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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2 Jun to 19 Jun 1998
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report date:
1998

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
Adopted 24 Feb 1987
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Version / remarks:
EEC methods for the determination of toxicity, Annex to Directive 92/69/EEC (OJ No. L383A, 29.12.92), Part B, Method B.1. Acute toxicity (oral)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Test animals

Species:
rat
Strain:
Sprague-Dawley
Remarks:
CD
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan UK Ltd, Bicester, Oxon, England
- Age at study initiation: five to seven weeks
- Weight at study initiation: 100 to 114 g
- Fasting period before study: overnight prior to and for 4 h after dosing
- Housing: metal cages with wire mesh floors, in groups of five rats by sex
- Diet: Special Diet Services RM1(E) SQC expanded pellet, ad libitum
- Water: drinking water, ad libitum
- Acclimation period: eight days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1.5 °C
- Humidity (%): 40-60
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 02 Jun 1998 To: 19 Jun 1998

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 1% w/v aqueous methylcellulose
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 20% (w/v) in 1% (w/v) aqueous methylcellulose
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: no data

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION: the substance was prepared on the day of dosing

CLASS METHOD
- Rationale for the selection of the starting dose: The dose level chosen for the main study was based on results of a preliminary study.
Doses:
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: animals were observed soon after dosing and at frequent intervals for the remainder of the day of dosing (Day 1), then twice per day with the exception of Day 15 - morning only. The nature and severity of clinical signs was recorded at each observation. Individual body weights were recorded prior to dosing (Day 1), and on Days 8, and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: no
Statistics:
Means were calculated on body weights.

Results and discussion

Preliminary study:
A group of two rats (one male and one female) were dosed at 1000 mg/kg bw. Clinical signs were confined to piloerection, hunched posture, waddling/unsteady gait and abnormal faeces (soft to liquid or yellow/brown in colour), seen in both animals. Recovery was complete by Day 8. There were no deaths. Bodyweight gains were considered satisfactory, and no macroscopic abnormalities were noted at the terminal necropsy on Day 8.
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Clinical signs:
Signs of toxicity related to dose levels:
Clinical signs seen on the day of dosing were hunched posture (day of dosing only) and piloerection (within 6 minutes of dosing) in 10/10 animals. There were no other clinical signs, and 10/10 animals were observed to have fully recovered by Day 5 of the study.
Body weight:
All animals were considered to have achieved satisfactory bodyweight gains throughout the study.
Gross pathology:
Effects on organs:
All animals were free of macroscopic postmortem abnormalities at necropsy.

Any other information on results incl. tables

 Table 1 Clinical Signs and Mortality

Signs

No. of rats in Groups of 1#or 5 showing signs

Dose (1000 mg/kg bw)

Dose (2000 mg/kg bw)

Male

Female

Male

Female

Piloerection

 1

5

Hunched posture

 1

5

Waddling/unsteady gait

 1

 0

0

Abnormal faeces##

 1

 0

0

 Mortality

 0  0  0  0

#= Preliminary study comprised of one male and one female

##= Characterised by discoloured soft to liquid, yellow/brown faeces

Applicant's summary and conclusion

Interpretation of results:
other: CLP/EU GHS criteria are not met, no classification required according to Regulation (EC) No 1272/2008.
Conclusions:
The acute oral LD50 of the test substance in Sprague-Dawley CD rats was estimated according to this OECD 401 as being > 2000 mg/kg bw.