1-bromo-3-chloro-2-methylpropane

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1995-2-10 to 1995-3-28

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Report date:

1995

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

1987 version

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: US EPA guideline (1985)

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Test material

Test material information

Constituent 1

Reference substance name:

1-bromo-3-chloro-2-methylpropane

EC Number:

230-224-6

EC Name:

1-bromo-3-chloro-2-methylpropane

Cas Number:

6974-77-2

Molecular formula:

C4H8BrCl

IUPAC Name:

1-bromo-3-chloro-2-methylpropane

Specific details on test material used for the study:

Batch Number 48241

Test animals

Species:

rat

Strain:

other: CD strain

Remarks:

remote Sprague-Dawley origin

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Limited (UK)
- Females (if applicable) nulliparous and non-pregnant: [yes/no] not specified
- Age at study initiation: approximately five weeks
- Weight at study initiation: for males from 111 - 163 g for females from 103 - 172 g
- Fasting period before study: Overnight
- Housing:five animals of the same sex are housed in stainless grid cages (RS Biotech, Northants, England)
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Target ; 21 C (19 - 25 C)
- Humidity (%): Target 55 % R.H.(40 % - 70% RH)
- Air changes (per hr): at least 10 complete air changes per hour without re-circulating
- Photoperiod (hrs dark / hrs light): 12 hrs darks/12 hrs light

IN-LIFE DATES: From: 1 To:15 days

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

maize oil

Details on oral exposure:

The test material was prepared at appropriate concentrations in maize oil to permit administration at constant volume-dosage of 10 ml/kg bodyweight

Doses:

2000, 2515, 3162 and 5000 mg/kg bodyweight

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

Observation: Three separate recordings of signs were made during the first hour after dosing and two further recordings during the remainder of Day1. From Day 2 onwards, the animals were inspected twice daily and recordings were made one daily. Circumstances of any death were recorded. ANy animal showing severe or enduring signs of pain or distress was humanely killed. The bodyweight of each animal was recorded on the day before dosing and on Days 1, 8 and 15. The test was terminated the morning of Day 15.
Necropsy: Carcases were stored in a refrigerator at approximately 4 C until traiined necropsy staff were available. Surviving animals were killed by carbon dioxide inhalation at termination of the study.
All animals were throughly examined for abnormality of tissues or organs. All body cavities were opened, larger organs were sectioned and the gastro-intestinal tract was opened at intervals for examination of the mucosal surfaces. All abnormalities were described or the normal appearance of majo organs was confirmed.
Macroscopically abnormal tissues were preserved in 4% neutral buffered formaldehyde and retained against future possible histopathological requirement.

Statistics:

Probit analysis by the method of Finney (1971) was used to determine the acute median lethal dosage, 95% confidence interval and slope of the dose response curve of the test material for both sexes. The calculation were performed by the GLIM statistics program (Baker and Neder, 1978) using a special macro program developed by Baker (Baker, 1980)

Results and discussion

Preliminary study:

The preliminary study was carried out using two groups of one male and one female rat given an oral administration of 2-MBCP at dosage of 800 or 2000 mg/ke, at a constant volume-dosage of 10 ml/kg in maize oil. There were no deaths, but significant signs were obsered at 2000 mg/kg.

Effect levels

Effect levels 1

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

2 239 mg/kg bw

Based on:

test mat.

95% CL:

>= 1 981 - <= 2 497

Effect levels 2

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

2 248 mg/kg bw

Based on:

test mat.

95% CL:

>= 1 714 - <= 2 781

Effect levels 3

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

22 434 mg/kg bw

Based on:

test mat.

95% CL:

>= 2 093 - <= 2 393

Remarks on result:

other: combined

Mortality:

The majority of animals treated at 2515 mg/kg or above died. The deaths occurred during the first four days after dosing. There was a single death, on Day 3, at the low dosage of 2000 mg/kg.

Clinical signs:

Ante mortem signs comprised lethargy, under activity, prone position, nconsciousness, reddening, staggering gait, tremor, slow deep respiration, gasping, piloerection, ungroomed fur, hypothermia, pigmented staining of the snout, ocular discharge, hunched posture and closed eyes. Four animals treated at 3162 mg/kg appeared to show some stereotype behaviour (continous ear scratching).
Signs of reaction in animals surviving to termination comprised under activity, prone position, reddening staggering gait, lethargy, respiratory abnormalities, ungroomed fur, hunched posture, thin body conformation and closed eyes.
Suvivors treated at 2000 mg/kg were overtly normal to Day 5, while the suvivor treated at 2515 mg/kg had fully recovered by Day 10.

Body weight:

The surviving animals achieved aniticipated bodyweigjht gains.

Gross pathology:

Necropsy findings for the decendents comprised incidences of altered gastro-intestinal contents, distended urinary bladder, firm luinmgs and fur staining. Necropsy of the survivors, on Day 15, revealed no significant lesion.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Under the conditions of this study the acute oral median lethal dosage (LD50) of 1-bromo-3-chloro-2-methylpropane was 2248 mg/kg (1714 - 2781 mg/kg) for males, 2239 mg/kg (1981 - 2947 mg/kg) for females and 2243 mg/kg (2093 - 2393 mg/kg) combined.

Executive summary:

Under the conditions of this study the acute oral median lethal dosage (LD50) of 1-bromo-3-chloro-2-methylpropane was 2248 mg/kg for males, 2239 mg/kg for females and 2243 mg/kg combined. This substance was classified as category 4 based on this study.