Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.28 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:
7.05 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 (8) x 1/0.38 m3/kg bw x 6.7 m3/10 m3 = 14.11 mg/m3. As a worst case, oral absorption in rats is assumed to be 50% and inhalation absorption in humans is assumed to be 100%. Therefore, NAECcorr_inh = 17.63 x 50/100 = 7.05 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 AF; no remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
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
Value:
80 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Assuming that oral absorption in rats is 100% and that dermal absorption in humans is 10%. Therefore dose descriptor after route to route extrapolation is 8 x 100/10 = 80 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 for remaining differences
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; no remaining uncertainties
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:
medium hazard (no threshold derived)

Additional information - workers

The lowest NOAEL value was obtained in the 90 day repeated dose toxicity study therefore this NOAEL (8 mg/kg bw/day) was selected as a 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 on the skin or the respiratory system. Acute systemic DNELs (dermal and inhalation) were not derived because the substance is not classified for acute dermal and inhalation effects. It is considered that the derivation from long term systemic effects provides a suitable margin of safety for use.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.07 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:
3.48 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 (8) x 1/1.15 m3/kg bw = 6.96 mg/m3. As a worst case, oral absorption in rats in humans is assumed to be 50% and inhalation absorption in humans is assumed to be 100%. Therefore, NAECcorr_inh = 6.96 x 50/100 = 3.48 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 for good quality database, in accordance with REACH Guidance R.8
AF for remaining uncertainties:
1
Justification:
Default AF; no remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
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
Value:
80 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Assuming that oral absorption in rats is 100% and that dermal absorption in humans is 10%. Therefore dose descriptor after route to route extrapolation is 8 x 100/10 = 80 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 for good quality database, in accordance with REACH Guidance R.8
AF for remaining uncertainties:
1
Justification:
Default; no remaining uncertainties
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:
0.04 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:
8 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Assume oral absorption in rats = oral absorption in humans.
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 for good quality database, in accordance with REACH Guidance R.8
AF for remaining uncertainties:
1
Justification:
Default; no remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population

The lowest NOAEL value was obtained in the 90 day repeated dose toxicity study therefore this NOAEL (8 mg/kg bw/day) was selected as a starting point for deriving the long-term systemic inhalation DNEL, the long-term systemic dermal DNEL and the long-term systemic oral DNEL. Acute and long-term local DNELs (dermal and inhalation) were not derived as the substance is not classified for local effects on the skin or the respiratory system. Acute systemic DNELs (dermal and inhalation) were not derived because the substance is not classified for acute effects by the dermal/inhalation routes. An acute systemic DNEL (oral) was not derived because high peak exposures are not predicted. It is considered that the derivation from long term systemic effects provides a suitable margin of safety for use.