1H-Pyrazole-5-carboxylic acid, 3-bromo-1-(3-chloro-2-pyridinyl)-

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

October 4, 2005 - January 13, 2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well documented GLP & OECD guideline study.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)

Deviations:

yes

Remarks:

Dosing preparations were not analyzed for stability, homogeneity, or accuracy of concentration. The report concludes that this finding does not impact the validity of the study.

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

Dosing preparations were not analyzed for stability, homogeneity, or accuracy of concentration. The report concludes that this finding does not impact the validity of the study.

GLP compliance:

yes

Test type:

up-and-down procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

481-150-8

EC Name:

-

Cas Number:

500011-86-9

Molecular formula:

C9H5BrClN3O2

IUPAC Name:

3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid

Constituent 2

Reference substance name:

1H-Pyrazole-5-Carboxylic Acid, 3-Bromo-1-(3-Chloro-2-Pyridinyl)-

IUPAC Name:

1H-Pyrazole-5-Carboxylic Acid, 3-Bromo-1-(3-Chloro-2-Pyridinyl)-

Constituent 3

Reference substance name:

DBC 80

IUPAC Name:

DBC 80

Details on test material:

Synonyms/Codes:
- IN-DBC80
- IN-DBC80-008 (Batch Number)
- 1H-Pyrazole-5-carboxylic acid, 3-bromo-1-(3-chloro-2-pyridinyl)- (inverted CAS name)
-Purity: 96.7% by analysis

Test animals

Species:

rat

Strain:

other: CD (SD)IGS BR

Sex:

female

Details on test animals or test system and environmental conditions:

- All animals were housed singly in stainless steel, wire-mesh cages suspended above cage boards.
- Animal rooms were maintained at a temperature of 18-26°Celcius and a relative humidity of 30-70%.
- Animal rooms were artificially illuminated (fluorescent light) on an approximate 12-hour light/dark cycle.
- Excursions outside of these ranges were of insufficient magnitude and/or duration to have adversely affected the validity of the study.
- PMI Nutrition International, LLC Certified Rodent LabDiet 5002 and water were available ad libitum except during dosing.
- The rats were fasted approximately 16-18 hours prior to dosing, with food being returned to the rats approximately 3-4 hours after dosing.
- The rats were approximately 10 or 11 weeks old on the day of dosing.
- The rats were weighed and observed for general health during the quarantine period (at least 6 days).

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: acetone:corn oil (total volume was 15% acetone)

Details on oral exposure:

- IN-DBC80 was administered by oral gavage to one fasted female rat each at a dose of 175, 550, or 1750 mg/kg and to three fasted female rats at a dose of 5000 mg/kg.
- The rats were dosed one at a time at a minimum of 48-hour intervals.
- A software package (A0T425StatPgm) was used to determine the dose progression and to calculate the LD50.
- The dosing suspensions were stirred prior to and throughout the dosing procedure.
- Individual dose volumes were calculated using the fasted body weights obtained prior to dosing.
- The rats were dosed at a volume of 10 mL per kg of body weight.

Doses:

175, 550, 1750, and 5000 mg/kg.

No. of animals per sex per dose:

One each at 175, 550, and 1750 mg/kg and 3 at 5000 mg/kg.

Control animals:

not specified

Details on study design:

Observations for mortality and signs of illness, injury, or abnormal behavior were made daily. The rats were observed for clinical signs at the beginning of fasting, just before dosing (test day 0), once during the first 30 minutes after dosing and 2 more times on the day of dosing, and once each day thereafter. The rats were weighed on test days –1, 0, 7, and 14. On test day 14, the rats were euthanized and necropsied to detect grossly observable evidence of organ or tissue damage or dysfunction. The rats were anesthetized by carbon dioxide and euthanized by exsanguination.

Statistics:

A software package (A0T425StatPgm) was used to determine the dose progression and to calculate the LD50.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Mortality:

All rats survived until the scheduled sacrifice.

Clinical signs:

other: One of the rats dosed at 5000 mg/kg exhibited yellow-stained fur/skin of the perineum on test days 1 and 2. No clinical signs were observed in the remaining rats.

Gross pathology:

No gross lesions were present in the rats at necropsy.

Any other information on results incl. tables

Under the conditions of this study, the oral LD50 for IN-DBC80 was greater than 5000 mg/kg for female rats. In accordance with the provisions of Directive 67/548/EEC, classification is not required based on the results of this study. According to the U.S. EPA and under the conditions of this study, IN-DBC80 is classified in Toxicity Category IV.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD50 in female rats is greater than 5000 mg/kg.