Registration Dossier

Toxicological information

Acute Toxicity: inhalation

Currently viewing:

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
27th November 1995 - March 28th 1996
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted in accordance with generally accepted scientific principles, possibly with incomplete reporting or methodological deficiencies, which do not affect the quality of the relevant results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report Date:
1997

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River France, 59 rune de la Paix, 76140 SAINT-AUBIX-LES ELBEUF (FRANCE).
- Age at study initiation: 6 - 8 weeks
- Weight at study initiation: Mean weight of males per group: 244, 254, 216, 227 and 241 g. Mean weight of females per group: 178, 186, 175, 184 and 191 g.
- Fasting period before study:
- Housing: Makrolon type 3 cages.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days minimum.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2 ºC
- Humidity (%): 40 - 70 %
- Air changes (per hr): NDA
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: 27th November 1995 To: 23rd May 1996

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
nose only
Vehicle:
other: dry air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: oro-nasal exposure chamber.
- Exposure chamber volume: 2 litres
- Method of holding animals in test chamber: NDA
- Source and rate of air: 1-bromopropane vapours were generated by bubbling air through a circular flask containing pure 1-bromopropane liquid. Total flow rate was 1000 L/hour
- Method of conditioning air: NDA
- System of generating particulates/aerosols: N/A
- Method of particle size determination: N/A
- Treatment of exhaust air: exhaust air goes to activated charcoal.
- Temperature, humidity, pressure in air chamber: 20 - 27 ºC, 0 mm C.E. relative pressure, humidity not measured due to use of dry air for generation of 1-bromopropane vapours but assumed to be approximately 0%.

TEST ATMOSPHERE
- Brief description of analytical method used: FIrstly, adsorption/desorption took place on a graphite carbon filter. The 1-bromopropane was then separated from the filter by a known volume of carbon disulfide. The obtained solution was analysed by FID chromatography.
- Samples taken from breathing zone: no, samples taken at different levels in the exposure chamber.

VEHICLE
dry air
Analytical verification of test atmosphere concentrations:
yes
Remarks:
FID chromatography.
Duration of exposure:
4 h
Concentrations:
Nominal concentrations: 27.1, 34.5, 37.2, 45.9, 47.7 g/cubic metre.
Measured concentrations: 34.6 ± 2.7, 42.5 ± 1.0, 37.0 ± 0.6, 35.1 ± 1.5, 30.2 ± 0.2 g/cubic metre.
No. of animals per sex per dose:
5 rats per sex per dose.
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality recorded at the beginning and end of every day. Clinical signs recorded at least once daily. Body weights recorded upon arrival and daily during study.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, haemotological examination.
Statistics:
The LC50 was determined using the method of Litchfield and Wilcoxon.

Results and discussion

Preliminary study:
A preliminary study was used to determine the method for creating a limit concentration of 20 g/m^3 in the exposure chamber and perform any adjustments necessary. In fact, the first adjustment led to a concentration of 35 g/m^3 due to a saturation problem in the analysis method during the preliminary study of generation. Because some rats were found dead using a concentration of 35 g/m^3, four other concentrations were also used for the definitive study.
Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LC50
Effect level:
35 000 mg/m³ air
Based on:
test mat.
95% CL:
34 000 - 36 000
Exp. duration:
4 h
Remarks on result:
other: Lower and upper limits of 34 and 36 g/m^3. The probability threshold was 5 %.
Sex:
male/female
Dose descriptor:
other: Inferred NOAEC
Effect level:
30 200 mg/m³ air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: This value is inferred from the dose level that caused no mortalities.
Mortality:
30 of the 80 rats which were included in the study died during the observation period. All other rats were killed at the end of the 14 day observation period.
See table 1.
Clinical signs:
other: No specific information is available from the exposure period due to the difficulty to analyse the animals whilst in the chamber. Only excessive salivation was noted after removal. Signs during the observation period noted were noisy respiration, abdomina
Body weight:
Because of the early mortality in groups 4 and 5, it was not possible to evaluate statistically the weight change in relation to control groups. No significant differences were noted in the other dosage groups compared to the controls during the 14 day observation period.
Gross pathology:
The main observation involved the thoracic cavity which contained a cloudy fluid. A mottled and dark red appearance was observed in the lung as well. These observations were more severe in rats found dead.
Other findings:
- Organ weights: A significant increase of lung weight was observed in rats found dead.
- Histopathology: The main lesions were oedema and pulmonary emphysema. No testis lesions were observed in male rats sacrificed at the end of the 14 day observation period. Acute pulmonary lesions were responsible for severe respiratory distress which was observed by clinical examination and led to the death of animals.
- Haematological examination: An increase in white blood cells was shown 24 hours after exposure, due to a significant increase of Poly-Morphnuclear Neutrophils in the blood. An increase in red cell count, haemoglobin concencentration and packed cell volume was shown at day 2. The changes were reversible: they disappeared at the end of the observation period.
- Target Organs: Lungs

Any other information on results incl. tables

Table 1: Mortality

Exposure concentration (g/m3)

Group Number

Mortality

Males

Female

Total

30.2

7

0/5

0/5

0/10

34.6

2 (Satellite 1)

1/5

2/5

3/10

35.1

6

4/5

3/5

7/10

37.0

5

5/5

5/5

10/10

42.5

4

5/5

5/5

10/10

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The main target organ for the toxicity of 1-bromopropane was found to be the lung.
Mortality induced by 1-bromopropane is correlated to an acute respiratory deficiency which seemed to be due to an inflammation of the lung parenchyma characterised by pulmonary emphysema and oedema.
The LC50 in rats after 4 hours exposure was determined as 35 g/m^3
Executive summary:

In an acute inhalation toxicity study (97-CR-2866), 6 - 8 week old male and female Wistar Crl rats were exposure to 1 -bromopropane for 4 hours in a 2 litre oro-nasal exposure chamber.

The main target organ for the toxicity of 1-bromopropane was determined as the lung.

Mortality induced by 1-bromopropane is correlated to an acute respiratory deficiency which seemed to be due to an inflammation of the lung parenchyma characterised by pulmonary emphysema and oedema.

The LC50 in rats after 4 hours exposure was determined as 35 g/m3 with lower and upper limits of 34 and 36 g/m3. The probability threshold was 5 %.