Reaction mass of benzyldodecylbis(2-hydroxypropyl)ammonium chloride and benzylbis(2-hydroxypropyl)tetradecylammonium chloride

Endpoint summary

Description of key information

Katalysator WAZ 5596-B contains the following substances in the concentration range specified in section 1.2:
quaternary propoxylated fatty amine, propoxylated fatty amine, hydrochloride propoxylated fatty amine, propane-1,2-diol, alpha-chlorotoluene, water

Additional information

Katalysator WAZ 5596-B

Information/Assumptions regarding Toxicokinetics

Katalysator WAZ 5596 contains the substances specified in section 1.2.

Katalysator WAZ 5596-B is a yellowish-brown liquid with a characteristic odor. The pH-value of a 10% (w/w) solution in water is in the range of 5 to 6. A vapor pressure of 103 hPa at 50°C was determined. The water solubility of Katalysator WAZ 5596-B was experimental determined. Results of the tests show, that the test item Katalysator WAZ 5596-B is soluble in demineralized water in each ratio to clear homogenous solutions. The logPow values of the compounds of Katalysator WAZ 5596-B are in the range between -0.92 and 4.73. The logPow of the main component accounts for 2.22 (quaternary propoxylated fatty amine).

In an acute oral toxicity study an oral LD50 = 1457 mg/kg bw for male and female rats was determined for Katalysator WAZ 5596-B. The LC50 was 280 mg/m³ in an acute inhalation toxicity study with Katalysator WAZ 5596-B in male and female rats.

In an Ames test and a HPRT test, Katalysator WAZ 5596 B was negative, with and without metabolic activation (S-9 mix).

The compounds of Katalysator WAZ 5596-B belong to different chemical classes and therefore the toxicological profile and toxicokinetic behaviour of the compounds of Katalysator WAZ 5596-B have to be regarded separately for each compound or group of compounds (amines).

Due to the ionic character of quarternary propoxylated fatty amine a penetration of these compounds through biological membranes (skin and and stomach) is limited. Thus, upon dermal contact or ingestion, the bioavailability is expected to be low. Due to its low vapour pressure, quarternary propoxylated fatty amine and the hydrochloride propoxylated fatty amine are assumed to be inhaled only as aerosols, and excreted by the nasal and bronchiolar mucosa due to their high water solubility.

Therefore a low toxicity and a low bioaccumulation potential can be assumed for the (quaternary) amine compounds due to the ionic character and the high water solubility of these compounds.

As the substances are highly water-soluble, metabolising is not necessary to achieve water-soluble / excretable metabolites and therefore the formation of more reactive (toxic) products is not likely. Based on molecular weight and water solubility, the substances are most likely excreted via the kidneys in the urine.

For alpha-chlorotoluene an oral LD50 of 1230 mg/kg bw and a LC50 of 740 mg/m³ (2 h exposure) were found

A numerical modeling for alpha-chlorotoluene indicated no relevant dermal resorption (MAK, 39. Supplement, 2004). Kinetic experiments with 14C-alpha-chlorotoluene applied per gavage to rats, revealed a nearly complete intestinale resporption. After 24 hours 65-75% of the applied substance was detected in the urine. In a study with monkeys the greater part of the radioactivity was also in the urine after 24 hours.

For both species benzylmercapturic acid was the main metabolite in the urine. Other important metabolites are hippuric acid and benzylcysteine.

The intramuscular application of 200 mg/kg bw alpha-chlorotoluene indicated an elimination of the substance from plasma with a first-order half-life time of 20 minutes and a second-order half-life time of 30 hours.

An application per gavage of 14C-alpha-chlorotoluene in rats indicated a half-life time for elimination (first-order) of 58.53 hours. Within 72 hours 76 % of the applicated substance was found in the urine, about 7% were detected in the respiratory air. As metabolites benzylmercapturic acid, benzylalcohol and benzaldehyde were found in the urine.

The chemical is toxic in a repeated dose study (i.e. stomach, heart, liver) and carcinogenic in rats (thyroid) and mice (liver, stomach, lung). Genotoxicity of the chemical seems weakly positive. The chemical is also considered as an irritant to skin, eyes and respiratory system. The chemical is considered as a possible carcinogen although there is no clear evidence in human (OECD SIDS for alpha-chlorotoluene).

Propylene glycol (PG) is not acutely toxic. The lowest oral LD50 values range between 18 and 23.9 grams (5 different species) and the reported dermal LD50 is 20.8 grams. Repeated exposures of rats to propylene glycol in drinking water or feed did not result in adverse effects at levels up to 10% in water (estimated at about 10 g/kg bw/day) or 5% in feed (dosage reported as 2.5 g/kg bw/day) for periods up to 2 years.

Propylene glycol did not cause fetal or developmental toxicity in rats, mice, rabbits, or hamsters (NOAELs range from 1.2 to 1.6 g/kg bw/day in four species). No reproductive effects were found when propylene glycol was administered at up to 5% in the drinking water (reported as 10.1 g/kg bw/day) of mice. No increase in tumors was found in all tissues examined when propylene glycol was administered in the diet of rats (2.5 g/kg bw/day for 2 years), or applied to the skin of female rats (100% PG; total dose not reported; 14 months) or mice (mouse dose estimated at about 2 g/kg bw/week; lifetime). These data support a lack of carcinogenicity for PG (OECD SIDS for benzylchloride).

Absorption of orally administered propylene glycol from the gastrointestinal tract, and its

removal from the body, follow first order kinetics. Clearance from blood is rapid in humans, with a mean half- life of approx. 2 hr. Its metabolism is inhibited by pyrazole, indicating a role for alcohol dehydrogenase in this process. Once absorbed it is readily converted into lactic and pyruvic acids, which then enter the general metabolic pool (OECD SIDS for benzylchloride).

Overall, from the available data, alpha-chlorotoluene seems be the compound which determines the toxicity of Katalysator WAZ 5596-B. Due to its lipophilic character it is absorbed through biologic membranes. Most of the absorbed substance is excreted in the urine within a few days.

For the other compounds a low bioavailability is expected due to their ionic character and a fast excretion is expected due to their high water solubility if any absorption occurs.