Pyrocatechol

Endpoint summary

Description of key information

Two studies are used in a weight of evidence approach.

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:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Remarks:

It is a study on derivatives of catechol. In this study, Catechol was used as inducer for sensitization. Lack of details in results.

Guideline:

other: Freund's complete adjuvant test

GLP compliance:

no

Type of study:

Freund's complete adjuvant test

Justification for non-LLNA method:

An appropriate guinea pig Freund's complete adjuvant test is available which would not justify conducting an additional LLNA due to animal welfare. In addition, this study predates the adoption of the Local Lymph Node Assay (LLNA; TG 429).

Species:

guinea pig

Strain:

Hartley

Sex:

male

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: from the National Institutes of Health Animal Production section.
- Age at study initiation:
- Weight at study initiation: approx. 400 g
No more data.

Route:

intradermal

Vehicle:

other: emulsion

Concentration / amount:

1 mL (combined volume of the three injections)

Route:

epicutaneous, semiocclusive

Vehicle:

other: emulsion

Concentration / amount:

1 ml (combined volume of the three injections)

No. of animals per dose:

8 to 12 animals.

Details on study design:

- Sensitisation was carried out by injection of an emulsion in complete Freund's adjuvant, at weekly intervals, successively into the nuchal area, the inguinal-axillary region and the foot pads. 
- The combined volume of the three injections was 1 ml. The emulsion was prepared from an oil phase containing Drakeol 6VR and Arlacel A (65:35), Mycobacterium butyricum (dried, Difco), Catechol (2 mg/ml) and an equal volume of phophate buffered saline (PBS).
- Thus, 1 mg of catechol was injected into each animal, that was determined in previous study as the dose inducing maximal sensitisation.
- Animals were given a skin test (topical application of catechol in acetone) 4 weeks after the last sensitising injection and then given two repetitive tests at 2-weeks intervals.
- The end point is the smallest quantity giving a discernible erythema at 48 hr.

Challenge controls:

Control animals were topically applied with catechol but they were not previously injected with the inducer solution. They were employed at each dose level and almost never responded to the maximum test dose used.

Positive control substance(s):

not specified

Group:

positive control

Remarks on result:

no indication of skin sensitisation

Remarks:

Control animals were topically applied with catechol but they were not previously injected with the inducer solution. They were employed at each dose level and almost never responded to the maximum test dose used.

Group:

negative control

Remarks on result:

other: no data

Group:

test chemical

Remarks on result:

not measured/tested

Remarks:

The end point of this study is the smallest quantity giving a discernible erythema at 48 hr

Catechol never induced an observable sensitivity to less than 0.2 µmole with a geometric mean of 3.2 µmoles.

Interpretation of results:

Category 1 (skin sensitising) based on GHS criteria

Conclusions:

Catechol induced delayed contact sensitivity in guinea pigs since majority of animals injected became sensitized. Catechol had low degree of sensitivity compared with other n-alkylcatechol.

Executive summary:

In a dermal sensitization study (Baer et al., 1967) with Catechol, 8 to 12 Hartley guinea pigs were tested using a modified method of Freund's complete adjuvant test.

Sensitisation was carried out by injection of an emulsion in complete Freund's adjuvant, at weekly intervals, successively into the nuchal area, the inguinal-axillary region and the foot pads.

Animals were given a skin test (topical application of catechol in acetone) 4 weeks after the last sensitising injection and then given two repetitive tests at 2-weeks intervals.

In this study, Catechol was used as inducer of sensitization and gave the appropriate response as “sensitizing”.

Catechol is considered as a skin sensitizer in this study.

Reference 2

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Remarks:

Study not according to recognized guidelines, and results were not detailed.

Principles of method if other than guideline:

The method derives from the split adjuvant technique, in which chemical allergen and Freund's adjuvants are administered separately to the skin rather than as emulsion.

GLP compliance:

not specified

Type of study:

split adjuvant test

Justification for non-LLNA method:

An appropriate guinea pig split adjuvant test is available which would not justify conducting an additional LLNA due to animal welfare. In addition, this study predates the adoption of the Local Lymph Node Assay (LLNA; TG 429).

Species:

guinea pig

Strain:

Hartley

Sex:

male

Details on test animals and environmental conditions:

TEST ANIMALS
- Weight at study initiation: approx. 300 g
- Diet: Purina guinea pig chow supplemented with green vegetables, ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): controlled
- Humidity (%): controlled
- Photoperiod (hrs dark / hrs light): controlled
No more data.

Route:

intradermal and epicutaneous

Vehicle:

no data

Route:

other: epicutaneous, no more precision

Vehicle:

no data

No. of animals per dose:

10

Details on study design:

Prior to conduct the sensitisation test, the irritation potency of the chemical was tested. The highest concentration that did not cause primary irritation was used for the guinea pig sensitisation test. 
Induction phase:
A topical application of 0.1 ml aliquot of the test material to the clipped and depilated backs of 10 guinea pig was performed 4 times in 10 days. At the time of the third application, 0.2 ml of Freund's adjuvant (Bacto-Adjuvant complete, H 37 Ra, Difco Lab.) was injected intradermally at one point adjacent to the insult site. 

Challenge phase:
After a 2 week rest period, the guinea pigs were challenged on the clipped flanks with the test material on one flank. The other flank served as control. 

The challenge site was evaluated for erythema and oedema at 24 and 48 h. A moderate erythema and/or oedema in two or more guinea pigs was considered sufficient to classify the test material as a potential human skin sensitiser.

At the same time, 10 guinea pigs were subjected to the same dosing regimen with the diglycidyl ether of 2,2-di-(p,p'-hydroxyphenyl)propane (DER* 331 Epoxy Resin - Dow chemical), a known sensitiser to serve as a positive control. This epoxy resin sensitises at least 70 % of the guinea pig, producing slight to marked erythema and slight to moderate oedema on the challenge application site.

Positive control substance(s):

yes

Remarks:

diglycidyl ether of 2,2-di-(p,p'-hydroxyphenyl)propane

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

0.1 ml

No. with + reactions:

2

Total no. in group:

9

Reading:

2nd reading

Hours after challenge:

48

Group:

positive control

Dose level:

0.1 ml

No. with + reactions:

7

Total no. in group:

10

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

0.1 ml

No. with + reactions:

0

Total no. in group:

9

2/9 animals showed positive response, that corresponding at 22% of the animals.

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results of this study, Catechol is not classified as a skin sensitizer according to EU GHS criteria.

Executive summary:

In a dermal sensitization study (Rao et al., 1981) with Catechol, 9 adult Hartley guinea pigs were tested using a modified method of Split adjuvant test. 

Chemical allergen and Freund's adjuvant are administered separately to the skin rather than as emulsion. Induction phase was made by 4 topical applications in 10 days. At the third application, intradermal injection of 0.2 ml FCA was made. Challenge was realised 2 weeks later.

 

In this study, 2 animals on 9 presented positive reaction. It was considered as not sufficient to classify Catechol as a potential skin sensitizer.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

Two Key studies with reliability 2 were available.

In one study (Rao, 1981) the sensitization of catechol was tested by a Split adjuvant test. In the other study (Baer, 1967), Catechol was tested with n-alkylcatechol in a Freund's complete adjuvant test.

In both studies Catechol showed positive response, but Split Adjuvant test indicated a positive response in 22% of the animals that is not sufficient for a classification as sensitizer.

The majority of the animals injected became sensitized lead to the conclusion that Catechol is a potential skin sensitizer.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the available data and according to classification criteria of EC regulation 1272/2008 the catechol should be self-classified as skin sensitizer category 1 (H317: May cause an allergic skin reaction). The available data do not allow the distinction between the subcategories 1A and 1B.

In the 13 th ATP of the CLP Regulation, no harmonised classification is proposed for this endpoint.