Registration Dossier

Administrative data

Description of key information

oral: LD50 > 2000 < 5000 mg/kg bw (WoE: Rudnev et al. 1979, rat and mouse, Smyth et al. 1954, rat)
inhalation: LC 50 (rat) > 7.74 mg/L air (90-0524-FGT)

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
March 1st- 31th, 1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP - Guideline study
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
, 1981
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Lippische Versuchstierzucht HAGEMANN GmbH & Co., Exertal 1, Germany
- Age at study initiation: 51 - 54 days
- Weight at study initiation: 229 - 249 g (males); 212 - 250 g (females)
- Fasting period before study: 16 hours
- Housing: in groups of two or three in MAKROLON cages (type III)
- Diet: ad libitum standardized diet for rats ALTROMIN 1324 (ALTROMIN GmbH, Lage/Lippe, Germany); analysed for contaminants
- Water: ad libitum tap water; analysed regularly
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/-2
- Humidity (%): 50 +/- 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: Feb. 1990 To: March 15th, 1990
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: dynamic inhalation apparatus with a nose-only exposure according to Kimmerle & Trepper.
- Exposure chamber volume: 40 L
- Method of holding animals in test chamber: Apparatus consists of a cylindrical exposure chamber which holds a maximum of 20 animals in pyrex tubes at the edge of the chamber in a radial position
- Source and rate of air: 400 L/h
- System of generating particulates/aerosols: A mixture of test substance and air was obtained using a spray-jet. The spray-jet was fed with compressed air from a compressor and with the test article using an infusion pump and a 50 mL syringe.
- Temperature, humidity, pressure in air chamber: 22 +/- 3°C

TEST ATMOSPHERE
- Brief description of analytical method used: GC-analyses of two air samples
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: Test substance is of volatile nature at room temperture (vapour pressure 10700 Pa at 20°C). This resulted in an almost complete gas phase in the inhalation chamber after the test substance air mixture escaped from the spray-jet.


Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
1.49 and 7.74 mg/L air (actual concentrations)
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Observations and clinical examiniations: on the day of exposure 5, 15, 30 and 60 min, 3 h and 24 h after end of exposure; during recovery period at least once a day until all symptoms had subsided, thereafter each working day.
Individual body weight: before the exposure and after exposure in weekly intervals; if animals died body weight at time-point of death was recorded.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight gain
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 7.74 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No mortality occured.
Clinical signs:
No substance-related intolerance reactions were observed.
Body weight:
No inhibition of body weight gain was examined.
Gross pathology:
Macroscopic inspection revealed no pathological findings.
Interpretation of results:
study cannot be used for classification
Remarks:
Migrated information
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Oral:

In acute oral toxicity tests Rudnev et al. (1979) exposed albino rats and white mice to 1-chlorobutane. LD50s of 2200 mg/kg bw and 5600 mg/kg bw were examined, respectively, indicating that rats may be more sensitive to 1-chlorobutane than mice. No further information on mortality, clinical signs or necropsy were provided. In another acute oral toxicity test 5 female rats were intubated with a logarithmic series of doses (Smyth et al., 1954). 14 days after dosing, mortality was considered to be complete (LD50: 2670 mg/kg bw).

Taken together in a weight of evidence approach, the data indicate that the test material has a low toxic potential to rats and mice after oral ingestion.

 

Inhalation:

In a GLP-guideline study according to OECD 403 (1981) rats were exposed to 1-chlorobutane via aerosol inhalation to actual concentrations of 1.49 and 7.74 mg/L air over an exposure period of 4 hours (90-0524-FGT). No substance-related toxicity was observed and no mortality occurred. Macroscopic inspection revealed no pathological findings. Thus the LC50 was determined to be > 7.74 mg/L air. An inhalative LC50 value for male rats was reported as > 8000 ppm (> 30 mg/L) after an exposure period of 4 hours to the vapour of 1-chlorobutane by Smyth et al.(1954). Two of six male rats died within an observation period of 14 days after exposure.

 

Dermal:

In an acute dermal toxicity study with rabbits, available as short abstract only, no effects were detected after 24 hours of exposure to very high amounts of 1-chlorobutane (LD50 > 20 ml/kg).The test substance was applied occlusively to 1/10 of the body surface (Smyth et al., 1954).


Justification for selection of acute toxicity – oral endpoint
Weight of evidence approach.

Justification for classification or non-classification

The available data is conclusive but not sufficient for classification according to DSD (67/548/EEC) and CLP (1272/2008/EC).