1-bromobutane

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

08/09/1993 to 22/09/1993

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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)

Version / remarks:

O.E.C.D. guideline No. 401, 24 February 1987.

Deviations:

not specified

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1-bromobutane

EC Number:

203-691-9

EC Name:

1-bromobutane

Cas Number:

109-65-9

Molecular formula:

C4H9Br

IUPAC Name:

1-bromobutane

Test material form:

liquid

Details on test material:

name:
protocol and labelling: n-BUTYL BROMIDE
batch number:
protocol and labelling: 5-241-1 / 0-201-1
Elf Atochem filing number: CAL 6777/95
description: colourless liquid
quantity and container: 150 gin one glass flask
date of receipt: 19.12.95
storage conditions: at room temperature and protected from light
purity: 99.8%.

Specific details on test material used for the study:

No further details specified in the study report.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Species, strain: rat, Sprague-Dawley ICO: OFA-SD (IOPS Caw).
Reason for choice: rodent species currently required by International Authorities 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 weight of 179 ± 6 g for the males and 152 ± 2 g for the females.
Acclimatisation: at least 5 days before commencement of the study.
Animal identification: the animals were identified individually using perforations or notches in the flap of the ear.

Environment
During the acclimatisation period and during the study, the maintenance conditions of the animal housing facility were as follows:
Temperature: 22 ± 3°C
Humidity: 50 ± 20%
Nyctohemeral period: 12 hrs/12 hrs
Ventilation: around 13 cycles/hour of filtered and non-recycled air.
The temperature and humidity were recorded continuously and the results retained. The accommodation conditions (temperature, humidity, nyctohemeral period and ventilation) were checked each month.
The animals were housed in polycarbonate cages (48 x 27 x 20 cm) fitted with a stainless steel lid. Each cage housed 4 to 7 animals of the same sex for the acclimatisation period and 5 rats of the same sex for the treatment period. Each cage contained sawdust litter made from wood that was screened and had the dust removed (SICSA 94142 Alfortville, France).
Bacteriological analysis of the litter and testing for main contaminants (pesticides, heavy metals) were carried out regularly.

Food and drink
All animals had access to food "Rats and mice maintenance reference A04 C" (U.A.R., 91360 Villemoisson-sur-Orge, France), presented in the form of standardised stoppers.
Each batch of food was analysed (composition and contaminants) by the supplier.
Drinking water, filtered through an F.G. Millipore (0.22 microns), was distributed amongst feeding bottles.
Bacteriological and chemical as well as main contaminants (pesticides, heavy metals and nitrosamines) analyses were carried out regularly.

The non-nutritional substances that may have been present in the food, drinking water or litter were at a level where they were not able to interfere in the good conduct of the study.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

The product was administered untouched, taking into account the density of the product d = 1.27.

Doses:

2000 mg/kg

No. of animals per sex per dose:

10 animals (5 males and 5 females).

Control animals:

no

Details on study design:

Administration was carried out once, orally, using a tube with a stainless steel eccentric tip (diameter: 18 G.2", Perfektum: Poffer & Sons Inc., New Hyde Park, New York 11040, U.S.A.) mounted on a 1 ml glass syringe (graduations of 0.01 ml, Record: Carrieri, 75005 Paris, France).
The volume administered to each animal was adjusted to the body weight determined on the day of treatment.

CLINICAL EXAMINATIONS
Clinical signs
Observation of the animals was carried out frequently during the hours following administration of the product. It was carried out at least once a day for the 14 days afterwards to note reversible or irreversible clinical signs. The appearance or disappearance of clinical signs was recorded for each animal.

Mortality
The mortality check was carried out frequently just after administration of the product and at least twice a day for a minimum of 14 days of observation.

Body weight
The animals were weighed individually just before administration of the product, then on days 5, 8 and 15.
The weight development of the treated animals was compared to a reference curve drawn up at C.I.T from untreated animals of the same initial weight.

PATHOLOGY
Autopsy
On day 15, the animals were sacrificed using inhalation of an excess of CO2 and underwent a macroscopic examination.

Macroscopic examination
After opening the abdominal and chest cavities, a macroscopic examination of the main organs was carried out: digestive tract, heart, kidneys, liver, lungs, pancreas, spleen and other organs with abnormalities.
The macroscopic observations were recorded individually. The organs presenting macroscopic lesions were sampled and preserved in a formaldehyde buffer at 10%.

Microscopic examination
No microscopic examination was carried out.

Statistics:

Not specified.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD0

Effect level:

>= 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was found during the observation period.

Clinical signs:

other: At 2000 mg/kg, signs of hypoactivity or sedation and piloerection were observed in the 4 hours following the treatment. No clinical sign was observed between days 2 and 15.

Gross pathology:

There was no proof of a visible abnormality in the macroscopic examination of the main organs of the animals sacrificed at the end of the study.

Other findings:

No further findings reported.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the experimental conditions, the LD 0 of the product n-BUTYL BROMIDE administered orally in rats is greater than or equal to 2000 mg/kg.

Executive summary:

At the request of the Sponser, the acute toxicity of the product n-BUTYL BROMIDE was assessed orally in rats in accordance with the O.E.C.D guidelines. (No. 401, 24 February 1987). The study was carried out in accordance with the Good Laboratory Practice regulations.

 

Methods

The product was administered orally to a group of 10 Sprague-Dawley rats (5 males and 5 females) on a liquid diet. Administration was carried out with the product untouched at a dosage of 2000 mg/kg, taking into account the density of the product d = 1.27.

 

The clinical signs, mortality and weight development of the animals was monitored for a period of 14 days after single-dose administration of the product.

 

An anatomical pathological examination was carried out on each of the animals that were sacrificed at the end of the study.

 

Results

At 2000 mg/kg, a significant reduction in the spontaneous activity and piloerection were observed in the four hours following the treatment. No clinical signs were noted at day 2.

 

Mortality was zero at a dose of 2000 mg/kg.

 

The weight development in males was slightly slowed between days 1 and 5. The weight development in females was normal.

The autopsy of the animals that were sacrificed at the end of the study did not show any macroscopic abnormality.

 

Conclusion

Under the experimental conditions, the LD 0 of the product n-BUTYL BROMIDE administered orally in rats is greater than or equal to 2000 mg/kg.