1-bromo-4-chlorobutane

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1991

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1992

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Test material

Test material information

Constituent 1

Reference substance name:

1-bromo-4-chlorobutane

EC Number:

230-089-3

EC Name:

1-bromo-4-chlorobutane

Cas Number:

6940-78-9

Molecular formula:

C4H8BrCl

IUPAC Name:

1-bromo-4-chlorobutane

Test material form:

liquid

Specific details on test material used for the study:

Purity 99.6%
Lot No. 917

Test animals

Species:

rat

Strain:

other: CD

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Sprague-Dawley
- Females (if applicable) nulliparous and non-pregnant: [yes/no] no information
- Age at study initiation: five weeks old
- Weight at study initiation: 106 - 139 g for female, 100 - 132 g for male
- Fasting period before study: 18 hours
- Housing: 54 x 33 x 20 cm
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period:at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 °C (18 - 25 °C)
- Humidity (%): 55 % (40 - 70 %)
- Air changes (per hr): 15 complete air changes per hours without re-circulation.
- Photoperiod (hrs dark / hrs light): 12 hrs dark/12 hrs light

IN-LIFE DATES: From: To: from one to fifteen

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

maize oil

Details on oral exposure:

VEHICLE
- Amount of vehicle (if gavage): 10 ml/kg

Doses:

Preliminary study :400 mg/kg, 800 mg/kg, 2000 mg/kg
Main study : 800 mg/kg, 1265 mg/kg, 2000 mg/kg, 3162 mg/kg

No. of animals per sex per dose:

Preliminary study: one male and one female rat per dose group
Main study: five male and five female rats per dose group

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Frequency of observation: The first hour after dosing and two further inspection during the remainder of Day 1. From Day 2 onwards, inspected twice a day.
The body weight Recorded on the day before dosing and on Days 1, 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:none

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 calculations were performed by the GLIM statistics program (Baker and Nelder, 1978) using a special macro program developed by Baker (Baker, 1980)

Results and discussion

Preliminary study:

Dosage (mg/kg) Mortality
Male Female
400 0/1 0/1
800 0/1 0/1
2000 1/1 0/1

Effect levels

Effect levels 1

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

1 591 mg/kg bw

Based on:

test mat.

95% CL:

>= 1 160 - <= 2 021

Effect levels 2

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

2 167 mg/kg bw

Based on:

test mat.

95% CL:

>= 1 354 - <= 2 981

Effect levels 3

Key result

Sex:

male/female

Dose descriptor:

LD50

Remarks:

combined

Effect level:

1 885 mg/kg bw

Based on:

test mat.

95% CL:

>= 1 542 - <= 2 228

Mortality:

Animals died at dosages of 1265 mg/kg or above. The deaths occurred during the first over-night period and on the second and fourth days after dosing

Clinical signs:

Ante mortem signs comprised lethargy, decreased motor activity, prone position, staggering gait, muscle tremor, bradypnoea, tachypnoea, hyperpnoea, hypopnoea, cold to touch, pigmented staining of the snout, piloerection, ungroomed apprearance, thin body conformation, salivation, hunched posture, closed eyes, pigmented and serous orbital secretion and reddening.
Sign of reaction to treatment in the surviving animals comprised irritability, lethargy, staggering gait, decreased motor activity, cold to the touch, piroerection, salivation, hunched posture, eyes, serous orbital discharge and reddening The animas were overtly normal six days after treatment.

Body weight:

The surviving animals achieved expected body weight gains.

Gross pathology:

Necropsy of the decendents revealed low incidences or single cases of abnormal stomack contents, dark areas on the stomach glandular mucosa, pale cranial fur staining, hairloss on cervical dorsum, pale areas on the liver, large liver and pale kidneys.

Necropsy of the surviving animals revealed pale areas on the liver with interlobular adhesions, abnormal gastro-intestinal contents, dark sub-mandibular and mandibular lymph nodes and testicular masses amongst two males and distended uterus in two females

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) were 1591 mg/kg for male, 2167 mg/kg for female and 1885 mg/kg as combined. Accordingly, TMCB was assigned to the class 'slight oral toxicity.

Executive summary:

Under the conditions of this study the acute oral median lethal dosage (LD50) were 1591 mg/kg for male, 2167 mg/kg for female and 1885 mg/kg as combined. Accordingly, TMCB was assigned to the class 'slight oral toxicity.