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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
126.63 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Modified dose descriptor starting point:
NOAEC
Value:
6 300 mg/m³
Explanation for the modification of the dose descriptor starting point:

No route to route extrapolation needed. Experimental rat inhalatory NOAEC was converted into human inhalatory NOAEC considering: the duration of animals and workers exposure ratio (6h/24h).

AF for dose response relationship:
1
Justification:
Starting point for the DNEL calculation is a NOAEC Duration of exposure:
AF for differences in duration of exposure:
2
Justification:
Duration is extrapolated from sub-chronic (90-day) to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Allomatric scaling is not applicable when setting an inhalation DNEL based on an inhalation animal study
AF for other interspecies differences:
2.5
Justification:
Default factor mentioned in ECHA Guidance R8
AF for intraspecies differences:
10
Justification:
"it is usually assumed that a default assessment factor of 10 is sufficient to protect the larger part of the population, including e.g. children and the elderly".
AF for the quality of the whole database:
1
Justification:
The read accross study has been performed according to OECD guidelines (Klimisch code 2)
AF for remaining uncertainties:
1
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:
11.97 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
NOAEL
Value:
1 197 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Route to route extrapolation is needed. Experimental rat inhalatory NOAEC was converted into human dermal NOAEL considering: the "8h exposure rat standard Respiratory Volume" (0.38 m3/kg); the "rat inhalatory absorption"/"human dermal absorption" ratio (50/100).

AF for dose response relationship:
1
Justification:
Starting point for the DNEL calculation is a NOAEC (as mentioned in ECHA Guidance R8 v2.1
AF for differences in duration of exposure:
2
Justification:
Duration is extrapolated from sub-chronic (90 days) to chronic (as mentioned in ECHA Guidance R8 v2.1
AF for interspecies differences (allometric scaling):
4
Justification:
An AS factor of 4 for rat as compared to humans is presented in ECHA Guidance R8 v2.1
AF for other interspecies differences:
2.5
Justification:
Default factor mentioned in ECHA Guidance R8 v2.1
AF for intraspecies differences:
5
Justification:
As mentioned in ECHA Guidance R8 v2.1: "For workers, as standard procedure for threshold effects a default assessment factor of 5 is to be used, based on the fact that this sub population does not cover the very young, the very old, and the very ill".
AF for the quality of the whole database:
1
Justification:
The read accross study has been performed according to OECD guidelines (Klimisch code 2)
AF for remaining uncertainties:
1
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

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
31.5 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Modified dose descriptor starting point:
NOAEC
Value:
1 575 mg/m³
Explanation for the modification of the dose descriptor starting point:

No route to route extrapolation needed. Experimental rat inhalatory NOAEC was converted into human inhalatory NOAEC considering: the duration of animals and workers exposure ratio (6h/24h).

AF for dose response relationship:
1
Justification:
Starting point for the DNEL calculation is a NOAEC Duration of exposure:
AF for differences in duration of exposure:
2
Justification:
Duration is extrapolated from sub-chronic (90-day) to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Allomatric scaling is not applicable when setting an inhalation DNEL based on an inhalation animal study
AF for other interspecies differences:
2.5
Justification:
Default factor mentioned in ECHA Guidance R8
AF for intraspecies differences:
10
Justification:
"it is usually assumed that a default assessment factor of 10 is sufficient to protect the larger part of the population, including e.g. children and the elderly".
AF for the quality of the whole database:
1
Justification:
The read accross study has been performed according to OECD guidelines (Klimisch code 2)
AF for remaining uncertainties:
1
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:
18.11 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
200
Modified dose descriptor starting point:
NOAEL
Value:
3 622.5 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Route to route extrapolation is needed. Experimental rat inhalatory NOAEC was converted into human dermal NOAEL considering: the "24h exposure rat standard Respiratory Volume" (1.15 m3/kg); the worst-case "rat inhalatory absorption"/"human dermal absorption" ratio (50/100).

AF for dose response relationship:
1
Justification:
Starting point for the DNEL calculation is a NOAEC (as mentioned in ECHA Guidance R8 v2.1
AF for differences in duration of exposure:
2
Justification:
Duration is extrapolated from sub-chronic (90 days) to chronic (as mentioned in ECHA Guidance R8 v2.1
AF for interspecies differences (allometric scaling):
4
Justification:
An AS factor of 4 for rat as compared to humans is presented in ECHA Guidance R8 v2.1
AF for other interspecies differences:
2.5
Justification:
Default factor mentioned in ECHA Guidance R8 v2.1
AF for intraspecies differences:
10
Justification:
As mentioned in ECHA Guidance R8 v2.1: "it is usually assumed that a default assessment factor of 10 is sufficient to protect the larger part of the population, including e.g. children and the elderly".
AF for the quality of the whole database:
1
Justification:
The read accross study has been performed according to OECD guidelines (Klimisch code 2)
AF for remaining uncertainties:
1
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:
36.225 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
200
Modified dose descriptor starting point:
NOAEL
Value:
7 245 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Route to route extrapolation is needed. Experimental rat inhalatory NOAEC was converted into human oral NOAEL considering: the "24h exposure rat standard Respiratory Volume" (1.15 m3/kg); the "rat inhalatory absorption"/"human oral absorption" ratio (100/100) because a two times higher oral compared to inhalation absorption appears on empirical grounds not justified.

AF for dose response relationship:
1
Justification:
Starting point for the DNEL calculation is a NOAEC
AF for differences in duration of exposure:
2
Justification:
Duration is extrapolated from sub-chronic (90 days) to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
An AS factor of 4 for rat as compared to humans is presented in ECHA Guidance R8 v2.1.
AF for other interspecies differences:
2.5
Justification:
Default factor mentioned in ECHA Guidance R8
AF for intraspecies differences:
10
Justification:
As mentioned in ECHA Guidance R8 : "it is usually assumed that a default assessment factor of 10 is sufficient to protect the larger part of the population, including e.g. children and the elderly".
AF for the quality of the whole database:
1
Justification:
The read accross study has been performed according to OECD guidelines (Klimisch code 2)
AF for remaining uncertainties:
1
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

Starting point of DNEL derivation is NOAEC = 6300 mg/m³ from a sub-chronic (90-day inhalation repeated dose with Methylal)