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Toxicological information

Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted in compliance with GLP using methodologies consistent with OECD Guideline

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999
Report Date:
1999

Materials and methods

Test guidelineopen allclose all
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Qualifier:
equivalent or similar to
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Principles of method if other than guideline:
This study was conducted to examine the acute inhalation toxicity of 2-bromopropane and select the exposure concentrations of the 14-day inhalation study, which will be followed by an OECD 422 study (combined repeated inhalation toxicity with the reproduction/developmental toxicity screening test)
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 2-Bromopropane
- Physical state: Colorless liquid
- Analytical purity: 99.96%
- Lot/batch No.: 60323
- Storage condition of test material: Packed in chemidrum (steel with polyethylene lining) under notrogen. Chemidrum stored at temperature below 20°C.

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Japan, Inc.
- Age at study initiation: 8 weeks
- Weight at study initiation: 212 - 283 g
- Fasting period before study: Not fasted
- Housing: Stainless, wire-mesh cages
- Diet (e.g. ad libitum): CFR-1 pellet diet, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 60 +/- 10
- Air changes (per hr): 15-17
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
Route and Rationale of Test Substance Administration

Inhalation by whole body exposure was the route of administration, since this is an anticipated route of exposure to humans.

Inhalation Methods

The fresh HEPA filtered dry air was used for bubbling and dilution of test substance at a constant temperature. Test substance vapor was generated from reservoir by bubbling. The vapor was diluted to the target concentrations of each exposure group and supplied into the inhalation chambers. Rats were then exposed to the test substance in the exposure chambers. Chambers were constructed of stainless-steel and glass and were operated under dynamic conditions.

Exposure Period

Male and female rats were exposed once to the test substance for six hours.

Target Exposure Concentration Levels

Rats were exposed to the test substance at target concentrations of 0, 300, 1,000, 3,000, 10,000 and 30,000 ppm.

Measurement of Actual Exposure Concentrations

Actual exposure concentrations of the test substance in each chamber were measured every 15 minutes by gas chromatography (GC). The GC samples were constantly drawn by vacuum pump (7000 mL/min) through stainless steel lines (15-20m) from each chamber to GC. This constant flow assured the delivery of fresh sample to GC without condensation. The GC was equipped with an automatic stream selector valve, a 0.2mL sample loop, flame ionization detector, and a 3mmx1.5m column packed with 15% chromosorb W on silicon D.C.200 80/100, operated at 80°C. The carrier gas was nitrogen.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
ca. 6 h
Concentrations:
Target concentrations 0, 300, 1000, 3000, 10000 and 30000 ppm. Mean actual concentrations 0, 295, 991, 2963, 9923 and 29440 ppm.
No. of animals per sex per dose:
5 male/5 female per dose level
Control animals:
yes
Details on study design:
OBSERVATIONS AND EXAMINATIONS

Survival and Clinical Observations

Treatment period-- During the exposure, all animals were observed for mortality.
Observation period--Following (at least 6 hours) the exposure, all animals wereobserved twice for detailed clinical reactions and mortality.
From the next day, all animals were observed for mortality twice daily. Detailed clinical observations were performed once daily.

Body Weight Measurements

Exposure and Observation Periods --Males and females were weighed on days 0, 1, 2, 4, 7, 10 and 14.

Food Consumption Measurements

Food consumption of all animals was measured once a week.

Pathological Examinations

Method of sacrifice-- All animals were sacrificed by exsanguination under ether anesthesia.

Necropsy

Gross postmortem examinations were performed on all animals which died or were sacrificed during the study period. All surviving rats were sacrificed and examined grossly on day 15.

The following tissues were collected from two animals of each group. All tissues except left epididymis and left testis were fixed in 10% neutral buffered formalin. Left epididymis and left testis were fixed in Bouin's fixing fluid.

Integumentary system-- Skin
Respiratory system--Nasal cavity, Nasopharynx, Larynx, Trachea, Lungs
Hematopoietic system -- Bone marrow (with femur bone), Lymph node (inguinal and axillary), Thymus, Spleen
Circulatory system -- Heart
Digestive system-- Tongue, Salivary glands, Esophagus, Stomach, Small intestine (includes duodenum), Large intestine, Liver, Pancreas
Urinary system-- Kidneys, Urinary bladder
Endocrine system-- Pituitary, Thyroid (with parathyroid), Adrenals
Reproductive system-- Males - Testes, Epididymides, Seminal vesicle, Prostate; Females - Ovaries, Uterus, Vagina, Mammary glands
Nervous system-- Brain, Spinal cord, Peripheral nerve (sciatic)
Special sense organs/appendage-- Eyes, Harderian glands
Musculoskeletal system-- Muscle (thigh), Bone (femur)
Other-- All gross lesions
Statistics:
Body weight and food consumption were analyzed using a t-test for the differences between the control group and each treated group.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 9 923 - < 29 440 ppm
Based on:
test mat.
Exp. duration:
6 h
Mortality:
All rats except rats in the 29440 ppm group survived to the end of the study. All male and female rats in the 29440 ppm exposure group died within 3 hrs from the start of exposure.
Clinical signs:
No clinical signs were noted in all surviving rats.
Body weight:
Mean body weights of male and femal rats in all exposure groups were similar to that of the control group. However, the mean body weight of female rats in the 9923 ppm exposure group was slightly lower on day 1 than day 0 of the study.
Gross pathology:
There were no substance-related gross findings detected in any exposure group.
Other findings:
Food consumption of males in the 991 ppm exposure group increased significantly comared with control group at week 2 of the study. However, since it was not a concentration-related change, it was considered to be spontaneous change. Food consumption of male and female rats in the other exposure groups were similar to that of the control group.

Applicant's summary and conclusion

Interpretation of results:
sligthly toxic
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
Based on the results of this key study, the LC50 value for both male and female rats exposed to 2-bromopropane for 6 hr was between 9923 and 29440 ppm.
Executive summary:

In a CoR 1 acute inhalation toxicity study, groups of young adult Crj: CD (SD) rats (5 males/5 females per dose) were whole body exposed by the inhalation route to 2 -bromopropane (99.96% purity) for 6 hours at concentrations of  0, 295, 991, 2963, 9923 and 29440 ppm.  Animals then were observed for 14 days.

 

LC50Males =    >9,923 ppm but <29,440 ppm

      Females = >9,923 ppm but <29,440 ppm

      Combined =   >9,923 ppm but < 29,440 ppm