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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
26 June 2001 to 12 July 2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
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)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: Solid. The test article was stored in the dark under nitrogen immediately prior to formulation.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: Young adult animals approximately 7 weks old
- Weight at study initiation: The bodyweight variation did not exceed ±20% of the sex mean
- Fasting period before study: Food was withheld overnight (for a maximum of 20 hours) prior to dosing until approximately 3-4 hours after administration of the test substance.
- Housing: Group housing of three animals per sex per cage in laballed cages (type IV; height 15 cm) containing purified sawdust as bedding.
- Diet: Free access to standard pelleted laboratory animal diet supplied by Altromin (code VRF 1), Lage, Germany
- Water: Free access to tap water
- Acclimation period: At least five days


ENVIRONMENTAL CONDITIONS
- Temperature: 21 ± 3 °C
- Humidity: Relative humidity 30 to 70%
- Air changes: The rate of air exchange was at approximately fifteen changes per hour
- Photoperiod: 12 hours artificial fluorescent light and 12 hours dark per day

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: Poly alpha olefin
Details on oral exposure:
VEHICLE
- Concentration in vehicle: The formulations (w/w) were prepared within 4 hours prior to dosing to give a dose level of 2000mg/kg bodyweight
- Amount of vehicle: Not stated
- Justification for choice of vehicle: The vehicle was selected based on information provided by the sponsor
- Lot/batch no. (if required): Not stated
- Purity: Not stated

MAXIMUM DOSE VOLUME APPLIED: 10mL/kg bodyweight

DOSAGE PREPARATION (if unusual): To dissolve the substance, ethyl acetate was added to the test substance (final concentration in formulation preferably below 30%). After mixing, poly alpha olefin (supplied by sponsor) was added until the requested concentration was reached. This preparation method was selected, in mutual agreement with the sponsor, to facilitate dosing of a homogeneous formulation. It was indicated by the sponsor that by using this method the test substance is stable.

CLASS METHOD (if applicable)
- Ration for the selection of the starting dose: The toxicity of the test substance was assessed by stepwise treatment of groups of three animals. The first group was treated at a dose level of 2000 mg/kg bodyweight. The absence or presence of mortality of animals dosed at one step determined the next step, based on the test procedure defined in the guidelines. The onset, duration and severity of the signs of toxicity were taken into account for determination of the time interval between the dose groups.
Doses:
Three females dosed at 2000 mg/kg bodyweight, followed two days later by three males dosed at 2000 mg/kg bodyweight.
No. of animals per sex per dose:
3 females at 2000 mg/kg bodyweight
3 males at 2000 mg/kg bodyweight
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were made on the day of dosing (day 1) and once daily thereafter, until day 15. Mortality/viability checks were made twice daily. Individual bodyweights were recorded on Day 1 (the day of dosing) and on Days 8 and 15.
- Necropsy of survivors performed: Yes
Statistics:
No statistical analysis was performed.

Results and discussion

Preliminary study:
Not applicable
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
- Lethal results: There were no deaths
Clinical signs:
- Non-lethal results: Lethargy, hunched posture and piloerection were noted among animals between days 1 and 3.
Body weight:
- Bodyweight results: The mean bodyweight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain.
Gross pathology:
- Gross pathology results: No abnormalities were noted at macroscopic post mortem examination of the animals.
Other findings:
No data reported

Any other information on results incl. tables

Table1: Clinical Signs

 

Test Day

1

1

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

Hours After Treatment

0

2

4

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Female at 2000 mg/kg

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Animal 1

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Behaviour - Lethargy

-

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

Posture – Hunched Posture

-

-

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Skin/Fur/Plumage - Piloerection

-

-

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

Female at 2000 mg/kg

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Animal 2

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Behaviour - Lethargy

-

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

Posture – Hunched Posture

-

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Skin/Fur/Plumage - Piloerection

-

-

1

1

 

-

-

-

-

-

-

-

-

-

-

-

-

Female at 2000 mg/kg

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Animal 3

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Behaviour - Lethargy

-

2

2

1

-

-

-

-

-

-

-

-

-

-

-

-

-

Posture – Hunched Posture

-

1

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

Skin/Fur/Plumage - Piloerection

-

-

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

Male at 2000 mg/kg

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Animal 1

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Behaviour - Lethargy

-

1

.

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Posture – Hunched Posture

-

1

.

1

-

-

-

-

-

-

-

-

-

-

-

-

-

Skin/Fur/Plumage - Piloerection

-

1

.

1

-

-

-

-

-

-

-

-

-

-

-

-

-

Male at 2000 mg/kg

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Animal 2

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Behaviour - Lethargy

-

1

.

1

-

-

-

-

-

-

-

-

-

-

-

-

-

Posture – Hunched Posture

-

1

.

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Skin/Fur/Plumage - Piloerection

-

1

.

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Male at 2000 mg/kg

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Animal 3

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Behaviour - Lethargy

-

1

.

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Posture – Hunched Posture

-

1

.

1

-

-

-

-

-

-

-

-

-

-

-

-

-

Skin/Fur/Plumage - Piloerection

-

1

.

1

-

-

-

-

-

-

-

-

-

-

-

-

-

- = sign not observes,. = Observation not made, + = Animal dead

Applicant's summary and conclusion

Interpretation of results:
other: Criteria for classification as an acute oral toxicant not met
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The acute oral median lethal dose (LD50) of in both the male and female Wistar strain rat was estimated to be greater than 2000 mg/kg bodyweight.
Executive summary:

Introduction. 

The study was performed to assess the acute oral toxicity of the test material in the Wistar strain rat.The acute oral toxicity of the test item to the Wistar strain rat was assessed in a GLP-compliant study following OECD guideline 423 (adopted 1996) andEU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)in a proprietary, experimental study (NOTOX 2013). The study is considered reliable and relevant for use for this endpoint.

Method. 

A group of three fasted females was given a single oral dose of test material, as a suspension in poly alpha olefin, at a dose level of 2000 mg/kg bodyweight. A group of three fasted males were treated in the same way. Clinical signs and bodyweight development were monitored during the study period of 15 days (starting from day of dosing). All animals were subjected to gross necropsy.

Mortality. 

There were no deaths.

 

Clinical Observations.

Lethargy, hunched posture and piloerection were noted among animals between days 1 and 3.

 

Bodyweight. 

The mean bodyweight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain.

 

Necropsy. 

No abnormalities were noted at macroscopic post mortem examination of the animals..

 

Conclusion. 

The acute oral median lethal dose (LD50) of in both the male and female Wistar strain rat was estimated to be greater than 2000 mg/kg bodyweight.