[1-[[(2-hydroxyphenyl)imino]methyl]-2-naphtholato(2-)-N,O,O']copper

Endpoint summary

Description of key information

The substance was not skin sensitizing in the guinea pig maximization test (OECD 406, GLP) at intradermal and epicutaneous induction at 1 and 10%, respectively.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1987

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

- 1981 followed, reliability scoring based on 1992 guideline

Deviations:

no

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

The LLNA had not yet been invented in 1987.

Species:

guinea pig

Strain:

other: Pirbright White (Tif: DHP)

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: CIBA-GEIGY Limited (Animal Production) 4332 Stein/Switzerland
- Age at study initiation: approx 10 weeks
- Weight at study initiation: 340 to 481 g
- Housing: Housed individually in Macrolon cages (Type 3)
- Diet (e.g. ad libitum): standard guinea pig pellets NAFAG No. 845, Gossau SG, ad libitum
- Water (e.g. ad libitum): fresh water, ad libitum
- Acclimation period: 6 days (start March 16, 1987)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 to 70
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): 12/12

Route:

intradermal

Vehicle:

other: sesame oil

Concentration / amount:

1%

Day(s)/duration:

single injection

Adequacy of induction:

highest technically applicable concentration used

Route:

intradermal

Vehicle:

physiological saline

Concentration / amount:

1%

Day(s)/duration:

single injection

Adequacy of induction:

highest technically applicable concentration used

Route:

epicutaneous, occlusive

Vehicle:

petrolatum

Concentration / amount:

10%

Day(s)/duration:

48h

Adequacy of induction:

non-irritant substance, but skin pre-treated with 10% SDS

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

petrolatum

Concentration / amount:

3%

Day(s)/duration:

24h

Adequacy of challenge:

highest non-irritant concentration

No. of animals per dose:

Test group: 10/sex
Control group: 10/sex

Details on study design:

RANGE FINDING TESTS:
The concentration for the intradermal injections was selected on account of the solubility of the test article in standard vehicles and its local and systemic tolerability.

MAIN STUDY
Control group: One side of flank induced with vehicle and challenged with vehicle; other side of flank induced with vehicle and challenged with test substance
Test group: One side of flank induced with test substance and challenged with vehicle; other side of flank induced with test substance and challenged with test substance

A. INDUCTION EXPOSURE
- No. of exposures: 2
- Exposure period: single exposure (intradermal); 48 hours (epidermal)
- Test groups:
First induction week, intradermal injection:
Three pairs of intradermal injections (0.1 ml per injection) were made simultaneously into the shaved neck of the guinea pigs as follows:
- adjuvant/saline mixture 1:1 (v/v)
- test article in sesame oil
- test article TK 10047 in the adjuvant saline mixture (w/v)

Second induction week, epidermal application:
In the second week of induction the substnace was incorporated in vaseline (w/w) and applied on a filterpaper patch to the neck of the animals (patch 2x4 cm; approx. 0.4 g paste per patch; occluded administration for 48 hours).
The application sites were pretreated the day before with 10 % sodium lauryl sulfate (open application).

- Control group:
A control group of 10 animals (5 m/5 f) was treated with adjuvant and the vehicle during the induction period.
- Site: Intradermal injections into the neck region, followed by closed patch exposure over the injection sites
- Frequency of applications: Single dose exposure (epidermal application)
- Duration: 48h (occluded)


B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: Two weeks a f t e r the epidermal induction application
- Exposure period: 24 hours
- Test groups: The animals were tested on the flank in vaseline (w/w) and the vehicle alone (patch 2x2 cm; approx. 0.2 g paste per patch; occluded administration).
- Control group: During the challenge period the group was treated with the vehicle as well as with the test article to check the maximum subirritant concentration of the test article in adjuvant treated animals.
- Site: flank
- Concentrations: 3% in vaseline (epidermal challenge)
- Evaluation (hr after challenge): 24 and 48 hrs

Challenge reactions: Twenty four and forty eight hours after removing the dressings, the challenge reactions were graded according to the Draize scoring scale (Appraisal of the Safety of chemicals in Foods, Drugs and Cosmetics (1959), The US Association of Food and Drug Officials (AFDO).
General: The sensitising potential was classified according to the grading of Magnusson and Kligman.
Maximization grading:
Sensitization rate (%) - Grade - Classification
(0 – 8) - I - weak
(9 – 28) - II - mild
(29 – 64) - III - moderate
(65 – 80) - IV - strong
(81 – 100) - V - extreme

Challenge controls:

During the challenge period the group was treated with the vehicle as well as with the test article to check the maximum subirritant concentration of the test article in adjuvant treated animals.

Positive control substance(s):

yes

Remarks:

The sensitivity of the strain was checked every six months with Paraphenylene-diamine or Potassium-dichromate.

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

3%

No. with + reactions:

0

Total no. in group:

20

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

3%

No. with + reactions:

0

Total no. in group:

20

Reading:

1st reading

Hours after challenge:

24

Group:

other: control (induced with vehicle, challenged with test article)

Dose level:

3%

No. with + reactions:

0

Total no. in group:

10

Reading:

2nd reading

Hours after challenge:

48

Group:

other: control (induced with vehicle, challenged with test article)

Dose level:

3%

No. with + reactions:

0

Total no. in group:

10

Body weight development was not affected by the treatment.

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

The substance was tested in a GLP-compliant guinea pig maximization test following OECD guideline 406. Induction concentrations were 1% in sesame oil (intradermal) and 10% (epidermal.). The challenge concentration was 3%. There were two control groups: In one group, challenge was done with the vehicle, in the other, the test substance was used.

The concentration for the intradermal injections was selected on account of the solubility of the test article in standard vehicles and its local and systemic tolerability.

Overall, no skin reactions were observed - neither in the control groups nor in the test group.

The test material was not characterized for particles in the nano-size range.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

 Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for skin sensitization under Regulation (EC) No. 1272/2008, as amended for the thirteenth time in Regulation (EC) No. 2018/1480.