Registration Dossier

Diss Factsheets

Administrative data

Description of key information

There are no experimental data for DTDMAC available. Read-across was performed to the structural closely related quaternary ammonium compounds didecyldimethylammonium chloride (CAS No. 7173-51-5) and DHTDMAC (CAS No. 92129-33-4). Read-across is scientifically justified by the structural similarities and the comparable physico-chemical properties of these dialkyladimethylammonium chlorides. There are two valid guideline studies on repeated dose toxicity available for assessment purposes. Following subchronic dietary administration of didecyldimethylammonium chloride to rats, moderate toxicity was observed at higher dose levels and the NOAEL was established at 46mg/kg body weight per day for the male and female rat. This is in line with findings from a subacute (28 day) oral toxicity study in rats administered DHTDMAC via gavage. The NOAEL in this study was established at 100 mg/kg body weight per day. Based hereupon, the NOAEL of 46 mg/kg body weight per day from the 90-day feeding study is taken for the risk characterization. With regard to the dermal route of exposure, limited information is available from a subacute dermal toxicity study in rabbits. Following topical treatment no signs of clinical or morphological signs of substance related systemic toxicity was observed. The NOAEL for dermal systemic effects of this study was greater 40 mg/kg body weight per day.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
46 mg/kg bw/day
Study duration:

Additional information

Didecyldimethylammonium chloride was investigated for systemic toxicity in a subchronic (90 -day) feeding study using dose levels of 6000, 3000 and 1500 ppm corresponding to 42, 84 or 175 mg/kg body weight per day in males, and 49, 96 or 201 mg/kg body weight per day in females. There were no unspecific deaths throughout the study. Unspecific findings of moderate toxicity consisting of soft faeces, lower body weight gain and food consumption, perturbation of haematological and blood biochemical parameters, distension of the cecum/colon with faeces in all animals, histiocytosis, mastocytosis and sinusal haemorrhage in the mesenteric lymph node, which all are consistent with a continued action of an irritant, were observed in high dose animals and partly also in the mid dose group. At 1500 ppm only minor changes of no biological significance in haematological and blood biochemical parameter were recorded which were not considered to be of toxicological relevance. Based on the findings it was concluded that the NOAEL of didecyldimethylammonium chloride was 1500 ppm which corresponds to 42 mg DDAC/kg body weight per day for the males and 49 mg DDAC/kg body weight per day for the females.The overall NOAEL for both males and females is set at 46 mg/kg body weight per day.

The finding of moderate toxicity after repeated administration of quaternary ammonium compounds is supported by experimental data from a subacute (28 -day) gavage study with DHTDMAC in rats. Dosages were 0, 20, 100, and 500 mg/kg body weight per day. Treatment has not resulted in unscheduled deaths throughout the study. Behaviour and general state of health remained unaffected by the administration of the test compound in the low and mid-dose groups. Main treatment related findings were restricted to the high dose animals and consisted of slightly reduced body weight gain, increased mean values for segmented neutrophils and gamma-globulin values as well as increased absolute and relative adrenal weights. Corresponding to the observations in the adrenals, cortical necrosis was observed in two females of the high dose group. Furthermore, in one high dose female ulceration of the forestomach was noted. The overall picture of treatment related findings is consistent with a secondary response stimulated by local inflammatory changes. The NOAEL from this study was considered to be 100 mg/kg body weight per day. Taking the different exposure durations into account, this NOAEL is reasonably comparable to the NOAEL of 46 mg/kg body weight per day derived from the 90 -day feeding study. The comparable toxicity profile observed for DHTDMAC following repeated administration for 28 days via gavage leading to a NOAEL of 100 mg/kg body weight per day also supports the use of read-across for evaluation purposes of DTDMAC.

Technical grade dihydrogenatedtallowalkyldimethylammonium chloride (DHTDMAC; "Präpagen WK") containing approximately 77% in isopropanol/water was tested in a dermal repeated dose study in rabbits. The study predated official test guidelines and GLP but is of sufficient quality to give some information on the potential systemic toxicity of DHTDMAC via the dermal route of exposure. Groups of 3 male and 3 female rabbits (strain "Gelbsilber") received 20 dermal applications (5 days per week for 4 consecutive weeks) of aqueous solutions containing 0, 0.2 and 2% DHTDMAC (corresponding to about 0, 4 and 40 mg/kg body weight per day). General behaviour, general health condition, food consumption were not influenced by the treatment. Additionally no neurological disturbances, tooth cognition or ophthalmologic investigations of the cornea showed no findings. Haematology, clinical chemistry and urinalysis revealed no significant findings. Gross pathology of the animals at study termination as well as histopathological investigations of heart, lung, liver, spleen, adrenals, testes and ovaries, pituitary gland, and thyroids revealed no substance related changes. Local skin effects in form of slight redness and foldings were observed in some of the high dose animals. Based on the results of this study the NOAEL for systemic dermal effects was greater 2% (v/v) aqueous DHTDMAC solution or greater 40 mg/kg body weight per day.

Based on all available data, the NOAEL of 46 mg/kg body weight from the 90 day subchronic feeding study with didecyldimethylammonium chloride is used for the assessment of DTDMAC with regard to repeated dose toxicity. The available data support the conclusion that, because of their closely related structure and similar physico-chemical properties, DHTDMAC possess similar human health-related effects and no additional testing is required.

Justification for classification or non-classification

Based on the results of the repeated dose toxicity studies performed on the structural analogue compounds didecyldimethylammonium chloride and DHTDMAC, and in accordance with EU regulation (EC) 1272/2008/EC (CLP) and EU directive 67/548/EEC (DSD), DTDMAC is not classified for repeated dose toxicity by the oral route.

Categories Display