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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:
5.61 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):
25
Modified dose descriptor starting point:
NOAEC
Explanation for the modification of the dose descriptor starting point:
There is no repeated dose inhalation data. For this substance it is unlikely that the toxicological profile is route dependent. Therefore the repeated dose oral data has been used. 1,2-Benzenedicarboxylic acid, di-C8-10-alkylesters is expeted to be rapidly absorbed from the gastro-intestinal tract, means 100 %, no data exist for the inhalative absorption, therefore as worst case 100 % is expected, whereas dermal absorption is expected to be slower. However, because no exact absorption factors are available, in conclusion it is expected that the absoption factors for all routes are 100 %. That means an overestimation of the dermal DNELs. That means also an additional AF for route-to-route is not required.
AF for dose response relationship:
1
Justification:
Starting point is a NOAEL
AF for differences in duration of exposure:
2
Justification:
subchronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Not tpyically applied in the derivation of an inhalation DNEL
AF for other interspecies differences:
2.5
Justification:
Default value
AF for intraspecies differences:
5
Justification:
worker
AF for the quality of the whole database:
1
Justification:
good quality
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties identified
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:
0.8 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
Modified dose descriptor starting point:
NOAEL
DNEL value:
80 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
There is no repeated dose dermal data. For this substance it is unlikely that the toxicological profile is route dependent. Therefore the repeated dose oral data has been used. 1,2-Benzenedicarboxylic acid, di-C8-10-alkylesters is expeted to be rapidly absorbed from the gastro-intestinal tract, means 100 %, whereas dermal absorption is expected to be slower. However, because no exact absorption factors are available, in conclusion it is expected that the absoption factors for all routes are 100 %. That means an overestimation of the dermal DNELs. That means also an additional AF for route-to-route is not required.
AF for dose response relationship:
1
Justification:
starting point is a NOAEL
AF for differences in duration of exposure:
2
Justification:
subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for other interspecies differences:
2.5
Justification:
default value
AF for intraspecies differences:
5
Justification:
worker
AF for the quality of the whole database:
1
Justification:
good quality
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties identified
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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

The most appropriate endpoint for derivation of a DNEL is the rat oral NOAEL of 79.6 mg/kg bw/d with the read-across substance 1,2-Benzenedicarboxylic acid, di-C8-10-alkyl esters taken from a well conducted subchronic toxicity study (liver weight effects). Based on the acute toxicity data, DNELs do not need to be derived for local or systemic effects for the worker population since the material has a low potential for acute toxicity.

Worker long term exposure - systemic effects (dermal and inhalation) DNELs were calculated from the NOAEL, assuming a 100% dermal absorption rate (worst case). The value was divided by an adjustment factor of 100 according to REACH TGD (exposure duration factor of 2, interspecies factor of 10, and intraspecies (worker population) factor of 5), leading to a DNEL of 0.8 mg/kg/d.

The corrected worker inhalation starting point was the corrected NOAEC of 140.3 mg/m3 and was derived from the oral NOAEL of 79.6 mg/kg/d by multiplying by the inverse of the standard respiratory volume of the rat during an 8 hour period (2.63) and multiplied by the ratio of standard respiratory volume for humans to the 8 hour worker standard respiratory volume (0.67). The corrected starting point was adjusted by a factor of 25 (interspecies factor of 2.5, intraspecies factor (worker) of 5, and exposure duration of 2), resulting in a calculated DNEL of 5.61 mg/m3.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.386 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):
50
Modified dose descriptor starting point:
NOAEC
DNEL value:
69.3 mg/m³
Explanation for the modification of the dose descriptor starting point:
There is no repeated dose inhalation data. For this substance it is unlikely that the toxicological profile is route dependent. Therefore the repeated dose oral data has been used. 1,2-Benzenedicarboxylic acid, di-C8-10-alkylesters is expeted to be rapidly absorbed from the gastro-intestinal tract, means 100 %, no data exist for the inhalative absorption, therefore as worst case 100 % is expected, whereas dermal absorption is expected to be slower. However, because no exact absorption factors are available, in conclusion it is expected that the absoption factors for all routes are 100 %. That means an overestimation of the dermal DNELs. That means also an additional AF for route-to-route is not required.
AF for dose response relationship:
1
Justification:
Starting point is a NOAEL
AF for differences in duration of exposure:
2
Justification:
subchronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Not tpyically applied in the derivation of an inhalation DNEL
AF for other interspecies differences:
2.5
Justification:
default value
AF for intraspecies differences:
10
Justification:
General population
AF for the quality of the whole database:
1
Justification:
good quality
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties identified
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:
0.4 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
Modified dose descriptor starting point:
NOAEL
DNEL value:
80 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
There is no repeated dose dermal data. For this substance it is unlikely that the toxicological profile is route dependent. Therefore the repeated dose oral data has been used. 1,2-Benzenedicarboxylic acid, di-C8-10-alkylesters is expeted to be rapidly absorbed from the gastro-intestinal tract, means 100 %, whereas dermal absorption is expected to be slower. However, because no exact absorption factors are available, in conclusion it is expected that the absoption factors for all routes are 100 %. That means an overestimation of the dermal DNELs. That means also an additional AF for route-to-route is not required.
AF for dose response relationship:
1
Justification:
Starting point is a NOAEL
AF for differences in duration of exposure:
2
Justification:
subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for other interspecies differences:
2.5
Justification:
default value
AF for intraspecies differences:
10
Justification:
General population
AF for the quality of the whole database:
1
Justification:
good quality
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties identified
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

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.4 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
Modified dose descriptor starting point:
NOAEL
DNEL value:
80 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
it is the same route
AF for dose response relationship:
1
Justification:
Starting point is a NOAEL
AF for differences in duration of exposure:
2
Justification:
subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for other interspecies differences:
2.5
Justification:
default value
AF for intraspecies differences:
10
Justification:
General population
AF for the quality of the whole database:
1
Justification:
good quality
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties identified
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

The most appropriate endpoint for derivation of a DNEL is the rat oral NOAEL of 79.6 mg/kg bw/d (ca. 80 mg/kg bw/d) with the read-across substance 1,2-Benzenedicarboxylic acid, di-C8-10-alkyl esters taken from a well conducted subchronic toxicity study (liver weight effects). Based on the acute toxicity data, DNELs do not need to be derived for local or systemic effects for the general population since the material has a low potential for acute toxicity.

General population long term exposure - systemic effects (oral, dermal and inhalation) DNELs were calculated from the NOAEL, assuming a 100% dermal absorption rate (worst case). The value was divided by an adjustment factor of 200 (exposure duration factor of 2, interspecies factor of 10, and intraspecies (general population) factor of 10), leading to a DNEL of 0.4 mg/kg/d.

The corrected general population inhalation starting point was the corrected NOAEC of 69.3 mg/m3 and was derived from the oral NOAEL of 79.6 mg/kg/d by multiplying by the inverse of the standard respiratory volume of the rat during a 24 hour period (0.87). The corrected starting point was adjusted by a factor of 50 (interspecies factor of 2.5, intraspecies factor (general population) of 10, and exposure duration of 2), resulting in a calculated DNEL of 1.39 mg/m3.

The general population oral starting point is 79.6 mg/kg/d (ca. 80 mg/kg bw/d). An adjustment factor of 200 is applied (interspecies factor of 10, intraspecies factor (general population) of 10, and exposure duration of 2), leading to a DNEL of 0.4 mg/kg bw/day.