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Description of key information

LD50 oral, rat = 17400 mg/kg, 
LD50 dermal, rat = 17400 mg/kg and
LC50 vapour, rat = 30.8 mg/l

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:
1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well documented, according to accepted guidelines.
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
-reliability scoring based on 2001 guideline for Test No. 423
Deviations:
yes
Remarks:
-purity of the test article and age of the animals were not reported, and relative humidity was 50 to 85%, which exceeds guideline recommendations of 30 to 70%
Qualifier:
according to guideline
Guideline:
other: EEC directive 84/449/EEC, September 19, 1984.
Deviations:
yes
Remarks:
-purity of the test article and age of the animals were not reported, and relative humidity was 50 to 85%, which exceeds guideline recommendations of 30 to 70%
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Crl:(WI) BR - Wistar, white
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Firma Charles River Wiga, Sandhofer Weg 7, 8714 Sulzfeld.
- Age at study initiation: Not reported
- Weight at study initiation: 160 to 174 g (males); 150 to 165 g (females)
- Fasting period before study: 16 hours prior to administration until 3 to 4 hours after administration
- Housing: Group housing up to a maximum of 5 animals per cage (Macrolon type III)
- Diet (e.g. ad libitum): Ssniff-R Alleindiät pellets (Ssniff Spezialdiäten GmbH); ad libitum
- Water (e.g. ad libitum): drinking water (drinking bottles); ad libitum
- Acclimation period: at least 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 2
- Humidity (%): 50 to 85
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
other: Oleum arachidis
Details on oral exposure:
VEHICLE
-Test article was administered as a 20% dilution in Oleum arachidis.
-The pH value was 6.6.

MAXIMUM DOSE VOLUME APPLIED: Approximately 10 mL/kg bw
Doses:
Range finding study: 1000 and 2000 mg/kg body weight, conducted on four female rats
Main study: 2000 mg/kg body weight
No. of animals per sex per dose:
Range finding study: 2 female animals (each tested at 2 dose levels)
Main study: 5 animals/sex
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were conducted at regular intervals (20 min, 1, 2, 3, 6, and 24 hr, and thereafter once daily up to Day 14) during the 14-day observation period. Body weights were measured on Days 0, 7, and 14.
- Necropsy of survivors performed: Yes
- Other examinations performed: Gross pathological examinations were performed on animals sacrificed at termination.
Statistics:
LD50 values were calculated according to Finney D.Y., Probit Analysis, 3rd edition, Cambridge, 1971.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: No deaths were reported following the administration of a single dose of 2,000 mg/kg bw of sec-butylchloride to rats.
Mortality:
Range finding study: No deaths in the preliminary study were reported.
Main study: No animals died during the course of the main study.
Clinical signs:
No abnormal clinical signs were observed.
Body weight:
Weight gains were normal in all animals.
Gross pathology:
No test-article-dependent findings were reported following gross pathological examination on Day 14. The authors reported that the macroscopic changes observed were attributed to the sacrificing procedure or to minor variations, which often occur spontaneously in rats of this strain and age.
Other findings:
None.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LD50 (oral, rat) in this valid guideline study was determined to be > 2000 mg/kg bw.
Executive summary:

No mortality was observed in this study when dosed 2000 mg/kg bw in rats. Consequently, as a result the substance 2 -chlorobutane is not classifiable according to CLP (Regulation (EC) No 1272/2008, DSD (Directive 67/548/EEC) nor GHS for acute oral toxicity.

As no study related effects were observed during the study regards weight gain or at gross pathological examination, no indication for Target Organ Syste Toxicity at Single Exposure classification is given (STOT SE).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
17 400 mg/kg bw
Quality of whole database:
Two valid studies are available, one study being more reliable performed as limit test showing no mortality at highest tested concentration (2000 mg/kg bw) and one study actually determining a LD50. Thus the LD50 value for the supporting study is used further.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1990
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study without detailed documentation.
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
-reliability scoring based on 2009 guideline.
Deviations:
yes
Remarks:
-Purity, source, and physico-chemical properties of test substance not reported; 2 concentrations tested; oxygen and carbon dioxide concentrations were not provided; no individual data for clinical examination results
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: Sprague-Dawley rats, Tif: RAI f (SPF)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Lippische Versuchstierzucht HAGEMANN GmbH & Co., D-4923 Extertal 1.
- Age at study initiation: 49 to 50 days at the start of quarantine.
- Weight at study initiation: 224-248 g (males); 195-213 g (females).
- Fasting period before study: Food was discontinued approximately 16 hours before exposition.
- Housing: Groups of 2 or 3 in MAKROLON cage (type III).
- Diet (e.g. ad libitum): Standardized diet for rats ALTROMIN 1324 (supplied by ALTROMIN GmbH, D-4937 Lage/ Lippe), ad libitum.
- Water (e.g. ad libitum): Tap water, ad libitum.
- Acclimation period: Not reported.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21±2
- Humidity (%): 50± 10
- Air changes (per hr): Not reported.
- Photoperiod (hrs dark / hrs light): 12 / 12
Route of administration:
inhalation: vapour
Type of inhalation exposure:
nose only
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: A dynamic inhalation apparatus with a nose only exposure of the animals according to KIMMERLE & TREPPER (Supplier: RHEMA-LABORTECHNIK, D-6238 Hofheim/Taunus). The 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.
- Exposure chamber volume: 40 L
- Method of holding animals in test chamber: 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; source not reported.
- Method of conditioning air: A mixture of test substance and air was obtained using a spray-jet. The spray-jet was fed with compressed air (5.0 bar) from a compressor and with the test article using an infusion pump and a 50 mL syringe. At the bottom of the exposure chamber the air was sucked off at the same flow rate as created by the spray-jet in order to produce a homogenous distribution in the exposure chamber.
- System of generating particulates/aerosols: The test substance is at room temperature of volatile nature. The vapour pressure for the test substance is approximately 0.49 bar (49 kPa) 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.
- Method of particle size determination: Not applicable (vapor test).
- Treatment of exhaust air: Not reported.
- Temperature, humidity, pressure in air chamber:
Temperature 22±3°C; humidity and pressure not reported.


TEST ATMOSPHERE
- Brief description of analytical method used: Two air samples were drawn from within the inhalation chamber close to the nose of the animals and analysed by gas chromatography.
- Samples taken from breathing zone: yes
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
Analytical concentrations: 1.51 and 6.76 mg/L air
No. of animals per sex per dose:
5 per sex per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed continuously during and following the exposure time and during the recovery period, all possible findings were recorded systematically; individual records were maintained for each animal. On the day of exposure, observations were performed immediately, 5, 15, 30, and 60 minutes, 3 and 24 hours after end of exposure.
During the recovery period, careful clinical examination was conducted at least once a day until all symptoms had subsided, thereafter each working day. Observations on mortality were made at least once daily with appropriate actions taken to minimize loss of animals to the study, e.g., necropsy or refrigeration of those animals found dead and isolation or sacrifice of weak or moribund animals.
Cage-side observations included, but were not limited to, changes in the skin and fur, the eyes, mucous membranes, respiratory, circulatory, autonomic and central nervous systems, and somatomotor activity as well as behavioural pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep, and coma. Individual body weights of the animals were determined before the exposure and after exposure in weekly intervals. Surviving animals were weighed at study termination and were sacrificed afterwards.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: see above
Statistics:
Not reported.
Preliminary study:
Not applicable.
Sex:
male/female
Dose descriptor:
LC0
Effect level:
> 6.76 mg/L air (analytical)
Exp. duration:
4 h
Remarks on result:
other: No intolerance reactions were seen at the highest concentration of 6.76 mg/L. No pathological findings.
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 6.76 mg/L air (analytical)
Exp. duration:
4 h
Sex:
male/female
Dose descriptor:
other: Lowest toxic concentration
Effect level:
> 6.76 mg/L air (analytical)
Exp. duration:
4 h
Mortality:
No mortality occurred.
Clinical signs:
other: No substance-related intolerance reactions were observed.
Body weight:
Not reported
Gross pathology:
Macroscopic inspection revealed no pathological findings.
Other findings:
Not reported.
Interpretation of results:
not classified
Remarks:
Migrated information Based on the applicable OECD guidance available in 1990. Criteria used for interpretation of results: EU
Conclusions:
In this study the acute LC0 and LC50 (rat, inhal. vapour, 4h) was found to be > 6.76 mg/l, the highest tested concentration in this study.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
30 800 mg/m³
Quality of whole database:
Three studies being available all determining toxicity to vapours, whereas one did not show mortality at 6.76 mg/l (highest tested concentration, analytically confirmed), one showed all animals to be killed at 35 mg/l and one study determining a LC50 of 8000 ppm (i.e. 30800 mg/m3). This value is used as it fits within the other two study findings in a weight of evidence approach.

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:
1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well documented, according to accepted guidelines
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
Collective housing up to a maximum of 5 animals per cage, relative humidity was 50-85%, temperature was 20 ± 2°C.
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Firma Charles River Wiga, Sandhofer Weg 7, 8714 Sulzfeld
- Age at study initiation: Not reported
- Weight at study initiation: m: 194-233 g, f: 155-220 g
- Fasting period before study: Not reported
- Housing: Collective housing up to a maximum of 5 animals per cage (Macrolon type III)
- Diet (e.g. ad libitum): Ssniff-R Alleindiat (ad libitum). Ssniff Spezialdiaten GmbH 4770 Soest/Westfalen.
- Water (e.g. ad libitum): Drinking water as for human consumption in drinking bottles (ad libitum)
- Acclimation period: at least 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 2°C
- Humidity (%): 50 - 85%
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): artificial lighting from 7am - 7pm (12/12)


Type of coverage:
occlusive
Vehicle:
other: Oleum arachidis
Details on dermal exposure:
Prior to study initiation, the animals were acclimated to laboratory conditions for at least 7 days. 24 h before treatment, the fur was removed with electric clippers from an area of roughly 5 x 10 cm on the back of each animal. The skin was subsequently examined for abrasions and animals with healthy, intact skin were then marked (in color) for individual identification. The test article was applied as a 20 % dilution in Oleum arachidis. The pH value was 6.6. A single dermal application of the test article was performed. The substance was held in contact with the skin with a porous gauze dressing and ElastoplastR (Beiersdorf). The exposure period was 24 h.
Duration of exposure:
Test article was applied for 24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
5/sex/dose
Control animals:
not required
Details on study design:
In each animal a number of clinical-toxicological signs were evaluated according to a modified Irwin-Screening procedure. Any change from the normal condition was noted (increase or decrease) and the degree of severity of any clinical symptoms was assessed. The animals were examined at the following intervals after treatment: 20 min, 1, 2, 3, 6, and 24 h and thereafter once daily up to day 14. After patch removal, dermal irritation was evaluated once daily for 14 days according to a scheme based on Draize. The body weights of all animals were recorded immediately before treatment (day 0) and surviving animals were reweighed on days 7 and 14 (termination). Animals found dead or killed in extremis were immediately necropsied. The surviving animals were sacrificed by CO2 asphyxiation after 14 days and gross pathological examinations were subsequently performed.

EVALUATION OF SKIN REACTION
(based on Draize):

Erythema and Eschar Formation Value

No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness) to slight eschar
formation (injuries in depth) 4

Maximum possible = 4

Oedema Formation Value

No oedema 0
Very slight oedema (barely perceptible) 1
Slight oedema (edges of area well defined
by definite raising) 2
Moderate oedema (raised approximately 1
millimetre) 3
Severe oedema (raised more than 1
millimetre and extending beyond area
of exposure) 4

Maximum possible = 4

Sex:
male/female
Dose descriptor:
LD0
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no mortality observed
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no mortality observed
Mortality:
No pre-terminal deaths occurred
Clinical signs:
No abnormal clinical signs were observed
Body weight:
All animals showed normal weight gains
Gross pathology:
Gross pathological examinations at 14 days p.a (terminal necropsy) revealed no test article-dependent findings.
Other findings:
No other findings
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute LD0 and LD50 (dermal, rat) in this experimentwere both found to be > 2000 mg/kg bw. No mortality was observed
Executive summary:

No abnormal clinical signs were observed. No signs of erythema and oedema were observed. No pre-terminal deaths occurred. All animals showed normal weight gains. Gross pathological examinations at 14 days p.a. (terminal necropsy) revealed no test article-dependent findings. The following LD50 values were determined at 24 h and 14 days: male and female >2000 mg/kg bw.

Thus the substance is not subject to classification according to CLP (Regulation (EC) No 1272/2008) or DSD (Directive 67/548/EEC) for acute dermal toxicity.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
17 400 mg/kg bw
Quality of whole database:
Two valid acute dermal studies are available, one study being more reliable performed as limit test showing no mortality at highest tested concentration (2000 mg/kg bw) and one study actually determining a LD50. Thus the LD50 value for the supporting study is used further.

Additional information

Oral toxicity:

In an OECD401 -guideline study no mortality was observed when tested at 2000 mg/kg bw. This finding is supported by Smyth et al (1969) that reported an LD50 (oral, rat) of 20 ml/kg bw (i.e. 17400 mg/kg bw). Thus the substance is of low acute oral toxicity

and the result of Smyth et al. is taken forward for hazard and risk assessment.

Inhalative toxicity:

Two experimental studies performed according to OECD403 are available. In the key study concentrations of 1.51 and 6.76 mg/l (vapour) had been tested and no mortality had been observed nor any other treatment related effects. In the second acute inhalative toxicity study a single dose of 35 mg/l had been applied that killed all male rats within 3 hours and all female rats within 4 hours of exposure. All animlas were found narcoticed after half an hour. In a third study, published by Smyth et al. actually an LC50 has been determined to be 8000 ppm (equivalent to 30.8 mg/l taking into account the vapour density of 3.85 g/l) an this fits well with the observations made in the two studies described before. Therefore, an LC50 (inhal. vapour, rat) of 30.8 mg/l is taken forward for hazard and risk assessment in a weigth of evidence approach and the substance is considered to be of low acute inhalative toxicity.

Dermal toxicity:

In an OECD402 -guideline GLP-study no mortality was observed when tested at 2000 mg/kg bw. This finding is supported by Smyth et al (1969) that reported an LD50 (oral, rat) of 20 ml/kg bw (i.e. 17400 mg/kg bw). Thus the substance is of low acute oral toxicity

and the result of Smyth et al. is taken forward for hazard and risk assessment


Justification for selection of acute toxicity – oral endpoint
Valid OECD-guideline study

Justification for selection of acute toxicity – inhalation endpoint
Well conducted OECD403-guideline study under GLP with 2 doses tested and analytical control of test atmosphere conditions.

Justification for selection of acute toxicity – dermal endpoint
Well conducted OECD402-guideline study under GLP.

Justification for classification or non-classification

All acute toxicity data available for the substance (LD50 oral, rat = 17400 mg/kg, LD50 dermal, rat = 17400 mg/kg and LC50 vapour, rat = 30.8 mg/l) are outside the boundaries for classification and labelling according to CLP (Regulation (EC) No 1272/2008) and DSD (Directive 67/548/EEC). Thus the substance is not to be classified for acute toxicity. In addition narcotic effects have been observed at doses high as 35 mg/l and thus far above the guidance value for classification of 20 mg/l. As narcotic effects of this substance was not reported at the two other inhalative toxicity studies, a classification for Target organ system toxicity, single exposure due to narcotic effects is not required.