Reaction product of Chloro[29H,31H-phthalocyaninato(2-)-N29,N30,N31,N32]aluminium, sulphuric acid and caustic soda

Endpoint summary

Description of key information

Based on the weight of evidence of the available data, the substance is considered not to be a skin sensitiser.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Reference 1

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

No positive control tested

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

GLP compliance:

no

Remarks:

Study pre-dates GLP regulations

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

Study performed before the LLNA guidelines were published.

Specific details on test material used for the study:

- Name used in the study report: FAT 60'149/B
- Batch number: Partie 1

Species:

guinea pig

Strain:

other: Pirbright white

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Ivanovas, Germany
- Age at study initiation: approximately 10 weeks
- Weight at study initiation: 300-400 g
- Housing: individually in Macrolon cages (type 3)
- Diet: ad libitum standard guinea pig pellets - NAFAG No. 830, Gossau SG, supplemented with fresh carrots
- Water: ad libitum
- Acclimation period: 12 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 1
- Humidity (%): 50 ± 5
- Photoperiod (hrs dark / hrs light): 10/14

Route:

intradermal and epicutaneous

Vehicle:

other: intradermal: saline, and adjuvant and saline; epicutaneous: vaseline phH VI

Concentration / amount:

- intradermal application: 0.1% ; 0.1 mL per injection
- epicutaneous application: 30%

Day(s)/duration:

7 days after the intradermal application, the substance was applied epicutaneous for 48 hours.

Adequacy of induction:

other: The concentrations of the test compound for the induction and challenge periods were determined on separate animals before starting the test procedure.

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

other: soft white paraffin

Concentration / amount:

30%

Day(s)/duration:

24 hours

Adequacy of challenge:

other: The concentrations of the test compound for the induction and challenge periods were determined on separate animals before starting the test procedure.

No. of animals per dose:

20

Details on study design:

Test procedure
The concentrations of the test compound for the induction and challenge periods were determined on separate animals before starting the test procedure. A control group was treated with the vehicles alone (negative control).

INDUCTION, INTRADERMAL:
Two intradermal injections (0.1 ml per injection) were made into the nape of the guinea pigs with a mixture of adjuvant and saline, with the test compound in saline and with the test compound in the adjuvant saline mixture.

INDUCTION, EPIDERMAL:
One week later the test substance was incorporated in soft white paraffine and applied on a filterpaper patch to the nape of the animals (occlusive administration for 48 hours). Twenty-four hours before the compound application the induction site was treated epidermal open with 10 % sodium lauryl sulphate in vaseline.

CHALLENGE:
Two weeks after the epidermal induction application the animals were tested on one flank with 30 % FAT 60'149/B in soft white paraffine (24 h occlusive application). Twenty-four hours after removing the dressings the challenge reactions were graded according the Draize scoring scale. The application sites were chemically depilated 3 hours before examination (Veet , 5 minutes).

Challenge controls:

A control group was treated with the vehicles alone (negative control).

Positive control substance(s):

no

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

30%

No. with + reactions:

0

Total no. in group:

20

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

30%

No. with + reactions:

0

Total no. in group:

20

None of the animals of the test or control group reacted after epidermal occlusive challenge application.

Interpretation of results:

GHS criteria not met

Reference 2

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:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

no guideline followed

Principles of method if other than guideline:

The optimization test according to Maurer et al. (1975) was used, an intracutaneous sensitization procedure exceeding the sensitivity of the method recommended in the "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959), the US Association of Food and Drug Officials (AFDO). During induction, animals received one intracutaneous injection every second day (except weekends) for a total of 10 injections. Fourteen days after the last sensitizing injection, a challenge injection was administered into the skin of the left flank. Twenty-four hours after each injection during the first week of the induction period and 24 hours after the challenge injection the reactions were recorded. Ten days after the intracutaneous challenge injection a subirritant dose of the test compound (10 % substance in vaseline) was applied epicutaneously under occlusive dressings which were left in place for 24 hours. The reactions were evaluated 24 h after removing of the bandages according the Draize scoring scale.

GLP compliance:

no

Remarks:

Study pre-dates GLP regulations

Type of study:

Maurer optimisation test

Justification for non-LLNA method:

Study performed before the LLNA guidelines were published.

Specific details on test material used for the study:

- Name used in the study report: FAT 60'149/A
- Batch number: Versuch 124 - 4 + 5

Species:

guinea pig

Strain:

other: Pirbright white

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: bred on premises
- Age at study initiation:approximately 10 weeks
- Weight at study initiation: 290-400 g
- Housing: individually in Macrolon cages (type 3)
- Diet: ad libitum standard guinea pig pellets - NAFAG No. 830, Gossau SG, supplemented with fresh carrots
- Water: ad libitum
- Acclimation period: 10 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 1
- Humidity (%): 55 ± 5
- Photoperiod (hrs dark / hrs light): 10/14

Route:

intradermal

Vehicle:

other: 1 injection in physiological saline; 9 following injections in physiological saline and complete Freund adjuvant (1:1)

Concentration / amount:

0.1% in 0.1 mL.

Day(s)/duration:

10 injections, every other day, except weekends

Adequacy of induction:

not specified

No.:

#1

Route:

intradermal

Vehicle:

physiological saline

Concentration / amount:

0.1% in 0.1 mL

Day(s)/duration:

14 days after the last sensitising injection

Adequacy of challenge:

not specified

No.:

#2

Route:

epicutaneous, occlusive

Vehicle:

other: vaseline

Concentration / amount:

10%

Day(s)/duration:

Ten days after the intradermal challenge; challenge for 24 hours

Adequacy of challenge:

not specified

No. of animals per dose:

20

Details on study design:

TESTING PROCEDURE
During the induction period the animals received one injection every second day (except weekends) to a total of 10 intracutaneous injections of a freshly prepared 0.1 % solution of the substance in physiological saline. One control group was treated with the vehicle alone ("negative control"). On the first day, injections of 0.1 ml were administered into the shaven skin of the right flank and the back, while on the following days a single intracutaneous injection was given into the back. During the second and third week of the induction period the test material was incorporated in a mixture of the normal vehicle with complete Bacto Adjuvant (vehicle : adjuvant = 1 : 1). Fourteen days after the last sensitizing injection, a challenge injection of 0.1 ml of a freshly prepared 0.1 % solution of the substance in physiological saline was administered into the skin of the left flank. Twenty-four hours after each injection during the first week of the induction period and 24 hours after the challenge injection the reactions were recorded. The two largest perpendicular diameters (in mm) and the increase in the skin- fold thickness (in mm) were measured and by multiplication of these values "reaction volume" was obtained (in µl) for each reading from each animal. The mean volume plus one standard deviation of the induction reactions observed in the individual animal in the first week was taken as representing the skin irritation "threshold" for each animal. Any challenge reaction greater than this threshold value in the induction period was graded as an allergic reaction and the animal termed "positive". The number of "positive" animals in the test group was compared with the number of animals in the control group (treated with the vehicle alone) that showed a non-specific reaction of at least the same magnitude ("negative control"). Ten days after the intracutaneous challenge injection a subirritant dose of the test compound (10 % test substance in vaseline) was applied epicutaneously under occlusive dressings which were left in place for 24 hours. The reactions were were evaluated 24 h after removing of the bandages according the Draize scoring scale

Positive control substance(s):

no

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

0.1%

No. with + reactions:

11

Total no. in group:

20

Remarks on result:

other: intradermal challenge

Remarks:

p < 0.01

Reading:

rechallenge

Hours after challenge:

24

Group:

test chemical

Dose level:

10%

No. with + reactions:

1

Total no. in group:

20

Clinical observations:

one animal with erythema score (according to Draize system) of 2

Remarks on result:

other: epicutaneous challenge

Remarks:

p> 0.01

Interpretation of results:

GHS criteria not met

Reference 3

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:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

Five challenge applications are given, first two epicutaneous, followed by a simultaneous epicutaneous and intradermal, a fourth epicutaneous and a second epidermal challenge.

GLP compliance:

no

Remarks:

Study pre-dates GLP regulations

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

Study performed before the LLNA guidelines were published.

Specific details on test material used for the study:

- Name used in study report: Tinolux 4204 HC

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: bred on the premises
- Weight at study initiation: 348-492 g
- Housing: in pairs of the same sex in suspended cages with wire-mesh floors.
- Diet: ad libitum pelleted commercial guinea pig diet, a handful of hay every working day, several pieces of cabbage every second day.
- Water: ad libitum

Route:

intradermal

Vehicle:

physiological saline

Concentration / amount:

0.8%; two injections of 0.1 mL

Adequacy of induction:

other: The concentration which caused a definite irritation reaction was selected as the intradermal injection induction concentration.

Route:

epicutaneous, open

Vehicle:

water

Concentration / amount:

10%

Day(s)/duration:

48 hours

Adequacy of induction:

other: For shoulder induction, a concentration causing slight but definite irritation was selected.

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

water

Concentration / amount:

2.5%

Day(s)/duration:

two weeks after the application of the shoulder induction patch; challenge for 24 hours

Adequacy of challenge:

highest non-irritant concentration

No.:

#2

Route:

epicutaneous, occlusive

Vehicle:

water

Concentration / amount:

2.5%

Day(s)/duration:

One week after challenge 1; challenge for 24 hours

Adequacy of challenge:

highest non-irritant concentration

No.:

#3

Route:

intradermal and epicutaneous

Vehicle:

other: intradermal: physiological saline; epicutaneous: water

Concentration / amount:

- intradermal: 0.8% (0.1 mL)
- epicutaneous: 8% (0.1 mL)

Day(s)/duration:

Ten days after challenge 2; challenge for 24 hours

Adequacy of challenge:

other: Intradermal: concentration which caused a definitive irritation reaction; epicutaneous: maximum concentration which dissolved completely in distilled water

No.:

#4

Route:

epicutaneous, occlusive

Vehicle:

water

Concentration / amount:

2.5%

Day(s)/duration:

five days after challenge 3; challenge for 24 hours

Adequacy of challenge:

highest non-irritant concentration

No.:

#5

Route:

intradermal

Vehicle:

physiological saline

Concentration / amount:

0.8% (0.1 mL)

Day(s)/duration:

Eight days after the fourth challenge.

Adequacy of challenge:

other: The concentration which caused a definite irritation reaction

No. of animals per dose:

10

Details on study design:

RANGE FINDING TESTS:
INTRADERMAL INJECTION PRELIMINARY IRRITATION TEST:
The hair was clipped from both flanks of the 8 (4 male, 4 female) guinea pigs. Four female guinea pigs were each injected with 0.1 ml of 0.1%, 0.25%, 0.5%, 0.8% substance in physiological saline. Four male guinea pigs were each injected with 1%, 2.5%, 5% substance in physiological saline. Twenty-four hours later the length and breadth of each reaction was measured in millimetres and erythema graded on the following scale: fp = faint pink; pp = pale pink; p = pink; dp = deep pink; Any oedema (el), white necrotic centres (w), induration or erosion (n) or any other features of the responses were recorded.
OCCLUDED PATCH PRELIMINARY IRRITATION TEST:
Eight millimetre diameter filter paper patches in 11 mm diameter altiminium patch test cups were saturated with 2.5%, 5% and 10% substance in distilled water. The cups were applied to the closely shaved flanks of the 4 female guinea pigs and held in place for 24 hours with adhesive plaster wound around the trunk. Twenty-four and 48 hours after removal of the patches, the skin, sites were examined and graded on the following scale: 0 = no reaction; ± = barely perceptible erythema; + = scattered, mild erythema (faint pink); ++ = moderate and diffuse erythema (pale pink); ; +++ = intense erythema (deep pink) and oedema; sp = spots of erythema; n = necrosis

MAIN STUDY
A. INDUCTION EXPOSURE
INTRADERMAL INJECTION:
The hair of each of the 10 test animals was clipped and shaved from a 2 x 4 cm area of skin in the dorsal shoulder region and 3 pairs of intradermal injections made within the shaved area as follows. (i) two 0.1 ml injections of 50% FCA in physiological saline; (ii) two 0.1 ml injections of 0.8% substance in physiological saline; (iii) two 0.1 ml injections of substance in physiological saline mixed 50/50 with FCA such that the final concentration of substance was 0.8% AI.
The 4 male guinea pigs selected as treated controls were treated in the same way as the test animals except that physiological saline alone was used instead of substance.
OCCLUDED PATCH APPLICATION:
One week after injection the same 2 x 4 cm area was clipped and shaved. For each test animal, a 2 x 4 cm filter paper patch attached by double-sided adhesive tape to a 4 x 6 cm piece of thin polythene was saturated with 10% substance in distilled water and placed over the injection site. The patch was held in place for 48 hours by adhesive plaster wrapped around the trunk behind the forelimbs. The treated-control guinea pigs were treated in the scime way but with distilled water alone instead of substance.
B. CHALLENGE EXPOSURE
Challenge 1: Two weeks after the application of the shoulder induction patch the test animals were challenged on one flank (first flank) by occluded patch. For each animal, an 8mm diameter filter paper patch, in an 11mm aluminium patch test cup was saturated with 2.5% substance in distilled water. The cup was applied to one clipped and shaved flank and held in place for 24 hours by adhesive plaster wound around the trunk. Challenge sites were examined for evidence of sensitization 24 and 48 hours after removal of the patches. The 4 treated-control guinea pigs and 4 previously-untreated control guinea pigs of similar weight to the test animals were treated in the same way as the test animals.
Challenge 2: One week after challenge 1 the test animals were challenged on the opposite flank (second flank) with 2.5% substance in distilled water applied for 24 hours in the same way as for challenge 1. The resulting reactions were assessed 24 and 48 hours after removal of the patches. At this challenge 4 previously untreated control animals of similar weight to the test animals were treated in the same way as the test animals.
Challenge 3: Ten days after challenge 2 the test animals were challenged on the first flank with 0.8% substance in physiological saline by intradermal injection and with 8% substance in distilled water (0.1 ml aliquot) by open topical application. Intradermal injection reactions were assessed 24 hours later a. Open topical application reactions were scored 24 hours later on the following scale. 0 = no reaction; ± = barely perceptible erythema; + = faint pink erythema; ++ = pale pink erythema; +++ =pink erythema with oedema; ++++ = deep pink erythema with oedema, with or without necrosis; sp = small spots of erythema; At this challenge 4 previously untreated control animals of similar weight to the test animals were treated in the same way as the test animals.
Challenge 4: Five days after challenge 3 the test animals were challenged on the second flank with 2.5% substance in distilled water applied in the same way as for challenge 1. The resulting reactions were assessed 24 and 48 hours after removal of the patches as described earlier. At this challenge 4 previously untreated control animals of similar weight to the test animals were treated in the same way as the test animals.
Challenge 5: Eight days after the fourth challenge, the test animals were challenged on the first flank with 0.8% substance in physiological saline by intradermal injection. Intradermal injection reactions were assessed 24 hours later as described earlier At this challenge 4 previously untreated control animals of similar weight to the test animals were treated in the same way as the test animals.

Challenge controls:

See details on study design

Positive control substance(s):

no

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

2.5%

No. with + reactions:

3

Total no. in group:

10

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

2.5%

No. with + reactions:

0

Total no. in group:

8

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

2.5%

No. with + reactions:

3

Total no. in group:

10

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

2.5%

No. with + reactions:

0

Total no. in group:

8

Reading:

rechallenge

Hours after challenge:

24

Group:

test chemical

Dose level:

2.5%

No. with + reactions:

4

Total no. in group:

10

Reading:

rechallenge

Hours after challenge:

24

Group:

negative control

Dose level:

2.5%

No. with + reactions:

0

Total no. in group:

4

Reading:

rechallenge

Hours after challenge:

48

Group:

test chemical

Dose level:

2.5%

No. with + reactions:

3

Total no. in group:

10

Reading:

rechallenge

Hours after challenge:

48

Group:

negative control

Dose level:

2.5%

No. with + reactions:

0

Total no. in group:

4

Reading:

other: third challenge

Hours after challenge:

24

Group:

test chemical

Dose level:

0.8% intradermal and 8% epicutaneous

No. with + reactions:

3

Total no. in group:

9

Clinical observations:

One animal was culled prior to the challenge, as the neck lesion due to the induction procedure had deteriated to a level that could cause undue discomfort and pain

Remarks on result:

other: only positive results at intradermal challenge; all epicutaneous challenge results negative

Reading:

other: third challenge

Hours after challenge:

24

Group:

negative control

Dose level:

0.8% intradermal and 8% epicutaneous

No. with + reactions:

0

Total no. in group:

4

Reading:

other: fourth challenge

Hours after challenge:

24

Group:

test chemical

Dose level:

2.5%

No. with + reactions:

0

Total no. in group:

9

Reading:

other: fourth challenge

Hours after challenge:

24

Group:

negative control

Dose level:

2.5%

No. with + reactions:

0

Total no. in group:

4

Reading:

other: fourth challenge

Hours after challenge:

48

Group:

test chemical

Dose level:

2.5%

No. with + reactions:

0

Total no. in group:

9

Reading:

other: fourth challenge

Hours after challenge:

48

Group:

negative control

Dose level:

2.5%

No. with + reactions:

0

Total no. in group:

4

Reading:

other: fifth challenge

Hours after challenge:

24

Group:

test chemical

Dose level:

0.8% (intradermal)

No. with + reactions:

3

Total no. in group:

9

Reading:

other: fifth challenge

Hours after challenge:

24

Group:

negative control

Dose level:

0.8% (intradermal)

No. with + reactions:

0

Total no. in group:

4

Interpretation of results:

other: weak sensitizer

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Animals

Three in vivo skin sensitisation studies are available. Two of these studies are guinea pig maximisation tests, according to or similar to Magnusson and Kligman. One study is a Maurer optimisation test.

The first guinea pig maximisation test was performed in a very similar way to the method described in OECD 406 (CIBA-GEIGY, 1980). Twenty test animals and twenty negative controls were used, but no positive controls. It was reported, that the concentrations of the test compound for the induction and challenge periods were determined on separate animals before starting the test procedure, however, no details on this preliminary testing procedure are reported. Induction was done via two intradermal injections with adjuvant and saline, with 0.1% substance in saline and with 0.1% substance in the adjuvant saline mixture. Epidermal application for induction was done in paraffin with 30% substance under occlusion for 48 hours, 24 hours after treating the induction site with 10% sodium lauryl sulphate. The challenge was done with 30% substance in paraffin (24 h occlusive application). A control group was treated with the vehicles alone. No animal from either the test group or negative control group showed a positive response.

The Mauer optimization test was performed on 20 guinea pigs in the test group and 20 negative controls (CIBA-GEIGY, 1979). During the induction period the animals received one injection every second day (except weekends) to a total of 10 intracutaneous injections of a freshly prepared 0.1 % solution of substance in physiological saline. One control group was treated with the vehicle alone ("negative control"). Fourteen days after the last sensitizing injection, a challenge injection of 0.1 ml of a freshly prepared 0.1 % solution of the substance in physiological saline was administered into the skin of the left flank. Ten days after the intracutaneous challenge injection a subirritant dose of the test compound (10 % in vaseline) was applied epicutaneously under occlusive dressings which were left in place for 24 hours. In the test group, 11 animals showed a positive reaction after intradermal challenge and 1 animal showed a positive reaction after epicutaneous challenge. Under the experimental conditions employed, significant differences between the test group and the vehicle-treated controls were only seen after intradermal challenge application when the skin barrier was intentionally by-passed. No difference between the test and the control group was seen after epidermal challenge application. The negative results upon epidermal challenge demonstrate that, in artificially sensitized guinea-pigs, exposure of the intact skin to the test compound does not provoke contact dermatitis.

The third study used a variant of the guinea pig maximisation test with additional intradermal and open application challenges (Unilever 1980). Sensitization was induced in each of 10 guinea pigs by 6 intradermal injections in the nuchal region: these comprised 2 x 0.1 ml injections of 0.8% test substance in physiological saline, 2 x 0.1 ml injections of 50% Freund's complete adjuvant (FCA) in physiological saline, and 2 x 0.1 ml injections of a 50/50 mixture of FCA and test substance in physiological saline such that the final concentration of test substance was 0.8%. Sensitization was boosted one week later by an occlusive patch with 10% test substance in distilled water applied over the injection sites for 48 hours. Two weeks after the booster induction the animals were challenged by occluded patch on the shaved flank with 2.5% substance in distilled water applied for 24 hours. The skin responses were examined 24 hours and 48 hours after removal of the patch. A second challenge identical to the first was made on the opposite flank one week later. Ten days after the second challenge the animals were challenged on the first flank by intradermal injection of 0.8% substance in physiological saline and by open topical application with 10% substance in distilled water. The skin responses were examined 24 hours later. Five days after the third challenge, an occluded patch challenge identical to challenge 1 and 2 was made on the second flank. Eight days after the fourth challenge, an intradermal injection identical to that made at challenge 3 was made on the first flank. In this study, at the challenges 1, 2, 3 (only intradermal) and 5, three or four animals in the test group showed a positive reaction, while at epicutaneous challenge in challenge 3 and at challenge 4 no clear positive reactions were observed. It was concluded that the substance is a weak sensitizer.

Humans

Maximization testing was done on a test panel of volunteer subjects (BASF, 1981). In total 30 volunteers completed the study in which they received a concentration of 10% of the substance, with another location on their back used as internal control site. The effect was maximised by using an mild irritant ( sodium lauryl sulfate) to both the test and control location. A total of five applications (for 48 hours) of the test subtsance was made with 24 hours rest in between as induction to the test location (the control location did not receive the test substance). After an eleven day rest period, a 48 hour challenge application was made to both locations. No reactions were seen at the test locations that were higher than the reaction at the control location and that were high enough to be considered as establishing sensitisation.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the weight of evidence, it is considered that the criteria for classification for skin sensitization according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 are not met. Two studies, including one with a protocol close to the guinea pig maximisation test in OECD 406, show a clear negative response. The negative guinea pig maximisation test included only one challenge, due to the clear negative result. A Maurer optimisation test also showed a negative result. Another guinea pig maximazation test included 5 challenges, of which two (partially) intradermal. This test used a much higher intradermal induction concentration, but a clearly lower epicutaneous induction concentration and lower challenge concentrations than the other guinea pig maximisation test. In this test, 3 out of 10 (and later 3 out of 9, since one animal had to be culled), animals showed a positive response. However, at the epicutaneous challenge as part of the third challenge and at the fourth (epicutaneous) challenge, no animal in the test group showed a clear positive response. A human volunteer maximisation test showed no sensitisation in any of the 30 volunteers. Overall, it is concluded that the substance does not fulfil the criteria for classification as a skin sensitiser.