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Description of key information

The acute oral toxicity of quaternary ammonium compound, di-C16-18-alkyldimethyl, chloride was assessed using:
- An acute oral toxicity limit test performed in rats according to OECD 401 guideline. A statement that the report and the study were audited by the Quality Assurance Unit of the testing laboratory was including in the study report (Kynoch, 1984).
- A standard acute oral test performed in rats. The study predates GLP requirements and OECD guidelines but the described method is very closed to the OECD guideline 401 (Oser, 1953).
The results of the above mentioned studies were supported by a third study for which only the executive summary of the study report was available (Hoechst, 1986a).
The substance is of very low acute toxicity following oral exposure: the oral median lethal dose( LD50) is greater than 2000 mg/kg bw .
The acute dermal toxicity of quaternary ammonium compound, di-C16-18-alkyldimethyl, chloride was assessed using:
- An acute dermal toxicity limit test performed in rats according to OECD 402 guideline in compliance with Good laboratory practices (Clouzeau, 1988).
The substance is of low acute toxicity following dermal exposure: The dermal median lethal dose (LD50) is greater than 2000 mg/kg bw.
The acute inhalation toxicity of quaternary ammonium compound, di-C16-18-alkyldimethyl, chloride was assessed using:
-An acute inhalation toxicity limit test study performed in rats according to a technique from the US Federal Hazardous Substances Regulations specified in the Revised, Federal Register, september 17, 1964 (Young, 1974). The study predates OECD guidelines and GLP requirements . Although, the study had somme limitations, it do not indicate major concerns. The LC50 was found to be in excess of 180 mg/l after one hour exposure whole-body.
In summary, it is concluded that the acute systemic toxicity of quaternary ammonium compound, di-C16-18-alkyldimethyl, chloride is very low for all routes of exposure.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Dose descriptor:
LC50
Value:
180 000 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

The acute systemic toxicity of quaternary ammonium compound, di-C16 -18 -alkyldimethyl, chloride by oral, dermal and inhalation routes was investigated by testing technical grade dihydrogenated tallowalkyldimethylammonium chloride (DHTDMAC, 70 to 75% active in isopropanol/water) as well as pure dioctadecyldimethylammonium chloride (DODMAC, 97% in water).

Acute Oral Toxicity:

Two valid studies were recorded for this endpoint and supported by the result of a third study for which only the executive summary of the study report was available . The study of Kynoch (1984) was a reliable without restriction study and the study of Oser (1953) was reliable with some restrictions: study predates GLP requirements and OECD guidelines. The study of Kynoch (1984) was identified as a key study and supported by the results of the study performed by Oser (1953) and the results described in the executive summary of the Hoechst study (1986a).

The study of Kynoch (1984) was designed to evaluate the toxicity of DHTDMAC (75% active in isopropanol/water) following a single oral administration in rats according to OECD guideline 401. A statement that the report and the study were audited by the quality Assurance Unit of the

testing laboratory was provided. the test material was prepared in 1% methylcellulose suspension and was administered by gavage under a dosage-volume of 10 ml/kg bw to 2 groups of 5 male and 5 female rats each.

Based on a preliminary study indicating no deaths in 2 males and 2 female rats at 5000 mg/kg bw, the main experiment was performed at the limit dose level of 5000 mg/kg bw.

Clinical signs, mortality and body weight were checked for a period of 14 days following the single administration of the test item. All animals were subjected to necropsy.

At the dose-level of 5000 mg/kg bw, no mortality and no effects on body weight gain were observed. Piloerection, pallor of the extremities and hunched posture were observed in all animals from day 1. Abnormal gait was also recorded in 2 out of 5 males and 5 out of 5 females. Recovery was complete by day 4. At necropsy, there were no apparent abnormalities.

Under these experimental conditions, the acute median lethal dose (LD50) of DHTDMAC was greater than 5000 mg/kg bw.

The study of Oser (1953) evaluated the toxicity of DHTDMAC (70% active in isopropanol/water) following a single oral administration in rats by gavage. The Study predates GLP requirements and OECD guidelines but the described method is very closed to the OECD guideline 401.

The dose-levels were selected from the results of a preliminary study indicating no deaths at 1000, 2000 and 4000 mg/kg bw in groups of 2 rats for each dose. No survivors were found when 2 rats were dosed with 10 000 mg/kg bw. Therefore, the main experiment was performed at the dose levels of 5000, 6000, 7000 and 8000 mg/kg bw. The test item was administered undiluted, to groups equally divided by sex of 20 rats for the 5000 mg/kg bw dose, 30 rats for the 6000 and 7000 mg/kg bw doses and 10 rats for the 8000 mg/kg bw dose.

Clinical signs, mortality and body weight were checked for a period of 14 days following the single administration of the test item. All animals were subjected to necropsy. The acute median lethal dose (LD50) was calculated according to the method of Miller and Tainer (1944) (Miller, L.C. and Tainter, M.L. (1944) Proc.Soc.Exper.Biol.Med. 57, 261).

3 out 20 rats, 14 out 30 rats, 15 out 30 rats and 9 out 10 rats were found dead in the 5000, 6000, 7000 and 8000 mg/kg bw dose groups respectively. All deaths occured after day 3. In the survivors, no effects on body weight gain were observed. Clinical signs and gross pathology were not reported.

Under these experimental conditions, the acute median lethal dose (LD50) was found to be 6350 mg/kg bw.

In the Hoechst study (1986a), the acute oral toxicity of DODMAC (97% in water) was investigated in rats using sesame oil as vehicle. Male and female rats were administered the test compound by a single-dose gavage at the dose level of 2000 mg/kg bw (limit dose). After administration of 2000 mg/kg bw, no mortalities occured. Clinical signs were mentioned but not qualified. Gross pathology revealed no macroscopically visible changes. Based on these findings, the acute median lethal dose (LD50) of DODMAC was higher than 2000 mg/kg bw in rats.

Acute dermal Toxicity:

One valid study was recorded for this endpoint. The study of Clouzeau (1988) was a reliable without restriction study and identified as a key study.

In the study of Clouzeau (1988), the acute dermal toxicity of DHTDMAC (dihydrogenated tallowalkyldimethyl ammonium chloride, purity approximately 97%) was investigated in rats according to OECD Test Guideline 402 in compliance with the principles of GLP. The test substance was applied as an aqueous suspension to the shaved skin of 5 male and 5 female animals at a dose level of 2000 mg/kg body weight (limit dose) under occlusive conditions. Mortality, general behaviour, clinical signs and body weight development were recorded daily for an observation period of 14 days. A necropsy was performed on each animal sacrificed at the end of the study. There was no mortality throughout the study period at the dose level of 2000 mg/kg body weight. General behaviour and bodyweight of the animals were not influenced by the treatment. Clinical signs of significance were not observed. Skin dryness was noted after the removal of the dressing up to day 6 in all animals. Additional signs of skin irritation were not observed. The macroscopic examination of the main organs did not reveal abnormalities in any of the animals sacrificed at the end of the observation period. Based on the study results, the median lethal dose (LD50) of the test material when administered dermally to rats is greater than 2000 mg/kg body weight. Additionally, at this dose level the test material did not induce any signs of toxicity.

Acute inhalation Toxicity:

One study performed with dihydrogenatedtallowalkyldimethylammonium chloride (DHTDMAC, 70% active in isopropanol/water) was recorded for this endpoint. The study predates OECD guidelines and Good Laboratory Practices.

The acute inhalation toxicity was assessed in male albino rats using a method recommended by the US Federal Hazardous Substances Regulations specified in the Revised, Federal Register .A group of ten rats were exposed whole-body to the test item in an inhalation chamber for 1 hour. The nominal concentration of the test item in the chamber atmosphere was calculated to be 180 mg/l of mist. At the end of the exposure period, the animals were removed from the chamber. The animals were observed continuously for appearance and behavior during the exposure period and at regular intervals thereafter for a total of 14 days. Rats were subjected to gross necropsy at the end of the study. No mortalities were recorded at any time. Clinical signs were only present on the day of exposure and included, excess salivation, serosanguineous stains around the nose, laboured respiration and damp/wet coats. For the remainder of the study, all rats exhibited normal behaviour and appearance. Necropsy revealed no significant gross pathological alterations. The acute LC50 of the test material was determined to be greater than180 mg/l after 1 hour exposure.

Based on all available results on acute systemic toxicity, quaternary ammonium compound, di C16 -18 -alkyldimethyl, chloride can be regarded to be practically non- toxic by either route of exposure (oral, dermal, inhalation). This conclusion is in line with the view taken in the existing EU risk assessment on dimethyldioctadecylammonium chloride (DODMAC).

Justification for classification or non-classification

Based on all available results on acute systemic toxicity, quaternary ammonium compound, di C16 -18 -alkyldimethyl, chloride can be regarded to be practically non-toxic by either route of exposure (oral, dermal, inhalation). According to the criteria laid down in EU regulation (EC) n° 1272/2008 (CLP) and the EU directive 67/ 548/EEC, the substance is not classified for acute systemic toxicity.

Quaternary ammonium compound, di C16 -18 -alkyldimethyl, chloride do not contain aliphatic, alicyclic and aromatic hydrocarbons and have a high viscosity and so do not indicate an immediate concern for aspiration hazard.