Ethanol, 2-[(3-nitropyrazolo[1,5-a]pyridin-2-yl)oxy]-

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 03 October 2014 to 16 December 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well described study performed according to OECD guideline and GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-[(3-nitropyrazolo 1,5-a] pyridine-2-yl)oxyethanol

IUPAC Name:

2-[(3-nitropyrazolo 1,5-a] pyridine-2-yl)oxyethanol

Constituent 2

Reference substance name:

R0056895A

IUPAC Name:

R0056895A

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Test animals

Species:

rat

Strain:

other: CRL:(WI)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, D-97633 Sulzfeld
- Age at study initiation: 10 weeks old
- Weight at study initiation: 230 – 249 g
- Fasting period before study: on the night before treatment (food only)
- Housing: 3 animals / cage (type II polypropylene/polycarbonate)
- Diet: ssniff® SM R/M "Autoclavable complete diet for rats and mice – breeding and maintenance", ad libitum
- Water: tap water from the municipal supply, ad libitum
- Acclimation period: at least 19 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20.5 – 24.3°C
- Humidity: 36 – 65 %
- Air changes: 15 – 20 air exchanges/hour
- Photoperiod: 12 hours daily, from 6.00 a.m. to 6.00 p.m.

IN-LIFE DATES: From 18 September 2014 to 22 October 2014

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 1% methyl cellulose

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: -

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

CLASS METHOD
- Rationale for the selection of the starting dose: in the lack of any preliminary toxicological information, 2000 mg/kg bw was selected to be the starting dose.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

2x3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
> Clinical observations were performed on all animals at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter.
> The body weight was recorded on the day before treatment (Day -1), on the day of the treatment (Day 0) and weekly thereafter.
- Necropsy of survivors performed: yes

Statistics:

not applicable

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortality

Mortality:

R0056895A did not cause mortality at a dose level of 2000 mg/kg bw.

Clinical signs:

other: At the dose level of 2000 mg/kg bw, the test item caused decreased activity and hunched back were observed in all animals and piloerection in three animals. All animals were symptom free from 6 hours after the treatment until the end of the observation pe

Gross pathology:

No evidence of the macroscopic observations at a dose level of 2000 mg/kg bw.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral LD50 value of R0056895A was found to be above 2000 mg/kg bw in female CRL:(WI) rats.

Executive summary:

The single-dose oral toxicity of R0056895A was performed according to the acute toxic class method (OECD 423 and Commission Regulation (EC) No 440/2008 of 30 May 2008, B.1.Tris) in CRL:(WI) rats.

Under the conditions of this study, the acute oral LD50 value of R0056895A was found to be above 2000 mg/kg bw in female CRL:(WI) rats. The only effects observed were a decreased activity, hunched back and piloerection, but all animals were symptom free from 6 hours after the treatment until the end of the observation period.