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Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.94 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:
447 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
789.9 mg/m³
Explanation for the modification of the dose descriptor starting point:

Relevant dose-descriptor

Value: 447 mg/kg (NOAEL). This is the concentration where no significant adverse effects were seen in a sub-chronic oral toxicity study.

 

Modification of starting point for rat respiratory volume (Allometric scaling)

Value: 0.38 m3/kg bw (rat 8-hour respiratory volume). 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). 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:
2
Justification:
This is a default assessment factor for a sub-chronic study per REACH Guidance R.8.4.3.1.
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:
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

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.47 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
Modified dose descriptor starting point:
NOAEL
Value:
447 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Relevant dose-descriptor

Value: 447 mg/kg (NOAEL). This is the concentration where no significant adverse effects were seen in a sub-chronic 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:
2
Justification:
This is a default assessment factor for a sub-chronic study per REACH Guidance R.8.4.3.1.
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:
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:
1
Justification:
Route-to-route extrapolation: 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
Explanation for the modification of the dose descriptor starting point:

No hazard identified, therefore no DNEL was calculated.

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - workers

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

 

This substance is classified as harmful via the dermal route and toxic via the inhalation route under REACH regulations and guidance. The rabbit dermal LD50 value is 1410 mg/kg. The rat 4-hour inhalation LC50 value for the structurally similar substance, terephthaloyl dichloride (CAS 100-20-9), which was used as a surrogate for acute inhalation data, is 700 mg/m3.

 

Male and female rats were fed daily for 13 weeks at levels of 0.5, 1.6, and 5% of the test substance in the diet. Following the first week of the study the weight gains of the rats were examined. It was concluded that the 5% dose level would not permit growth. Therefore, the high dose was reduced to 3%. An increase in crystalluria was observed. Examination of organs at necropsy revealed mild to moderate hyperplasia in kidneys in the highest dosage level. Based on this information, the 90 -day rat oral NOAEL was identified as 0.5% (calculated as 447 mg/kg-day for males and 474 mg/kg-day for females).

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.97 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):
400
Dose descriptor starting point:
NOAEL
Value:
447 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
388.7 mg/m³
Explanation for the modification of the dose descriptor starting point:

Relevant dose-descriptor

Value: 447 mg/kg (NOAEL). This is the concentration where no significant adverse effects were seen in a sub-chronic oral toxicity study.

 

Modification of starting point for rat respiratory volume (Allometric scaling)

Value: 1.15 m3/kg bw (rat 24-hour respiratory volume). 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:
2
Justification:
This is a default assessment factor for a sub-chronic study per REACH Guidance R.8.4.3.1.
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:
2.24 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):
200
Dose descriptor starting point:
NOAEL
Value:
447 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Relevant dose-descriptor

Value: 447 mg/kg (NOAEL). This is the concentration where no significant adverse effects were seen in a sub-chronic 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:
2
Justification:
This is a default assessment factor for a sub-chronic study per REACH Guidance R.8.4.3.1.
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: A factor of 1 is appropriate since the animal expoure 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:
high hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.24 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):
200
Dose descriptor starting point:
NOAEL
Value:
447 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Relevant dose-descriptor

Value: 447 mg/kg (NOAEL). This is the concentration where no significant adverse effects were seen in a sub-chronic 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:
2
Justification:
This is a default assessment factor for a sub-chronic study per REACH Guidance R.8.4.3.1.
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: 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:
high hazard (no threshold derived)

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 dermal route and toxic via the inhalation route under REACH regulations and guidance. The rabbit dermal LD50 value is 1410 mg/kg. The rat 4-hour inhalation LC50 value for the structurally similar substance, terephthaloyl dichloride (CAS 100-20-9), which was used as a surrogate for acute inhalation data, is 700 mg/m3.

Male and female rats were fed daily for 13 weeks at levels of 0.5, 1.6, and 5% of the test substance in the diet. Following the first week of the study the weight gains of the rats were examined. It was concluded that the 5% dose level would not permit growth. Therefore the high dose was reduced to 3%. An increase in crystalluria was observed. Examination of organs at necropsy revealed mild to moderate hyperplasia in kidneys in the highest dosage level. Based on this information, the 90 -day rat oral NOAEL was identified as 0.5% (calculated as 447 mg/kg-day for males and 474 mg/kg-day for females).