4-amino-m-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

Justification for type of information:

Based on the available in vivo oral acute study to investigate the oral LD50 , together with a toxicokinetics (ADME) study of topically applied compound, the acute dermal toxicity of 4-AMINO-m-CRESOL could be determined.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Qualifier:

no guideline required

Principles of method if other than guideline:

For the dermal end point, the data derived from the ADME study (with respect to the duration of test item and animal number) was in line with the OECD guideline 402 for acute dermal toxicity. The approach to determine dermal toxicity by using oral data is accepted by the German and EU regulatory bodies and is based on the current state-of-the-art science. For the determination of the acute dermal toxicity, the bioavailability after topical application was used, which is lower than the oral bioavailability, as demonstrated by kinetics data.

GLP compliance:

no

Test type:

other: Extrapolation calculation method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

4-amino-m-cresol

EC Number:

220-621-2

EC Name:

4-amino-m-cresol

Cas Number:

2835-99-6

Molecular formula:

C7H9NO

IUPAC Name:

4-amino-m-cresol

Test material form:

solid: particulate/powder

Results and discussion

Effect levels

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

2 409 mg/kg bw

Based on:

test mat.

Any other information on results incl. tables

Determination of the correction factor oral vs. dermal route:

100% oral vs. 36% dermal = 2.8 (105 / 36 = 2.77)                                        

Determination of the LD50 calc dermal:

870 mg/kg bw x 2.7 = 2409 mg/kg bw                                                        

Result:

LD50 calc dermal 4-AMINO-m-CRESOL = 2409 mg/kg bw

Applicant's summary and conclusion

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

As demonstrated by in vivo toxicokinetics data, the bioavailability after application to the skin is lower than the oral bioavailability. The calculated dermal toxicity of 4-AMINO-m-CRESOL is 2409 mg/kg bw. The LD50, calc, dermal value indicates that 4-AMINO-m-CRESOL 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).

Executive summary:

Based on the available in vivo oral acute study to investigate the oral LD50 , together with a toxicokinetics (ADME) study of topically applied compound, the aim of this report was to determine the acute dermal toxicity of 4-AMINO-m-CRESOL.

Values and assumptions used in the calculations:

•       4-AMINO-m-CRESOL LD50 oral = 870 mg/kg bw in the rat

•       Oral Bioavailability = 100% (at 60 mg/kg bw, using the data from the toxicokinetics study in Wistar rats).

•       Dermal bioavailability       = 36% (24 h exposure). This value was selected (assuming higher toxicity as a result of a higher bioavailability) because incorporation of this value into Equation 6 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.

Determination of the correction factor oral vs. dermal route:

100% oral vs. 36% dermal = 2.8 (105 / 36 = 2.77)                                        

Determination of the LD50 calc dermal:

870 mg/kg bw x 2.7 = 2409 mg/kg bw                                                        

Result:

LD50 calc dermal 4-AMINO-m-CRESOL = 2409 mg/kg bw

As demonstrated by in vivo toxicokinetics data, the bioavailability after application to the skin is lower than the oral bioavailability. The calculated dermal toxicity of 4-AMINO-m-CRESOL is 2409 mg/kg bw. The LD50, calc, dermal value indicates that 4-AMINO-m-CRESOL 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).

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