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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.24 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Dose descriptor starting point:
NOAEL
Value:
6 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
0.24 mg/m³
Explanation for the modification of the dose descriptor starting point:

The NOAEL of 6 mg/kg was the concentration where no significant adverse effects were seen in a subchronic oral toxicity study.

Modification of starting point for rat respiratory volume (Allometric scaling); Value: 0.38 m3/kg bw (rat 8-hour respiratory volume); Remark: A modification of starting point for rat respiratory volume was applied per REACH guidance R.8.4.2.

Modification of starting point for differences in respiratory volumes;Value: 0.67 (6.7 m3/10 m3); Remark: A modification was applied to account for the increased respiratory volumes in active workers as compared to individuals at rest per REACH guidance R.8.4.2.

AF for dose response relationship:
1
Justification:
A factor of 1 is appropriate since the dose descriptor is a NOAEL.
AF for differences in duration of exposure:
1
Justification:
A factor of 1 is appropriate since the chronic study demonstrated no different or greater toxicity following chronic exposure compared to subchronic exposure.
AF for interspecies differences (allometric scaling):
1
Justification:
A factor of 1 is appropriate since the adjusted start point was via mg/m3 (inhalation) and thus this assessment factor is not applicable per REACH guidance R.8.4.3.1.
AF for other interspecies differences:
2.5
Justification:
A default factor of 2.5 is appropriate per REACH guidance R.8.4.3.1.
AF for intraspecies differences:
5
Justification:
This is a default assessment factor for workers per REACH Guidance R.8.4.3.1.
AF for the quality of the whole database:
4
Justification:
A factor of 4 is appropriate because of the lack of repeat dose inhalation data warrants an uncertainty factor of greater than 1.
AF for remaining uncertainties:
2
Justification:
A factor of 2 is appropriate per REACH guidance R.8.4.2 (oral to inhalation).
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.12 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Dose descriptor starting point:
NOAEL
Value:
6 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Explanation for the modification of the dose descriptor starting point:

This is the concentration where no significant adverse effects were seen in a subchronic oral toxicity study.

Route–to-route extrapolation; Value: 1; Remark: A factor of 1 is appropriate since the animal exposure was via ingestion.

AF for dose response relationship:
1
Justification:
A factor of 1 is appropriate since the dose descriptor is a NOAEL.
AF for differences in duration of exposure:
4
Justification:
A factor of 4 is appropriate since the adjusted start point was via mg/kg per REACH guidance 8.4.3.1.
AF for interspecies differences (allometric scaling):
2.5
Justification:
A default factor of 2.5 is appropriate per REACH guidance R.8.4.3.1.
AF for other interspecies differences:
2.5
Justification:
A default factor of 2.5 is appropriate per REACH guidance R.8.4.3.1.
AF for intraspecies differences:
5
Justification:
This is a default assessment factor for workers per REACH Guidance
R.8.4.3.1.
AF for the quality of the whole database:
1
Justification:
A high quality, robust toxicity database exists for this substance.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.49 µg/cm²
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
250
Dose descriptor starting point:
other: LOAEL
AF for dose response relationship:
2
Justification:
A factor of 2 is appropriate as an EC3 value can be considered as a LOAEL for induction of skin sensitization per REACH R.8 Appendix R.8-10.
AF for interspecies differences (allometric scaling):
1
Justification:
A factor of 1 is appropriate since the adjusted start point was via μg/cm2 (dermal) and thus this assessment factor is not applicable per REACH guidance R.8.4.3.1.
AF for other interspecies differences:
10
Justification:
A default factor of 10 is appropriate per REACH guidance R.8.10.
AF for intraspecies differences:
5
Justification:
This is a default assessment factor for workers per REACH Guidance R.8.4.3.1.
AF for the quality of the whole database:
1
Justification:
A high quality, robust toxicity database exists for this substance.
AF for remaining uncertainties:
2.5
Justification:
Route–to-route extrapolation; Value: 1; Remark: A factor of 1 is appropriate since the animal exposure was via the dermal route.
Other interspecies; Value: 2.5; Remark: A default factor of 2.5 is appropriate per REACH guidance R.8.4.3.1.

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

Potential worker exposure would likely occur via the dermal or inhalation routes.

This substance is classified as harmful via the acute oral, inhalation, and dermal routes under REACH regulations and guidance.  The rat oral ALD is 450 mg/kg and the rat inhalation 4 -hour LC50 is 3.2 mg/L (3200 mg/m3). The rabbit dermal ALD for the structurally similar substance, o-phenylenediamine (CAS 95-54-5), which was used as a surrogate for acute dermal data, is 1500 mg/kg.

Male and female rats were exposed to 2, 6, and 18 mg/kg/d for 90 days by oral gavage. Degenerative lesions of the liver, increased frequency of pycnosis, and increased liver and kidney weights were observed in the highest dose group. The NOEL for systemic toxicity effects after 90 days was 6 mg/kg/day. The test substance did not cause cancer in a 19-month drinking water study in mice at any dose level tested. Based on this information, the NOAEL for significant systemic effects was determined to be 6 mg/kg-bw/day and can be used for development of a long-term DNEL for systemic effects.

Skin sensitization was observed in acute exposure studies; therefore a short-term DNEL for local effects was derived.

In a local lymph node assay, this substance was found to be positive for dermal sensitization with an EC3 value of 0.49% (122.5 µg/cm2). As per REACH R.8 Appendix R. 8-10 Skin sensitization, an EC3 value can be considered as a LOAEL for induction (expressed in µg/cm2) and can be used for development of a short-term DNEL for local effects.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.03 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
200
Dose descriptor starting point:
NOAEL
Value:
6 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
5.217 mg/m³
Explanation for the modification of the dose descriptor starting point:

The NOAEL of 6 mg/kg is the concentration where no significant adverse effects were seen in a subchronic oral toxicity study.

Modification of starting point for rat respiratory volume (Allometric scaling); Value: 1.15 m3/kg bw (rat 24-hour respiratory volume); Remark: A modification of starting point for rat respiratory volume was applied per REACH guidance R.8.4.2.

AF for dose response relationship:
1
Justification:
A factor of 1 is appropriate since the dose descriptor is a NOAEL.
AF for differences in duration of exposure:
1
Justification:
A factor of 1 is appropriate since the chronic study demonstrated no different or greater toxicity following chronic exposure compared to subchronic exposure.
AF for interspecies differences (allometric scaling):
1
Justification:
A factor of 1 is appropriate since the adjusted start point was via mg/m3 (inhalation) and thus this assessment factor is not applicable per REACH guidance R.8.4.3.1.
AF for other interspecies differences:
2.5
Justification:
A default factor of 2.5 is appropriate per REACH guidance R.8.4.3.1.
AF for intraspecies differences:
10
Justification:
This is a default assessment factor for the general population per REACH Guidance R.8.4.3.1.
AF for the quality of the whole database:
4
Justification:
A factor of 4 is appropriate because of the lack of repeat dose inhalation data warrants an uncertainty factor of greater than 1.
AF for remaining uncertainties:
2
Justification:
Route–to-route extrapolation: A factor of 2 is appropriate per REACH guidance R.8.4.2 (oral to inhalation).
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.06 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Dose descriptor starting point:
NOAEL
Value:
6 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
6 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The NOAEL of 6 mg/kg is the concentration where no significant adverse effects were seen in a subchronic oral toxicity study.

AF for dose response relationship:
1
Justification:
A factor of 1 is appropriate since the dose descriptor is a NOAEL.
AF for differences in duration of exposure:
1
Justification:
A factor of 1 is appropriate since the chronic study demonstrated no different or greater toxicity than the subchronic study.
AF for interspecies differences (allometric scaling):
4
Justification:
Remark: A factor of 4 is appropriate since the adjusted start point was via mg/kg per REACH guidance 8.4.3.1.
AF for other interspecies differences:
2.5
Justification:
A default factor of 2.5 is appropriate per REACH guidance R.8.4.3.1.
AF for intraspecies differences:
10
Justification:
is a default assessment factor for the general population per REACH Guidance R.8.4.3.1.
AF for the quality of the whole database:
1
Justification:
A high quality, robust toxicity database exists for this substance.
AF for remaining uncertainties:
1
Justification:
Route–to-route extrapolation: Value: 1; Remark: A factor of 1 is appropriate since the animal exposure was via ingestion.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.25 µg/cm²
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
500
Dose descriptor starting point:
other: LOAEL
AF for dose response relationship:
2
Justification:
A factor of 2 is appropriate as an EC3 value can be considered as a LOAEL for induction of skin sensitization per REACH R.8 Appendix R.8-10.
AF for interspecies differences (allometric scaling):
1
Justification:
A factor of 1 is appropriate since the adjusted start point was via μg/cm2(dermal) and thus this assessment factor is not applicable per REACH guidance R.8.4.3.1.
AF for other interspecies differences:
10
Justification:
A default factor of 10 is appropriate per REACH guidance R.8.10.
AF for intraspecies differences:
10
Justification:
This is a default assessment factor for workers per REACH Guidance R.8.4.3.1.
AF for the quality of the whole database:
1
Justification:
A high quality, robust toxicity database exists for this substance.
AF for remaining uncertainties:
2.5
Justification:
Route–to-route extrapolation; Value: 1; Remark: A factor of 1 is appropriate since the animal exposure was via the dermal route.
Other interspecies; Value: 2.5; Remark: A default factor of 2.5 is appropriate per REACH guidance R.8.4.3.1.

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.06 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Dose descriptor starting point:
NOAEL
Value:
6 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The NOAEL of 6 mg/kg is the concentration where no significant adverse effects were seen in a subchronic oral toxicity study.

AF for dose response relationship:
1
Justification:
A factor of 1 is appropriate since the dose descriptor is a NOAEL.
AF for differences in duration of exposure:
1
Justification:
A factor of 1 is appropriate since the chronic study demonstrated no different or greater toxicity than the subchronic study.
AF for interspecies differences (allometric scaling):
4
Justification:
A factor of 4 is appropriate since the adjusted start point was via mg/kg per REACH guidance 8.4.3.1.
AF for other interspecies differences:
2.5
Justification:
A default factor of 2.5 is appropriate per REACH guidance R.8.4.3.1.
AF for intraspecies differences:
10
Justification:
This is a default assessment factor for the general population per REACH Guidance R.8.4.3.1.
AF for the quality of the whole database:
1
Justification:
A high quality, robust toxicity database exists for this substance.
AF for remaining uncertainties:
1
Justification:
Route–to-route extrapolation; Value: 1; Remark: A factor of 1 is appropriate since the animal exposure was via ingestion.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

Potential general population exposure would likely occur via the dermal, oral, or inhalation routes.

This substance is classified as harmful via the acute oral, inhalation, and dermal routes under REACH regulations and guidance.  The rat oral ALD is 450 mg/kg and the rat inhalation 4 -hour LC50 is 3.2 mg/L (3200 mg/m3). The rabbit dermal ALD for the structurally similar substance, o-phenylenediamine (CAS 95-54-5), which was used as a surrogate for acute dermal data, is 1500 mg/kg.

Male and female rats were exposed to 2, 6, and 18 mg/kg/d for 90 days by oral gavage. Degenerative lesions of the liver, increased frequency of pycnosis, and increased liver and kidney weights were observed in the highest dose group. The NOEL for systemic toxicity effects after 90 days was 6 mg/kg/day. The test substance did not cause cancer in a 19-month drinking water study in mice at any dose level tested. Based on this information, the NOAEL for significant systemic effects was determined to be 6 mg/kg-bw/day and can be used for development of a long-term DNEL for systemic effects.

Skin sensitization was observed in acute exposure studies; therefore a short-term DNEL for local effects was derived.

In a local lymph node assay, this substance was found to be positive for dermal sensitization with an EC3 value of 0.49% (122.5 µg/cm2). As per REACH R.8 Appendix R. 8-10 Skin sensitization, an EC3 value can be considered as a LOAEL for induction (expressed in µg/cm2) and can be used for development of a short-term DNEL for local effects.