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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
May 12, 2006 - August 17, 2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well documented GLP & U.S. EPA guideline study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006
Report date:
2006

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1300 (Acute inhalation toxicity)
Deviations:
no
Remarks:
The study was conducted according to the guideline in effect at time of study conduct.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
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-DBC80-008A (IN-DBC80-008 was milled for inhalation testing and assigned IN-DBC80-008A)
- 1H-Pyrazole-5-carboxylic acid, 3-bromo-1-(3-chloro-2-pyridinyl)- (inverted CAS name)
- Purity: 96.7% by analysis
- Tan solid powder
- Test substance milled by sponsor to provide a particulate with a particle size of 1.8 μm.

Test animals

Species:
rat
Strain:
other: Crl:CD(SD)
Sex:
male/female
Details on test animals or test system and environmental conditions:
- Animals were quarantined after arrival for 6 days prior to testing.
- All animals were housed singly in stainless steel, wire-mesh cages suspended above cage boards.
- Animal rooms were maintained at a temperature of 18-26ºCelcius and a relative humidity of 30-70%.
- Animal rooms were artificially illuminated (fluorescent light) on an approximate 12-hour light/dark cycle.
- Except during exposure, PMI® Nutrition International, LLC Certified Rodent LabDiet® 5002 and tap water were available ad libitum.
- Male rats were approximately 10 weeks old and weighed between 330 and 375 grams at the time of exposure.
- Female rats were approximately 10 weeks old and weighed between 207 and 250 grams at the time of exposure.

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
nose only
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
The atmosphere was generated by suspension of the test substance in air with a Fluid Energy Processing model 00 jetmill. The test substance was metered into the jetmill with a K-Tron model T-20 Twin Screw volumetric feeder. Filtered, high-pressure air, metered into the jetmill, carried the resulting atmosphere through a 2-L glass cyclone and into the exposure chamber. Chamber concentrations of the test substance were controlled by varying the amount of test substance delivered to the jetmill or by varying the air flow.

Test atmospheres were exhausted through a high-capacity dust filter followed by an MSA charcoal/HEPA filter cartridge prior to discharge into the fume hood.

The exposure chamber was constructed of glass (cylindrical) with a nominal internal volume of 19 L. A polycarbonate baffle inside the chamber promoted uniform chamber distribution of the test atmosphere.

During exposure, animals were individually restrained in perforated stainless steel cylinders with conical nose pieces. The restrainers were inserted into a polymethacrylate faceplate attached to the exposure chamber so that the nose of each animal extended into the exposure chamber.

Atmospheric concentrations were determined by gravimetric analysis at approximately 30-minute intervals in the test chamber. The atmospheric concentration was calculated from the difference between the pre-and post-sampling filter weights divided by the volume of chamber atmosphere sampled.

Samples to determine particle size distribution (mass median aerodynamic diameter and percent particles less than 1, 3, and 10 um in diameter) weretaken during the exposure with a Sierra® series 210 cyclone preseparator/cascade and Sierra® series 110 constant flow air sampler.

Chamber temperature was targeted at 22 +/-2 degrees Celcius. Chamber relative humidity was 59 - 70%. Chamber airflow was25 to 30 L/min.. Chamber oxygen was 21%.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
Mean chamber concentration of IN-DBC80 was 2.0 ± 0.38 mg/L.
No. of animals per sex per dose:
5 male and 5 female
Control animals:
not specified
Details on study design:
- 14-day recovery period
- Animals were observed for mortality and response to alerting stimuli during the exposure and immediately following exposure.
- During the 14-day post-exposure period, animals were observed daily for mortality, and were weighed and observed for clinical signs of toxicity.
- At the end of the recovery period, all rats were sacrificed by carbon dioxide asphyxiation and subjected to gross pathology examination.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 2 mg/L air (analytical)
Exp. duration:
4 h
Mortality:
No animals died following the 4-hour exposure to 2.0 mg/L IN-DBC80 and the median lethal concentration was greater than 2.0 mg/L.
Clinical signs:
other: Following exposure, some male and female rats showed signs typically observed in restrained rats that had been exposed to extremely high dust concentrations including: ocular discharge, hair loss, and stained fur/skin.
Body weight:
Rats showed body weight losses on the day after exposure to IN-DB80 dust but appeared to recover within two days. Other than slight, sporadic weight losses, rats appeared to have a normal weight gain rate through the remainder of the recovery period.
Gross pathology:
No gross lesions were present in the rats at necropsy.
Other findings:
- The mean mass median aerodynamic diameter (MMAD) determined from 2 samples collected during the exposure was 2.8 μm ± 2.0

Any other information on results incl. tables

Under the conditions of this study, the 4-hour inhalation median lethal concentration (LC50) for IN-DBC80 in male and female rats was greater than 2.0 mg/L. According to the guidance provided by the U.S. EPA for toxicity classification and label statements for inhalation exposure of pesticides (EPA737-B-96-001), IN-DBC80 is classified in Toxicity Category IV (LC50 greater than 2 mg/L).

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: US EPA pesticides
Conclusions:
Under the conditions of this study, the 4-hour inhalation median lethal concentration (LC50) for IN-DBC80 in male and female rats was greater than 2.0 mg/L.