Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From June 11, 1980 to August 13, 1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1980
Report date:
1980

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
Not applicable
GLP compliance:
no
Remarks:
Pre-GLP
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Reference substance name:
Quaternary ammonium compounds, dicoco alkyldimethyl, chlorides
EC Number:
263-087-6
EC Name:
Quaternary ammonium compounds, dicoco alkyldimethyl, chlorides
Cas Number:
61789-77-3
Molecular formula:
Details not available
IUPAC Name:
Quaternary ammonium compounds, dicoco alkyldimethyl, chlorides
additive 1
Chemical structure
Reference substance name:
Water
EC Number:
231-791-2
EC Name:
Water
Cas Number:
7732-18-5
Molecular formula:
H2O
IUPAC Name:
water
additive 2
Chemical structure
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
Test material form:
not specified

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Sprague-Dawley, Madison, USA
- Age at study initiation: approximately 7 wk
- Weight at study initiation: 202-300 g
- Fasting period before study: Overnight
- Housing: 5 animals/sex/cage
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 7 d

ENVIRONMENTAL CONDITIONS
The animals were kept in temperature and humidity controlled quarters

IN-LIFE DATES: From: June 11, 1980 To: August 13, 1980

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED:
The average specific gravity of test substance was 890 mg/mL and the highest dose level was 3200 mg/kg bw. The maximum volume given to the animals was, therefore, 2.85 mL/kg bw.
Doses:
270, 430, 670, 1050, 1310, 2050 and 3200 mg/kg bw

No. of animals per sex per dose:
8
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 d
- Frequency of observations and weighing: animals were observed 1, 2.5, and 4 h after dosing. After that the animals were observed daily for clinical signs and twice daily for mortality. The bodyweight of the animals were determined at Day 0, 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: no
Statistics:
No data

Results and discussion

Preliminary study:
Not applicable
Effect levelsopen allclose all
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
ca. 930 mg/kg bw
95% CL:
ca. 750 - ca. 1 140
Remarks on result:
other: equivalent to 698 mg a.i./kg bw (563 - 855)
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
ca. 1 000 mg/kg bw
95% CL:
ca. 250 - ca. 4 090
Remarks on result:
other: equivalent to 750 mg a.i./kg bw (188 - 3068)
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 960 mg/kg bw
95% CL:
ca. 630 - ca. 1 470
Remarks on result:
other: equivalent to 720 mg a.i./kg bw (473 - 1103)
Mortality:
No rats died in the 270 and 430 mg/kg bw groups. All rats died in the 2050 and 3200 mg/kg bw groups. There was a decreased level of mortality in the females at 1310 mg/kg bw compared to the two lower doses and to males at the same dose.
Clinical signs:
Clinical signs such as diarrhoea, red stained around nose and mouth, hair loss, ataxia, decreased limb tone and hypoactivity were reported during the course of the study in most animals in the 670 mg/kg bw, 1050 mg/kg bw, 1310 mg/kg bw, 2050 mg/kg be and 3200 mg/kg bw
Body weight:
Reduced body weight gain was evident at doses of 670 mg/kg bw and above.



Gross pathology:
- The major signs reported at necropsy in animals that died during the study were external signs of diarrhoea and bloody discharge from the nose eyes and mouth.
- Adhesions involving the stomach and surrounding structures were seen at 1310 mg/kg bw, and were thought to suggest the presence of an inflammatory lesion involving the entire wall of the stomach with extension from the gastric serosa to adjacent tissues and healing fibrosis.
- Animals which received the higher dosage levels and died on test sooner possibly did not have adequate time for the lesion to develop. All other observations were considered incidental and not test related. A number of females that died during the study were partially cannibalised.
Other findings:
Dosage level of 270 mg/kg bw
Sixteen rats (eight male, eight female) were euthanized at the termination of the study and necropsied. Five of the males had lesions observed in the lungs which varied from red or white, pinpoint foci to a dark red, firm lobe. These lesions were noted to involve either the whole lung or a portion of one-lobe. The stomach in one female was noted to have a mildly thickened cardia mucosa. There were no visible lesions observed in the remaining animals.

Dosage level of 430 mg/kg bw
Sixteen rats (eight male, eight female) were euthanized at the termination of the study and necropsied. The lungs in one male were noted to have mild, diffuse, pinpoint, white, raised areas. Two females were noted to have mild hydromecra. There were no visible lesions observed in the remaining animals.

Dosage level of 670 mg/kg bw
Sixteen rats (eight male, eight female) were euthanized at the termination of the study and necropsied. Three males and five females died on test (DOT). One male DOT animal was noted to have a 4 mm crusty lesion on the skin of the right flank and the gastrointestinal tract distended with gas. The other two DOT male animals had a bloody nasal discharge and external signs of diarrhea (perianal fecal staining). Three of the DOT female animals had been partially cannibalized. The lungs in one of these three were noted to be mottled red to dark red and wet. Of the five DOT female animals, three had blood around the nose and mouth, one had a bloody ocular discharge, and two had external signs of diarrhea (perianal fecal staining). One female DOT animal had no visible lesions. The remaining animals in this group were euthanized at the termination of the study and except for scattered, white, raised areas (pinpoint to 1 mm in the lungs of one male, there were no visible lesions observed.

Dosage level of 1050 mg/kg bw
Sixteen rats (eight male, eight female) were necropsied. Two males and three females were euthanized at the termination of the study and had no visible lesions. The remaining ani!:ials died on test and each was noted to have external signs of diarrhea (perianal fecal staining). Four male and three female DOT animals had blood around the nose and mouth. One male and one female were noted to have a bloody ocular discharge. One female DOT animal had been cannabilized around the head and neck.

Dosage level of 1310 mg/kg bw
Sixteen animals (8 male, 8 female) were necropsied. Six males and four females died on test, all of which were noted to have external signs of diarrhea (perianal fecal staining). Two of the male DOT animals also had blood around the nose and mouth (one seen as bloody nasal discharge), as did all four of the female DOT animals. In addition, one female DOT animal had a bloody ocular dis­ charge and its tail was cannibalized. The remaining two males and four fe les were euthanized at the termination of the study. The stomach of each animal had adhesions .to the surrounding organs and/or abdominal wail. In addition, two of the females were noted to have small (4 mm and 8 mm) ulcers at the base of the tail. The spleen in each of the remaining two females was noted to be enlarged and the stomach wall (cardia) in one was greatly thickened.

Dosage level of 2050 mg/kg bw
Sixteen rats (eight male, eight female) were necropsied. All died on test and each.was noted to have external signs of diarrhea (perianal fecal staining). Eleven animals had blood around the nose and mouth and five had a bloody ocular discharge.

Dosage level of 3200 mg/kg bw
Sixteen rats (eight male, eight female) were necropsied. All the animals died on test. One male had no visible lesions. Each of the remaining animals had external signs of diarrhea (perianal fecal staining). Twelve animals had blood around the nose and/or mouth, two of which were seen as a.nasal discharge. Seven animalshad a bloody ocular discharge.

Any other information on results incl. tables

Table 1. Mortality rates in male and female rats administered the test substance by gavage

Dose (mg/kg bw)

Male Mortality

Female Mortality

270

0/8

0/8

430

0/8

0/8

670

3/8

5/8

1050

6/8

5/8

1310

6/8

4/8

2050

8/8

8/8

3200

8/8

8/8

 

For result details, kindly refer to the attached background material section of the IUCLID.

Applicant's summary and conclusion

Conclusions:
Under the studyconditions, the acute oral LD50 of test substance in rats was determined to be 960 mg/kg bw (630 - 1470) [equivalent to 720 mg a.i./kg bw (473 - 1103)].
Executive summary:

A study was performed to determine the acute oral toxicity of the test substance, C12-18 DAQ (75% active in hydroalcoholic solution), according to the method equivalent or similar to OECD guideline 401.The test substance was administered undiluted by gavage to groups of 8 male and 8 female rats at dose levels of 270, 430, 670, 1050, 1310, 2050 and 3200 mg/kg bw. The animals were observed 1, 2.5, and 4 h after dosing. After that the animals were observed daily for clinical signs and twice daily for mortality. The bodyweight of the animals were determined at Day 0, 7 and 14. Necropsy was performed on all animals.A decrease in bodyweight was observed for animals at higher dose levels.None of the animals of both sexes died at 270 and 430 mg/kg bw; all animals died at 2050 and 3200 mg/kg bw.In the surviving animals no specific lesions were detected. Some animals had discoloration of the lungs others showed mild hydrometra of the uterus, ulcer on the tail or adhesion of the non glandular region of the stomach to liver, spleen, cecum and abdominal wall. The signs observed in the animals that died during the study were: diarrhea, bloody nasal discharge or blood around the nose and mouth, bloody ocular discharge.Under the studyconditions, the acute oral LD50 of the test substance in rats was determined to be 960 mg/kg bw (630 - 1470) [equivalent to720 mg a.i./kg bw (473 - 1103)] (Thompson, 1980).

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