Registration Dossier

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
13.5 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
6
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
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:
9.6 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
24
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

N-C16-C18(even numbered), C18 insaturated-alkyl-N,N-dimethyl-C16-C18(even numbered), C18 insaturated-alkyl-1-aminium chloride (common name: Quaternary ammonium compounds, dimethylditallow alkyl chlorides, DTDMAC ) ) is a dialkyldimethylammonium chloride and belongs 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. DTDMAC share structural similarities, essential chemical key aspects and almost certainly the same mode of action with N-decyl-N,N-dimethyldecan-1 -aminium chloride (EC name: Didecyldimethylammonium chloride, DDAC, CAS No. 7173 -51 -5), N-octadecyl-N,N-dimethyl-1 -octadecanaminium chloride (EC name: Dioctadecyldimethylammonium chloride, DODMAC, CAS No. 107 -64 -2), and N,N-dimethyl-N,N-di-n-alkyl(C16 -18)-ammonium chloride (EC name: Dihydrogenated tallowalkyl dimethylammonium chloride, DHTDMAC, CAS No. 61789 -80 -8) so that it is scientifically appropriate to use data from these quaternary ammonium compounds for cross-reading to DTDMAC.

Dialkyldimethylammonium chlorides in general show the same chemical structure, with an ionic positively charged part and apolar fatty acid chains. The anionic part, generally chloride, is of no toxicological significance. The primary effect of dialkylquaternaries involves disruption of the cytoplasmic membrane causing cell damage. Their toxicity is related to the same mode of action: toxicity is related to concentration dependent cytotoxicity, with a lack of specific toxicity. The potency shows a dependence on chain length with an optimum at C10 representing by didecyldimethylammonium chloride. While having longer alkyl chains, DTDMAC has also unsaturated alkyl groups that contribute to its biological reactivity. That is why read-across is performed with DDAC which due to a shorter chain-length represents the worst-case scenario. On the other hand, to consider also comparable chain-length distributions, DODMAC and DHTDMAC are included in the read-across approach as well.

For the delineation of DNELs the following exposure patterns are considered: Since consumer uses for ditallowalkyldimethylammonium chloride neither exist nor is supported, the only exposed population considered are workers which are expected to have infrequent and short-term exposures. However, for DNEL calculation chronic exposure conditions were assumed as worst-case scenario.

Based hereupon, the following critical DNELs with regard to N-C16-C18(even numbered), C18 insaturated-alkyl-N,N-dimethyl -C16-C18(even numbered), C18 insaturated-alkyl-1-aminium chloride (common name: Quaternary ammonium compounds, dimethylditallow alkyl chlorides) have been identified:

·   DNEL long-term,dermal, systemic

·   DNEL long-term, inhalation, systemic

Long-term exposure - systemic toxicity (worker)

Dermal DNEL (worker)

Identified key study for DNEL derivation is a 90-day oral toxicity study in rats with the structural analogue didecyldimethylammonium chloride which results in a NOAEL of 46 mg/kg body weight per day in rats. Route to route extrapolation must therefore be applied. However, a modification of the NOAEL into an adequate starting point has to be performed to gain meaningful results.

Step 1) Relevant dose-descriptor:          

* NOAEL oral,systemic rat = 46 mg/kg bw/d

Step 2) Modification of starting point:

* Correction for differences in absorption between oral and dermal routes

For convertion into an adequate starting point an oral absorption rate of 5% (rat) and a dermal absorption rate of 1.0% (rat = human) is applied.

* Correction for dermal absorption difference between rabbits and human:

No difference in dermal absorption is expected between rats and humans,no correction factor will be applied.

Corrected dermal, systemic NOAEL = 230 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: 2 (extrapolation from a subchronic 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 Correcteddermal, systemicNOAEL = 230 mg/kg bw/d:

= 230 / (4 x 3 x 2 x 1 x 1) = 9.6 mg/kg bw/ day

Inhalation DNEL (worker)

Identified key study for DNEL derivation is a 90-day oral toxicity study in rats with the structural analogue didecyldimethylammonium chloride which results in a NOAEL of 46 mg/kg body weight per day. Route to route extrapolation must therefore be applied.

Step 1) Relevant dose-descriptor:          

* NOAELoral,systemicrat = 46 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 unlikely 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.

* 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 = 46 x 1.76 = 81 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: 2 (extrapolation from a subchronic 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 Correctedinhalation, systemicNOAEL = 81 mg/m3

= 81 / (3 x 2 x 1x 1) = 13.5 mg/m3

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.15 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
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected

Additional information - General Population

N-C16-C18(even numbered, C18 unsaturated)-alkyl-N,N-dimethyl-C16-C18(even numbered, C18 unsaturated)-alkyl-1-aminium chloride (common name: Quaternary ammonium compounds, dimethylditallow alkyl chlorides, DTDMAC )) is not used in the consumer sector. DNEL derivations for the general population are therefore not necessary and not required. However, although no consumer uses will be supported, an oral DNEL long-term (systemic) was derived to consider indirect exposures via the environment. For the derivation the following assessment factors were applied: Route-to-Route: AF = 1; Interspecies extrapolation: AF = 4 (allometric scaling rat to humans); Remaining differences = 1 (included in variability assessment); Intraspecies variability: AF = 5 (ECETOC 2010); Exposure duration: AF = 2 (reduced from 6 (subchronic to chronic) because effects mainly concentration but not dose driven); Dose-Response: AF = 1 (no conspicuous behaviour); Quality of database: AF=1 (judged sufficient for evaluation).

Long-term systemic toxicity (consumer exposure through the environment)

Orall DNEL (consumer)

Identified key study for DNEL derivation is a 90-day oral toxicity study in rats with the structural analogue didecyldimethylammonium chloride which results in a NOAEL of 46 mg/kg body weight per day. Route to route extrapolation must therefore not be applied.

Step 1) Relevant dose-descriptor:          

* NOAELoral, systemicrat = 46 mg/kg bw/d

Step 2) Modification of starting point:

No difference in oral absorption is expected between rats and humans, no correction factor will be applied.

Correctedoral, systemicNOAEL = 46 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 consumers a factor of 5 is sufficient for covering any intraspecies variability; ECETOC, 2010)

* Exposure duration: 2 (extrapolation from a subchronic 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 the correctedoral, systemicNOAEL = 46 mg/kg bw/d:

= 46 / (4 x 5 x 2 x 1 x 1) = 1.15 mg/kg bw/ day