Registration Dossier

Administrative data

Description of key information

Acute oral toxicity: LD50 > 2000 mg/kg bw, OECD Guideline 423; RL1; GLP

 

Acute inhalation toxicity: exposure consideration + no acute intrinsic toxicity expected; no testing required 

 

Acute dermal toxicity: LD50 expected to be > 2000 mg/kg bw; no testing required 

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
August 15, 2016 - November 23, 2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
December 17, 2001
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
May 30, 2008
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
other: CD / Crl: CD(SD)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: approx. 8 weeks
- Weight at study initiation: 162 - 195 g
- Fasting period before study: approx. 16 hours before administration
- Housing: n groups of 3 animals in MAKROLON cages (type III plus)
- Diet (e.g. ad libitum): Commercial diet, ssniff® R/M-H V1534 (ssniff Spezialdiäten GmbH)
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22± 3
- Humidity (%): 55 ± 15
- Air changes (per hr): 12 - 18
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 3.38 mL/kg b.w.
Doses:
2000 mg a.i./kg bw
No. of animals per sex per dose:
6 females (3 in each step)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- - Frequency of observations: before and immediately, 5, 15, 30, and 60 min, as well as 3, 6, and 24 hours after administration, least once a day afterwards
- Frequency of weighing: before administration of the test item and thereafter in weekly intervals
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology
No histopathology was carried out as no macroscopical findings were noted at autopsy.
Statistics:
No statistical analysis could be performed (the method used is not intended to allow a calculation of a precise LD50 value).
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
act. ingr.
Mortality:
One of the 6 animals died prematurely on test day 7.
Clinical signs:
No clinical signs were observed.
Body weight:
One animal showed a reduced body weight gain.
Gross pathology:
No pathological changes were observed at necropsy.
Interpretation of results:
GHS criteria not met
Conclusions:
The oral LD50 of Di-C12-18 alkyldimethyl ammonium chloride in rat exceeds 2000 mg a.i./kg bw.
Executive summary:

In an acute oral toxicity study according to OECD Guideline 423 (December 17, 2001) and EU Method B.1 tris (May 30, 2008), 2 groups of 3 fasted, approx. 8 weeks old, female CD / Crl: CD(SD) rats were given a single oral dose of Di-C12-18 alkyldimethyl ammonium chloride (68% a.i.) by gavage at a limit dose of 2000 mg a.i./kg bw and observed for 14 days.

One of the 6 animals died prematurely on test day 7. No clinical signs were observed. One animal showed a reduced body weight gain. No pathological changes were observed at necropsy.

 

Oral LD50 females >2000 mg a.i./kg bw

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
guideline study, GLP

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Acute oral toxicity

In an acute oral toxicity study according to OECD Guideline 423 (December 17, 2001) and EU Method B.1 tris (May 30, 2008), 2 groups of 3 fasted, approx. 8 weeks old, female CD / Crl: CD(SD) rats were given a single oral dose of Di-C12-18 alkyldimethyl ammonium chloride (68% a.i.) by gavage at a limit dose of 2000 mg a.i./kg bw and observed for 14 days.

One of the 6 animals died prematurely on test day 7. No clinical signs were observed. One animal showed a reduced body weight gain. No pathological changes were observed at necropsy.

Oral LD50 females >2000 mg a.i./kg bw

 

Similarly low acute toxicity was observed for the source substances DODMAC and DHTDMAC:

LD50 values of 11,300 mg/kg bw (2260 mg a.i./kg bw) for males and of 13,000 (2600 mg a.i./kg bw) mg/kg bw for females were detected for DODMAC. The LD0 of the 75% dilution of DHTDMAC is >/=5000 mg/kg bw (3750 mg a.i./kg bw).

In contrast to that, the source substance DDAC exhibited marked acute toxicity. The LD50(combined) of DDAC is reported to be 238 mg/kg bw in rat.

These data are used to justify the read-across for repeated dose toxicity.

 

Acute inhalation toxicity

Given that inhalation is not a relevant route of exposure, testing by the inhalation route is not necessary according to REACH Regulation Annex VIII 8.5.2 Column 2. Inhalation is not a relevant route of exposure to Di-C12-18 alkyldimethyl ammonium chloride. This applies to both workers and the general population and is due to the physicochemical properties of the substance and the nature of the products where it is used. Di-C12-18 alkyldimethyl ammonium chloride is a waxy solid. Generation of inhalable particles such as dust or aerosols is therefore not to be expected. Vaporisation needs not to be considered due to the substance’s very low vapour pressure of <4.12E-6Pa at 25°C.

Results of laboratory animal studies show a low acute toxicity after oral exposure. Therefore the acute intrinsic toxic activity of Di-C12-18 alkyldimethyl ammonium chloride is considered to be low. The occurrence of a systemic toxicity relevant to humans after inhalation is unlikely and therefore the conduct of an acute inhalation toxicity study is unjustified.

 

Acute dermal toxicity

The testing of acute dermal toxicity of Di-C12-18 alkyldimethyl ammonium chloride is scientifically not justified. According to the COMMISSION REGULATION (EU) 2016/863 of 31 May 2016 amending Annexes VII and VIII to Regulation (EC) No 1907/2006 of the European Parliament and of the Council on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) as regards skin corrosion/irritation, serious eye damage/eye irritation, skin sensitisation and acute toxicity, recent “scientific analysis of available data from in vivo acute toxicity studies have shown that substances that are not toxic via the oral route may be expected with high certainty to be also non-toxic via the dermal route. Therefore, testing those substances via the dermal route does not provide essential information for their safety assessment.” The oral LD50 of Di-C12-18 alkyldimethyl ammonium chloride was determined to be > 2000 mg/kg bw. Thus, no toxicity via the dermal route is to be expected.  

 

Based on the available information, the acute toxicity Di-C12-18 alkyldimethyl ammonium chloride is low. There are no data gaps in acute toxicity. Even though there is no information on acute toxicity in humans, there is no reason to believe that the low acute toxicity observed in experimental animals would not be relevant for human health.

Justification for classification or non-classification

Based on the available relevant and reliable data Di-C12-18 alkyldimethyl ammonium chloride does not need to be classified and labelled according to the CLP Regulation (EC) No 1272/2008 with respect to acute toxicity.