Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
calculation (if not (Q)SAR)
Adequacy of study:
key study
Study period:
February
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
accepted calculation method
Justification for type of information:
The calculation of acute toxicity values for N,N-BIS(2-HYDROXYETHYL)-P-PHENYLENEDIAMINE SULFATE is based on the current understanding and knowledge of the test substance.

Data source

Reference
Reference Type:
other company data
Title:
Unnamed
Year:
2018
Report Date:
2018

Materials and methods

Test guideline
Qualifier:
no guideline required
Principles of method if other than guideline:
For the determination of the acute dermal toxicity, the bioavailability after topical application was used. Since there were no in vivo toxicokinetics studies conducted for the dermal route, this was predicted using scientifically accepted equations to derive the absorbed amount of an infinite dose of N,N-BIS(2-HYDROXYETHYL)-P-PHENYLENEDIAMINE SULFATE. The bioavailability via the dermal route was predicted to be lower (15% of the applied dose) than the oral bioavailability of N,N-BIS(2-HYDROXYETHYL)-P-PHENYLENEDIAMINE SULFATE, and it was in line with that of a structurally similar chemical (A160). The resulting LD50 for dermal toxicity (LD50 calc dermal) was calculated.
GLP compliance:
no
Remarks:
Not required
Test type:
other: extrapolation calculation

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
light grey powder

Results and discussion

Effect levels
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
428 mg/kg bw
Based on:
test mat.

Any other information on results incl. tables

Calculation:

Determination of the correction factor oral vs. dermal route:

60% oral vs. 15% dermal = 4.0 (60 / 15 = 4.0)

Determination of the LD50 calc dermal for the sulfate salt:

107 mg/kg bw x 4.0 = 428 mg/kg bw Equation 10

Result:

LD50 calc dermal 2 N,N-BIS(2-HYDROXYETHYL)-P-PHENYLENEDIAMINE SULFATE = 428 mg/kg bw

Applicant's summary and conclusion

Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
The calculated LD50 value for the dermal toxicity of N,N-BIS(2-HYDROXYETHYL)-P-PHENYLENEDIAMINE SULFATE is 428 mg/kg bw. Therefore, it should be classified as Acute Tox Cat.3; H311: “Toxic in contact with skin”, according to the CLP criteria.
Executive summary:

For the determination of the acute dermal toxicity, the bioavailability after topical application was used. Since there were no in vivo toxicokinetics studies conducted for the dermal route, this was predicted using scientifically accepted equations to derive the absorbed amount of an infinite dose of N,N-BIS(2-HYDROXYETHYL)-P-PHENYLENEDIAMINE SULFATE. The bioavailability via the dermal route was predicted to be lower (15% of the applied dose) than the oral bioavailability of N,N-BIS(2-HYDROXYETHYL)-P-PHENYLENEDIAMINE SULFATE, and it was in line with that of a structurally similar chemical (A160).

The resulting LD50 for dermal toxicity (LD50 calc dermal) was calculated to be 428 mg/kg bw. The approach to determine dermal toxicity using oral data is accepted by the German and EU regulatory agencies.

Based on these data, N,N-BIS(2-HYDROXYETHYL)-P-PHENYLENEDIAMINE SULFATE should be classified as Acute Tox Cat.3; H302: “Toxic if swallowed”, according to the CLP criteria.