5-amino-o-cresol

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

calculation (if not (Q)SAR)

Adequacy of study:

weight of evidence

Study period:

August 2017

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

accepted calculation method

Data source

Reference

Reference Type:

publication

Title:

Hair Dye 4-AMINO-2-HYDROXYTOLUENE Colipa No. A027 Calculation of acute toxicity values using existing in vivo study data

Author:

Nicola J. Hewitt

Year:

2017

Bibliographic source:

Colipa No.1027

Report date:

2017

Materials and methods

Test guideline

Qualifier:

no guideline required

Principles of method if other than guideline:

The acute Oral LD50 was determined at 3600 mg/kg in rats in a Klimisch 2 study. Using this LD50, extrapolation calculation was performed in order to evaluate a LD50 value for dermal route.

GLP compliance:

no

Test type:

other: Extrapolation calculation

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

5-amino-o-cresol

EC Number:

220-618-6

EC Name:

5-amino-o-cresol

Cas Number:

2835-95-2

Molecular formula:

C7H9NO

IUPAC Name:

5-amino-2-methylphenol

Specific details on test material used for the study:

No test material was used for this report, the calculation was performed with the LD50 of a oral acute toxicity test with the test subtance for Inhalation LD50 determination.

Test animals

Species:

rat

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

not applicable

Results and discussion

Effect levels

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

5 688 mg/kg bw

Based on:

test mat.

Any other information on results incl. tables

Calculation:

Determination of the correction factor oral vs. dermal route:

84% oral vs. 53% dermal = 2.63 (84 / 53 = 1.58)                                  

Determination of the LD50 calc dermal:

3600 mg/kg bw x 1.58 = 5688 mg/kg bw                                              

Result:

LD50 calc dermal 4-AMINO-2-HYDROXYTOLUENE = 5688 mg/kg bw

Applicant's summary and conclusion

Interpretation of results:

Category 5 based on GHS criteria

Remarks:

not classified according to CLP

Conclusions:

The calculated acute dermal toxicity of 4-AMINO-2-HYDROXYTOLUENE (LD50, calc, dermal) is 5688 mg/kg bw. The LD50,calc,dermal value indicates that 4-AMINO-2-HYDROXYTOLUENE should be classified as Acute Tox Cat.5; H313: “may be harmful in contact with skin”, according to the Globally Harmonized System of Classification and Labeling (GHS) and not classified according to CLP regulation.

Executive summary:

This calculation was performed in order to determine the LD50 value in dermal route based on the experimental LD50 oral value (3600 mg/kg bw).

Values and assumptions used in the calculations:

•       4-AMINO-2-HYDROXYTOLUENE LD50 oral = 3600 mg/kg bw in the rat

•       Oral Bioavailability = 84% (at 500 mg/kg bw, using the data from the toxicokinetics study in Wistar rats). This value was selected to achieve a more conservative approach (worst case scenario) because incorporation of this value into Equations 7 results in a lower LC50 calc dermal. value (higher assumed toxicity) than if the value of 95% was selected.

•       Dermal bioavailability       = 53% (at 12.5 mg/kg bw). This value was selected (assuming higher toxicity as a result of a higher bioavailability) because incorporation of this value into equiation results in a lower LD50 calc dermal value (with an assumed higher toxicity). In addition, dermal absorption is dose-dependent, such that higher doses lead to lower absorption; therefore, the high LD50 dose would be expected to have lower absorption than assumed for this calculation.

Calculation:

Determination of the correction factor oral vs. dermal route:

84% oral vs. 53% dermal = 2.63 (84 / 53 = 1.58)                                  

Determination of the LD50 calc dermal:

3600 mg/kg bw x 1.58 = 5688 mg/kg bw                                              

Result:

LD50 calc dermal 4-AMINO-2-HYDROXYTOLUENE = 5688 mg/kg bw

The calculated acute dermal toxicity of 4-AMINO-2-HYDROXYTOLUENE (LD50, calc, dermal) is 5688 mg/kg bw. The LD50,calc,dermal value indicates that 4-AMINO-2-HYDROXYTOLUENE should be classified as Acute Tox Cat.5; H313: “may be harmful in contact with skin”, according to the Globally Harmonized System of Classification and Labeling (GHS).