Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
November-December 1986
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Complete report according to guidelines/standards.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1987
Report Date:
1987

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Appearance: clear, pale yellow coloured liquid
Date of receipt: 6 November 1986
Storage: room temperature

Test animals

Species:
rat
Strain:
other: Sprague-Dawley CFY
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Interfauna (UK) Ltd., Wyton, UK
- Age at study initiation: 5-8 weeks
- Weight at study initiation: 123-152 g (males), 120-146 g (females)
- Fasting period before study: overnight prior to dosing until ca. 2 hours after dosing
- Housing: 5/sex in solid floor polypropylene cages with sawdust bedding
- Diet (e.g. ad libitum): ad lib
- Water (e.g. ad libitum): ad lib
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23
- Humidity (%): 45-65
- Air changes (per hr): ca. 15
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 7 November To: 10 December 1986

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: neat test compound was used

MAXIMUM DOSE VOLUME APPLIED: 2.20 ml/kg bw
Doses:
1000, 1260, 1587, 2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations were made 1 and 4 h after dosing and once daily thereafter. BW were
measured weekly and at death
- Necropsy of survivors performed: yes
Statistics:
Method of Weil CS, Biometrics (1952), 8, 249

Results and discussion

Preliminary study:
A preliminary study was carried out using 2 groups of one male and one female each. Dose levels were 500 and 2000 mg/kg bw.
At 500 mg/kg the 2 animals survived, whereas both animals died at 2000 mg/kg bw.
Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 260 mg/kg bw
95% CL:
1 053 - 1 508
Sex:
male
Dose descriptor:
LD50
Effect level:
1 309 mg/kg bw
95% CL:
1 024 - 1 674
Sex:
female
Dose descriptor:
LD50
Effect level:
> 1 000 - < 1 587 mg/kg bw
Mortality:
All deaths occurred 2-3 days after treatment.
Clinical signs:
Major signs of toxicity noted in all dose groups during the day of dosing were hunched posture, pilo-erection, decreased respiratoryrate, increased salivation and ptosis. Surviving animals treated with 1000 mg/kg continued to show signs of toxicity on days one
and two. Most surviving animals from this group were normal on day three; occasional or isolated signs of pallor of the
extremities, ataxia, diarrhoea, diuresis and red/brown staining around the snout were noted on days three and four. All surviving
animals from this group were normal on day six. Surviving animals treated with 1260 mg/kg and above continued to show common signs of hunched posture, pilo-erection, lethargy, ataxia, decreased respiratory rate and ptosis with occasional signs of pallor of
the extremities, chromodacryorrhoea, diarrhoea, diuresis, emaciation, tiptoe gait and red/brown staining around the snout/eyes.
Signs of reactions continued to be noted in some survivors up to ten to thirteen days after treatment and in one female treated with 2000 mg/kg until termination. Increased lacrimation was noted on day one i n two decedents treated with 1260 mg/kg. Distended
abdomen was noted in one high dose animal on days seven to twelve.
Body weight:
All surviving animals treated with 1000 mg/kg and surviving females treated wtih 1260 and 1587 mg/kg showed expected body
weight gains over the study period. The majority of surviving males treated with 1260 mg/kg and above and the surviving high dose females showed body weight loss or marked reduced bodyweight gain at day seven. All these surviving animals recovered to
show expected body weight gain over the second week.
Gross pathology:
Common abnormalities noted at necropsy of decedents were congested or abnormally red lungs, dark livers, haemorrhage of the
gastric mucosa and congestion of the small intestines. Necropsy of animals killed at the end of the study revealed scattered
white thickened or raised areas on the non-glandular region of the stomach. The liver of two animals treated with 2000 mg/kg was adhering to the stomach. One decedent treated with 1000 mg/kg and two animals treated with 1587 mg/kg were cannabalised. No
necropsy was performed.
Other findings:
No data

Any other information on results incl. tables

Mortality data

Dose level (mg/kg bw)

Deaths

Male

Female

Total

%

1000

0/5

1/5

1/10

10

1260

3/5

3/5

6/10

60

1587

4/5

4/5

8/10

80

2000

3/5

4/5

7/10

70

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information
Conclusions:
The LD50 value was calculated to be 1260 mg/kg bw with 95% confidence limits of 1053 and 1508 mg/kg bw. The test compound was classied in Category IV according to OECD-GHS.
Executive summary:

A study was performed to determine the acute oral toxicity of the test material in the Sprague-Dawley CFY strain rat. The study was designed to comply with the recommendations o f the OECD Guidelines for Testing of Chemicals (1981) No. 401 "Acute Oral Toxicity". Following a range-finding study, four groups, each of ten fasted animals (five males and five females) were given a single oral dose of undiluted test material, at dose levels of 1000

t o 2000 mg/kg bodyweight. Deaths were noted two to three days after treatment. Major signs of toxicity noted during the day of dosing were hunched

posture, pilo-erection, lethargy , decreased respiratory rate, increased salivation and ptosis. Less frequent signs of ataxia, pallor of the extremities, diarrhoea, diuresis, chromodacryorrhoea, tiptoe gait, emaciation, red/brown staining around the snout/eyes were also noted. Signs of reaction continued to be noted up to three to fourteen days after treatment. Surviving animals treated with 1000 mg/kg showed expected body weight gains

over the study period. Effects on body weight were noted in other dose groups during the first week but all animals recovered to show expected

body weight gains over the second week. Necropsy of decedents revealed congested or abnormally red lungs, dark livers , haemorrhage of the gastric mucosa with congestion of the small intestines. Necropsy of animals killed at the end of the study revealed thickened or raised white areas on the non-glandular region of the stomach. The acute oral median lethal dose (LDS0) and 95% confidence limits were found to be:

All animals: 1260 (1053 - 1508) mg/kg body weight

Males only: 1309 (1024 - 1674) mg/kg body weight

Females only: between 1000 and 1587 mg/kg body weight (best estimate).