Oleyltrimethylammonium chloride (Oleyl TMAC); Trimethyloleylammonium chloride

Endpoint summary

Description of key information

Based on the results of the read across study, the oral LD50 value of the test substance is considered to be 630 mg a.i./kg bw in rats.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Study period:

From 07 November, 1986 to 10 December, 1986

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

KL2 due to RA

Justification for type of information:

Refer to the Quaternary ammonium salts (QAS) category or section 13 of IUCLID for details on the category justification.

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Interfauna (UK) Limited, Wyton, Huntingdon, Cambridgeshire
- Age at study initiation: 5-8 wks old
- Weight at study initiation: Males weighed: 130 - 162g and females weighed: 123 - 151g
- Fasting period before study: Overnight fast immediately before dosing and for approximately two hours after dosing.
- Housing: Solid-floor polypropylene cages with sawdust bedding
- Diet and water (e.g. ad libitum): Free access to mains drinking water and food (rat and mouse expanded diet No.1, special diet services limited, with am, Essex, U.K.) was allowed throughout the study.
- Acclimation period: 5 d

ENVIRONMENTAL CONDITIONS
- Temperature: 19-23°C
- Humidity: 45-65%
- Air changes: 15/h
- Photoperiod: 12 h light/12 h dark

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: Undiluted

MAIN STUDY:
Four groups of ten rats (five males and five females) were dosed at logarithmically spaced dose levels, selected using the results of the range-finding study. All animals were dosed once only at the appropriate dose level by gavage using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to its fasted bodyweight at the time of dosing.

Doses:

0, 1,000, 1,260, 1,587 and 2,000 mg/kg bw

No. of animals per sex per dose:

5/sex/dose

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 d
- Frequency of observations and weighing: Animals were observed 1 and 4 h after dosing and subsequently once daily for 14 d. Deaths and evidence of overt toxicity were recorded at each observation. Individual bodyweights were recorded on the day of treatment (day 0), Day 7 and 14, and at death.
- Necropsy of survivors performed: Yes, all animals were subjected to gross necropsy examination for any macroscopic abnormalities
- Other observations: Clinical signs

Statistics:

Method of Weil C.S. (1952) Biometrics 8, 249 was used to calculate the acute oral median lethal dose (LD50 )and 95% confidence limits of the test substance.

Preliminary study:

The results of the range finding study based on mortality indicated an oral LD50 between 1,000 and 2,000 mg/kg bw.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 260 mg/kg bw

Based on:

test mat.

95% CL:

ca. 1 061 - ca. 1 496

Remarks on result:

other: equivalent to 630 mg a.i./kg bw

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

1 289 mg/kg bw

Based on:

test mat.

95% CL:

ca. 1 151 - ca. 1 444

Remarks on result:

other: equivalent to 644.5 mg a.i./kg bw

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

ca. 1 000 - ca. 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: equivalent to be between 500 to 1000 mg a.i./kg bw

Mortality:

The number and percentage of mortality observed at different doses were:
- At 1,000 mg/kg bw: 0/5 (M); 2/5 (F); 2/10 (total), i.e., 20%
- At 1,260 mg/kg bw: 2/5 (M); 4/5 (F); 6/10 (total), i.e., 60%
- At 1,587 mg/kg bw: 5/5 (M); 2/5 (F); 7/10 (total), i.e., 70%
- At 2,000 mg/kg bw: 5/5 (M); 4/5 (F); 9/10 (total), i.e., 90%

Clinical signs:

Major signs of toxicity noted in decedent and survlvlng animals were hunched posture, lethargy, pilo-erection, decreased respiratory rate and diarrhoea. Animals treated with 1,260 mg/kg bw and above showed additional signs including: ataxia, tip-toe gait, ptosis, pallor of the extremities, increased lacrimation, chromodacryorrhoea, diuresis, occasional body tremors, emaciation and red/brown staining around the snout.
The single survivor in the 2,000 mg/kg bw dose group showed signs of toxicity until Day 12, but all other surviving animals appeared normal three to six days
after treatment.

Body weight:

Effects on bodyweight gain (reduction) were commonly noted in animals treated with 1,260 mg/kg bw and above at Day 7, but all survivors made expected bodyweight gains during the second week.

Gross pathology:

Necropsy of decedents revealed abnormally red lungs, dark livers, haemorrhage and ulceration of the gastric mucosa and congestion of the small intestines. Surviving animals necropsied at termination showed white raised areas on the non-glandular region of the stomach or general white thickening of this region. Isolated animals from the 1,260 and 2,000 mg/kg bw dose groups showed adhesion of the stomach to the abdominal wall and/or liver.

Interpretation of results:

other: Acute Tox. 4 based on CLP criteria

Conclusions:

Under the study conditions, the LD50 of the read across substance in SD rats was determined to be 1,260 mg/kg bw for males/females (i.e., equivalent to 630 mg a.i./kg bw).

Executive summary:

A study was conducted to determine the acute oral toxicity potential of the read across substance C16-18 and C18-unsatd. TMAC (50% active in isopropanol and water) in Sprague-Dawley rats, according to OECD Guideline 401, in compliance with GLP. Four groups of 10 fasted animals (five males and five females) were administered an oral gavage dose of the test substance (i.e., 50% active ingredient) at doses of 1,000, 1,260, 1,587 and 2,000 mg/kg bw. The animals were observed for 14 days and were then sacrificed and subjected to gross pathological examination. Mortality was observed at all doses (females: 2/5, 4/5, 2/5, 4/5; males: 0/5, 2/5, 5/5, 5/5, at each respective dose) with percentages ranging from 60-90 at ≥1,260 mg/kg bw. Major signs of toxicity noted in decedent and surviving animals were hunched posture, lethargy, pilo-erection, decreased respiratory rate and diarrhoea. All animals showed expected body weight gain during the second week of the study. Necropsy of decedents revealed abnormally red lungs, dark livers, haemorrhage and ulceration of the gastric mucosa and congestion of the small intestines. Surviving animals necropsied at termination showed white raised areas on the non-glandular region of the stomach or general white thickening of this region. Under the test conditions, the LD50 was determined to be 1,260 mg/kg bw for males/females (i.e., equivalent to 630 mg a.i./kg bw) (Jones, 1987). Based on the results of the read across study, similar LD50 value is expected for the test substance.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

630 mg/kg bw

Quality of whole database:

OECD 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

Reason / purpose for cross-reference:

data waiving: supporting information

Reason / purpose for cross-reference:

data waiving: supporting information

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 acute oral toxicity potential of the read across substance C16-18 and C18-unsatd. TMAC (50% active in isopropanol and water) in Sprague-Dawley rats, according to OECD Guideline 401, in compliance with GLP. Four groups of 10 fasted animals (five males and five females) were administered an oral gavage dose of the read across substance (i.e., 50% active ingredient) at doses of 1,000, 1,260, 1,587 and 2,000 mg/kg bw. The animals were observed for 14 days and were then sacrificed and subjected to gross pathological examination. Mortality was observed at all doses (females: 2/5, 4/5, 2/5, 4/5; males: 0/5, 2/5, 5/5, 5/5, at each respective dose) with percentages ranging from 60-90 at ≥1,260 mg/kg bw. Major signs of toxicity noted in decedent and surviving animals were hunched posture, lethargy, pilo-erection, decreased respiratory rate and diarrhoea. All animals showed expected body weight gain during the second week of the study. Necropsy of decedents revealed abnormally red lungs, dark livers, haemorrhage and ulceration of the gastric mucosa and congestion of the small intestines. Surviving animals necropsied at termination showed white raised areas on the non-glandular region of the stomach or general white thickening of this region. Under the test conditions, the LD50 was determined to be 1,260 mg/kg bw for males/females (i.e., equivalent to 630 mg a.i./kg bw) (Jones, 1987). Based on the results of the read across study, similar LD50 value is expected for the test substance.

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 it slippery solid-paste like physical state and low vapour pressure (VP = 8.0E-6 Pa at 25°C, which is below cut-off 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 (Category 1C) to the skin.

Justification for classification or non-classification

Based on the results from the read across acute oral study, the test substance warrants an ‘Acute Tox. 4; H302: harmful if swallowed’ classification according to EU CLP criteria (Regulation EC 1272/2008).