Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
166.67 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
6
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:
23.81 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
8.4
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

Only long term exposure values for worker and general population were calculated, because no concrete values (like NOAEL, LOAEL etc) are available from acute or irritation studies. The study design of the test conducted assessing the acute and local toxicity of N,N-dimethyldecanamiddoes not allow in general the derivation of local or acute DNEL, as most of the test were, for example, conducted as limit tests due to animal welfare. In some cases the result of an acute test allows to derive local or acute thresholds. If this is the case the values were entered otherwise this justification is to apply.

For long term effects a valid repeated dose animal studies is available to derive DNEL values.

In a 90-day gavage study (Bayer 2000, J. Ruf) beagle dogs were treated once daily with mixture of N,N-dimethyldecanamide and N,N-dimethyloctanamide.

To the applicant a NOEL at 40 mg/kg bw/d (0.4%) reported in this study is based on local effects caused by oral application of the test substance at irritating concentrations (≥2%). At 200 mg/kg bw/d clinical chemistry revealed only slightly increased liver findings (weight increase, N-DEM and CYP-450 increase) but this should not be regarded as adverse effects but as increased metabolic activity of the organ (adaptive response). Therefore the NOAEL is established at 200 mg/kg bw/d.

The 90-day dog study is considered the most appropriate study for a DNEL derivation as dogs were found to be the most sensitive species based on clinical findings at 500 mg/kg bw/d.

Therefore the following values were used to derive DNELs: Dog subchronic (13 weeks; gavage; mixture of N,N-dimethyldecanamide and N,N-dimethyloctanamide) NOAEL (systemic) = 200mg/kg bw/d; NOEL (local) = 40mg/kg bw/d

As local dermal or inhalation effects can not be evaluated from local oral effects the DNEL values for local effects were not derived.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
50 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
10
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:
14.29 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
14
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:
14.29 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
14
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Most sensitive endpoint:
repeated dose toxicity
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population

Only long term exposure values for worker and general population were calculated, because no concrete values (like NOAEL, LOAEL etc) are available from acute or irritation studies. The study design of the test conducted assessing the acute and local toxicity of N,N-dimethyldecanamid does not allow in general the derivation of local or acute DNEL, as most of the test were, for example, conducted as limit tests due to animal welfare. In some cases the result of an acute test allows to derive local or acute thresholds. If this is the case the values were entered otherwise this justification is to apply.

For long term effects a valid repeated dose animal studies is available to derive DNEL values.

In a 90-day gavage study (Bayer 2000, J. Ruf) beagle dogs were treated once daily with mixture of N,N-dimethyldecanamide and N,N-dimethyloctanamide.

To the applicant a NOEL at 40 mg/kg bw/d (0.4%) reported in this study is based on local effects caused by oral application of the test substance at irritating concentrations (≥2%). At 200 mg/kg bw/d clinical chemistry revealed only slightly increased liver findings (weight increase, N-DEM and CYP-450 increase) but this should not be regarded as adverse effects but as increased metabolic activity of the organ (adaptive response). Therefore the NOAEL is established at 200 mg/kg bw/d.

The 90-day dog study is considered the most appropriate study for a DNEL derivation as dogs were found to be the most sensitive species based on clinical findings at 500 mg/kg bw/d.

Therefore the following values were used to derive DNELs: Dog subchronic (13 weeks; gavage; mixture of N,N-dimethyldecanamide and N,N-dimethyloctanamide) NOAEL (systemic) = 200mg/kg bw/d; NOEL (local) = 40mg/kg bw/d

As local dermal or inhalation effects can not be evaluated from local oral effects the DNEL values for local effects were not derived.