2-bromopropane

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

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 and appropriate OECD Guidelines

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-bromopropane

EC Number:

200-855-1

EC Name:

2-bromopropane

Cas Number:

75-26-3

Molecular formula:

C3H7Br

IUPAC Name:

2-bromopropane

Details on test material:

- Name of test material (as cited in study report): Iso-Propyl Bromide
- Physical state: Colourless liquid
- Analytical purity: > 99%
- Lot/batch No.: 1-302-1
- Storage condition of test material: Room temperature and protected from light

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Test Animals

Species, strain: rat, Sprague-Dawley ICO: OFA-SD (lOPS Caw).
Reason for this choice: rodent species commonly requested by the international regulations for this type of study.
Breeder: Iffa Credo, 69210 L'Arbresle, France.
Number and sex: one group of 10 animals (5 males and 5 females).
Age/weight: on the day of treatment, the animals were approximately 6 weeks old, and had a mean body weight of 176 ± 5 g for the males and 151 ± 5 g for the females.
Acclimatization: at least 5 days before the beginning of the study.
Identification of the animals: the animals were identified individually by earmarks or earnotches.

Environmental Conditions

During the acclimatization period and during the main test, the conditions in the animal room were as follows:
temperature : 22 ± 3°C
relative humidity: 50 ± 20%
light/dark cycle: 12 h/12 h
ventilation: about 13 cycles/hour of filtered, non-recycled air.
The temperature and relative humidity were recorded continuously and records retained.
The housing conditions (temperature, relative humidity, light/dark cycle and ventilation) were checked monthly.
The animals were housed in polycarbonate cages (48 x 27 x 20 cm) covered with a stainless steel lid . Each cage contained 4 to 7 animals of the same sex during the acclimatization period and 5 rats of the same sex during the treatment period. Each cage contained graded, dust-free sawdust (SICSA, 94142 Alfortville, France).
Bacteriological analysis of the sawdust and detection of possible contaminants (pesticides, heavy metals) are performed periodically.

Food and water

All the animals had free access to A04 C pelleted diet (U.A.R., 91360 Villemoisson-sur-Orge, France). Each batch of food was analysed (composition and contaminants) by the supplier.
Drinking water filtered by a F.G. Millipore membrane (0.22 micron) was contained in bottles.
There were no contaminants in the diet, water or sawdust at levels likely to have influenced the outcome of the study.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

2,000 mg/kg

No. of animals per sex per dose:

5 male/5 female

Control animals:

no

Details on study design:

The administration was performed in a single dose by oral gavage. The volume administered to each animal was adjusted according to body weight determined on the day of treatment. The single administration was performed on Day 1 and was followed by a 14-day observation period.

The animals were observed frequently during the hours following administration of the test substance, for detection of possible treatment-related clinical signs. Observation of the animals was made at least once a day for a period of 14 days, to determine whether any of the clinical
signs were reversible or not. Clinical signs were recorded for each animal individually.

The animals were checked frequently during the hours following administration of the test substance for mortality or signs of morbidity, then at least twice a day thereafter.

The animals were weighed individually just before administration of the test substance, and then on days 5, 8 and 15 for the surviving animals.
The body weight gain of the treated animals was compared to a reference curve of C.I.T. control animals with the same initial weight.

On day 15, the animals were sacrificed by CO2 inhalation in excess and a macroscopic examination was performed.

After opening the thoracic and abdominal cavities, a macroscopic examination of the main organs (digestive tract, heart, kidneys, liver, lungs, pancreas, spleen and any other organs with obvious abnormalities) was performed. In case of macroscopic lesions, organ samples were taken and preserved in 10% buffered formalin. No microscopic examination was performed.

Evaluation of the innoxiousness or toxicIty of the test substance following a single oral administration in rats should include the relationship, if any, between the animals' exposure to the test substance and the incidence and severity of all abnormalities including behavioural and clinical abnormalities, macroscopic lesions, body weight changes, mortality and any other toxic effects.

Results and discussion

Mortality:

No deaths occurred during the observation period.

Clinical signs:

other: Hypoactivity (slight and marked), ataxia and piloerection were noted within 4 hours post-treatment. No clinical signs were observed thereafter.

Gross pathology:

Macroscopic examination of the main organs of the animals sacrificed at the end of the study revealed no apparent abnormalities.

Any other information on results incl. tables

Table 1 -- Individual Clinical Signs and Mortality
Dose (mg/kg)	Time	Males	Females	Clinical Signs
2000	15 min	01-02-03-04-05	01-02-03-04-05	hypoactivity
	30 min	01-02-03-04-05	01-02-03-04-05	Sedation
	1 hr	04	02-05	Sedation, ataxia
	1 hr	01-02-03-05	01-03-04	Sedation
	2 hr	01-02-03-04-05	01-02-03-04-05	Sedation, piloerection
	4 hr	01-02-03-04-05	01-02-03-04-05	None
	Days 2 to 15	01-02-03-04-05	01-02-03-04-05
Table 2 -- Individual Body Weight and Body Weight Change of Treated Rats (g)
Dose	Sex	Animal No.	Days
mg/kg			1	(1)	5	(1)	8	(1)	15
2000	Male	01	184	50	234	27	261	58	319
		02	72	46	218	30	248	49	297
		03	173	52	225	28	253	62	315
		04	175	52	227	22	249	61	310
		05	175	43	218	26	244	60	304
2000	Female	01	159	43	202	13	215	27	242
		02	148	44	192	16	208	18	226
		03	148	45	193	0	193	16	209
		04	147	26	173	14	187	20	207
		05	152	57	209	7	216	10	226
(1) = Body weight gain
Table 3 - Individual Macroscopic Post-Mortem Examinations
Dose (mg/kg)	Time	Males	Females	Macroscopic Abnormalities
2000	Day 15	01-02-03-04-05	01-02-03-04-05	None

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

Under the experimental conditions described in this study, the LDo of the test substance Iso-Propyl Bromide when administered by oral route in rats was higher than 2,000 mg/kg.

Executive summary:

In a CoR 1 acute oral toxicity study, five male and five female Sprague-Dawley rats were administered a single dose of 2,000 mg/kg bw 2 -bromopropane (>99% purity) and were observed for 14 days following exposure. No deaths occurred as the result of exposure. No lasting clinical signs were noted. Bodyweight gain was unaffected. No apparent aabnormalities to organs or tissues were noted on gross pathology.

 

Oral LD₀ Males = > 2,000 mg/kg bw

      Females =  > 2,000 mg/kg bw

      Combined =  > 2,000 mg/kg  bw