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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
0.164 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):
75
Dose descriptor starting point:
NOAEL
Value:
10 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
12.3 mg/m³
Explanation for the modification of the dose descriptor starting point:

For potential inhalation exposure, route-to-route extrapolation from the oral NOEL value was considered appropriate. As a worst-case, the NOEL from the rat subacute repeated dose toxicity study study, 10 mg/kg bw/day, was selected as the relevant starting point for DNEL derivation. Regarding absorption, in the absence of reliable data for both the starting route (oral) and the end route (inhalation), worst case assumptions were made. It was assumed that a limited absorption occurs by the oral route, leading to a low (conservative) internal NOAEL. To secure a conservative external NOAEL, a maximum absorption should be assumed for the inhalation route (i.e.; 100%) leading to a low external NOAEL. Thus, in the case of oral-to- inhalation extrapolation, it is proposed to include a default factor of 2, i.e. the absorption percentage by oral route is half that of the inhalation absorption as suggested in the ECHA Guidance Document, Chapter R.8 (Version 2.1, November 2012). To convert the oral NOAEL into inhalatory NOAEC, a rat default respiratory volume was used corresponding to the daily duration of human exposure (sRVrat: 0.38 m3/kg bw/8 h). For workers a correction was added for the difference between respiratory rates under standard conditions (sRVhuman: 6.7 m3 for an 8-h exposure period) and under conditions of light activity (wRV: 10 m3 for an 8-h exposure period). In addition, a correction was included to take into account the number of exposure day per week. Thus, the corrected dose descriptor for inhalation is 10 x (1/ 0.38) x (6.7 / 10) x (7 / 5) x (1/2) = 12.3 mg/m3 for workers.

AF for dose response relationship:
1
Justification:
Default factor - the dose descriptor is a NOEL.
AF for differences in duration of exposure:
6
Justification:
Default factor - subacute to chronic extrapolation.
AF for interspecies differences (allometric scaling):
1
Justification:
Default factor - not applicable for oral to inhalation extrapolation
AF for other interspecies differences:
2.5
Justification:
Default factor - toxicodynamic and toxicokinetic remaining differences
AF for intraspecies differences:
5
Justification:
Default factor - Workers
AF for the quality of the whole database:
1
Justification:
The quality of the database wad already taken into account to select the starting point (NOEL), therefore further assessment factor is not justified.
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
46.7 µg/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):
300
Dose descriptor starting point:
NOAEL
Value:
10 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
14 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

For potential dermal exposure, route-to-route extrapolation from the oral NOAEL value was considered appropriate. In the absence of reliable data and on the assumption that, in general, dermal absorption will not be higher than oral absorption, no additional factor was introduced. A correction was included to take into account the number of exposure day per week. Thus, the corrected dose descriptor for inhalation is 10 x (7 / 5) = 14 mg/kg bw/day for workers.

AF for dose response relationship:
1
Justification:
Default factor - the dose descriptor is a NOEL.
AF for differences in duration of exposure:
6
Justification:
Default factor - subacute to chronic extrapolation.
AF for interspecies differences (allometric scaling):
4
Justification:
Default factor - rat.
AF for other interspecies differences:
2.5
Justification:
Default factor - toxicodynamic and toxicokinetic remaining differences
AF for intraspecies differences:
5
Justification:
Default factor – Workers
AF for the quality of the whole database:
1
Justification:
The quality of the database wad already taken into account to select the starting point (NOEL), therefore further assessment factor is not justified.
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
29 µg/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):
150
Dose descriptor starting point:
NOAEL
Value:
10 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
4.35 mg/m³
Explanation for the modification of the dose descriptor starting point:

For potential inhalation exposure, route-to-route extrapolation from the oral NOEL value was considered appropriate. As a worst-case, the NOEL from the rat subacute repeated dose toxicity study study, 10 mg/kg bw/day, was selected as the relevant starting point for DNEL derivation. Regarding absorption, in the absence of reliable data for both the starting route (oral) and the end route (inhalation), worst case assumptions were made. It was assumed that a limited absorption occurs by the oral route, leading to a low (conservative) internal NOAEL. To secure a conservative external NOAEL, a maximum absorption should be assumed for the inhalation route (i.e.; 100%) leading to a low external NOAEL. Thus, in the case of oral-to- inhalation extrapolation, it is proposed to include a default factor of 2, i.e. the absorption percentage by oral route is half that of the inhalation absorption as suggested in the ECHA Guidance Document, Chapter R.8 (Version 2.1, November 2012). o convert the oral NOAEL into inhalatory NOAEC, a rat default respiratory volume was used corresponding to the daily duration of human exposure (sRVrat: 1.15 m3/kg bw/24 h). Thus, the corrected dose descriptor for inhalation is 10 x (1/ 1.15) x (1/2) = 4.35 mg/kg bw/day for general population.

AF for dose response relationship:
1
Justification:
Default factor - the dose descriptor is a NOEL.
AF for differences in duration of exposure:
6
Justification:
Default factor - subacute to chronic extrapolation.
AF for interspecies differences (allometric scaling):
1
Justification:
Default factor - not applicable for oral to inhalation extrapolation
AF for other interspecies differences:
2.5
Justification:
Default factor - toxicodynamic and toxicokinetic remaining differences
AF for intraspecies differences:
10
Justification:
Default factor – General population
AF for the quality of the whole database:
1
Justification:
The quality of the database wad already taken into account to select the starting point (NOEL), therefore further assessment factor is not justified.
Justification:
Due to the uncertainties linked to the deviations observed in the OECD TG No. 422 study, the NOEL value of 10 mg/kg bw/day was used as the worst-case starting point for DNEL derivation.
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
16.7 µg/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):
600
Dose descriptor starting point:
NOAEL
Value:
10 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
10 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:



For potential dermal exposure, route-to-route extrapolation from the oral NOAEL value was considered appropriate. In the absence of reliable data and on the assumption that, in general, dermal absorption will not be higher than oral absorption, no additional factor was introduced.




AF for dose response relationship:
1
Justification:
Default factor - the dose descriptor is a NOEL.
AF for differences in duration of exposure:
6
Justification:
Default factor - subacute to chronic extrapolation.
AF for interspecies differences (allometric scaling):
4
Justification:
Default factor - rats
AF for other interspecies differences:
2.5
Justification:
Default factor - toxicodynamic and toxicokinetic remaining differences
AF for intraspecies differences:
10
Justification:
Default factor – General population
AF for the quality of the whole database:
1
Justification:
The quality of the database wad already taken into account to select the starting point (NOEL), therefore further assessment factor is not justified.
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
16.7 µg/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):
600
Dose descriptor starting point:
NOAEL
Value:
10 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
10 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:



No route-to-route extrapolation needed.




AF for dose response relationship:
1
Justification:
Default factor - the dose descriptor is a NOEL.
AF for differences in duration of exposure:
6
Justification:
Default factor - subacute to chronic extrapolation.
AF for interspecies differences (allometric scaling):
4
Justification:
Default factor - rats.
AF for other interspecies differences:
2.5
Justification:
Default factor - toxicodynamic and toxicokinetic remaining differences
AF for intraspecies differences:
10
Justification:
Default factor – General population
AF for the quality of the whole database:
1
Justification:
The quality of the database wad already taken into account to select the starting point (NOEL), therefore further assessment factor is not justified.
Justification:
Due to the uncertainties linked to the deviations observed in the OECD TG No. 422 study, the NOEL value of 10 mg/kg bw/day was used as the worst-case starting point for DNEL derivation.
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population