Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
176 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
other: MAK assessmment (2016)
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:
12 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):
50
Modified dose descriptor starting point:
NOAEL
Value:
582 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Several studies available  

AF for dose response relationship:
1
Justification:
dose-response available
AF for differences in duration of exposure:
1
Justification:
chronic study
AF for interspecies differences (allometric scaling):
4
Justification:
standard factor
AF for other interspecies differences:
2.5
Justification:
standard factor
AF for intraspecies differences:
5
Justification:
standard factor
AF for the quality of the whole database:
1
Justification:
database OK
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

DNEL Workers via the dermal route

Systemic Long term exposure

From the available data set, regarding the oral route of exposure a chronic NOAEL of 6 mg/kg bw/day based on liver and haematological effects (LOAEL of 52 mg/kg bw/day) is selected as most critical one. This NOAEL is used as starting point for the DNEL derivation.

 

Long-term – dermal, systemic effects (based on 2-year oral toxicity study with rats)

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL oral: 6 mg/kg bw/day

liver and haematological effects

Step 2) Modification of starting point

NOAEL oral 6 mg/kg bw/day*(97/1) = corrected NOAEL dermal 582 mg/kg bw/day

Step 3) Assessment factors

Interspecies

4 x 2.5

Assessment factor for allometric scaling and remaining uncertainties.

Intraspecies

5

Default assessment factor

Exposure duration

1

No factor for exposure duration is needed since the NOAEL was derived in a chronic study.

Dose response

1

Quality of database

1

DNEL

Value

582 / (4 x 2.5 x 5 x 1 x 1 x 1) =12 mg/kg bw/day

*Oral absorption set at 97% (see above); dermal absorption set at 1% under non-occlusive conditions

 

Guidance by e.g., the exposure model ECETOC TRA, indicates that although EASE (and hence ECETOC TRA) provides an exposure estimate for high volatile liquids (i.e., with a vapour pressure > 10 kPa), in practice such exposure would not occur in the case of very volatile substances as the substance would never be in contact with the skin for a sufficient period of time (due to fast evaporation) to enable significant dermal permeation to occur (Patel et al., 2002). Therefore, in the case of nonocclusive conditions, this means that any quantitative estimate may be set at the level of PROC 1 and 3 for substances having a vapour pressure greater than ca. 30 kPa (ECETOC TRA vs 3). Dichloromethane has a vapour pressure of 58.4 kPa at 25ºC and as such is highly volatile.

PROC 1 results in a predicted dermal exposure of 0.03 mg/kg bw/day, whereas PROC 3 (worst case) results in a predicted dermal exposure of 0.69 mg/kg bw/day, thus indicating safe use for the worker.

 

Regarding absorption through the skin, we have already advised in each exposure scenario: ‘Avoid all skin contact with product, clean up contamination/spills as soon as they occur. Wear gloves (tested to EN374) if hand contamination is likely, and wash off any skin contamination immediately. Provide basic employee training to prevent / minimise exposures and to report any skin problems that may develop.’ In addition the substance is to be labelled with ‘P280: Wear protective gloves/protective clothing/eye protection/face protection.’

 

12 mg/kg bw/day, will be used in the risk characterisation.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
44 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
other: based on MAK (2016)
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:
5.82 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:
582 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Several studies available  

AF for dose response relationship:
1
Justification:
dose-response available
AF for differences in duration of exposure:
1
Justification:
chronic study
AF for interspecies differences (allometric scaling):
4
Justification:
standard factor
AF for other interspecies differences:
2.5
Justification:
standard factor
AF for intraspecies differences:
10
Justification:
standard factor
AF for the quality of the whole database:
1
Justification:
database OK
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.06 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:
6 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

not applicable (oral study)

AF for dose response relationship:
1
Justification:
dose-response available
AF for differences in duration of exposure:
1
Justification:
chronic study
AF for interspecies differences (allometric scaling):
4
Justification:
standard factor
AF for other interspecies differences:
2.5
Justification:
standard factor
AF for intraspecies differences:
10
Justification:
standard factor
AF for the quality of the whole database:
1
Justification:
database OK
AF for remaining uncertainties:
1
Justification:
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:
low hazard (no threshold derived)

Additional information - General Population

DNEL General population via the dermal route

Systemic Long terme exposure

From the available data set, regarding the oral route of exposure a chronic NOAEL of 6 mg/kg bw/day based on liver and haematological effects (LOAEL of 52 mg/kg bw/day) is selected as most critical one. This NOAEL is used as starting point for the DNEL derivation.

 

Long-term – dermal, systemic effects (based on 2-year oral toxicity study with rats)

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL oral: 6 mg/kg bw/day

liver and haematological effects

Step 2) Modification of starting point

NOAEL oral 6 mg/kg bw/day*(97/1) = corrected NOAEL dermal 582 mg/kg bw/day

Step 3) Assessment factors

Interspecies

4 x 2.5

Assessment factor for allometric scaling and remaining uncertainties.

Intraspecies

10

Default assessment factor

Exposure duration

1

No factor for exposure duration is needed since the NOAEL was derived in a chronic study.

Dose response

1

Quality of database

1

DNEL

Value

582 / (4 x 2.5 x 10 x 1 x 1 x 1) =5.82 mg/kg bw/day

*Oral absorption set at 97% (see above); dermal absorption set at 1% under non-occlusive conditions (for more information see above in discussion for workers).

 

5.82 mg/kg bw/day, will be used in the risk characterisation.

DNEL General population via the oral route

Systemic Long termexposure

From the available data set,regarding the oral route of exposure a chronic NOAEL of 6 mg/kg bw/day based on liver and haematological effects (LOAEL of 52 mg/kg bw/day) is selected as most critical one. This NOAEL is used as starting point for the DNEL derivation.

Long-term – oral, systemic effects (based on 2-year oral toxicity study with rats)

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL: 6 mg/kg bw/day

liver and haematological effects

Step 2) Modification of starting point

-

not applicable

Step 3) Assessment factors

 

 

Interspecies

4 x 2.5

Assessment factor for allometric scaling and remaining uncertainties.

Intraspecies

10

Default assessment factor

Exposure duration

1

No factor for exposure duration is needed since the NOAEL was derived in a chronic study.

Dose response

1

 

Quality of database

1

 

DNEL

Value

 

6 / (4 x 2.5 x 10 x 1 x 1 x 1) =0.06 mg/kg bw/day

 0.06 mg/kg bw/day, will be used in the risk characterisation.