Cobaltate(1-), bis[2-(3-chlorophenyl)-2,4-dihydro-4-[[2-hydroxy-5-(methylsulfonyl)phenyl]azo]-5-methyl-3H-pyrazol-3-onato(2-)]-, hydrogen, compd. with [1R-(1α,4aβ,10aα)]-1,2,3,4,4a,9,10,10a-octahydro-1,4a-dimethyl-7-(1-methylethyl)-1-phenanthrenemethanamine (1:1)

Endpoint summary

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:

1979-11-05 to 1980-01-23

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:

other: "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959), the US Association of Food and Drug Officials (AFDO)

Deviations:

not specified

GLP compliance:

no

Type of study:

Freund's complete adjuvant test

Justification for non-LLNA method:

No LLN study has been performed since valid data obtain in guinea pigs are available.

Species:

guinea pig

Strain:

Pirbright-Hartley

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Bantin and Kingman Ltd. Grimston, Hull, England
- Weight at study initiation: 385 - 404 g (f); 395 - 401 g (m)
- Housing: individually in macrolon cages (Type 3)
- Diet: ad libitum, standard diet (NAFAG, No. 830, Gossau SG)
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±2
- Humidity (%): 55±10
- Photoperiod (hrs dark / hrs light): 14/10

Route:

epicutaneous, open

Vehicle:

propylene glycol

Concentration / amount:

Induction: 0.1 % in physiological saline (during 2nd and 3rd week the test substance was solved in a 1:1 mixture of normal vehicle and Freund complete adjuvant)

Route:

intradermal and epicutaneous

Vehicle:

propylene glycol

Concentration / amount:

epicutaneous: 0.1 % in physiological saline
intradermal: 30 % in vaseline

No. of animals per dose:

20 (10/sex)

Details on study design:

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 10
- Test group: Injection of a freshly prepared suspension of the test substance
- Control group: Injection of the vehicle (propylene glycol)
- Site: right flank and the back
- Frequency of applications: every second day (except weekends)
- Duration: 3 weeks
- Concentrations: 0.1 %

B. CHALLENGE EXPOSURE (INTRADERMAL)
- No. of exposures: 1
- Day(s) after induction: 14 days
- Test group: Injection of a freshly prepared suspension of the test substance
- Control group: Injection of a freshly prepared suspension of the test substance
- Site: left flank and the back
- Concentrations: 0.1 %
- Evaluation (hr after challenge): 24 hours

C. CHALLENGE EXPOSURE (EPICUTANEOUS)
- No. of exposures: 1
- Days after induction: 24 days
- Test group: Epicutaneous application of the test substance in vaseline.
- Control group: Epicutaneous application of the test substance in vaseline.
- Site: left flank and the back
- Concentrations: 30 %
- Evaluation (hr after challenge): 24 hours

Challenge controls:

Not available

Positive control substance(s):

no

Reading:

other: Reading after intradermal exposure

Hours after challenge:

24

Group:

negative control

Dose level:

0.1 %

No. with + reactions:

4

Total no. in group:

20

Reading:

other: Reading after intradermal exposure

Hours after challenge:

24

Group:

test chemical

Dose level:

0.1 %

No. with + reactions:

17

Total no. in group:

20

Reading:

other: Reading after epicutaneous occlusive exposure

Hours after challenge:

24

Group:

negative control

Dose level:

30 % in vaseline

No. with + reactions:

0

Total no. in group:

20

Reading:

other: Reading after epicutaneous occlusive exposure

Hours after challenge:

24

Group:

test chemical

Dose level:

30 % in vaseline

No. with + reactions:

0

Total no. in group:

20

Under the experimental conditions employed, significant differences between the test group and the vehicle treated controls were only seen after intradermal challenge application i.e. 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.

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

In a dermal sensitisation study equivalent or similar to OECD guideline 406, guinea pigs (10/sex) were tested in a Freund´s complete adjuvant test (BASF, 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 the test 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 onto the shaved 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 test substance in physiological saline was administered onto 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 was applied epicutaneously under occlusive dressings which were left in place for 24 hours.

Intradermal injections of the vehicle alone induced sensitization in 4 animals. Significant differences between the test group and the vehicle treated controls were only seen after intradermal challenge application of the test substance, i.e. 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.

Migrated from Short description of key information:
A Freund´s complete adjuvant test with guinea pigs did not show any sensitising effects. (BASF, 1979)

Justification for selection of skin sensitisation endpoint:
Scientifically acceptable study report.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available study is considered reliable and suitable for classification purposes under 67/548/EEC. As a result, the substance does not need to be classified and labelled as sensitising under Directive 67/548/EEC, as amended for the 31st time in Directive 2009/2/EC.

 

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

The available experimental test data is reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance does not need to be classified and labelled as sensitising under Regulation (EC) No 1272/2008, as amended for the sixth time in Regulation (EC) No 605/2014.