2-chloro-p-phenylenediamine

Endpoint summary

Description of key information

2-chloro-p-phenylenediamine (2-chloro-PPD) is skin sensitizing as a positive response is observed upon application to the brows of a 29 yr old lady.

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:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Justification for type of information:

Data is from peer-reviewed journal.

Qualifier:

no guideline available

Principles of method if other than guideline:

Allergic contact dermatitis from 2-chloro-p-phenylenediamine in a cream dye was evaluated on a 29- yr old woman.

GLP compliance:

not specified

Type of study:

not specified

Justification for non-LLNA method:

not specified

Specific details on test material used for the study:

- Name of test material (as cited in study report): 2-chloro-p-phenylenediamine (2-chloro-PPD)
- Molecular formula: C6-H7-Cl-N2
- Molecular weight: 142.588 g/mole
- Substance type: Organic
- Physical state: Solid
- Purity: No data available

Species:

other: humans

Strain:

not specified

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: No data available
- Age at study initiation: 29-year
- Weight at study initiation: No data available
- Housing: No data available
- Diet (e.g. ad libitum): No data available
- Water (e.g. ad libitum): No data available
- Acclimation period: No data available

ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data available
- Humidity (%):No data available
- Air changes (per hr): No data available
- Photoperiod (hrs dark / hrs light): No data available

IN-LIFE DATES: From: To: No data available

Route:

epicutaneous, occlusive

Vehicle:

petrolatum

Concentration / amount:

1%

Route:

other: no data

Vehicle:

petrolatum

Concentration / amount:

1%

No. of animals per dose:

1

Details on study design:

RANGE FINDING TESTS: No data available

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: Several years
- Exposure period: Several years
- Test groups: 1
- Control group: 10
- Site: lashes and brows.
- Frequency of applications: No data available
- Duration: Several years
- Concentrations: 1%

B. CHALLENGE EXPOSURE
- No. of exposures: No data available
- Day(s) of challenge: No data available
- Exposure period: No data available
- Test groups: No data available
- Control group: No data available
- Site: No data available
- Concentrations: No data available
- Evaluation (hr after challenge): No data available

OTHER: No data available

Challenge controls:

No data available

Positive control substance(s):

not specified

Positive control results:

No data available

Reading:

1st reading

Group:

test chemical

Dose level:

1%

No. with + reactions:

1

Total no. in group:

1

Clinical observations:

Intensely itchy dermatitis at the brows were observed

Remarks on result:

positive indication of skin sensitisation

Table 1. PPD derivatives and metabolites tested (D3 readings)

Allergen	Concentration	Case no. 1
2-chloro-PPD	1%	+++
Cream dye	As is	++

Interpretation of results:

other: Category 1 (skin sensitising) based on CLP criteria

Conclusions:

2-chloro-p-phenylenediamine (2-chloro-PPD) is skin sensitizing as a positive response is observed upon application to the brows of a 29 yr old lady.

Executive summary:

Allergic contact dermatitis from 2-chloro-p-phenylenediamine in a cream dye was evaluated on a 29- yr old woman. She had used the same product for several years without any side-effects. The colour was semipermanent and applied only 4X a year. She had developed an intensely itchy dermatitis at her brows but not at her lashes, despite these having been coloured at the same time. After treatment with corticosteroids, the dermatitis disappeared within a week.

 

The case was patch tested with the European standard series and PPD derivatives used for hair colouring, as well as their own cream dyes and constitu ents, including chloro-PPD. At D3, she had a +++ reaction to chloro-PPD (1% pet.) and a ++reaction to the cream dye as is. She also had a + reaction to PPD but no reaction to the other derivatives or metabolites of PPD tested.

 

No further positive reactions were found at D7. 10 controls were negative to the chloro-PPD test.

 

According to the publication, the test material classifies as a skin sensitizer.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

Skin sensitisation

In various studies, 2-chloro-p-phenylenediamine (CAS No. 615-66-7) has been investigated to observe the potential for skin sensitization to a greater or lesser extent. Often are the studies based on human case studies and experimental study in rodents for 2-chloro-p-phenylenediamine. The predicted data using the QSAR toolbox has also been compared with the experimental data. The studies are summarize ed as below:

 

Allergic contact dermatitis from 2-chloro-p-phenylenediamine in a cream dye was evaluated by Christer Hansson (Contact Dermatitis, 2001, 45, 235–236) on a 29- yr old woman. She had used the same product for several years without any side-effects. The colour was semipermanent and applied only 4X a year. She had developed an intensely itchy dermatitis at her brows but not at her lashes, despite these having been coloured at the same time. After treatment with corticosteroids, the dermatitis disappear red within a week.  

The case was patch tested with the European standard series and PPD derivatives used for hair colouring, as well as their own cream dyes and constituents, including chloro-PPD. At D3, she had a +++ reaction to chloro-PPD (1% pet.) and a ++reaction to the cream dye as is. She also had a + reaction to PPD but no reaction to the other derivatives or metabolites of PPD tested.  

No further positive reactions were found at D7. 10 controls were negative to the chloro-PPD test. According to the study, the test material 2-Chloro-p-Phenylenediamine was sensitizing.

 

The above study is supported by another case study on humans by Christer Hansson (Contact Dermatitis, 2001, 45, 235–236). Allergic contact dermatitis from 2-chloro-p-phenylenediamine in a cream dye was evaluated on a 30- yr old woman. She used to regularly colour her lashes and brows. The last 2X, she had developed an itchy dermatitis on her eyelids, which had disappeared within a few weeks without treatment.  

The case was patch tested with the European standard series and PPD derivatives used for hair colour ing, as well as their own cream dyes and constituents, including chloro-PPD. At D3, she had a +++ reaction to both chloro-PPD (1% pet.) and a cream dye as is.  

No further positive reactions were found at D7. 10 controls were negative to the chloro-PPD test.  According to the study, the test material 2-Chloro-p-Phenylenediamine was sensitizing.

 

In addition to these studies, the sensitization potential of 2-Chloro-p-Phenylenediamine (CAS No.- 615 -66 -7) was examined using the maximization test of Magnusson and Kligman by Lynn Willis (Journal Of The American College Of Toxicology Volume 11, Number 4,1992). Fifteen female Pirbright white guinea pigs received 5 intracutaneous injections (amount not stated) of 0.3% 2-Chloro-p-Phenylenediamine in distilled water over a period of 5 days. Ten female Pirbright white guinea pigs, which received no injections, served as controls. This was followed by a 4-wk nontreatment period. Animals were then patch tested with 0.003, 0.006, 0.03, and 0.3% 2-Chloro-p-Phenylenediamine, and their reactions were scored after 24 and 48 h. A Student’s t-test was used to compare the skin reaction scores of the test and control animals. 2-Chloro-p-Phenylenediamine was strongly sensitizing.

 

Moreover, the sensitization potential of 2 chloro-p-phenylenediamine was estimated by using a quantitative structure–activity relationship (QSAR) model. The predicted sensitizing potential of 2 chloro-p-phenylene diamine was estimated to be in the strong/moderate sensitizer group.

 

So, based on the above mentioned studies for target substance 2-chloro-p-phenylenediamine (CAS No. 615-66-7) and by applying weight of evidence approach, skin reactions indicative of sensitisation were found in humans and in guinea pigs. Thus based on the human experience and animal study, it infers that 2-chloro-p-phenylenediamine (CAS No. 615-66-7) is classified as skin sensitiser in category 1 as per CLP classification criteria.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

According to Regulation (EC) 1272/2008 and based on the human and animal studies, it is concluded that the substance 2-chloro-p-phenylenediamine (CAS No. 615-66-7) is classified as skin sensitiser in category 1 as per CLP classification criteria.