3-phenyl-1H-pyrazole-4-carbaldehyde

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 2020-10-07 to 2020-11-10

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2020

Report date:

2020

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

December 2001

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

May 2008

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

December 2002

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

3-phenyl-1H-pyrazole-4-carbaldehyde

EC Number:

632-673-7

Cas Number:

26033-20-5

Molecular formula:

C10H8N2O

IUPAC Name:

3-phenyl-1H-pyrazole-4-carbaldehyde

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch number of test material: M19LD3723
- Expiration date of the lot/batch: 2021-11-11 (retest date)
- Purity: 103.6%
- Purity test date: not indicated


STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at room temperature
- Stability under storage conditions: not indicated
- Stability under test conditions: not indicated
- Solubility and stability of the test substance in the solvent/dispersant/vehicle/test medium: not indicated


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

OTHER SPECIFICS
- Correction factor: 1.00

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: female rats (nulliparous and non-pregnant), Wistar strain Crl:WI (Han) (outbred, SPF-Quality); Charles River Deutschland, Sulzfeld, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8-9 weeks old
- Weight at study initiation: 143 - 191 kg
- Fasting period before study: animals were deprived of food overnight (for a maximum of 20 hours) prior to dosing and until 3-4 hours after administration of the test item. Water was available.
- Housing: group housed (up to 3 animals per of the same sex and same dosing group together) in polycarbonate labeled cages (Makrolon MIV type; height 18 cm.) containing sterilized sawdust as bedding material (Lignocel S 8-15, JRS - J.Rettenmaier & Söhne GmbH + CO. KG, Rosenberg, Germany) equipped with water bottles. For psychological/environmental enrichment, animals were provided with paper (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom), except when interrupted by study procedures/activities.
- Diet (e.g. ad libitum): ad libitum, free access to pelleted rodent diet
- Water (e.g. ad libitum): ad libitum, free access to municipal tap water via water bottles.
- Acclimation period: at least 5 days before the commencement of dosing.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-24 °C (actual: 21°C)
- Humidity (%): 40-70% (actual: 40-69%)
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 2020-10-08 To: 2020-11-10

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Remarks:

Polyethylene glycol 400

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30 and 200 mg/mL - Analysis of test item in vehicle for concentration was not performed.
- Amount of vehicle (if gavage): 10mL/kg
- Justification for choice of vehicle: The vehicle was selected based on trial preparations performed at Charles River Den Bosch and on test item data supplied by the Sponsor. The vehicle was chosen from (in order of preference): water (Elix) (test item did not dissolve), 1% aq. carboxymethyl cellulose (test item did not dissolve), propylene glycol (spec. gravity 1.036) (test item did not dissolve), polyethylene glycol 400 (spec. gravity 1.125) (yellow suspension) and corn oil (spec. gravity 0.92) (test item did not dissolve). There was no information available regarding the solubility or stability in vehicle. These trials were not performed as part of this study and these preparations were not used for dosing. Raw Data of these trials are retained by the Test Facility.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

DOSAGE PREPARATION (if unusual):
- Test item dosing formulations (w/w) were homogenized to visually acceptable levels at appropriate concentrations to meet dose level requirements.
The dosing formulations were kept at room temperature until dosing. The dosing formulations were stirred until and during dosing. No correction was made for purity of the test item.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The dose levels were based on the OECD test guidelines and were selected from the series 5 (lowest dose level), 50, 300 and 2000 (highest dose level) mg/kg body weight. Since it is the intention to minimize the number of animals to be used, a starting dose level of 300 mg/kg was selected by the Study Director, since limited toxicity data were available.

Doses:

300 and 2000 mg/kg body weight (single dosage)

No. of animals per sex per dose:

3 females per dose, 3 groups in total

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days (until day 15)
- Frequency of observations and weighing:
mortality/moribundity: twice daily, in the morning and at the end of the working day. Animals were not removed from cage during observation, unless necessary for identification or confirmation of possible findings.
body weights: days 1 (pre-dose), 8 and 15. A fasted weight was recorded on the day of dosing;
clinical signs: at periodic intervals on the day of dosing (at least three times) (day 1) and once daily thereafter. The observation period was 14 days. All the animals were examined for reaction to dosing. The onset, intensity and duration of these signs was recorded (if appropriate). Signs were graded for severity and the maximum grade was predefined at 3 or 4. Grades were coded as slight (grade 1), moderate (grade 2), severe (grade 3) and very severe (grade 4). For certain signs, only its presence (grade 1) or absence (grade 0) was scored.
- Necropsy of survivors performed: yes, all animals were sacrificed by oxygen/carbon dioxide procedure at the end of observation period. All animals assigned to the study were subjected to necropsy and descriptions of all internal macroscopic abnormalities recorded.

Statistics:

No statistical analysis was performed.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occured.

Clinical signs:

other:

Body weight:

other body weight observations

Remarks:

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

Gross pathology:

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

Any other information on results incl. tables

Number of dead animals in each test group with 3 animals each:

Females 300 mg/kg: 0

Females 2000 mg/kg: 0

Females 2000 mg/kg: 0

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The oral LD50 value of JNJ-39125190-AAA (T003897) in Wistar Han 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, JNJ-39125190-AAA (T003897) 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 (2017) (including all amendments) and Regulation (EC) No 1272/2008 on
classification, labelling and packaging of items and mixtures (including all amendments).