Bis(4-hydroxy-N-methylanilinium) sulphate

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Justification for type of information:

Data is from SCCP, 2006

Data source

Reference

Reference Type:

secondary source

Title:

Opinion on p-Methylaminophenol Sulphate

Author:

European Commission

Year:

2006

Bibliographic source:

Scientific Committee On Consumer Products, SCCP/0963/05, 2006

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Principles of method if other than guideline:

A rat bone marrow micronucleus assay was performed to determine the mutagenic nature of N-Methyl-p-aminophenol sulfate.

GLP compliance:

yes

Type of assay:

other: Rat bone marrow micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

Bis(4-hydroxy-N-methylanilinium) sulphate

EC Number:

200-237-1

EC Name:

Bis(4-hydroxy-N-methylanilinium) sulphate

Cas Number:

55-55-0

Molecular formula:

C14H20N2O6S

IUPAC Name:

bis(4-hydroxy-N-methylanilinium) sulfate

Test material form:

solid: crystalline

Details on test material:

- Name of test material: p-Methylaminophenol sulfate- IUPAC name: Bis(4-hydroxy-N-methylanilinium) sulphate- Molecular formula: C14H20N2O6S- Molecular weight: 344.386 g/mole- Smiles:CNc1ccc(cc1)O.CNc1ccc(cc1)O.OS(=O)(=O)O- Inchl: 1S/2C7H9NO.H2O4S/c2*1-8-6-2-4-7(9)5-3-6;1-5(2,3)4/h2*2-5,8-9H,1H3;(H2,1,2,3,4)- Substance type: Organic- Physical state: Solid crystalline (off white - white)

Specific details on test material used for the study:

- Name of test material: N-Methyl-p-aminophenol sulfate- IUPAC name: 4-(Methylamino)phenol Sulfate - Molecular formula: C7H9NO.1/2H2O4S- Molecular weight: 344.386 g/mol- Substance type: Organic- Physical state: No data - Purity: 98.7%- Impurities (identity and concentrations): 1.3%

Test animals

Species:

rat

Strain:

Sprague-Dawley

Details on species / strain selection:

No data available

Sex:

male/female

Details on test animals or test system and environmental conditions:

No data available

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

No data available

Details on exposure:

PREPARATION OF DOSING SOLUTIONS: The test chemical was mixed with the suitable vehicle at dose levels of 0, 100, 200 or 400 mg/kg bwDIET PREPARATION- Rate of preparation of diet (frequency): No data available- Mixing appropriate amounts with (Type of food): No data available- Storage temperature of food: No data availableVEHICLE- Justification for use and choice of vehicle (if other than water): Water- Concentration in vehicle: 0, 100, 200 or 400 mg/kg bw- Amount of vehicle (if gavage): No data available- Lot/batch no. (if required): No data available- Purity: No data available

Duration of treatment / exposure:

24 and 48 (highest dose group only) hours after the treatment

Frequency of treatment:

Once

Post exposure period:

No data available

Doses / concentrations

Remarks:

Doses/Concentrations: 0, 100, 200 or 400 mg/kg bw

No. of animals per sex per dose:

Total: 50 ratsControl: 5 males, 5 femalesPositive control: 5 males, 5 females100 mg/kg bw: 5 males, 5 females200 mg/kg bw: 5 males, 5 females400 mg/kg bw: 5 males, 5 females

Control animals:

yes, concurrent vehicle

Positive control(s):

Yes, in accordance with the OECD guideline

Examinations

Tissues and cell types examined:

Micronuclei isolated from bone marrow

Details of tissue and slide preparation:

No data available

Evaluation criteria:

The test chemical was considered positive only if a significant increase in the MNPCE frequency was noted.

Statistics:

No data available

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

not specified

Vehicle controls validity:

not specified

Negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

There was no indication of bone marrow toxicity in the micronucleus test because the PCE/NCE ratio was not lower in all treated groups than in the negative control group.

Applicant's summary and conclusion

Conclusions:

p-Methylaminophenol sulphate did not induce chromosome aberrations or damage to the mitotic apparatus in bone marrow cells of rats after oral treatment and hence it is not likely to classify as a gene mutant in vivo.

Executive summary:

A rat bone marrow micronucleus assay was performed to determine the mutagenic nature of p-Methylaminophenol sulfate in male and female Sprague-Dawley rats. On the basis of a preliminary toxicity study conducted, the doses for the main study was 0, 100, 200 or 400 mg/kg bw, and concurrent negative and positive controls were included in the study. The highest dosed group animals were sacrificed after 24 and 48 hrs after the treatment. The results showed no indication of bone marrow toxicity in the micronucleus test because the PCE/NCE ratio was not lower in all treated groups than in the negative control group. However, oral bioavailability can be assumed by the systemic clinical signs and the death of one animal treated with 400 mg/kg. The mean MNPCE frequencies were not significantly increased in any of the groups treated with the test substance. In addition, p-Methylaminophenol sulphate did not induce chromosome aberrations or damage to the mitotic apparatus in bone marrow cells of rats after oral treatment. Therefore, since no mutagenic effects could be observed, it is not likely to classify as a gene mutant in vivo.