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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
04 JULY 2016 - xxxxxxx
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2016

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Osalmid
EC Number:
208-385-9
EC Name:
Osalmid
Cas Number:
526-18-1
Molecular formula:
C13H11NO3
IUPAC Name:
2-hydroxy-N-(4-hydroxyphenyl)benzamide
Test material form:
solid
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material:20160401
- Expiration date of the lot/batch: April 2019
- Purity test date:99.20%

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature
- Quantity: 69.00 g (container + content)
- Appearance: solid
- Colour: white



FORM AS APPLIED IN THE TEST (if different from that of starting material)

OTHER SPECIFICS:

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Elevage JANVIER LABS (53940 Le Genest St Isle –France)
- Females (if applicable) nulliparous and non-pregnant: Yes
- Age at study initiation: 8 weeks old
- Weight at study initiation: 194.2 ± 6.4
- Fasting period before study: Food was removed on D-1 and then redistributed 4 hours after the test item administration.
- Housing: bottomed clear polycarbonate cages with a stainless steel mesh lid. Each cage contains sawdust bedding which was changed at least 2 times a
week.
- Diet (e.g. ad libitum): foodstuff (A04C, SAFE) ad libitum
- Water (e.g. ad libitum): tap-water from public distribution system ad libitum
- Acclimation period: ≥ 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19°C to 25°C
- Humidity (%): 30% to 70%,
- Air changes (per hr): ≥10/hr
- Photoperiod (hrs dark / hrs light): 12 hrs dark/ 12 hrs light

IN-LIFE DATES:
From: 12 July 2016 To: 26 July 2016

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
DMSO
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 10 mL/kg body weight
- Amount of vehicle (if gavage): 10 mL


MAXIMUM DOSE VOLUME APPLIED:

DOSAGE PREPARATION (if unusual):
The preparations were stirred by vortex and magnetically during 2 minutes to obtain yellowish solutions just before the administration.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The animals of the treated group received an effective dose of 2000 mg/kg body weight of the test item Osalmid (2-hydroxy-N-(4-hydroxy phenyl)benzamide. This dose is used according to O.E.C.D. Test Guideline No. 423, which recommend this dose as Step 1
Doses:
2.0010 g and 2.0000 g of the test item were weighed dimethyl sulfoxide was added to two 10 mL volumetric flask
No. of animals per sex per dose:
3
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days (or other?)
- Frequency of observations and weighing: The animals were weighed on day D0 (just before administering the test item) then on D2, D7, and D14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: Spontaneous activity , Preyer’s reflex (noise), Respiratory rate, Convulsion , Tremors, Body temperature, muscle tone, palpebral opening, pupil appearance, salvation, llachrymation, righing reflex, back hair appearance.
Statistics:
Weight diferences between observation days were calculated and compared between control group and treated group

Results and discussion

Preliminary study:
Clinical examinations: Nothing to report. Animal normal (3/3)
Bodyweight evolution: normal during the test
Necropsy: No treatment related changes were observed
Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
act. ingr.
Mortality:
One animal (1/6) was found dead at one hour post dose
Clinical signs:
In the surviving animals (5/6), a decrease or absence of spontaneous activity (4/5), Preyer’s reflex (4/5), muscle tones (4/5) and righting reflex (4/5), associated with bradypnea (1/5) or dypsnea (3/5), myosis (1/5) and eye partially closed (1/5) were noted in first hour post dose. The animals recovered a normal behaviour at 3 hours post dose.
Body weight:
The body weight evolution of the animals remained normal.
Gross pathology:
The macroscopic examination of the animals at the end of the study did not reveal treatment related changes.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 of the test item Osalmid (2-hydroxy-N-(4-hydroxy phenyl)benzamide is higher than 2000 mg/kg body weight by oral route in the rat.
In accordance with the O.E.C.D. Test Guideline No. 423, the LD50 cut-off of the test item may be considered as 2500 mg/kg body weight by oral route in the rat.
The test item Osalmid (2-hydroxy-N-(4-hydroxy phenyl)benzamide does not have to be classified in accordance with the Regulation EC No. 1272/2008 on classification, labelling and packaging of substances and mixtures.
No signal word or hazard statement is required.