Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
12 Nov - 3 Dec 1996
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report Date:
1996

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
adopted 24 Feb 1987
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Version / remarks:
Commission Directive 92/69/EEC
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:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Remarks:
Crl: CD®BR
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Ltd., Margate, UK
- Females nulliparous and non-pregnant: not specified
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: 221 - 239 g (males) and 213 - 233 g (females)
- Fasting period before study: Animals were fasted overnight prior to dosing and approx. 4 h after dosing.
- Housing: in groups of up to 5 animals by sex in solid-floor polypropylene cages, wood flakes bedding
- Diet: Rat and Mouse Expanded Diet No. 1 (Special Diets Services Limited, Witham, Essex, UK), ad libitum
- Water: mains drinking water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 21
- Humidity (%): 46 - 55
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
DMSO
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle: 10 mL/kg bw

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
Range-finding study: 1 male and 1 female
Main study: 5 males and 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for deaths or overt signs of toxicity 1/2, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days. Individual body weights were recorded prior to dosing on Day 0 and on Days 7 and 14 or at death.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, gross pathology

Results and discussion

Preliminary study:
In the range-finding study, no deaths were reported. Clinical signs of toxicity noted were ataxia, hunched posture, lethargy, pilo-erection, ptosis, decreased respiratory rate, laboured respiration and splayed gait. Based on this information, a dose level of 2000 mg/kg body weight was selected for the main study.
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
2/5 males were found dead 2 days after dosing.
Clinical signs:
Common signs of systemic toxicity noted for were ataxia, hunched posture, lethargy, decreased respiratory rate and laboured respiration with additional signs of ptosis, increased salivation and red/brown stains around the mouth or snout. lncidents of systemic toxicity noted were pilo-erection, gasping and noisy respiration, loss of righting reflex and splayed gait. Surviving animals recovered 3 - 6 days after dosing.
Body weight:
Surviving animals showed expected gain in body weight during the study except for one female which showed body weight loss during the first week and expected gain in bodyweight during the second week.
Gross pathology:
Abnormalities noted at necropsy of the males that died during the study were haemorrhagic lungs, dark liver and dark kidneys. 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 oral toxicity study.

Dose level

(mg/kg bw)

Mortalities

Clinical signs

 

n

n

males

2000

2/5

5/5

females

2000

0/5

5/5

Applicant's summary and conclusion

Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
In this acute oral toxicity study in rats an LD50 value of > 2000 mg/kg bw was found.
Executive summary:

A study was performed to assess the acute oral toxicity of the test material in the Sprague-Dawley CD strain rat according to OECD Guideline 401. A group of ten fasted animals (five males and five females) was given a single oral dose of test material as a solution in dimethyl sulphoxide at a dose level of 2000 mg/kg bodyweight. The animals were observed for fourteen days after the day of dosing and were then killed and subjected to gross pathological examination. Two males were found dead two days after dosing. Common signs of systemic toxicity noted were ataxia, hunched posture, lethargy, decreased respiratory rate and laboured respiration with additional signs or incidents of pilo-erection, ptosis, gasping and noisy respiration, loss of righting reflex, increased salivation, red/brown stains around the mouth or snout and splayed gait. Surviving animals recovered three to six days alter dosing. The LD50 was > 2000 mg/kg.