Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
07 Mar - 29 Mar 2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-Guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001
Report Date:
2001

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
adopted 22 March 1996
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
The Department of Health of the Government of the United Kingdom
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 8 weeks
- Weight at study initiation: males: 227 - 249 g; females: 201 - 230 g
- Fasting period before study: overnight
- Housing: animals were housed in groups of three by sex in solid-floor polypropylene cages with woodflakes
- Diet: Rat and Mouse Expanded Diet No. 1 (Special Diet Services Limited, Witham, UK), ad libitum
- Water: mains drinking water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25
- Humidity (%): 30 - 70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
arachis oil
Remarks:
Only for the 200 mg/kg bw dose level, the test material was prepared as solution in arachis oil. For the 2000 mg/kg dose level, the test material was used ad supplied.
Details on oral exposure:
VEHICLE
- Justification for choice of vehicle: test material did not dissolve or suspend in distilled water

MAXIMUM DOSE VOLUME APPLIED: 1.83 mL/kg bw (2000 mg/kg bw); 10 mL/kg bw (200 mg/kg bw)

Doses:
2000 mg/kg bw (step 1)
200 mg/kg bw (step 2)
No. of animals per sex per dose:
3 females at 2000 mg/kg bw
3 males and females at 200 mg/kg bw
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days. Individual bodyweights were recorded prior to dosing and 7 and 14 days after treatment or at death.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 300 - 500 mg/kg bw
Based on:
test mat.
Remarks on result:
other: according to Appendix 3c in OECD Guideline 423 (adopted Mar 1996)
Mortality:
Two animals treated with 2000 mg/kg bw were found dead one or three days after dosing. One animal treated with 2000 mg/kg bw was killed in extremis one day after dosing. No mortalities were observed at a dose level of 200 mg/kg bw until the end of the study.
Clinical signs:
Signs of systemic toxicity noted at a dose level of 2000 mg/kg bw were hunched posture, lethargy, decreased respiratory rate, gasping, laboured and noisy respiration, ataxia, ptosis, dehydration, increased lachrymation, hypothermia, body tremors, prostration, chromodacryorrhea, loss of righting reflex, pilo-erection and splayed gait. Two animals treated with 2000 mg/kg bw were found comatose 4 hours or 1 day after dosing. Signs of systemic toxicity noted at a dose level of 200 mg/kg bw were hunched posture, lethargy, ataxia, decreased respiratory rate, laboured respiration, increased salivation and splayed gait.
Body weight:
All surviving animals showed expected gains in bodyweight over the study period.
Gross pathology:
Abnormalities noted at necropsy of animals that died or were killed in extremis during the study were haemorrhagic lungs, dark liver or patchy pallor of the liver, dark kidneys, haemorrhage and sloughing of the gastric mucosa, sloughing of the non-glandular region of the stomach and haemorrhagic small intestine. No abnormalities were noted at necropsy of animals that were killed at the end of the study.

Any other information on results incl. tables

Table 1. Results of the acute toxicity study.

Dose level (mg/kg bw)

Mortalities

Male

Female

2000

-

3/3

200

0/3

0/3

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In this acute oral toxicity study in rats a LD50 value of > 300 - 500 mg/kg bw was found.