Quaternary ammonium compounds, N-(C16-18 and C18-unsatd. alkyl)-N,N,N',N',N'-pentamethyltrimethylenedi-, dichlorides

Endpoint summary

Description of key information

Key information:

Due to lack of quantitative data, absorption rates of 100% are indicated for all three routes in order to express that there is no difference of absorption expected between the different routes of exposure. Especially for dermal exposures this represents a very conservative approach. Available studies do not indicate a concern for bioaccumulation.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

100

Absorption rate - dermal (%):

100

Absorption rate - inhalation (%):

100

Additional information

Diamine quaternised C16-18, C18 unsaturated (CAS 1211950-04-7, N,N,N',N',N'-Pentamethyl-N-C16-18(even numbered)C18 unsatured-alkyl-1,3 propanediammonium chloride). Also identified with CAS 68607-29-4,N,N,N',N'.N''-Pentamethyl-N-tallowalkyl-1,3-propanediammonium chloride.

 

There are no available studies on the toxicokinetics of N,N,N',N',N'-Pentamethyl-N-C16-18(even numbered)C18 unsatured-alkyl-1,3 propanediammonium chloride, i.e. (Diamine quaternised C16-18, C18 unsaturated). The toxicokinetic parameters were therefore derived based on a read-across approach from other quaternary amines, didecyldimethylammonium chloride (DDAC, CAS: 7173-51-5), and C12-16-alkyldimethylbenzylammonium chloride (BKC, CAS: 68424-85-1. These substances share common structural features, most importantly the carbon chain (C12-C18) and a nitrogen group with varying degrees of substitution. The charge of the N atom is dependent on the degree of substitution and is expected to potentially impact the toxicokinetics of these substances. Further justification for read-across approach is included in the discussion below.

 

Absorption

These substances are absorbed from the GI tract to a relatively low degree. A study performed according to OECD 417 with DDAC indicated absorption of less than 5%, while a study performed with a diamine, CAS: 68603-64-5, also indicated a very low level of absorption. Absorption from the GI tract is dependent on many variables. However, the quaternary diamine is expected to follow similar uptake as indicated above as the carbon chain will most likely be the determining factor in uptake. As this substance has a +2 charge (the highest of these substances), transport across biological membranes is most likely further reduced which again would reduce oral absorption and bioavailability.

However, based on lack of quantitative data, and for comparative analysis for absorption over different routes, the oral absorption is set at 100%.

 

At this stage no data are available on dermal absorption. Itis not expected to easily pass the skin in view of its ionised form at physiological conditions.Based on the severe corrosive properties, dermal absorption as a consequence of facilitated penetration through damaged skin can be anticipated.

Although dermal absorption is not expected at any considerable rate, also the absorption via dermal out is set at 100% as conservative approach.

 

Also for inhalationno data are available on absorption, and100% is proposed as worst case. With a very low vapour pressure, the potential for inhalation is limited. Relevant (in view of possible systemic absorption) exposures are only possible as aerosol. If any inhalation from aerosols does occur, this can only be in the form of larger droplets, as the use does not include fine spraying. Droplets will deposit mainly on upper airways, and will be subsequently swallowed following mucociliary transportation to pharynx. This results to no principal difference in absorption compared oral route.

Absorption via respiratory route is therefore also set at 100%.

 

Distribution

Neither of these substances are well distributed in tissues. The diamine, CAS: 68603-64-5, and DDAC were identified primarily associated with the intestinal mucosa. This was confirmed with BKC. Quantifiable levels were identified in some tissues, but generally at very low concentrations and not of toxicologically relevant concentrations. These observations suggest that the degree of substitution of the N-atom, and the corresponding charge, in itself is most likely not a determining factor in distribution. Accordingly, it is justified to conclude that the quaternary diamine would follow a similar distribution pattern.

 

Excretion

Data on DDAC and BKC indicate that excretion is rapid and primarily in the faeces and with a minor contribution from urine. Both substances were generally eliminated within 48-72 hours. Accordingly, the bioaccumulation potential in mammals is considered to be low. No data is available on the diamine, CAS: 68603-64-5.

 

Metabolism

The only available information on metabolism comes from studies on DDAC. The majority of this substance underwent oxidation in a process similar to beta-oxidation of fatty acids. Less than 20% of radioactivity was eliminated as parent compound. It is believed that oxidation occurs via an initial hydroxylation of the carbon adjacent to the terminal carbon, which is then followed by formation of a hydroxyketone. All metabolites were more soluble and presumed to be of less toxicity than the parent compound. A small percentage also underwent conjugation to either the glucuronide or the sulphate. This will also enhance solubility. The most likely metabolic pathway of the quaternary diamine is a partial oxidation of the carbon chain similar as to for DDAC.

 

Overall, these substances demonstrate a relatively similar toxicokinetic profile with low oral absorption, low tissue distribution, oxidative metabolism of the carbon chain, and primarily faecal excretion. Furthermore, there does not seem to be a significant impact of the positively charged N-atom on these parameters. In conclusion, the structural similarity of the quaternary diamine to DDAC, BKC and the diamines, and the similar toxicokinetic parameters seen within toxicokinetic studies of these substances, suggests that a read-across is appropriate.