Trimethyloctadecylammonium chloride

Endpoint summary

Description of key information

 The oral LD50 value of the test substance was determined to be 560 mg a.i./kg bw in rats, suggesting a moderate acute toxicity potential. 

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:

From January 03, 1996 to February 21, 1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: Hoe: WISKf (SPF71)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hoechst aktiengesellschaft, Kastengrund, SPF breeding colony
- Age at study initiation: Approximately 7 wk (m) and 8 wk (f)
- Weight at study initiation: Mean: 185g (m) and 171g (f)
- Fasting period before study: Yes
- Housing: In fully air-conditioned rooms in macrolon cages on soft wood granulate in group of 5 animals
- Diet: Ssniff R/M-H (V 1534), ad libitum
- Water: Tap water, ad libitum
- Acclimation period: Atleast one day

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%): 50 ± 20%

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

Deionized

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 6.3, 8, 12.5 and 20% in deionised water
- Justification for choice of vehicle: Test substance is soluble in water

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Dose range finding study

Doses:

800 and 2,000 mg/kg bw for males and 630, 800, 1,250 and 2,000 mg/kg bw

No. of animals per sex per dose:

5 per sex per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14d
- Frequency of observations and weighing: Symptoms and lethality were recorded twice every day, on weekends and public holiday only once. weighing was done weekly
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology

Statistics:

The LD50 and the equation of the probit line were established in female animals on the basis of the lethality rates by probit analysis.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

ca. 702.5 mg/kg bw

Based on:

test mat.

Remarks on result:

other: equivalent to 560.5 mg a.i./kg bw

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

> 800 - < 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: equivalent to >638 to <1596 mg a.i./kg bw

Mortality:

Yes, although in males there was no mortality at 800 mg/kg bw, all animals died at 2,000 mg/kg bw. In females, only 2 and 3 animals survived at 630 and 800 mg/kg bw, respectively. At 1,250 and 2,000 mg/kg bw, all females died.

Clinical signs:

other: Decreased spontaneous activity, squatting posture, narrowed palpebrae fissures and irregular respiration. Also, stupor was observed only in the animals of the 2,000 mg/kg bw group. One female animal of the 800 mg/kg bw group showed blood encrusted lid mar

Gross pathology:

Macroscopic examination of the dead animals:
Stomach: Full of clear fluid, full of gas, detachment of the mucosa, petechial bleeding
Intestinal tract: Full of yellowish mucous, full of clear fluid, detachment of the mucosa, full of reddish mucosa

The animals killed at the end of the observation period showed macroscopically visible changes.

Conclusions:

Under the study conditions, the LD50 values for the female and male Wistar rats were determined to be 702.5 and >800 to <2000 mg/kg bw, respectively (equivalent to 560.5 and >638 to <1596 mg a.i./kg bw, respectively).

Executive summary:

A study was conducted to determine the oral acute toxicity of the test substance, C18 TMAC (79.8% active) according to OECD Guideline 401 and EU Method B.1, in compliance with GLP. The experiment was performed in Wistar rats. The test substance was administered as a single dose to 5 female rats per group at 630, 800, 1250 and 2000 mg/kg bw (equivalent to 503, 638, 998 and 1596 mg a.i./kg bw) and to 5 males rats per group at doses of 800 and 2000 mg/kg bw (equivalent to 638 and 1596 mg a.i./kg bw, after which animals were examined for 14 days. Examinations performed were mortality, body weights, clinical signs and gross necropsy for any macroscopic abnormalities. In males, there was no mortality at 800 mg/kg bw, however all animals died at 2000 mg/kg bw. In females, only 2 and 3 animals survived at 630 and 800 mg/kg bw respectively. At 1250 and 2000 mg/kg bw, all females died. Females, therefore, appeared to be more susceptible to the effects of treatment than males. Decreased spontaneous activity, squatting posture, narrowed palpebrae fissures and irregular respiration were recorded. Also, stupor was observed only in the animals of the 2000 mg/kg bw group. One female animal of the 800 mg/kg bw group showed blood encrusted lid margin on Day 6 of the study. All clinical signs were reversible at Day 8 of the study. No effects were seen on the body weight. The animals killed at the end of the observation period showed macroscopically visible changes. Under the study conditions, the LD50 values for the female and male Wistar rats were determined to be 702.5 and >800 to <2000 mg/kg bw, respectively (equivalent to 560.5 and >638 to <1596 mg a.i./kg bw, respectively) (Jensch, 1996).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

560.5 mg/kg bw

Quality of whole database:

Guideline compliant study

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the substance is classified as corrosive to the skin

other:

Reason / purpose for cross-reference:

data waiving: supporting information

Clinical signs:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the substance is classified as corrosive to the skin

Reason / purpose for cross-reference:

data waiving: supporting information

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Oral:

A study was conducted to determine the oral acute toxicity of the test substance, C18 TMAC (79.8% active) according to OECD Guideline 401 and EU Method B.1, in compliance with GLP. The experiment was performed in Wistar rats. The test substance was administered as a single dose to 5 female rats per group at 630, 800, 1250 and 2000 mg/kg bw (equivalent to 503, 638, 998 and 1596 mg a.i./kg bw) and to 5 males rats per group at doses of 800 and 2000 mg/kg bw (equivalent to 638 and 1596 mg a.i./kg bw, after which animals were examined for 14 days. Examinations performed were mortality, body weights, clinical signs and gross necropsy for any macroscopic abnormalities. In males, there was no mortality at 800 mg/kg bw, however all animals died at 2000 mg/kg bw. In females, only 2 and 3 animals survived at 630 and 800 mg/kg bw respectively. At 1250 and 2000 mg/kg bw, all females died. Females, therefore, appeared to be more susceptible to the effects of treatment than males. Decreased spontaneous activity, squatting posture, narrowed palpebrae fissures and irregular respiration were recorded. Also, stupor was observed only in the animals of the 2000 mg/kg bw group. One female animal of the 800 mg/kg bw group showed blood encrusted lid margin on Day 6 of the study. All clinical signs were reversible at Day 8 of the study. No effects were seen on the body weight. The animals killed at the end of the observation period showed macroscopically visible changes. Under the study conditions, the LD50 values for the female and male Wistar rats were determined to be 702.5 and >800 to <2000 mg/kg bw, respectively (equivalent to 560.5 and >638 to <1596 mg a.i./kg bw, respectively) (Jensch, 1996).

Inhalation:

In accordance with Annex VII, Section 8.5, Column 2, additional acute toxicity study for inhalation route does not need to be conducted because the substance is classified as corrosive to the skin. Further, due to its low vapour pressure (VP = 2.9E-6 at 25°C, which is below cutoff of 0.01 Pa as per the ECHA R.7a guidance), it is unlikely that the test substance will form inhalable dust, mist or fumes when handled and used in solid form. In case inhalable forms of the substance (either pure or in aqueous solutions) are created under particular conditions (e.g., spraying, elevated temperature/pressure), appropriate risk management measures such as closed systems, exhaust ventilation or wearing of respirators are implemented to control exposure. Under such conditions, the risk to humans following inhalation exposure can be considered minimal and further testing involving vertebrate animals may also be omitted, in accordance with Annex XI, section 1.2 (weight of evidence) of the REACH regulation.

Dermal:

In accordance with Annex VII, Section 8.5, Column 2, additional acute toxicity study for dermal route does not need to be conducted because the substance is classified as corrosive to the skin (Category 1C).

Justification for classification or non-classification

Based on the oral LD50 value, the test substance warrants an ‘Acute Tox. 4; H302: harmful if swallowed’ classification according to EU CLP criteria (Regulation EC 1272/2008). In addition, for the inhalation route, although C18 TMAC is classified to be corrosive (see section 5.3) and this drives its mechanism of action of toxicity, its inherent low vapour pressure prohibits the occurrence of respiratory irritation or corrosion by vapour. Therefore, it does not warrant an additional labelling as: EUH071 — ‘Corrosive to the respiratory tract’ according to EU CLP criteria (Regulation EC 1272/2008).

Further, the available data does not show indication that classification for STOT-SE cat 1 or 2 is indicated. For STOT-SE Cat 3: C18 TMAC or QAS substances are not narcotic.