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Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
26 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
10
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
19 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

Workers - Hazard for the eyes

Additional information - workers

MDEA has a low acute oral, inhalation and dermal toxicity.The oral LD50 is 4680 mg/kg bw in rats, in inhalation risk tests no mortality was observed after 6 and 8 hours exposure to a saturated MDEA vapour atmosphere. The LD50 for the dermal route is > 2000 mg/kg bw. Therefore, derivation of acute DNELs for systemic effects are not needed.

 

MDEA is not irritating to the skin and is also not a skin sensitiser. No DNELs have to be derived for these endpoints. The substance is classified for eye irritation.The available data do not allow a quantitative approach. According to the REACH guidance on information requirements and chemical safety assessment, Part E: Risk Characterisation, a qualitative risk characterisation should be performed for this endpoint. In order to guarantee ‘adequately control of risks’, it is necessary to stipulate risk management measures that prevent eye irritation.

In a sub-chronic dermal toxicity study (similar to OECD guideline 411), rats were exposed to 100, 250 and 750 mg/kg bw/day. The observed local effects were dose-related irritation in the mid and high dose groups; major histopathological features were acanthosis, hyperkeratosis, parakeratosis, dermatitis, dermal fibrosis, eschar, and ulceration. No systemic effects were observed up to the highest does tested. Local and systemic NOAELs of 100 mg/kg bw/day (corresponding to 0.8 mg/cm2) and 750 mg/kg bw/day were established upon dermal exposure, respectively.

 

MDEA is not considered mutagenic and carcinogenic. Furthermore, MDEA is not considered a reproductive and developmental toxicant.

Long-term – inhalation, systemic effects (based on a sub-chronic dermal toxicity study in rats)

 

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL: 750 mg/kg bw/day

No systemic effects were observed up to the highest dose tested

Step 2) Modification of starting point

: 0.38

 

 

 

x 6.7 m3/10 m3

 

 

 

x 20/100

An 8 h respiratory volume of 0.38 m3/kg bw for rats is used for conversion into NOAEL upon inhalation exposure.

 

Correction for activity driven differences of respiratory volumes in workers compared to workers in rest (6.7 m3/10 m3).

 

Correction for absorption: 20% absorption after dermal administration; 100% absorption is assumed for inhalation.

Modified dose-descriptor

750 x 6.7 x 20 / (0.38 x10 x 100) = 264 mg/m3

Step 3) Assessment factors

 

 

Interspecies

1

No allometric scaling has to be applied in case of dermal to inhalation route to route extrapolation. Furthermore, no factor for remaining uncertainties is applied as no effects were observed up to the highest dose tested.

Intraspecies

5

Default assessment factor

Exposure duration

2

Extrapolation to chronic exposure based on a sub-chronic toxicity study

Dose response

1

 

Quality of database

1

 

DNEL

Value

 

264 / (1 x 5 x 2 x 1 x 1) = 26 mg/m3

 

Long-term – dermal, systemic effects(based on a sub-chronic dermal toxicity study in rats)

 

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL: 750 mg/kg bw/day

No systemic effects were observed up to the highest dose tested

Step 2) Modification of starting point

-

-

Step 3) Assessment factors

 

 

Interspecies

4

Assessment factor for allometric scaling. No factor for remaining uncertainties is applied as no effects were observed up to the highest dose tested.

Intraspecies

5

Default assessment factor

Exposure duration

2

Extrapolation to chronic exposure based on a sub-chronic toxicity study

Dose response

1

 

Quality of database

1

 

DNEL

Value

 

750 / (4 x 5 x 2 x 1 x 1) = 19 mg/kg bw/day

 

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
6.5 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
20
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
9.4 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
80
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.9 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
80
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

General Population - Hazard for the eyes

Additional information - General Population

Long-term – oral, systemic effects (based on a sub-chronic dermal toxicity study in rats)

 

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL: 750 mg/kg bw/day

No systemic effects were observed up to the highest dose tested

Step 2) Modification of starting point

x 20/100

Correction for absorption; 20% absorption after dermal administration; 100% absorption is assumed for oral exposure.

Modified dose-descriptor

750 x 20/100 = 150 mg/kg bw/day

Step 3) Assessment factors

 

 

Interspecies

4

Assessment factor for allometric scaling. No factor for remaining uncertainties is applied as no effects were observed up to the highest dose tested.

Intraspecies

10

Default assessment factor

Exposure duration

2

Extrapolation to chronic exposure based on a sub-chronic toxicity study

Dose response

1

 

Quality of database

1

 

DNEL

Value

 

150 / (4 x 10 x 2 x 1 x 1) = 1.9 mg/kg bw/day

 

 

Long-term – inhalation, systemic effects (based on a sub-chronic dermal toxicity study in rats)

 

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL: 750 mg/kg bw/day

No systemic effects were observed up to the highest dose tested

Step 2) Modification of starting point

: 1.15

 

 

 

x 20/100

An 24 h respiratory volume of 1.15 m3/kg bw for ratswas used for conversion into NOAEL upon inhalation exposure.

 

Correction for absorption: 20% absorption after dermal administration; 100% absorption is assumed for inhalation.

Modified dose-descriptor

750 x 20 / (1.15 x 100) = 130 mg/m3

Step 3) Assessment factors

 

 

Interspecies

1

No allometric scaling has to be applied in case of dermal to inhalation route to route extrapolation. Furthermore, no factor for remaining uncertainties is applied as no effects were observed up to the highest dose tested.

Intraspecies

10

Default assessment factor

Exposure duration

2

Extrapolation to chronic exposure based on a sub-chronic toxicity study

Dose response

1

 

Quality of database

1

 

DNEL

Value

 

130 / (1 x 10 x 2 x 1 x 1) = 6.5 mg/m3

 

 

Long-term – dermal, systemic effects(based on a sub-chronic dermal toxicity study in rats)

 

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL: 750 mg/kg bw/day

No systemic effects were observed up to the highest dose tested

Step 2) Modification of starting point

-

-

Step 3) Assessment factors

 

 

Interspecies

4

Assessment factor for allometric scaling. No factor for remaining uncertainties is applied as no effects were observed up to the highest dose tested.

Intraspecies

10

Default assessment factor

Exposure duration

2

Extrapolation to chronic exposure based on a sub-chronic toxicity study

Dose response

1

 

Quality of database

1

 

DNEL

Value

 

750 / (4 x 10 x 2 x 1 x 1) = 9.4 mg/kg bw/day