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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

Constituent 1
Chemical structure
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 levelsopen allclose all
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
1 591 mg/kg bw
Based on:
test mat.
95% CL:
>= 1 160 - <= 2 021
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
2 167 mg/kg bw
Based on:
test mat.
95% CL:
>= 1 354 - <= 2 981
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.