Bis[3-[[4-[benzylmethylamino]phenyl]azo]-1,4-dimethyl-1H-1,2,4-triazolium] tetrachlorozincate(2-)

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:

other: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

From July 16, 1979 to September 6, 1979

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

The test was conducted on a similar substance, the complete justification for the Read Across approach is reported at section 13. The original Reliability of the test is 2

Qualifier:

according 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:

guinea pig maximisation test

Justification for non-LLNA method:

Test conducted in 1979. No LLNA is required if older data is available.

Species:

guinea pig

Strain:

Pirbright-Hartley

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source:bred at Bantin and Kingman Ltd
- Age at study initiation: ~10 weeks old
- Weight at study initiation: 375 to 485 g
- Housing: housed individually in Macrolon cages, type 3, assigned to the different groups by means of random numbers.
- Diet : The animals received ad libitum standard guinea pig pellets - NAFAG, N°. 830 supplemented with fresh carrots.
- Water: ad libitum
- Acclimation period: 10 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1°C
- Humidity (%): 55± 5%
- Photoperiod (hrs dark / hrs light): 10 hours light cycle day

Route:

intradermal

Vehicle:

physiological saline

Remarks:

complete Bacto Adjuvant

Concentration / amount:

first induction exposure: 0.1 ml of 0.1 % of test substance
secndary induction exposure: mixture of the normal vehicle with complete Bacto Adjuvant (vehicle : adjuvant = 1 : 1)
challenge exposure: 0.1 % suspension of test substance in physiological saline
Rechallenge exposure: 3 % of test item in Vaseline

Route:

intradermal

Vehicle:

physiological saline

Remarks:

complete Bacto Adjuvant

Concentration / amount:

first induction exposure: 0.1 ml of 0.1 % of test substance
secndary induction exposure: mixture of the normal vehicle with complete Bacto Adjuvant (vehicle : adjuvant = 1 : 1)
challenge exposure: 0.1 % suspension of test substance in physiological saline
Rechallenge exposure: 3 % of test item in Vaseline

No. of animals per dose:

10 per sex per dose

Details on study design:

MAIN STUDY
A. INDUCTION EXPOSURE INTRADERMAL
- No. of exposures: the animals received one injection every second day (except weekends) to a total of 10 intracutaneous injections of a freshly prepared 0.1 % suspension of test item in physiological saline.
- Test groups: 10 males and 10 females guinea pigs
- Control group: 10 males and 10 females guinea pigs, one control group was treated with the vehicle alone
- Site: shaven skin of the right flank and the back
- Frequency of applications: daily
- Duration: 10 intracutaneous injections
- Concentrations: 0.1 % suspension of test substance

MAIN STUDY
A2. INDUCTION EXPOSURE INTRADERMAL
- No. of exposures: 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)
- Exposure period: During the second and third week of the induction period
- Test groups: 10 males and 10 females guinea pigs
- Control group: 10 males and 10 females guinea pigs
- Site: shaven skin of the right flank and the back
- Duration: Fourteen days

B. CHALLENGE EXPOSURE
- No. of exposures: challenge injection of 0.1 ml
- Day(s) of challenge: Fourteen days after the last sensitizing injection
- Exposure period: Fourteen days after the last sensitizing injection (induction period)
- Test groups: 10 males and 10 females guinea pigs
- Control group: 10 males and 10 females guinea pigs
- Site: skin of the left flank
- Concentrations: 0.1 % suspension of test substance in physiological saline
- Evaluation (hr after challenge): 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.

C. SUBIRRITANT DOSE (RECHALLENGE):
It was applied epicutaneously under occlusive dressings which were left in place for 24 hours. The 3% of test item in Vaseline.

OTHER:
Bodyweights were recorded immediately before starting the experiment (control values) and at termination of the study.

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

0.1 ml of 0.1 % suspension of test item in physiological saline

No. with + reactions:

20

Total no. in group:

20

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0.1 ml of 0.1 % suspension of test item in physiological saline . No with. + reactions: 20.0. Total no. in groups: 20.0.

Reading:

rechallenge

Hours after challenge:

24

Group:

test chemical

Dose level:

30% of test item in vaseline

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

other: Reading: rechallenge. . Hours after challenge: 24.0. Group: test group. Dose level: 30% of test item in vaseline. No with. + reactions: 0.0. Total no. in groups: 20.0.

No difference between the test and the control group was seen after epidermal challenge application.

Interpretation of results:

other: Not classified according to the CLP Regulation

Conclusions:

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.

Executive summary:

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

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

No tests are available on the substance in itself, nevertheless the skin sensitisation potential of the target substance was assessed by means of the Read Across approach. The complete Justification for the Read Across is detailed at section 13.

Two tests were proposed in order to complete the assessment:

 

The selected key study [Huntsman Textile Effects GmbH, 1979] was conducted according to the AFDO Method on the Similar Substance 01. Under the test condition no animal showed positive reaction, therefore under the test condition the substance is considered as non sensitizer for skin.

Even the second study was conducted on the Similar Substance 01, reported as supporting study [Huntsman Textile Effects GmbH, 1979], and showed no positive reaction on the tested animals.

 

The key study was chosen due to the purity of the test item higher than the one of the supporting study.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

According to the CLP Regulation (EC n. 1272/2008) 3.4.1.2 Skin sensitiser means a substance that will lead to an allergic response following skin contact. The experiment conducted in read across clearly shows that the substance is not capable to produce positive reactions after treatment with the test substance and no toxic symptoms were recorded.

Basred on the experimental results the test article is considered a non sensitizer and no classification is warranted.