Quaternary ammonium compounds, C18 and C18 (unsaturated) alkyltrimethyl, chlorides

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 07 November, 1986 to 10 December, 1986

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1987

Report date:

1987

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

Test material

Test material information

Constituent 1

Reference substance name:

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

EC Number:

268-074-9

EC Name:

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

Cas Number:

68002-61-9

Molecular formula:

Representative molecular formula of the major constituents, as the substance is an UVCB: C16 TMAC: C19H42CL1N1 C18 TMAC: C21H46CL1N1 C18-unsatd. TMAC: C21H44CL1N1

IUPAC Name:

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

Constituent 2

Reference substance name:

Propan-2-ol

EC Number:

200-661-7

EC Name:

Propan-2-ol

Cas Number:

67-63-0

Molecular formula:

C3H8O

IUPAC Name:

propan-2-ol

Constituent 3

Reference substance name:

Water

EC Number:

231-791-2

EC Name:

Water

Cas Number:

7732-18-5

Molecular formula:

H2O

IUPAC Name:

water

Constituent 4

Reference substance name:

Free amines

Molecular formula:

No information available

IUPAC Name:

Free amines

Test material form:

liquid

Test animals

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

Administration / exposure

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.

Results and discussion

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.

Effect levels

Effect levels 1

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

Effect levels 2

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

Effect levels 3

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:

other: 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,

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.

Applicant's summary and conclusion

Interpretation of results:

other: Acute Tox. 4 based on CLP criteria

Conclusions:

Under the study conditions, the LD50 of the test 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 test 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).