Quaternary ammonium compounds, di-C14-18-alkyldimethyl, Me sulfates

Endpoint summary

Description of key information

Acute oral toxicity: LD50 > 10000 mg/kg bw, performed before implementation of GLP and OECD guidelines; RL2

 

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:

not reported

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Principles of method if other than guideline:

- Principle of test: Six male Sprague-Dawley rats were administered either 5 or 10 g/kg bw of a 25 % solution (in distilled water) of the test substance by oral gavage.The animals were observed for two weeks.
- Short description of test conditions: Animals were given a single dose and then placed in screen bottom cages with free access to water and laboratory chow for a two week observation period.
- Parameters analysed / observed: Mortality

GLP compliance:

no

Remarks:

performed before implementation of GLP

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 150-250 g
- Fasting period before study: 24 h
- Housing: screen bottom cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

distilled water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 25%

MAXIMUM DOSE VOLUME APPLIED: not specified

DOSAGE PREPARATION (if unusual): none

Doses:

5 and 10 g/kg bw

No. of animals per sex per dose:

6 males

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: not examined
- Necropsy of survivors performed: no

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

> 10 000 mg/kg bw

Based on:

act. ingr.

Mortality:

One animal died on day 7 in the 10 g/kg bw group

Clinical signs:

other: not reported

Gross pathology:

not examined

Interpretation of results:

GHS criteria not met

Conclusions:

The single administration of 10 mg/kg bw C14-18 alykldimethyl ammonium methosulfate to male Sprague-Dawley rats caused one death among 6 animals in this dosage group on observation day 7. The other animals, i.e. 6 animals in the 5 g/kg bw dosage group and 5 animals in the 10 g/kg bw dosage group survived during the whole experimental time Thus, the LD50 of the test substance was considered to be > 10 g/kg bw.

Executive summary:

In an acute oral toxicity study (performed before implementation of GLP and OECD guidelines), groups of 6 male fasted Sprague-Dawley rats were given a single oral dose of C14 -18 alkyldimethyl ammonium methosulfate (89% a.i.) in water at doses of 5 or 10 g/kg bw and observed for 14 days. One animal died on day 7 in the 10 g/kg bw group; all animals of the 5 g/kg bw group survived to the end of the observation period.

 

Oral LD50 Males >10 g/kg bw

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

10 000 mg/kg bw

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 (performed before implementation of GLP and OECD guidelines), groups of 6 male fasted Sprague-Dawley rats were given a single oral dose of C14 -18 alkyldimethyl ammonium methosulfate (89% a.i.) in water at doses of 5 or 10 g/kg bw and observed for 14 days. One animal died on day 7 in the 10 g/kg bw group; all animals of the 5 g/kg bw group survived to the end of the observation period.

 

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-C14-18 alkyldimethyl ammonium methosulfate. 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-C14-18 alkyldimethyl ammonium methosulfate 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 </=1.13E-013 Pa at 25°C. Results of laboratory animal studies show a low acute toxicity after oral exposure. Therefore the acute intrinsic toxic activity of Di-C14-18 alkyldimethyl ammonium methosulfate 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 C14 -18 alkyldimethyl ammonium methosulfate 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 C14 -18 alkyldimethyl ammonium methosulfate was determined to be > 10000 mg/kg bw. Thus, no toxicity via the dermal route is to be expected.  

 

Based on the available information, the acute toxicity C14 -18 alkyldimethyl ammonium methosulfate 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 C14 -18 alkyldimethyl ammonium methosulfate does not need to be classified and labelled according to the CLP Regulation (EC) No 1272/2008 with respect to acute toxicity.