was spread in a thick layer to saturation over a 2 x 4 cm patch (gauze). The latter was firmly secured over the previous injection sites by an occlusive dressing for 48 h. The test substance was applied in the highest concentration producing mild to moderate irritation. Control animals received a patch loaded with the vehicle alone.

Challenge:
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 substance was applied to the left flank and the vehicle to the right using the patch technique described above. The patches were sealed to the flanks for 24 h under an occlusive dressing. If necessary, the skin was cleaned with 70 % ethanol 21 h after removal of the patch. 24 and 48 h after patch removal, allergic responses were evaluated according to the following scheme:
No reaction: 0
Scattered mild redness: 1
Moderate and diffuse redness: 2
Intense redness and swelling: 3
Positive control substance(s):
not specified
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
test substance 10 %
No. with + reactions:
5
Total no. in group:
20
Clinical observations:
sensitisation rate 25 %
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
test substance 10 %
No. with + reactions:
2
Total no. in group:
20
Clinical observations:
sensitisation rate 10 %
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
2nd reading
Group:
positive control
Remarks on result:
other: not reported
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation

Pilot Study (range finding):

intradermal:

5 % and 2.5 %: black discolored injection sites surrounded by immoderate erythema

1 %: no specific findings

dermal:

50 % and 25 %: slight to moderate erythema

10 %: no skin irritation

Main study

The sensitization rate at 24 h was 25 %

The sensitization rate at 24 h was 25 %

 

According to the maximization grading scheme of Magnusson and Kligman (J. Invest. Dermatol., 52, 268-276, 1969) the test substance may be classified as a "mild" sensitizer.

Interpretation of results:
GHS criteria not met
Conclusions:
Under the study conditions, the sensitisation rate at 24 h was 25% and 10% after 48 h, therefore the test substance was considered to be non-sensitiser under CLP criteria.
Executive summary:

A study was conducted to determine the skin sensitising potential of the test substance in the guinea pig maximization test according to OECD Guideline 406. Twenty test and ten control animals were used for the main study. Following induction exposure to the test substance or the vehicle, the animals were subjected two weeks later to a challenge exposure with the test substance. Allergic responses to the challenge procedure were evaluated 24 and 48 h after the end of the exposure period. Under the study conditions, the sensitisation rate at 24 h was 25% and 10% after 48 h, therefore the test substance was considered to be non-sensitiser under CLP criteria (Oetjen, 1990).

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
From November 03, 1999 to November 26, 1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of study:
Buehler test
Justification for non-LLNA method:
The study was conducted before the requirement for LLNA testing came into force.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
Thirty-four male albino Dunkin Hartley guinea pigs supplied by David Hall Limited, Burton-on-Trent, UK were used. At the start of the main study the animals weighed 360 to 427 g, and were approximately eight to twelve weeks old. After a minimum acclimatisation period of five days, each animal was selected at random and given a number unique within the study which was written on a small area of clipped rump using a black indelible marker-pen.

The animals were housed singly or in pairs in solid-floor polypropylene cages furnished with woodflakes. Free access to mains tap water and food (Guinea Pig FD1 Diet, Special Diets Services Limited, UK) was allowed throughout the study.

The temperature and relative humidity were set to achieve limits of 17 to 23 °C and 30 to 70 % respectively. The rate of air exchange was approximately fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light and twelve hours darkness.
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
50 % v/v (35% a.i.)
Day(s)/duration:
6 hours
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
No.:
#20
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
25% (17.5% a.i.) in distilled water
Day(s)/duration:
6 hours
Adequacy of challenge:
highest non-irritant concentration
No.:
#20
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
10% v/v (7% a.i. in distilled water
Day(s)/duration:
6 hours
Adequacy of challenge:
other: second highest non-irritant concentration
No. of animals per dose:
Sighting Tests: 2
Main Study: 20
Details on study design:
Selection of Concentrations for Main Study (Sighting Tests):

The concentrations of test substance to be used at each stage of the main study were determined by 'sighting tests' in which groups of guinea pigs were treated with various concentrations of test substance. The procedures were as follows:

Selection of Concentration for Topical Induction:
Two previously untreated guinea pigs were treated with the undiluted test substance and three concentrations of the test substance (75 %, 50 % and 25 % v/v in distilled water). Applications were made to the clipped flanks under occlusive dressings for an exposure period of 6 hours. The degree of erythema and oedema was evaluated 24 and 48 hours after dressing removal. The highest concentration of the test substance producing only mild dermal irritation was selected for the topical induction stage of the main study.

Selection of Concentration for Topical Challenge:
Two guinea pigs were treated with four concentrations of the test substance (25 %, 10 %, 5 % and 2 % v/v in distilled water). These animals had been treated identically to the control animals of the main study on Days 0, 7 and 14. Applications were made to the clipped flanks under occlusive dressings for an exposure period of 6 hours. The degree of erythema and oedema was evaluated 24 and 48 hours after dressing removal. The highest concentration of the test substance which produced no evidence of dermal irritation, and one lower concentration were selected for the topical challenge stage of the main study.

Main Study:

A group of thirty guinea pigs was used for the main study, twenty for treatment with the test substance and ten control. The bodyweight of each animal was recorded at the start and end of the study.

Induction:
Induction of the test animals: The hair was removed from an area on the left flank of each animal with veterinary clippers and treated with topical application of the test substance formulation. An absorbent cotton lint patch (approximate size 20 mm x 20 mm) saturated with the test substance formulation (50 % v/v in distilled water; reflecting 35% a.i.) was applied to the prepared skin and held in place under a strip of surgical adhesive tape and covered with an overlapping length of aluminium foil. The patch and foil were further secured by a strip of elastic adhesive bandage wound in a double layer around the torso of each animal. This occlusive dressing was kept in place for 6 hours. After 6 hours the dressing was carefully cut using scissors, removed and discarded. The treatment sites were decontaminated using distilled water and diethyl ether and the position of the treatment sites was identified using a black indelible marker-pen. The induction procedure was repeated on the same site on Days 7 and 14 for a total of three 6 hour exposures. Approximately 24 hours after each induction application (Days 1, 8 and 15) the degree of erythema and oedema was quantified.

Challenge:
Shortly before treatment on Day 28 the right flank of each animal was clipped free of hair with veterinary clippers.
An absorbent cotton lint patch (approximate size 20 mm x 20 mm) saturated with the test substance formulation at the maximum non­irritant concentration (25 % v/v in distilled water; reflecting 17.5% a.i.) was applied to the shorn right flank of each animal and was held in place with a strip of surgical adhesive tape. To ensure that the maximum non-irritant concentration was used at challenge, the test substance at a concentration of 10 % v/v in distilled water (i.e., 7% a.i.) was similarly applied to a separate skin site on the right shorn flank.
The patches were covered with an overlapping length of aluminium foil and further secured by a strip of elastic adhesive bandage wound in a double layer around the torso.
After 6 hours, the dressing was carefully cut using blunt-tipped scissors, removed and discarded. The treatment sites were decontaminated using distilled water and diethyl ether and the position of the treatment sites was identified by using a black indelible marker-pen. On Day 29 the flanks were clipped free of hair using veterinary clippers.
Evaluation of Skin Reactions
Approximately 24 and 48 hours after dressing removal, the degree of erythema and oedema was quantified. Any other reactions were also recorded.
Positive control substance(s):
not specified
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
25% v/v (17.5% a.i.) in distilled water
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
0 % sensitisation rate
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
10% v/v (7% a.i.) in distilled water
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
0 % sensitisation rate
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
50% in acetone/Peg 400 (70:30)
No. with + reactions:
10
Total no. in group:
19
Remarks on result:
positive indication of skin sensitisation
Remarks:
53%
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation

Main study:

Skin reactions observed after topical induction.

Discrete or patchy to moderate and confluent erythema with or without very slight oedema was noted at the topical induction sites of sixteen test group animals at the Day 1 observation, fourteen test group animals at the Day 8 observation and eighteen test group animals at the Day 15 observation.

No skin reactions were noted at the topical induction sites of control group animals at the Day 1, 8 or 15 observations.

Skin Reactions Observed After Topical Challenge.

No skin reactions were noted at the challenge sites of the test or control group animals at the 24 or 48 hour observations.

 

Bodyweight:

Bodyweight gains of guinea pigs in the test group, between Day 0 and Day 30, were comparable to those observed in the control group animals over the same period.

Interpretation of results:
GHS criteria not met
Conclusions:
Under the study conditions, the test substance produced a 0 % (0/20) sensitisation rate.
Executive summary:

A study was conducted to determine the sensitisation potential of the test substance in the albino guinea pig according to OECD Guideline 406 and EU Method B6, in compliance with GLP. Twenty test and ten control animals were used for the main study. Based on the results of sighting tests, the concentrations of test substance for the induction and challenge phases were selected as follows, for the topical the induction: 50% v/v of the test substance in distilled water (i.e., 35% a.i.) and for the topical challenge: 25% (17.5% a.i.) and 10% v/v (7% a.i.) in distilled water. Under the study conditions, the test substance produced a 0% (0/20) sensitisation rate (Sanders, 2000).

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
other: publication
Adequacy of study:
weight of evidence
Study period:
2002 /2014
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature
Qualifier:
no guideline required
Principles of method if other than guideline:
Few specialized hairdresser’s centres performed preliminary studies, followed by a formal DKG study to try (i) to determine appropriate patch test preparations for ATL and TA and (ii) to analyse the frequency of sensitisation to either substance in patients tested with the hairdressers’ series. During the exploratory period, variable numbers of patients were tested in the different hairdresser’s centers.
Type of study:
other: publication
Justification for non-LLNA method:
Data from published article.
Specific details on test material used for the study:
Purity: 60 %
Key result
Reading:
other:
Group:
test chemical
Dose level:
ATL 1% or 2%
Remarks on result:
other: not too irritant
Key result
Reading:
other:
Group:
test chemical
Dose level:
TLA 0.3 %
Remarks on result:
other: irritant
Interpretation of results:
Category 1B (indication of skin sensitising potential) based on GHS criteria
Conclusions:
Under the study conditions, ATL and TA are difficult allergens to test, being potentially irritant and chemically unstable, depending on percentage and vehicle. Even after testing many patients, the ideal test percentage and vehicle can only be approximated: ATL 1% and 2% aq., freshly prepared from stock solution (renewed regularly), appear adequate and not too irritant. In contrast, TA 0.3% pet. is largely irritant.
Executive summary:

A study was conducted to determine the skin sensitisation potential of the test substance. A few specialized centers performed preliminary studies, followed by a formal DKG study to try (i) to determine appropriate patch test preparations for ammonium thiolactate (ATL) and thiolactic acid (TA) and (ii) to analyse the frequency of sensitisation to either substance in patients tested with the hairdressers’ series. TA 1% pet. was soon withdrawn due to obvious irritancy. However, 0.3% TA also appeared quite irritant at first (18.9%cases), whereas the commercially prepared TA used later was much less irritant (4.7% and 6.7% or IR reactions, respectively). Consequently, the later test panel was restricted to the latter 2 preparations and 2 concentrations (1% and 2%) of freshly prepared ATL. With freshly prepared ATL in water, test results varied between the 3 periods (probably attributable to different patient selection criteria and an expanding spectrum of study participants, respectively). Under the study conditions, ATL and TA are difficult allergens to test, being potentially irritant and chemically unstable, depending on percentage and vehicle. Even after testing many patients, the ideal test percentage and vehicle can only be approximated: ATL 1% and 2% aq., freshly prepared from stock solution (renewed regularly), appear adequate and not too irritant. In contrast, TA 0.3% pet. is largely irritant (Uter, 2002).

Endpoint:
skin sensitisation: in vitro
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin sensitisation study does not need to be conducted because adequate data from an in vivo skin sensitisation study are available
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

Study 1:

A study was conducted to determine the potential skin sensitising properties of the test substance in a solution at 58.23% (a.i.) and at 20.38% (a.i.) in the guinea pig sensitisation test (Buehler) according to OECD Guideline 406, in compliance with GLP. Twenty test and ten control animals were used. Initially a 6 h induction exposure to the test substance was performed in the test group once weekly for three weeks. Two weeks later both test and control groups were subjected to a single 6 h challenge exposure with the test substance. Allergic responses to the challenge procedure were evaluated 24 and 48 h after the challenge. Under the study conditions, test substance at 58.23% gave a positive response in 5% of the animals. There was no positive sensitisation response at treatment with the test substance at 20.38% (Kaufmann, 1999).

 

Study 2:

A study was conducted to determine the sensitisation potential of the test substance in the albino guinea pig according to OECD Guideline 406 and EU Method B6, in compliance with GLP. Twenty test and ten control animals were used for the main study. Based on the results of sighting tests, the concentrations of test substance for the induction and challenge phases were selected as follows, for the topical the induction: 50% v/v of the test substance in distilled water (i.e., 35% a.i.) and for the topical challenge: 25% (17.5% a.i.) and 10% v/v (7% a.i.) in distilled water. Under the study conditions, the test substance produced a 0% (0/20) sensitisation rate (Sanders, 2000).

 

Study 3:

A study was conducted to determine the skin sensitising potential of the test substance in the guinea pig maximization test according to OECD Guideline 406. Twenty test and ten control animals were used for the main study. Following induction exposure to the test substance or the vehicle, the animals were subjected two weeks later to a challenge exposure with the test substance. Allergic responses to the challenge procedure were evaluated 24 and 48 h after the end of the exposure period. Under the study conditions, the sensitisation rate at 24 h was 25% and 10% after 48 h, therefore the test substance was considered to be non-sensitiser under CLP criteria (Oetjen, 1990).

 

Study 4:

A study was conducted to determine the skin sensitisation potential of the test substance. A few specialized centers performed preliminary studies, followed by a formal DKG study to try (i) to determine appropriate patch test preparations for ammonium thiolactate (ATL) and thiolactic acid (TA) and (ii) to analyse the frequency of sensitisation to either substance in patients tested with the hairdressers’ series. TA 1% pet. was soon withdrawn due to obvious irritancy. However, 0.3% TA also appeared quite irritant at first (18.9%cases), whereas the commercially prepared TA used later was much less irritant (4.7% and 6.7% or IR reactions, respectively). Consequently, the later test panel was restricted to the latter 2 preparations and 2 concentrations (1% and 2%) of freshly prepared ATL. With freshly prepared ATL in water, test results varied between the 3 periods (probably attributable to different patient selection criteria and an expanding spectrum of study participants, respectively). Under the study conditions, ATL and TA are difficult allergens to test, being potentially irritant and chemically unstable, depending on percentage and vehicle. Even after testing many patients, the ideal test percentage and vehicle can only be approximated: ATL 1% and 2% aq., freshly prepared from stock solution (renewed regularly), appear adequate and not too irritant. In contrast, TA 0.3% pet. is largely irritant (Uter, 2002).

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Given the conflicting skin sensitization data available for ATL, the skin sensitization endpoint for ATL needs to be seen in the broader context of skin sensitization information available for the category of mercaptocarboxilic acids, their salts and esters. Hoffmann (2016) reviewed all relevant skin sensitization data available for mercaptocarboxilic acid category including ATL and its close analogue thiolactic acid (TLA) and concluded that all category members should be considered to be skin sensitisers. The skin sensitization potency correlates with the number of thiol groups, which are assumed to increase protein reactivity, the first step in the skin sensitization adverse outcome pathway. Category members with one thiol group should be classified as skin sensitiser subcategory 1B and category members with more than one thiol group as subcategory 1A (Hoffmann, 2016). As Ammonium thiolactate and thiolactic acid are substances with one thiol group, this requires classifying them into subcategory 1B

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ATL is suggested to be classified as Skin Sens. Cat. 1B according to EU CLP (EC 1272/2008) criteria.

 

Reference

Hoffmann S 2016: Category approach for the skin sensitization potential and potency of mercaptocarboxilic acids, their salts and esters. Unpublished report prepared by Dr. Sebastian Hoffmann, she consulting & services to Bruno Bock, Chemische Fabrik GmbH & Co, 17 June 2016.