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Description of key information

Both acute oral and dermal toxicities were examined. 1 -Bromo-4 -chlorobutane has slight toxicity for oral and low toxicity for dermal.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
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
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Specific details on test material used for the study:
Purity 99.6%
Lot No. 917
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
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)
Preliminary study:
Dosage (mg/kg) Mortality
Male Female
400 0/1 0/1
800 0/1 0/1
2000 1/1 0/1
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
1 591 mg/kg bw
Based on:
test mat.
95% CL:
>= 1 160 - <= 2 021
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
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.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
1 885 mg/m³

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1992 - 1993
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes
Specific details on test material used for the study:
Lot No. 0917
Species:
rat
Strain:
other: CD strain
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: remote Sprague-Dawley origin
- Females (if applicable) nulliparous and non-pregnant: not applicable
- Age at study initiation: male: seven to eight weeks old, female: ten to eleven weeks old
- Weight at study initiation: male: 226 - 254 g, female: 223 - 247 g
- Fasting period before study: not applicable
- 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, (range: 18 - 25C)
- Humidity (%): 55% R.H. (range 40% - 70% R.H.)
- Air changes (per hr): 15 times per hour
- Photoperiod (hrs dark / hrs light): 12 hours dark/ 12 hours light
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 5 cm x 5cm
- % coverage: 10 % of the body surface
- Type of wrap if used: the test material was applied to a gauze patch, placed on the dorsum and occulated with aluminium foil.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): wipe with wet disposal towels
- Time after start of exposure:24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg
- Concentration (if solution): neat
- Constant volume or concentration used: no
- For solids, paste formed: no

VEHICLE
- Amount(s) applied (volume or weight with unit):not specified
- Concentration (if solution):
- Lot/batch no. (if required):
- Purity:
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
five male and five female
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:The first hour after administration and two further inspections during the remainder of Day 1. From Day 2 onwards, the animals were inspected twice daily. Each dermal application site was examined at the morning observation.
The body weight was 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:
Not applicable
Preliminary study:
A preliminary study was carried out using a group of one male and one female given TMCB at a dosage of 1000 mg/kg bodyweight. There was no death.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
One animal died during the day after dosing.
Clinical signs:
Ante mortem signs comprised underactivity, staggering gait, hunched poisture and bulging eyes.
Signs of reaction to treatment in the surviving animals comprised underactivity, staggering gait, ungroomed appearance, pigmented staining of the snout, hunched posture, thin body conformation and bulging eyes. The female wer overtly normal by Day 3, while the males had recovered by Day 8.

There were no local signs of reaction to treatment at the dermal application site.
Body weight:
Reduced bodyweight gain or slight bodyweight loss was recorded during the first week of observation for the majority of surviving animals. Increments during the second week were generally satisfactory.
Gross pathology:
Necropsy of the decedent and the surviving animals, revealed no significant macroscopic lesion.
Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this study, the acute percutaneous median lethal dosage (LD50) of the test material was greater than 2000 mg/kg. Accordingly, 1-bromo-4-chlorobutane, TMCB, was assigned into the class ' low percutaneous toxicity',
Executive summary:

Under the conditions of this study, the acute percutaneous median lethal dosage (LD50) of the test material was greater than 2000 mg/kg. Accordingly, 1-bromo-4-chlorobutane, TMCB, was assigned into the class ' low percutaneous toxicity',

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

Justification for classification or non-classification