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
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECETOC technical report
Overall assessment factor (AF):
6
Dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
1 000 mg/m³
Explanation for the modification of the dose descriptor starting point:
Starting point correction NOAEL oral -> NOAEC human (8h worker): NOAEC human (8h worker) = oral NOAEL dog 200 / sRVdog (AS) 1.4 x bw human 70 / 8h Volume 10 =1000mg / m3 / 24h
AF for dose response relationship:
1
Justification:
AF according to ECETOC report
AF for differences in duration of exposure:
2
Justification:
Exposure duration (sub chronic to chronic) 2 AF according to ECETOC report
AF for interspecies differences (allometric scaling):
1
Justification:
Already in starting point correction
AF for other interspecies differences:
3
Justification:
Interspecies (worker) 3 AF according to ECETOC report
AF for intraspecies differences:
1
Justification:
AF according to ECETOC report
AF for the quality of the whole database:
1
Justification:
AF according to ECETOC report
AF for remaining uncertainties:
1
Justification:
AF according to ECETOC report
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
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:
23.81 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECETOC technical report
Overall assessment factor (AF):
8.4
Dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
worst case assumption (not necessary correct) NOAEL oral -> NOAEL dermal = NOAEL oral x 1(Echa assumption)
AF for dose response relationship:
1
Justification:
AF according to ECETOC report
AF for differences in duration of exposure:
2
Justification:
Exposure duration (sub chronic to chronic) 2
AF for interspecies differences (allometric scaling):
1.4
Justification:
Interspecies (AS, dog) 1.4
AF for other interspecies differences:
3
Justification:
Interspecies (worker) 3 AF according to ECETOC report
AF for intraspecies differences:
1
Justification:
AF according to ECETOC report
AF for the quality of the whole database:
1
Justification:
AF according to ECETOC report
AF for remaining uncertainties:
1
Justification:
AF according to ECETOC report
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
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

There are no reliable data available for the repeated dose toxicity of N,N-Dimethyldecan-amide (CAS 14422 -76 -2). In order to fulfil the standard information requirements set out in Annex VIII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, read-across from structurally related substances was conducted. A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).

For systemic long term effects a valid repeated dose animal studies conducted with the analogue "Mixture of dimethylamides (CAS 67359-57-3)" is

available to derive DNEL values.

In this 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

Only systemic 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-dimethylalkylamides 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. Therefore qualitative Riskassessment for irritiation is performed:

QUALITATIVE CSA - SKIN IRRITATION AND EYE DAMAGE

(acute/long term exposure – local effects)

 

Worker

The available data for this effect do not provide quantitative dose-response information; thus, no

short-term local DNELs have been derived for dermal exposure and no quantitative risk assessment

was performed. Exposure assessment and risk characterization are performed on a qualitative basis.

The purpose of a qualitative risk characterization is to assess "the likelihood that effects are avoided

when implementing the exposure scenario…" (REACH Annex 1, Section 6.5) when there is no basis

for setting a DNEL/DMEL.

Implementation of risk management measures (RMMs) and operational conditions (OCs) need to be

proportional to the degree of concern for the health hazard presented by the substance. Therefore the

substance is categorized by the hazard according to ECHA Guidance on information requirements and

chemical safety assessment, Part E; November 2012.

Skin irritation Cat 2 as well as eye irritationCat 2 and STOT-Single Exposure Cat 3 (respiratory irritation)

are considered a low hazard therefore the substance is categorized to the low hazard group.

RMM should be appropriate for hazard class and operational condition.Therefore a code of behavior

is communicated via the Safety Data Sheet (SDS) containing precaution statements and response

phrases and general handling instructions.

The communicated hazard and the recommended general behavior and RMM are:

H315: Causes skin irritation, H319: Causes serious eye irritation

and

P262: Do not get in eyes, on skin, or on clothing, P280: Wear protective gloves/protective clothing/eye

protection/face protection., P303+P361+P353: IF ON SKIN (or hair): Remove/Take off immediately

all contaminated clothing. Rinse skin with water/shower.

P305+P351+P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact

lenses, if present and easy to do. Continue rinsing.

A review of this information on RMM and behavior advice given with the product indicates that, if the

user complies to the advice, the risk of exposure to skin and eye for worker and professional user can

be considered as adequately controlled.

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
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECETOC technical report
Overall assessment factor (AF):
10
Dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
500 mg/m³
Explanation for the modification of the dose descriptor starting point:
Starting point correction NOAEL oral -> NOAEC human (24h): NOAEC human (24h) = oral NOAEL dog 200 / sRVdog (AS) 1.4 x bw human 70 / 24h Volume 20 = 500mg / m3 / 24h
AF for dose response relationship:
1
Justification:
AF according to ECETOC report
AF for differences in duration of exposure:
2
Justification:
Exposure duration (sub chronic to chronic) 2
AF for interspecies differences (allometric scaling):
1
Justification:
Interspecies (AS, dog) (already in starting point mod.)
AF for other interspecies differences:
5
Justification:
Interspecies (general pop) 5
AF for intraspecies differences:
1
Justification:
AF according to ECETOC report
AF for the quality of the whole database:
1
Justification:
AF according to ECETOC report
AF for remaining uncertainties:
1
Justification:
AF according to ECETOC report
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
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:
14.29 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECETOC technical report
Overall assessment factor (AF):
14
Dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
worst case assumption (not necessary correct) NOAEL oral -> NOAEL dermal = NOAEL oral x 1(Echa assumption)
AF for dose response relationship:
1
Justification:
AF according to ECETOC report
AF for differences in duration of exposure:
2
Justification:
Exposure duration (sub chronic to chronic) 2
AF for interspecies differences (allometric scaling):
1.4
Justification:
Interspecies (AS, dog) 1.4
AF for other interspecies differences:
5
Justification:
x Interspecies (general pop) 5 AF according to ECETOC report
AF for intraspecies differences:
1
Justification:
AF according to ECETOC report
AF for the quality of the whole database:
1
Justification:
AF according to ECETOC report
AF for remaining uncertainties:
1
Justification:
AF according to ECETOC report
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
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:
14.29 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECETOC technical report
Overall assessment factor (AF):
14
Dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
no starting point correction
AF for dose response relationship:
1
Justification:
AF according to ECETOC report
AF for differences in duration of exposure:
2
Justification:
Exposure duration (sub chronic to chronic) 2
AF for interspecies differences (allometric scaling):
1.4
Justification:
Interspecies (AS, dog) 1.4
AF for other interspecies differences:
5
Justification:
Interspecies (general pop) 5
AF for intraspecies differences:
1
Justification:
AF according to ECETOC report
AF for the quality of the whole database:
1
Justification:
AF according to ECETOC report
AF for remaining uncertainties:
1
Justification:
AF according to ECETOC report
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

There are no reliable data available for the repeated dose toxicity of N,N-Dimethyldecan-amide (CAS 14433 -76 -2). In order to fulfil the standard information requirements set out in Annex VIII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, read-across from structurally related substances was conducted.A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).

For systemic long term effects a valid repeated dose animal studies conducted with the analogue "Mixture of dimethylamides (CAS 67359-57-3)" is

available to derive DNEL values.

In this 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.

Only systemic 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-dimethylalkylamid 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. Therefore qualitative Riskassessment for irritiation is performed:

QUALITATIVE CSA - SKIN IRRITATION AND EYE DAMAGE

(acute/long term exposure – local effects)

General population

The available data for this effect do not provide quantitative dose-response information; thus, no

short-term local DNELs have been derived for dermal exposure and no quantitative risk assessment

was performed. Exposure assessment and risk characterization are performed on a qualitative basis.

The purpose of a qualitative risk characterization is to assess "the likelihood that effects are avoided

when implementing the exposure scenario…" (REACH Annex 1, Section 6.5) when there is no basis

for setting a DNEL/DMEL.

The general population will not come into contact with the neat substances. For the substance in a

product/preparation the hazard may be decrease/lower due to lower concentration in the mixture.

Additional the consumer receives a general advice how to handle the product (for example: handle

only in well ventilated rooms, rinse skin with water / wash hands after contact etc.). Furthermore the

stricter handling conditions driven by the active substance in pesticide forces the user the take more

care than needed for the coformulant.

Unintended exposure to consumer may be happed for example by spray drift. In this scenario a further

dilution happens, this is quantitatively assessed in a ECPA scenario.

Additionally modern methods of pesticide application are designed to minimize spray. Therefore the

exposure of the consumer to the neat substance is very limited.

Thus, the irritating potential of substance in products for consumer are assumed to sufficiently

controlled, via a variety of risk management measures and based on available data, if the consumer /

professional users follows the advice given.