Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
15.9 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
Value:
396.7 mg/m³
Explanation for the modification of the dose descriptor starting point:
Modification of the dose descriptors is necessary, because the routes of exposure are different between animals (oral) and humans (inhalation). For this purpose the default respiratory volume for the rat corresponding to the daily duration of human exposure is considered in the first step, followed by a correction for the difference between respiratory rates of workers under standard conditions and under light activity in the second step. NAECcorr_inh = oral NOAEL (225) x 1/0.38 m3/kg bw x 6.7 m3/10 m3 = 396.7 mg/m3. As a worst case, oral absorption in rats in humans is assumed to be 100% and inhalation absorption in humans is assumed to be 100%. Therefore, NAECcorr_inh = 396.7 x 1 = 396.7 mg/m3.
AF for dose response relationship:
1
Justification:
Default factor, in accordance with REACH Guidance R.8
AF for differences in duration of exposure:
2
Justification:
Default assessment factor for extrapolation from subchronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
No allometric scaling required for inhalation route.
AF for other interspecies differences:
2.5
Justification:
Default factor, in accordance with REACH Guidance R.8
AF for intraspecies differences:
5
Justification:
Default factor, in accordance with REACH Guidance R.8
AF for the quality of the whole database:
1
Justification:
Default factor for good quality database, in accordance with REACH Guidance R.8
AF for remaining uncertainties:
1
Justification:
Default factor, in accordance with REACH Guidance R.8
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:
2.25 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
Value:
225 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Assume that oral absorption in rats is 100% and that dermal absorption in humans is 100%. Therefore dose descriptor after route to route extrapolation is 225 x 100/100 = 225 mg/kg bw/day.
AF for dose response relationship:
1
Justification:
Default factor, in accordance with REACH Guidance R.8
AF for differences in duration of exposure:
2
Justification:
Default assessment factor for extrapolation from subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Default factor (rat to human), in accordance with REACH Guidance R.8
AF for other interspecies differences:
2.5
Justification:
Default factor, in accordance with REACH Guidance R.8
AF for intraspecies differences:
5
Justification:
Default factor, in accordance with REACH Guidance R.8
AF for the quality of the whole database:
1
Justification:
Default factor, in accordance with REACH Guidance R.8
AF for remaining uncertainties:
1
Justification:
Default factor, in accordance with REACH Guidance R.8
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 lowest NOAEL value was obtained in male rats in the reproduction/development toxicity screening study with read-across substance,tris(2-ethylhexyl) benzene-1,2,4-tricarboxylate, however, the effects on spermatogenesis observed in this study were not seen in the 90-day study, which included a detailed analysis of the testes and an identical highest dose of 1000 mg/kg bw/day, therefore it is considered that the effects seen in male rats in the reproduction/developmental toxicity screening study are not related to the read-across substance. Consequently, the NOAEL from the 90 day repeated dose toxicity study in rats with read-across substance,tris(2-ethylhexyl) benzene-1,2,4-tricarboxylate, was selected as starting point for deriving the long-term systemic inhalation DNEL and the long-term systemic dermal DNEL. Acute and long-term local DNELs (dermal and inhalation) were not derived as the substance is not classified for local effects and it is considered that the derivation from long term systemic effects provides a suitable margin of safety for use. Acute systemic DNELs (dermal and inhalation) were not derived because the substance is not classified for acute effects.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.9 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
Value:
195.7 mg/m³
Explanation for the modification of the dose descriptor starting point:
Modification of the dose descriptors is necessary, because the routes of exposure are different between animals (oral) and humans (inhalation). For this purpose, the oral dose for the rat is converted to the corresponding air concentration using a standard breathing volume for the rat (1.15 m3/kg for 24 hrs exposure of general public). NAECcorr_inh = oral NOAEL (225) x 1/1.15 m3/kg bw = 195.7 mg/m3. As a worst case, dermal absorption in rats in humans is assumed to be 100% and inhalation absorption in humans is assumed to be 100%. Therefore, NAECcorr_inh = 195.7 x 1 = 195.7 mg/m3
AF for dose response relationship:
1
Justification:
Default factor, in accordance with REACH Guidance R.8
AF for differences in duration of exposure:
2
Justification:
Default assessment factor for extrapolation from subchronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
No allometric scaling required for inhalation route.
AF for other interspecies differences:
2.5
Justification:
Default factor, in accordance with REACH Guidance R.8
AF for intraspecies differences:
10
Justification:
Default factor, in accordance with REACH Guidance R.8
AF for the quality of the whole database:
1
Justification:
Default factor, in accordance with REACH Guidance R.8
AF for remaining uncertainties:
1
Justification:
Default factor, in accordance with REACH Guidance R.8
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:
1.13 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
Value:
225 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Assume that oral absorption in rats is 100% and that dermal absorption in humans is 100%. Therefore dose descriptor after route to route extrapolation is 225 x 100/100 = 225 mg/kg bw/day.
AF for dose response relationship:
1
Justification:
Default factor, in accordance with REACH Guidance R.8
AF for differences in duration of exposure:
2
Justification:
Default assessment factor for extrapolation from subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Default factor (rat to human), in accordance with REACH Guidance R.8
AF for other interspecies differences:
2.5
Justification:
Default factor, in accordance with REACH Guidance R.8
AF for intraspecies differences:
10
Justification:
Default factor, in accordance with REACH Guidance R.8
AF for the quality of the whole database:
1
Justification:
Default factor, in accordance with REACH Guidance R.8
AF for remaining uncertainties:
1
Justification:
Default factor, in accordance with REACH Guidance R.8
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:
1.13 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
Value:
225 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Not required.
AF for dose response relationship:
1
Justification:
Default factor, in accordance with REACH Guidance R.8
AF for differences in duration of exposure:
2
Justification:
Default assessment factor for extrapolation from subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Default factor (rat to human), in accordance with REACH Guidance R.8
AF for other interspecies differences:
2.5
Justification:
Default factor, in accordance with REACH Guidance R.8
AF for intraspecies differences:
10
Justification:
Default factor, in accordance with REACH Guidance R.8
AF for the quality of the whole database:
1
Justification:
Default factor, in accordance with REACH Guidance R.8
AF for remaining uncertainties:
1
Justification:
Default factor, in accordance with REACH Guidance R.8
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 lowest NOAEL value was obtained in male rats in the reproduction/development toxicity screening study with read-across substance,tris(2-ethylhexyl) benzene-1,2,4-tricarboxylate, however, the effects on spermatogenesis observed in this study were not seen in the 90-day study, which included a detailed analysis of the testes and an identical highest dose of 1000 mg/kg bw/day, therefore it is considered that the effects seen in male rats in the reproduction/developmental toxicity screening study are not related to the read-across substance. Consequently, the NOAEL from the 90 day repeated dose toxicity study in rats with read-across substance,tris(2-ethylhexyl) benzene-1,2,4-tricarboxylate, was selected as starting point for deriving the long-term systemic inhalation DNEL, the long-term systemic oral DNEL and the long-term systemic dermal DNEL. Acute and long-term local DNELs (dermal and inhalation) were not derived as the substance is not classified for local effects and it is considered that the derivation from long term systemic effects provides a suitable margin of safety for use. Acute systemic DNELs (dermal and inhalation) were not derived because the substance is not classified for acute effects.