Sodium [3-hydroxy-4-[(1-hydroxy-8-sulpho-2-naphthyl)azo]naphthalene-1-sulphonato(4-)]chromate(1-)

Endpoint summary

Description of key information

The test article is considered as sensitiser.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation, other

Remarks:

in vivo test

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From February, 14 to April, 21 1994

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

no

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

A non-LLNA skin sensitisation study does not need to be conducted because adequate data from an in vivo study are available.

Species:

guinea pig

Strain:

Pirbright-Hartley

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: CIBA-GEIGY Limited Animal Production
- Weight at study initiation: 339 to 404 g
- Housing: The animals were housed individually in Macrolon cages (Type 3)
- Diet: The animals received ad libitum standard guinea pig pellets NAFAG No. 845, All batches of the diet are assayed for nutritive ingredients and contamination level
- Water: fresh water ad libitum. The drinking water quality fulfilled the critical parameters in the specifications of the "Schweizerisches Lebensmittelbuch" (Edition 1972). The results of the routine chemical examination of water a t source (Grundwasserfassung Stein) as conducted periodically by the water authority (Baudepartement des Kantons Aargau, Abteilung Gewaesserschutz)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 30 to 70%
- Photoperiod (hrs dark / hrs light): 12 hours light cycle day.

Route:

intradermal and epicutaneous

Vehicle:

other: adjuvant and physiological saline mixture

Concentration / amount:

intradermal injections
Test group:
- adjuvant/saline mixture 1:1 (v/v)
- 5% in physiological saline (w/v)
- 5% in the adjuvant/saline mixture (w/v)
epidermal application
Test group:
- 50% in physiological saline approx. 0.4 g per patch
Control group:
- physiological saline only B.

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

physiological saline

Concentration / amount:

30% in physiological saline, approx 0.2 g per patch

No. of animals per dose:

5 per sex for the test group and 5 of one sex for controls

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 in a pretest.

PRETEST:
Intradermal Induction
- No. of exposures: one injection
- Concentrations: 5 % in physiological saline (w/v).
Epidermal Applications (induction and challenge)
- No. of exposures: one application
- Concentrations: 30 and 50 % in physiological saline. 50 % was the highest possible concentration of the test article in physiological saline.

MAIN STUDY
INDUCTION EXPOSURE: intradermal injections
- No. of exposures: Three pairs of intradermal injections (0.1 ml per injection)
- Exposure period: DAY 0- Test groups: 5 male and 5 female Guinea pigs
- Control group: 5 male and 5 female Guinea pigs- Site: left and right side of the shaved neck
- Frequency of applications: one
- Test group Concentrations:
adjuvant/saline mixture 1:1 (v/v)
5% in physiological saline (w/v)
5% in the adjuvant/saline mixture (w/v)
- Control group Concentrations:
adjuvant/saline mixture 1:1 (v/v)
physiological saline

INDUCTION EXPOSURE: epidermal application
- Application: The application site of all animals was pre treated with 10% sodium-laurylsulfate (open application) 24 hours prior to the epidermal induction application.
- No. of exposures: one application
- Exposure period: Day 8
- Test groups: 5 male and 5 female Guinea pigs
- Control group: 5 male and 5 female Guinea pigs
- Site: neck
- Frequency of applications: one
- Duration: 48 hours
- Test group Concentrations: 50% in physiological saline approx. 0.4 g per patch
- Control group Concentrations: physiological saline only

CHALLENGE EXPOSURE
- No. of exposures: one
- Day(s) of challenge: Day 21
- Exposure period: 24 hours
- Test groups: 5 male and 5 female Guinea pigs
- Control group: 5 male and 5 female Guinea pigs
- Site: one flank
- Concentrations of Test group: 30% in physiological saline, approx. 0.2 g per patch
- Concentrations of Control group: physiological saline only
- Evaluation (hr after challenge): 24 and 48 hours

Positive control substance(s):

no

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

30% in physiological saline (0.2 g)

No. with + reactions:

8

Total no. in group:

20

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 30% in physiological saline (0.2 g). No with. + reactions: 8.0. Total no. in groups: 20.0.

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

30% in physiological saline (0.2 g)

No. with + reactions:

8

Total no. in group:

20

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 30% in physiological saline (0.2 g). No with. + reactions: 8.0. Total no. in groups: 20.0.

The individual animal body weights were measured at the start and at the end of the test. Body weights were not affected by treatment.

Interpretation of results:

Category 1B (indication of skin sensitising potential) based on GHS criteria

Conclusions:

Sensitizer

Executive summary:

The study was conducted according to OECD Guideline 406, Guinea Pig Maximisation test. Ten animals (5 male and 5 female) were exposed to test article and 5 Guinea Pig were used as control. During the Intradermal induction the animals were exposed to test article at a concentration of 5 %. During the challenge after 24 and 48 hours 40 % of the treated animals showed a positive reaction to the test item. Based on these positive reaction the test article is considered as sensitizer for Guinea pig.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

The assessment was based on a single study (Huntsman, 1994) conducted according to OECD Guideline 406, Guinea Pig Maximisation test. Ten animals (5 male and 5 female) were exposed to test article and 5 Guinea Pig were used as control. During the Intradermal induction the animals were exposed to test article at a concentration of 5 %. During the challenge after 24 and 48 hours 40 % of the treated animals showed a positive reaction to the test item.

Another study is available on the substance in itself, nevertheless it was not considered as key study although the higher purity of the test item because during the first challenge the positive reactions observed were different to the ones observed during the second challenge (95 % positive reactions during the 1^stchallenge and 0 % during the 2^ndchallenge). Based on these information it was considered as most protective the Huntsman study of 1994. The method and the results of the test not considered for the classification purpose were summarized below:

The study (Huntsman, 1995) was conducted according to the OECD Guideline 406 in order to assess the sensitisation potential of the test item in Guinea pig. Ten male were used as control and 20 male were used as test group.

In this study positive skin reactions were observed in the both control and test group after the first challenge with the test article at 3 % in vaselinum album determined as the highest non-irritating concentration during the epidermal pretest procedure. During the experimental procedure it was concluded that the test article concentration used in the first challenge was irritant. Therefore a second challenge was performed with a lower concentration of 1 % in vaselinum album and with an additional control group. In this case, none of the animals of the control and test group were observed with skin reactions. Nevertheless the test is considered as not reliable considering the results of the skin and eye irritation (Not irritant), therefore it was not considered for the assessment.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

According to the CLP Regulation (EC n. 1272/2008): Skin sensitiser means a substance that will lead to an allergic response following skin contact.

Sub- category 1B: Substances showing a low to moderate frequency of occurrence in humans; or a probability of occurrence of a low to moderate sensitisation rate in humans based on animal or other tests. More specifically, as reported in the Table 3.4.4, a substance shall be classified as Sub category 1B if, in a Guinea pig mazimisation test, the tested animals showed a skin reaction in a percentage ≥ 30 % responding at > 1 % intradermal induction dose

Under the experimental conditions employed, 40 % of the treated animals showed skin reactions responding at an intradermal induction dose of 5 %.

According to the CLP Regulation (EC n. 1272/2008) the substance has met the criteria for classification as Skin sensitisation Category 1B.