2-chloro-6,7-dimethoxyquinazolin-4-amine

Skin sensitisation

Administrative data

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:

data from handbook or collection of data

Justification for type of information:

Data is from peer reviewed journal.

Data source

Reference

Reference Type:

publication

Title:

Final Report on the Safety Assessment of Amino Nitrophenols as Used in Hair Dyes

Author:

Burnett CL, Bergfeld WF, Belsito DV, Klaassen CD, Marks JG Jr, Shank RC, Slaga TJ, Snyder PW, Alan Andersen F.

Year:

2009

Bibliographic source:

International Journal of Toxicology 2009;Nov-Dec;28(6 Suppl 2):217S-51S.

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

The sensitizing potential of 4-amino-3-nitrophenol (CAS no: 610-81-1) was studied in a guinea pig maximization study on female Hartley albino guinea pigs (5 in a control group, 10 in the test group).

GLP compliance:

not specified

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

1-Hydroxy-3-nitro-4-aminophenol

Cas Number:

610-81-1

Molecular formula:

C6H6N2O3

IUPAC Name:

1-Hydroxy-3-nitro-4-aminophenol

Test material form:

solid

Details on test material:

- Name of test material (as cited in study report): 4-amino-3-nitrophenol
- Molecular formula : C6H6N2O3
- Molecular weight : 154.124 g/mole
- Substance type: organic
- Physical state: solid

Specific details on test material used for the study:

- Name of test material (as cited in study report): 4-amino-3-nitrophenol
- Molecular formula : C6H6N2O3
- Molecular weight : 154.124 g/mole
- Substance type: organic
- Physical state: solid

In vivo test system

Test animals

Species:

guinea pig

Strain:

other: Hartley albino

Sex:

female

Details on test animals and environmental conditions:

No data available

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal

Vehicle:

other: distilled water

Concentration / amount:

3 symmetrical intradermal injections of 0.1 mL that consisted

•Freund’s complete adjuvant (FCA) and distilled water (1:1 vol/vol),
•4-amino-3- nitrophenol diluted to 10% in distilled water, and
•4-amino-3- nitrophenol diluted to 10% in mixture 1:1 (vol/vol) with FCA and distilled water.

Day(s)/duration:

6 Days

Adequacy of induction:

not specified

Induction 2

Route:

epicutaneous, occlusive

Vehicle:

other: distilled water

Concentration / amount:

50% (0.5mL)

Day(s)/duration:

48 hours

Adequacy of induction:

other: the maximal nonirritant concentration

Challenge

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

not specified

Concentration / amount:

0.2ml

Day(s)/duration:

48 hours

Adequacy of challenge:

other: the maximal nonirritant concentration and a lower concentration were applied to all animals for a period of 24 hours.

No. of animals per dose:

15 (5 in a control group, 10 in the test group)

Details on study design:

RANGE FINDING TESTS: A preliminary test was conducted to determine the maximal nonirritant concentration.

A. INDUCTION EXPOSURE: intradermal
- No. of exposures: 1
- Exposure period: : 6 days
- Test groups:10
- Control group: : 5
- Site: : clipped dorsal
- Frequency of applications: no data
- Duration: : 6 days
- Concentrations: 3 symmetrical intradermal injections of 0.1 mL that consisted

• Freund’s complete adjuvant (FCA) and distilled water (1:1 vol/vol),
• 4-amino-3- nitrophenol diluted to 10% in distilled water, and
• 4-amino-3- nitrophenol diluted to 10% in mixture 1:1 (vol/vol) with FCA and distilled water.



A.II. INDUCTION EXPOSURE: topical
- No. of exposures:1
- Exposure period: 48 hours
- Test groups: 10
- Control group: 5
- Site: at reclipped injection sites
- Frequency of applications: no data
- Duration: 48 hours
- Concentrations: 50 % (0.5ml)

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: after 11 days
- Exposure period: 24 hours
- Test groups: 10
- Control group: 5
- Site: clipped dorsolumbar region
- Concentrations: 0.2ml
- Evaluation (hr after challenge): after 24 and 48 hours

Challenge controls:

Yes, concurrent vehicles were used.

Results and discussion

In vivo (non-LLNA)

Results

Reading:

1st reading

Hours after challenge:

48

Group:

test chemical

Dose level:

0.2mL

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

No skin sensitization was observed in treated group.

Remarks on result:

no indication of skin sensitisation

In vivo (LLNA)

Cellular proliferation data / Observations:

Because of the dyeing properties of the test substance, assessment of erythema was impossible. No edematous reactions were observed. The researchers concluded that 4-amino-3-nitrophenol was not sensitizing by contact with guinea pig skin.

Applicant's summary and conclusion

Interpretation of results:

other: Not sensitizing

Conclusions:

The chemical 4-amino-3-nitrophenol (CAS no: 610-81-1) was considered to be not sensitizing on female Hartley albino guinea pigs skin.

Executive summary:

The sensitizing potential of 4-amino-3-nitrophenol (CAS no: 610-81-1) was studied in a guinea pig maximization study on female Hartley albino guinea pigs (5 in a control group, 10 in the test group).

 

During induction, the test group received 3 symmetrical intradermal injections of 0.1 mL that consisted of Freund’s complete adjuvant (FCA) and distilled water (1:1 vol/vol), 4-amino-3- nitrophenol diluted to 10% in distilled water, and 4-amino-3-

nitrophenol diluted to 10% in mixture 1:1 (vol/vol) with FCA and distilled water. Adequate controls were used.

 

The guinea pigs were not treated for a period of 6 days and then were reclipped at the injection sites. Because the material did not produce local irritation, the test areas of both the control and treated animals were coated with 0.5 mL of sodium lauryl sulfate at 10% in liquid petrolatum to produce irritation. After 24 hours, the treated group was patched with 0.5 mL of 4-amino-3-nitrophenol diluted to 50% for 48 hours. The control group was patched with 0.5 mL of distilled water.

 

After an 11-day rest period, both groups of guinea pigs were clipped on the dorsolumbar region. Occlusive patches with 0.2 mL of 4-amino-3-nitrophenol at the maximal nonirritant concentration and a lower concentration were applied to all animals for a period of 24 hours. At 24 and 48 hours after challenge patch removal, the skin was observed for cutaneous reactions.

 

Because of the dyeing properties of the test substance, assessment of erythema was impossible. No edematous reactions were observed. The researchers concluded that 4-amino-3-nitrophenol was not sensitizing by contact with guinea pig skin.

 

Therefore the chemical 4-amino-3-nitrophenol (CAS no: 610-81-1) was considered to be not sensitizing onfemale Hartley albino guinea pigs’ skin.