Quaternary ammonium compounds, C12-18-alkyltrimethyl, chlorides

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 12 June, 1986 to 13 September, 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

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

One animal in the lowest dose group was not observed for clinical findings at 4 h after dosing on Day 0. this deviation does not affect the scientific validity or integrity of the study.

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPP 81-1 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

One animal in the lowest dose group was not observed for clinical findings at 4 h after dosing on Day 0. this deviation does not affect the scientific validity or integrity of the study.

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: Toxic Substances Control Act (TSCA) Health Effects Test Guidelines

Deviations:

yes

Remarks:

One animal in the lowest dose group was not observed for clinical findings at 4 h after dosing on Day 0. this deviation does not affect the scientific validity or integrity of the study.

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Quaternary ammonium compounds, coco alkyltrimethyl, chlorides

EC Number:

263-038-9

EC Name:

Quaternary ammonium compounds, coco alkyltrimethyl, chlorides

Cas Number:

61789-18-2

Molecular formula:

C(n+3) H(2n+10) N Cl (n=8-18)

IUPAC Name:

Quaternary ammonium compounds, cocoalkyl trimethyl, chloride

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: Charles River Breeding Laboratories, Inc., Portage, Michigan
- Weight at study initiation: 205-262 g
- Fasting period before study: 18 h
- Housing: Individually housed in wire-mesh cages
- Diet: Purina certified rodent chow # 5002, ad libitum
- Water: Drinking water, ad libitum
- Acclimation period: Minimum 7 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-21
- Humidity (%): more than 40%
- Photoperiod (h dark/h light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 0.93 mL/kg

Doses:

0, 512, 620, 750 and 908 mg/kg bw .

No. of animals per sex per dose:

Five animals per sex per dose except for the highest dose which has only 5 males.

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 d
- Frequency of clinical observation: 1, 2.5 and 4 h after dosing on Day 0 and subsequently once daily for 14 d.
- Frequency of weighing: On Days 0, 7 and 14
- Necropsy of survivors performed: Yes
- Examinations performed: Clinical signs, body weight and gross pathological examination.

Statistics:

LD50 values and slopes (with 95% confidence limit) were calculated by method of Litchfield and Wilcoxon.

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

684 mg/kg bw

Based on:

test mat.

95% CL:

ca. 629 - ca. 743

Remarks on result:

other: Category 3 as per CLP

Effect levels 2

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 226 mg/kg bw

Based on:

act. ingr.

95% CL:

ca. 207 - ca. 245

Remarks on result:

other: Category 3 as per CLP

Mortality:

There was no mortality in the 512 mg/kg bw group while 3 out of 10 and 7 out of 10 rats died in the 620 and 750 mg/kg bw groups, respectively. All the five animals died receiving the highest tested dose of 908 mg/kg bw.

Clinical signs:

other: Four males in the 512 mg/kg bw group had yellowish anogenital staining during early study period and one of these animals had diarrhoea. Several animals in the 620, 750 and 908 mg/kg bw showed anogenital staining, diarrhoea, brown staining around the mout

Gross pathology:

Changes were observed in the adrenal glands, brain, kidneys, stomach and intestines for more than one and half of all rats died during study. Abnormalities in the liver were found in of 7/15 of the dead rats. No significant changes for all tissues examined for rats that were terminally sacrificed, including control group.

Any other information on results incl. tables

In the range-finding study, all the rats dosed at 1000, 1500 and 2000 mg/kg bw died while rats dosed at 500 mg/kg bw survived.

Mortality and other observations

Table 1.                           Table for Acute Toxicity
Dose [mg a.s./kgbw]	Number of dead / number of investigated	Time of death (range)	Observations
0	0/10		No findings
169	0/10		Four females had wet yellow anogenital staining early in the study period. One of these also had diarrhea and one male had slight dried brown staining around the mouth. There were no other findings.
205	3/10	Found dead day 3	Anogenital staining, diarrhea, brown staining around the mouth, evidence of respiratory distress (respiratory rales and/or bradypnea), ataxia, lethargy, salivation, and hypothermia
248	7/10	Found dead day 1-3	Similar, but higher incidence.
300	5/5	Found dead day 1-3	diarrhea, wet yellow and/or brown urogenital staining, and respiratory distress (rales and bradypnea). Ataxia and lethargy were noted for three of the five rats. Other findings in this group included clear ocular discharge, hypothermia, tremors and various stains around the mouth
LD50 value	Male & female combined: 226 (207-245) mg a.i./kgbw

Applicant's summary and conclusion

Interpretation of results:

other: Category 3 based on CLP criteria

Conclusions:

Under the study conditions, the acute oral LD50 of the test substance in Sprague-Dawley rats was determined to be 684 mg test substance/kg bw (i.e., equivalent to 226 mg a.i./kg bw)

Executive summary:

A study was conducted to determine the acute oral toxicity of the test substance, Coco TMAC (33% active in water), in Sprague-Dawley rats according to OECD 401 and EPA OPP 81-2 Guidelines, in compliance with GLP. Groups of 10 fasted animals (five males and five females per dose except for five males only at the highest dose) were administered 0, 512, 620, 750 or 908 mg/kg bw of the test substance (i.e., equivalent to 0, 169, 205, 248 and 300 mg a.i./kg bw) via the oral route. The animals were observed for 14 days after dosing and then sacrificed and subjected to gross pathological examination. There was no mortality in the 512 mg/kg bw (or 169 mg a.i./kg bw) group while 3 out of 10 and 7 out of 10 rats died in the 620 mg/kg bw (or 205 mg a.i./kg bw) and 750 mg/kg bw (or 248 mg a.i./kg bw) groups, respectively. All five animals in the highest dose group (908 mg/kg bw or 300 mg a.i./kg bw) died. Under the study conditions, the acute oral LD50 of the test substance in Sprague-Dawley rats was determined to be 684 mg/kg bw (or 226 mg a.i./kg bw) with 95% confidence limits of 629 -743 mg/kg bw (or 207-245 mg a.i./kg bw) (Naas, 1987).