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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Link to relevant study record(s)

Description of key information

Absorption: Expected to occur via oral route. Dermal absorption and absorption via lungs are expected to be very limited.
Distribution: The product is expected to distribute throughout the major tissues.
Metabolism: Assumed that the product is not metabolised enzymatically and transformation may occur through direct reactions with organic compounds. No evidence on metabolic transformation of tetramethylammonium was observed.
Excretion: The product is expected to be excreted mainly in the urine.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

No specific studies have been conducted for the target substance. The target substance is a reaction mixture from blending of two components, solid benzotriazole and 25 % tetramethylammonium hydroxide water solution, followed by reaction with chlorine gas. The reaction mixture contains tetramethylammonium hypochlorite (ca. 15 wt. %)and tetramethylammonium chloride (ca. 13 wt. %). The main component of this reaction mass is tetramethylammonium hypochlorite which is a strong oxidiser and is comparable to other chlorinated bleaching agents.

Based on the behaviour and the composition of the reaction mass there is a mechanistic reasoning to use read-across toxicokinetic data from sodium hypochlorite and from chlorine (see read-across justification in IUCLID section 13). The toxicological properties of Halo Salt are related to the available chlorine concentration, which describes the oxidising power of a chlorine containing solution as if all chlorine species present were available as Cl2. The available chlorine concentration in the target substance (Cl2 -%) ranges between ca. 7.7― 8.6 %.

Relative amounts of different chlorine species present in the reaction mass depends mainly on the pH. In the biological systems, characterised by pH values in the range 6-8, the most abundant chemical species are tetramethylammonium hypochlorite and tetramethylammonium chloride. If mixed with acidic solutions chlorine gas is produced. This may occur also at the low pH typical the gastric environment.

In addition to the ADME studies conducted for hypochlorite also relevant studies conducted for tetramethylammonium iodide are discussed below.

Absorption

Abdel-Rahman et al. (1983) studied the toxicokinetics of hypochlorous acid (HOCl). Three groups of 4 Sprague-Dawley rats were orally administered with different quantities of HO36Cl solution (range of specific radioactivity 1340-2190 dpm/μg36Cl): the first group of 4 non-fasted rats received 3 ml of 250 mg/l HO36Cl aqueous solution (0.75 mg per animal); the second group of 4 fasted rats received 200 mg/l HO36Cl aqueous solution (0.60 mg per animal). Blood samples were taken from animals of these two groups at different times (0- 96hr) and tissue specimen were prepared at sacrifice for 36Cl content assessment. The third group of fasted rats receiving 200 mg/l HO36Cl aqueous solution (0.60 mg per animal) was housed in metabolic cages in order to collect urine, faeces and expired air at different times for 36Cl radioactivity measurement.

36Cl is readily absorbed and found into the bloodstream: a peak of radioactivity in rat plasma occurred 2 hours after HO36Cl administration in group I (fasted rats) (7.9 μg/ml) and 4 hr after administration in group II (non-fasted rats) (10.7 μg/ml). The half-life of 36Cl in group II resulted 2-fold higher (88.5 h) than the one measured in group I (44.1 h), very likely due to the different fasting conditions of animals (Abdel-Rahman et al., 1983)

Tetramethylammonium (TMA) is readily absorbed from the gastro-intestinal tract (Anthoni, U. et al. 1989). The study indicated that nearly 100% absorption occurred within 60-90 minutes.

The target substance is used at pH 9.0 or higher, so there is no risk of Cl2 release in use conditions. Since the substance is miscible to water and used only in water solutions the evaporation of the substance from the liquid preparations is negligible and, the exposure to the substance via inhalation route is insignificant.

Also the skin absorption is expected to be negligible due to the polarity of the chlorine species. Based on the surface tension of 82.95 mN/m, the target substance is not surface active and the dermal uptake is not considered significant.

Distribution

36Cl radioactivity was distributed throughout the major tissues, 96 hr after HO36Cl administration. The higher levels were found in plasma (1.92 μg/g), whole blood (1.59 μg/g), bone marrow (1.55 μg/g), testis (1.26 μg/g), skin (1.20 μg/g), kidney (1.13 μg/g) and lung (1.04 μg/g). The lowest levels were found in the liver (0.51 μg/g), carcass (0.40 μg/g), and fat tissue (0.09μg/g). The distribution of 36Cl in plasma and whole blood studied 24 hr after treatment showed that plasma 36Cl content was 4-fold higher than radioactivity measured in packed cells. In plasma about 20% of total 36Cl was bound to protein, while in red cells a high percentage of 36Cl was loosely bound to the erythrocyte membrane or exchangeable with chloride in saline. The subcellular distribution of 36Cl in the liver showed that the main fraction of the radioactivity recovered in hepatic homogenate was localised in the cytosol, and only 4% was bound to proteins (as measured in the TCA precipitate).

In the other study radio-labelled tetramethylammonium iodide was administered to mice showing that TMA was rapidly distributed to all parts of the body, with the highest concentrations being in the kidney and liver (Neef, C. et al. 1984).

Metabolism / Excretion

HO36Cl-derived radioactivity was not detected in expired air throughout the 96 hr study (Abdel-Rahman et al. 1983). During the same period, 36.43% + 5.67 (mean + S. E.) of the administered dose was excreted through the urinary route, while 14.8% + 3.7 was recovered in the faeces, giving a poor total recovery of 51.23% + 1.97.

HOCl is not enzymatically metabolised and its (bio) transformation readily occurs through direct reactions with organic compounds or with other chemicals present in the cellular environment, including hydrogen peroxide. Results from the toxicokinetic study carried out by Abdel-Rahman et al. (1983), showed that the chloride ion accounted for >80% 36Cl radioactivity present in rat plasma.

The other study conducted for radio-labelled tetramethylammonium iodide in rats resulted in almost the whole dose being excreted in urine, without any evidence of metabolic transformation after parenteral administration (Neef, C. et al. 1984).