Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
124.4 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
25
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:
176.4 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

Workers - Hazard for the eyes

Additional information - workers

Since the group concept is applied to the members of the SCAE Me category, data will be generated from a representative category member to avoid unnecessary animal testing.

The long-term systemic DNELs for workers are based on a subchronic 45 day oral gavage study performed on Methyl laurate (CAS No.): 111-82-0, in which the oral 45 day NOAEL for rat (male) was found to be 1000 mg/kg bw/day.

45-day oral NOAEL for Fatty acids, C16-18, Me esters (CAS No. 85586-21-6): A conversion factor on molar basis of 1.26 was used.

Smallest MW of Fatty acids, C16-18, Me esters: 270.5;

MW Methyl laurate (dodecanoic acid, methyl ester): 214.35 Conversion factor: 270.5/ 214.35 = 1.26. This refers to a 45-day oral NOAELcorr for Fatty acids, C16-18, Me esters of 1260 mg/kg bw/day

 

A dermal absorption difference of 10% and a factor of 7/5 (as the substance was adminsitered 7 days/week) was used to modify the oral NOAEL to the correct starting dose descriptor NOAELcorr dermal = 17640 mg/kg bw/day.

For the dermal long term systemic worker DNEL the following AF were applied:

inter species factor 2.5, allometric scaling factor 4, intra species factor 5, exposure duration factor 2(sub-chronic to chronic); => overall AF= 100

 

For calculating inhalation DNEL for workers, the inhalatory N(L)OAEC rat needs to be corrected for the difference between respiratory rates under standards conditions and under conditions of light activity (sRVhuman verus wRV). The route to route extrapolation from oral to inhalation was conducted according to R8 guidance document leading to a NOAECcorr inhal = 3110.2 mg/m3/d.

For the inhalation long term systemic DNEL the following AF were applied:

inter species 2.5, intra species factor 5, exposure duration factor 2; => overall AF = 25

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
21.9 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
50
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:
63 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
200
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:
6.3 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
200
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

General Population - Hazard for the eyes

Additional information - General Population

Since the group concept is applied to the members of the SCAE Me category, data will be generated from a representative category member to avoid unnecessary animal testing.

The long-term systemic DNELs for workers are based on a subchronic 45 day oral gavage study performed on Methyl laurate (CAS No.): 111-82-0, in which the oral 45 day NOAEL for rat (male) was found to be 1000 mg/kg bw/day.

45-day oral NOAEL for Fatty acids, C16-18, Me esters (CAS No. 85586 -21 -6): A conversion factor on molar basis of 1.26 was used.

Smallest MW of Fatty acids, C16-18, Me esters: 270.5;

MW Methyl laurate (dodecanoic acid, methyl ester): 214.35 Conversion factor: 270.5/ 214.35 = 1.26. This refers to a 45-day oral NOAELcorr for Fatty acids, C16-18, Me esters of 1260 mg/kg bw/day

A dermal absorption difference of 10% was used to modify the oral NOAEL to the correct starting dose descriptor NOAELcorr dermal = 12600 mg/kg bw/day

For the dermal long term systemic consumer DNEL the following AF were applied:

Inter species factor 2.5, allometric scaling factor 4, intra species factor 10, exposure duration factor 2(sub-chronic to chronic); => overall AF= 200

 

For calculating inhalation DNEL for consumers, the inhalatory N(L)OAEC rat needs to be corrected. The route to route extrapolation from oral to inhalation was conducted according to R8 guidance document leading to a NOAECcorr inhal = 1095.7 mg/m3/d.

For the inhalation long term systemic DNEL the following AF were applied:

inter species 2.5, intra species factor 10, exposure duration factor 2; => overall AF = 50

 

For the oral long term systemic worker DNEL the following AF were applied:

Inter species factor 2.5, allometric scaling factor 4, intra species factor 10, exposure duration factor 2(sub-chronic to chronic); => overall AF= 200