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Administrative data

Description of key information

The oral LD50 value of Bis-Tes (dried) in Wistar rats was established to exceed 2000 mg/kg body weight.
According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
24 June 2014 to 11 July 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted following OECD/EU guideline "Principles on Good Laboratory Practice (GLP) (as revised in 1997), ENV/MC/CHEM (98) 17" and in accordance with GLP. Study material is well characterized.
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany.
- Age at study initiation: Young adult animals (approx. 8 weeks old)
- Weight at study initiation: . Body weight variation did not exceed +/- 20% of the sex mean.
- Fasting period before study: Animals were deprived of food overnight prior to dosing and until 3-4 hours after administration of the test substance.
- Housing: Group Housing of 3 animals per cage
- Diet (e.g. ad libitum): Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water (e.g. ad libitum): ad libitum
- Acclimation period: .

ENVIRONMENTAL CONDITIONS

- Temperature (°C): Environmental controls for the animal room were set to maintain 18 to 24°C,
- Humidity (%): 40 to 70%
- at least 10 air changes/hour
- Photoperiod (hrs dark / hrs light):12-hour light/12-hour dark cycle.

Any variations to these conditions were maintained in the raw data and had no effect on the outcome of the study

IN-LIFE DATES: Start : 24 June 2014
Completion : 11 July 2014
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
The toxicity of the test substance was assessed by stepwise treatment of groups of 3 females. The first group was treated at a dose level of 2000 mg/kg. 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:
Single dosage on Day 1.
2000 mg/kg (2.381 mL/kg) body weight.
Dose volume calculated as dose level (g/kg) / density (g/mL).
No. of animals per sex per dose:
3 females in 2 groups- total of 6 females rats dosed
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: periodic intervals on day 1 and once daily thereafter until day 15. Body weights
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:
Statistics:
The signs were graded according to fixed scales and the time of onset, degree and duration were recorded:
Maximum grade 4: grading slight (1) to very severe (4) Maximum grade 3: grading slight (1) to severe (3) Maximum grade 1: presence is scored (1).
Sex:
female
Dose descriptor:
approximate LD50
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 3. No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD50 value)
Mortality:
No mortality occurred.
Clinical signs:
Hunched posture was noted for all animals on Days 1 and 2. Additionally, piloerection was noted for three animals on Days 1 and 2.
Body weight:
The body weight 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:
No abnormalities were found at macroscopic post mortem examination of the animals.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The oral LD50 value of Bis-Tes (dried) in Wistar rats was established to exceed 2000 mg/kg body weight.

According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.

Based on these results, Bis-Tes (dried) does not have to be classified and has no obligatory labelling requirement for acute oral toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2011) (including all amendments) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures (including all amendments).
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for selection of acute toxicity – oral endpoint
The oral LD50 value of Bis-Tes (dried) in Wistar rats was established to exceed 2000 mg/kg body weight.

According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.

Justification for classification or non-classification

The oral LD50 value of Bis-Tes (dried) in Wistar rats was established to exceed 2000 mg/kg body weight. According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight. Based on these results, Bis-Tes (dried) does not have to be classified and has no obligatory labelling requirement for acute oral toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2011) (including all amendments) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures (including all amendments)