2-amino-4-nitrophenol

Skin sensitisation

Administrative data

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:

data from handbook or collection of data

Justification for type of information:

data is from peer reviewed journals

Data source

Reference

Reference 1

Reference Type:

other: Authoritative data base

Title:

HSDB for the CAS- 99-57-0

Author:

U.S National Library of Medicine

Year:

2011

Bibliographic source:

HSDB (Hazardous Substances Data Bank); US national Library of Medicine reviewed by SRC, 2011

Reference 2

Reference Type:

publication

Title:

An animal model assessment of common dye-induced allergic contact dermatitis

Author:

JOE DINARDO, Raleigh N, C; and ZOE DIANA DRAELOS

Year:

2007

Bibliographic source:

JOURNAL OF COSMETIC SCIENCE, 58, 209-214 May/June 2007

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Buehler test a modification of the Buehler and the Klecak method for open epicutaneous testing (OET)

Principles of method if other than guideline:

Skin sensitisation of the test chemical was evaluated using a modification of the Buehler and the Klecak method for open epicutaneous testing (OET) in a guinea pig model

GLP compliance:

not specified

Type of study:

open epicutaneous test

Justification for non-LLNA method:

Currently no LLNA study is available for assessment. The Guinea Pig Maximization Test (GPMT) has been carried out as an animal test to predict human sensitization for over a decade and is recommended by international test guidelines such as OECD.

Test material

Test material information

Constituent 1

Reference substance name:

2-amino-4-nitrophenol

EC Number:

202-767-9

EC Name:

2-amino-4-nitrophenol

Cas Number:

99-57-0

Molecular formula:

C6H6N2O3

IUPAC Name:

2-amino-4-nitrophenol

Details on test material:

- Name of test material (as cited in study report): 2-amino-4-nitrophenol
- Molecular Formula: C6H6N2O3
- Molecular Weight: 154.125 g/mol
- SMILES Notation: C1=CC(=C(C=C1[N+](=O)[O-])N)O
- InChI: 1S/C6H6N2O3/c7-5-3-4(8(10)11)1-2-6(5)9/h1-3,9H,7H2
- Substance type: Organic
- Physical state: solid

In vivo test system

Test animals

Species:

guinea pig

Strain:

not specified

Sex:

not specified

Study design: in vivo (non-LLNA)

Induction

Route:

epicutaneous, open

Vehicle:

propylene glycol

Concentration / amount:

0.1 ml of test chemical [10% in propylene glycol]

Day(s)/duration:

3 times weekly(Monday, Wednesday , Friday) for 3 weeks

Adequacy of induction:

not specified

Challenge

No.:

#1

Route:

epicutaneous, open

Vehicle:

propylene glycol

Concentration / amount:

10%, 5%,2.50% in propylene glycol

Day(s)/duration:

single

Adequacy of challenge:

not specified

No. of animals per dose:

10 albino guinea pigs

Details on study design:

Details on study design
RANGE FINDING TESTS: no data available

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures:3 times weekly(Monday, Wednesday , Friday)
- Exposure period:3 weeks
- Test groups: Yes
- Control group:No
- Site:Left flank shaved albino guinea pigs
- Frequency of applications:3 times weekly
- Duration:3 weeks
- Concentrations:0.1 ml of 10 % test chemical in propylene glycol

B. CHALLENGE EXPOSURE
- No. of exposures:Once
- Day(s) of challenge:After 2 weeks of rest period from induction exposure
- Exposure period: No data available
- Test groups: Yes
- Control group: No
- Site:Right flank of shaved guinea pig
- Concentrations:10,5 and 2.5 % of the induction concentration
- Evaluation (hr after challenge):24-hrs

OTHER: All test sites were graded for erythema and edema 24 and 48 hours post-application using a four-point ordinal scale
0 = no reaction,
1 -- slight reaction,
2 = moderate reaction,
3 = severe reaction

Challenge controls:

no data available

Positive control substance(s):

yes

Remarks:

0.5% of 2,4-dinitrochlorobenzene (DNCB) in ethanol was included for both the induction and challenge phases

Results and discussion

In vivo (non-LLNA)

Results

Results 1

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

10% in propylene glycol

Total no. in group:

10

Clinical observations:

80% animals exhibited a positive allergic reactions

Remarks on result:

positive indication of skin sensitisation

Results 2

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

5% in propylene glycol

Total no. in group:

10

Clinical observations:

70% animals exhibited a positive reaction

Remarks on result:

positive indication of skin sensitisation

Results 3

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

2.50% in propylene glycol

Total no. in group:

10

Clinical observations:

40% animals exhibited a positive reaction

Remarks on result:

positive indication of skin sensitisation

Any other information on results incl. tables

Table 1: Allergic contact dermatitis of dyes

CAS number	Chemical class	Induction concentration in propylene glycol	Challenge concentration in propylene glycol*
			10%	5%	2.5%
99-57-0	nitroaminophenol	10%	+(80%)	+(70%)	+(20%)

 

Table 2: Dose-response of dyes eliciting positive response at 10% concentration

CAS number	Chemical class	Induction concentration in propylene glycol	Challenge concentration in propylene glycol*
			1%	0.5%	0.25%
99-57-0	nitroaminophenol	1%	+(30%)	Negative	Negative

*results expressed as negative or positive (+) with percent of animals in the group demonstrating an allergic reaction in parenthesis

Applicant's summary and conclusion

Interpretation of results:

other: sensitizing

Conclusions:

Since a positive response was observed in the challenge exposure at 10% challenge exposure, the test chemical was re-tested using a 1% induction exposure and challenge concentrations of 1.0%, 0.5%, and 0.25%.
The test chemical produced a positive reaction at 10% challenge exposure, also in the retest at 1% challenge concentration, but no reactions were noted at 0.5 and 0.25% challenge concentrations.
Hence, it was considered that the test chemical was positive sensitizer in guinea pigs.

Executive summary:

A modified Buehler and Klecak method for open epicutaneous testing[OET] was performed to assess the sensitization potential of the test chemical.

The test chemical was tested at an induction concentration of 10% and challenge concentrations of 10.0%, 5.0%, and 2 .5% in propylene glycol.

During the induction phase, the left flanks of ten albino guinea pigs were shaved and the dye test material applied three times weekly (Monday, Wednesday, Friday) for three consecutive weeks. Each animal received 0.1 ml of the dye test material over a 1.8-cm circular area. Following the induction period, the guinea pigs entered the challenge phase. The challenge phase began after a two-week rest period when the right flank of each guinea pig was shaved and exposed to three different dye test material concentrations in propylene glycol(10.0%, 5.0%, and 2 .5%). Twenty-four hours after the last induction and challenge application, the animals were depilated to clearly observe dermal reactions.

All test sites were graded for erythema and edema 24 and 48 hours post-application using a four-point ordinal scale.A positive control of 0.5% 2,4-dinitrochlorobenzene(DNCB) in ethanol was included for both the induction and challenge phases.

Since a positive response was observed in the challenge exposure at 10% challenge exposure, the test chemical was re-tested using a 1% induction exposure and challenge concentrations of 1.0%, 0.5%, and 0.25%.

The test chemical produced a positive reaction at 10% challenge exposure, also in the re-test at 1% challenge concentration, but no reactions were noted at 0.5 and 0.25% challenge concentrations.

Hence, it was considered that the test chemical was positive sensitizer in guinea pigs.