Registration Dossier

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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
42.7 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):
150
Modified dose descriptor starting point:
NOAEC
Value:
6 408.4 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/8h) and the "8h human standard Respiratory volume" / "8h worker Respiratory volume" ratio (6.7 m3/10 m3).

AF for dose response relationship:
1
Justification:
Starting point for the DNEL calculation is a NOAEC (as mentioned in ECHA Guidance R8 v2, december 2010)
AF for differences in duration of exposure:
12
Justification:
Duration is extrapolated from sub-acute (14 days) to chronic (as mentioned in ECHA Guidance R8 v2, december 2010)
AF for interspecies differences (allometric scaling):
1
Justification:
Allomatric scaling is not applicable when setting an inhalation DNEL based on an inhalation animal study (as mentioned in ECHA Guidance R8 v2, december 2010)
AF for other interspecies differences:
2.5
Justification:
Default factor mentioned in ECHA Guidance R8 v2, december 2010
AF for intraspecies differences:
5
Justification:
As mentioned in ECHA Guidance R8 v2, 2010: "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 starting study has been performed according to OECD TG 412 and GLP (Klimisch code 1)
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:
6 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):
600
Modified dose descriptor starting point:
NOAEL
Value:
3 616.5 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 "8h exposure rat standard Respiratory Volume" (0.38 m3/kg); the "rat inhalatory absorption"/"human dermal absorption" ratio (50/100); the "8h worker Respiratory Volume"/"8h human standard Respiratory volume" ratio (10 m3/6.7 m3).

AF for dose response relationship:
1
Justification:
Starting point for the DNEL calculation is a NOAEC (as mentioned in ECHA Guidance R8 v2, december 2010)
AF for differences in duration of exposure:
12
Justification:
Duration is extrapolated from sub-acute (14 days) to chronic (as mentioned in ECHA Guidance R8 v2, december 2010)
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, december 2010
AF for other interspecies differences:
2.5
Justification:
Default factor mentioned in ECHA Guidance R8 v2, december 2010
AF for intraspecies differences:
5
Justification:
As mentioned in ECHA Guidance R8 v2, 2010: "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 starting study has been performed according to OECD TG 412 and GLP (Klimisch code 1)
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:
10.6 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):
300
Modified dose descriptor starting point:
NOAEC
Value:
3 188.25 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 (as mentioned in ECHA Guidance R8 v2, december 2010)
AF for differences in duration of exposure:
12
Justification:
Duration is extrapolated from sub-acute (14 days) to chronic (as mentioned in ECHA Guidance R8 v2, december 2010)
AF for interspecies differences (allometric scaling):
1
Justification:
Allomatric scaling is not applicable when setting an inhalation DNEL based on an inhalation animal study (as mentioned in ECHA Guidance R8 v2, december 2010)
AF for other interspecies differences:
2.5
Justification:
Default factor mentioned in ECHA Guidance R8 v2, december 2010
AF for intraspecies differences:
10
Justification:
As mentioned in ECHA Guidance R8 v2, 2010: "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 starting study has been performed according to OECD TG 412 and GLP (Klimisch code 1)
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:
6.1 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):
1 200
Modified dose descriptor starting point:
NOAEL
Value:
7 333
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 "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, december 2010)
AF for differences in duration of exposure:
12
Justification:
Duration is extrapolated from sub-acute (14 days) to chronic (as mentioned in ECHA Guidance R8 v2, december 2010)
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, december 2010
AF for other interspecies differences:
2.5
Justification:
Default factor mentioned in ECHA Guidance R8 v2, december 2010
AF for intraspecies differences:
10
Justification:
As mentioned in ECHA Guidance R8 v2, 2010: "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 starting study has been performed according to OECD TG 412 and GLP (Klimisch code 1)
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:
12.2 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):
1 200
Modified dose descriptor starting point:
NOAEL
Value:
14 666 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 (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, december 2010)
AF for differences in duration of exposure:
12
Justification:
Duration is extrapolated from sub-acute (14 days) to chronic (as mentioned in ECHA Guidance R8 v2, december 2010)
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, december 2010
AF for other interspecies differences:
2.5
Justification:
Default factor mentioned in ECHA Guidance R8 v2, december 2010
AF for intraspecies differences:
10
Justification:
As mentioned in ECHA Guidance R8 v2, 2010: "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 starting study has been performed according to OECD TG 412 and GLP (Klimisch code 1)
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

DNEL have been derived from the NOAEL of 3000 ppm (or 12753 mg/m3) coming from the 12-day exposure inhalation toxicity study performed with ethylal (Katz, 1987). This value has been used as the worst case in comparison with supporting NOAEC of 6300 mg/m3 coming from the read-across (90 day inhalation study with methylal_Hofman, 1994). NOAEL coming from study of Katz (1987) is the worst-case due to extapolation from 14d to 90 day duration, leading to an extrapolation factor of 12 in DNEL calculation (2 for 14d to subacute and 6 for subacute to chronic exposure). An absenc of adverse effect has been observed in a 22d repeated dose inhalation perform with 1000 ppm of methylal (Rutsky, 1996), supporting the relevance of shorter duration studies.

Note that these studies (2 with methylal and 1 with ethylal) are characterised by an absence of adverse effects by inhalation route, supporting the same toxicokinetic profile of methyal and etyhlal.