Quaternary ammonium compounds, bis(C16-18 and C18-unsatd. alkyl)dimethyl, chlorides

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Dose descriptor:

NOAEL

125 mg/kg bw/day

Additional information

Reproductive toxicity studies with special focus on fertility are not available for ditallowalkyldimethylammonium chloride itself. However, a read-across approach based on SAR (structure-activity-relationship) considerations is used as predictive tool to evaluate potential reproductive toxic effects of DTDMAC. Relevant experimental data on reproductive toxicity are available for dioctadecyldimethylammonium chlorid as well as from repeated dose toxicity studies with dioctadecyldimethylammonium chloride and didecyldimethylammonium chloride. To use a read-across approach based on SAR (structure-activity-relationship) as predictive tool is scientifically justified due to the close structural similarities and comparable physico-chemical properties of this class of compounds. Clustering quaternary ammonium compounds for assessment purposes was also considered appropriate by the U.S. EPA for registration purposes under FIFRA because of similar toxicological profiles of dialkyldimethylammonium chlorides.

In a reproductive/developmental toxicity screening study according to OECD guideline 421 following the principles of GLP, rats received daily doses of 62.5, 125, and 500 mg/kg body weight per day by gavage. Male animals were treated daily from two weeks before mating, during mating and until a dosing period of a total of 28 days had completed. Females were treated daily from two weeks before mating until the 4th day of lactation.With regard to maternal data, key findings were unspecific clinical observations and body weight loss during the first week of treatment at the highest dose. No toxicological effects were observed at dosages of 125 and 62.5 mg/kg body weight per day. At 500 mg/kg body weight per day, the percentage of postimplantation losses was increased resulting in a significantly lower rate of live borns. However, the viability index on postnatal day 4 was in the range of the controls and the lower treatment groups. No indication of embryotoxicity was found. The NOAEL from this study with regard to reproductive toxicity was established at 125 mg/kg body weight per day and adopted for an existing EU risk assessment on this compound as well. Additionally, from repeated dose toxicity studies with oral administration of the structural analogous compounds dioctadecyldimethylammonium chloride and didecyldimethylammonium chloride also no indications with regard to histopathological changes of reproductive organs exist.

The available data support the conclusion that, because of their closely related structure and similar physico-chemical properties, ditallowdimethylammonium chloride posses` similar human health-related effects and no additional testing is required.

Short description of key information:
There are no experimental data on DTDMAC itself available with special focus on toxicity to reproduction. However, read-across can be made to experimental results from structural closely related dialkyldimethylammonium chlorides. For assessment purposes a reproduction/developmental toxicity screening test according to OECD 421 with dioctadecyldimethylammonium chloride is used which has not revealed any indication of significant reproductive concern. The NOAEL from this study with regard to reproductive effects was established at 125 mg/kg body weight per day via gavage and was adopted for an existing EU risk assessment on this compound as well. Additionally, from repeated dose toxicity studies available on structural analogous compounds, no indication of effects on reproductive organs exist.

Effects on developmental toxicity

Description of key information

Ditallowdimethylammonium chloride was investigated for prenatal developmental toxicity in one study following the principles of OECD guideline 414. Additionally, read-across can be made for assessment purposes to a reproductive/developmental toxicity screening study with the structural closely related dioctadecyldimethylammonium chloride. From both studies no indications of significant reproductive properties of DTDMAC are deducible

Effect on developmental toxicity: via oral route

Dose descriptor:

NOAEL

500 mg/kg bw/day

Additional information

Ditallowalkyldimethylammonium chloride (DTDMAC, CAS No. 68783 -78 -8) was investigated in a prenatal developmental toxicity study similar to OECD guideline 414. No formal GLP was present at the time of performance. A reliability check performed by an expert panel from the American Chemical Council however, revealed a Klimisch reliability score 2A (reliable with restrictions). In this study 25 female rats per dose group were administered DTDMAC either by oral gavage (dose levels 100 and 500 mg active per kg body weight per day) in isopropanol as vehicle, or in the diet at a single dose of 0.65% active (corresponding to 508 mg/kg body weight per day) beginning of day 6 of gestation. Two control groups were run concurrently, one gavage vehicle control and one receiving control feed only. Ten rats per group were sacrificed after the day 13 treatment and 15 rats per group were treated through day 18 and sacrificed on day 21 of gestation. Beside depressed body weight gains during gestation in the group that received DTDMAC in the diet but not in the gavaged groups, no treatment-related maternal toxic effect occurred. With regard to fetal data, no differences considered to be related to the administration of DTDMAC were noted in fetal size and sex, variations in degree of ossification or malformations. The NOAEL for maternal toxicity was set at greater 500 mg/kg body weight per day for the gavage group and the NOAEL for developmental toxicity was established with greater 500 mg/kg body weight per day by gavage and greater 508 mg/kg body weight per day via diet.

Justification for classification or non-classification

Based on the results available on DTDMAC and from the studies performed on the structural analogues compound dioctadecyldimethylammonium chloride, no reproductive toxicity or effects on fertility of DTDMAC are anticipated. The substance is not selectively toxic to the embryo or fetus and is not teratogenic via gavage dosing to rats. No classification is required according to the criteria laid down in EU regulation (EC) 1272/2008/EC (CLP) and EU directive67/548/EEC (DSD).