Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
May 09, 2006 - June 28, 2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006
Report Date:
2006

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
other: 2004/73/EC B.1 tris (acute-toxic-class-method)
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
, 2001
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
signed 2005-11-21
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Name: BIO 1031/1
Substance type: pure active substance
Physical state: solid
Storage condition of test material: ambient temp., dark, dry, in original container

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Sprague-Dawley CD (Crl: CD (SD) IGS BR) strain rats were supplied by Charles River (UK) Ltd. The rats were nulliparous and non-pregnant.
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 208-224 g
- Fasting period before study: an overnight fast immediately before dosing
- Housing: The animals were housed in groups of three in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet: Certified Rat and Mouse Diet (Code 5LF2) supplied by BCM IPS Limited, London; ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature: 19-25 °C
- Humidity: 30-70%
- Air changes: 15 per hour
- Photoperiod: 12 hours light/dark cycle

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
All animals were dosed once only by gavage, using a metal cannula attached to a graduated syringe. The volume administered to each rats was calculated according to the fasted body weight at the time of dosing. Treatment of animals were sequential. Sufficient time was allowed between each group to confirm the survival of the previously dosed animals.
Doses:
Using available information on the toxicity of the test material, 2000 mg/kg was chosen as the starting dose.
No. of animals per sex per dose:
2 x 3 rats per dosing group (2000 mg/kg)
Control animals:
no
Details on study design:
- Duration of observation period following administration: The animals were observed for deaths or overt signs of toxicity 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days.
- Frequency of observations and weighing: Individual bodyweights were recorded prior to dosing and 7 and 14 days after treatment.
- Necropsy of survivors performed: yes; At the end of the observation period the rats were killed by cervical dislocation. All animals were subjected to gross pathological examination. This consisted of an external examination and opening of the abdominal and thoracic cavities for examination of major organs. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Evaluation of data: Data evaluations included the relationship, if any, between the exposure of the animal to the test material and the incidence and severity of all abnormalities including behavioural and clinical observations, gross lesions, bodyweight changes, mortality and any other toxicological effects. Using the mortality data obtained, an estimate of the acute oral median lethal dose (LD50) of the test material was made.
Statistics:
not applicable

Results and discussion

Preliminary study:
not applicable
Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
5 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
Signs of toxicity related to dose levels: Hunched posture and pilo erection were observed after one hour at one animal in group two.
Other signs of systemic toxicity noted during the study were hunched posture, lethargy, pilo-erection and decreased respiratory rate in all three animals in each group at a observation time at 4 hours. At observation day 2 no signs were noted.
Body weight:
All animals showed expected gains in bodyweight over the study period.
Gross pathology:
No abnormalities were noted at necropsy.

Any other information on results incl. tables

Table 1: Individual clinical observations

Dose level (mg/kg)

Animal number and sex

Effects noted after dosing (hours)

Effects noted during period after dosing (days)

0.5

1

2

4

1

2-14

2000

1-0

female

0

0

0

HLP

Rd

HP

Rd

0

1-1

female

0

0

0

HLP

Rd

HP

Rd

0

1-2

female

0

0

0

HLP

Rd

HP

Rd

0

2-0

female

0

0

HP

HLP

Rd

HP

Rd

0

2-1

female

0

0

0

HLP

Rd

HP

Rd

0

2-2

female

0

0

0

HLP

Rd

HLP

Rd

0

H = hunched posture, L = lethargy, P = pilo-erection, Rd = decreased respiratory rate

Table 2: Individual bodyweights and weekly bodyweight changes

Dose level (mg/kg)

Animal number and sex

Bodyweight (g) at day

Bodyweight gain (g) during week

0

7

14

1

2

2000

1-0

female

208

237

261

29

24

1-1

female

210

248

250

38

2

1-2

female

209

239

251

30

12

2-0

female

224

257

279

33

22

2-1

female

214

235

270

21

35

2-2

female

210

253

259

43

6

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Since no deaths occurred in any of the 6 animal tested at the highest dose of 2000 mg/kg bw, according to the guideline the substance belongs to the Category 5 (GHS) “unclassified” and the corresponding LD 50 > 5000 mg/kg bw.