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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:
9.7 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
18
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
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
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
14 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
72
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

Local effects

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

Workers - Hazard for the eyes

Additional information - workers

Quaternary ammonium compound, di-C16 -18 -alkyldimethyl, chlorides are dialkyldimethylammonium chlorides and belong to the group of the quaternary ammonium compounds for which a common toxicological profile can be expected based on structure-activity relationships. On that background, read-across to structural closely related dialkyldimethylammonium chlorids is scientifically justified and is included in the assessment where appropriate.

For the delineation of DNELs the following exposure patterns are considered:

On account of the physico-chemical properties (ionic substance, vapour pressure) of quaternary ammonium compound, di-C16 -18 -alkyldimethyl, chloride, inhalative exposure to vapours is assumed to be negligible but exposure to dusts at the workplace during the handling of the powdery substance must be taken into consideration. Taking into account the corrosive effect of the paste-like preparation (ie the primary product), it is expected that repeated daily dermal contact is avoided. However, dermal exposure is to be considered when the powdered substance or diluted preparations are handled.

Based hereupon, the following critical DNELs with regard to quaternary ammonium compound, di-C16 -18 -alkyldimethyl, chloride have been identified:

·   DNEL long-term,dermal, systemic

·   DNEL long-term, inhalation, systemic

Long-term exposure - systemic toxicity

2 .1- Dermal DNEL

Identified key study for DNEL derivation is the 28-day oral toxicity study in rats (Hoechst, 1990) which results in a NOAEL of 100 mg/kg body weight per day. Route to route extrapolation must therefore be applied.

Step 1) Relevant dose-descriptor:          

* NOAELoral,systemicrat = 100 mg/kg bw/d

Step 2)Modification of starting point:

* Absorption by dermal route in experimental animals and human

Experimental in vivo study in rabbits and in vitro data on human skin have revealed that the dermal absorption was very low. An increase of the concentration in the skin following dermal application was also not observed. These experimental findings are supported by the physico-chemical

properties of the substance being poorly soluble in water and having a molecular weight of about 580 g/mol, usually only substance with lower molecular weight are absorbed. Therefore, the default factor of 10% skin absorption is used and no correction factor for differences in absorption between animals and human is applied

Correcteddermal, systemicNOAEL = 1000 mg/kg bw/d

Step 3) Assessment factors:

* Interspecies : 4 (Allometric scaling from rat to human)

* Intraspecies : 3 Analysis of various data sets have revealed that for workers a factor of 3 is sufficient for covering any intraspecies variability (ECETOC, 2010)

* Exposure duration: 6 (extrapolation from a subacute exposure to a chronic exposure)

* Dose response : 1 (the starting point for DNEL calculation is a NOAEL)

* Quality of database: 1 (there is no reason to assume a special concern)

DNEL Value based on theCorrecteddermal, systemicNOAEL = 1000 mg/kg bw/d:

= 1000 /(4 x 3 x 6 x 1 x 1) = 14 mg/kg bw/ day

2.2 - Inhalation DNEL

Identified key study for DNEL derivation is the 28-day oral toxicity study in rats (Hoechst 1990) which results in a NOAEL of 100 mg/kg body weight per day. Route to route extrapolation must therefore be applied.

Step 1) Relevant dose-descriptor:          

* NOAELoral,systemicrat = 100 mg/kg bw/d

Step 2)Modification of starting point:

* Correction for differences in absorption between oral and inhalation routes

Due to the low vapour pressure , the potential for generating vapour and thus the risk of inhaling the substance is minimal. In the event that aerosols or particulates are inhaled, the pulmonary physiology and clearance dynamics would largely favour the oral absorption rather than the inhalation. Therefore, based on the physico-chemical properties of fatty nitriles and their derivatives, the default factor of 2 in case of oral to inhalation extrapolation seems unjustified and is reduced to 1. This approach is in line with the conclusions of the EU RAR on DODMAC (final report 2002).

* Correction for respiratory volume between rat and human : 1/ 0.38 m3 /kg bw

* Correction for activity driven differences of respiratory volumes in workers compared to workers in rest: 6.7 m3/10 m3

Correctedinhalation, systemicNOAEL = 100 x 1.76 = 176 mg/m3

Step 3) Assessment factors:

* Interspecies: 1 No correction is made for differences in body size, because extrapolation is based on toxicological equivalence of a concentration of a chemical in the air of experimental animals and humans. Animals and humans breathe at a rate depending on their caloric requirements and this was already taken into account into step 2.The default factor for "remaining differences" is not considered scientifically justified. Analysis of various data sets have revealed that for workers a factor of 3 may be appropriate and that potential residual interspecies differences is largely accounted for already in the assessment factor for intraspecies variability (ECETOC 2010).

* Intraspecies : 3 (ECETOC 2010, see the above mentioned justification)

* Exposure duration: 6 (extrapolation from a subacute exposure to a chronic exposure)

* Dose response : 1 (the starting point for DNEL calculation is a NOAEL)

* Quality of database: 1 (there is no reason to assume a special concern)

DNEL Valuebased on theCorrectedinhalation, systemicNOAEL = 176 mg/m3

= 176 /(3 x 6 x 1x 1) = 9.8 mg/m3

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
exposure based waiving
Acute/short term exposure
Hazard assessment conclusion:
exposure based waiving
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
exposure based waiving
Acute/short term exposure
Hazard assessment conclusion:
exposure based waiving
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
DNEL related information

Local effects

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

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.83 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
120
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
exposure based waiving
DNEL related information

General Population - Hazard for the eyes

Additional information - General Population

For the delineation of DNELs the following exposure patterns are considered:

 

Oral DNEL (general population via the environment):

Identified key study for DNEL derivation is a 28-day oral toxicity study in rats (Hoechst, 1990) which results in a NOAEL of 100 mg/kg body weight per day. Route to route extrapolation must therefore be not applied.

 

Step 1) Relevant dose-descriptor:           * NOAELoral,systemicrat = 100 mg/kg bw/d

Step 2) Modification of starting point:

 

No correction necessary. DNEL is based on an oral toxicity study.

 

Correctedoral, systemicNOAEL = 100 mg/kg bw/d

 

Step 3) Assessment factors:

* Interspecies : 4(Allometric scaling from rat to human)

* Intraspecies : 5 Analysis of various data sets have revealed that for general population a factor of 5 is sufficient for covering any intraspecies variability (ECETOC, 2010)

* Exposure duration: 6 (extrapolation from a subacute exposure to a chronic exposure)

* Dose response : 1 (the starting point for DNEL calculation is a NOAEL)

* Quality of database: 1 (there is no reason to assume a special concern)

 

DNEL Value based on the Correctedoral systemicNOAEL = 100 mg/kg bw/d:

 

= 100 /(4 x 5 x 6 x 1 x 1) = 0.833 mg/kg bw/ day