Registration Dossier

Administrative data

Description of key information

acute toxicity, oral (OECD 401, RL1), female and male rats: LD50 > 2000 mg/kg bw

acute toxicity, inhalation (OECD 403, RL2), female and rats: LC50 > 6.54 mg/L air

acute toxicity, dermal (OECD 402, RL1), female and male rats: LD50 > 2000 mg/kg bw

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.
Justification for type of information:
Please refer to the read-across justification document attached to section 13 in IUCLID.
Reference:
Composition 1
Qualifier:
according to
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:
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. certificate)
Test type:
standard acute method
Limit test:
yes
Test material information:
Composition 1
Species:
rat
Strain:
other: Crl:(WI) BR - Wistar, white
Sex:
male/female
Details on test animals 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: 176 to 193 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 6.5.

MAXIMUM DOSE VOLUME APPLIED: Approximately 10 mL/kg bw
Doses:
Range finding study: 1000 and 2000 mg/kg body weight
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.
Key result
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 isopropylchloride 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:
Category 4 based on GHS criteria
Conclusions:
CLP: Acute toxicity, Cat. 4, H302
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
The available information comprises an adequate and reliable study from a reference substance with similar structure and intrinsic properties. Read-across is justified based on common functional groups and similarities in PC/ECO/TOX properties (see additional information). The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

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:
1990
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study without detailed documentation.
Justification for type of information:
Please refer to the read-across justification document attached to section 13 in IUCLID.
Reference:
Composition 1
Qualifier:
according to
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
Test material information:
Composition 1
Species:
rat
Strain:
other: Sprague-Dawley rats, Tif: RAI f (SPF)
Sex:
male/female
Details on test animals 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: 1.94 and 6.54 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:
> 6.54 mg/L air (analytical)
Exp. duration:
4 h
Remarks on result:
other: No intolerance reactions were seen at the highest concentration of 6.54 mg/L. No pathological findings.
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 6.54 mg/L air (analytical)
Exp. duration:
4 h
Sex:
male/female
Dose descriptor:
other: Lowest toxic concentration
Effect level:
> 6.54 mg/L air (analytical)
Exp. duration:
4 h
Mortality:
No mortality occurred.
Clinical signs:
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:
Category 4 based on GHS criteria
Conclusions:
CLP: Acute toxicity, Cat. 4, H332
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
6 540 mg/m³
Quality of whole database:
The available information comprises an adequate and reliable (Klimisch score 2) study, from a reference substance with similar structure and intrinsic properties. Read-across is justified based on common functional group(s) and similarities in PC/ECO/TOX properties (see additional information). The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

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
Justification for type of information:
Please refer to the read-across justification document attached to section 13 in IUCLID.
Reference:
Composition 1
Qualifier:
according to
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. certificate)
Test type:
standard acute method
Limit test:
no
Test material information:
Composition 1
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals 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 6.5. 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:
LD50
Effect level:
> 2 000 mg/kg bw
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:
Category 4 based on GHS criteria
Conclusions:
CLP: Acute toxicity, Cat. 4, H312
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
The available information comprises an adequate and reliable study from a reference substance with similar structure and intrinsic properties. Read-across is justified based on common functional groups and similarities in PC/ECO/TOX properties (see additional information). The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Additional information

Acute toxicity

Justification for read-across

There are no reliable data available regarding acute toxicity for 1-chloropropane (CAS 540-54-5). Read-across from an appropriate substance (2-chloropropane (CAS 75-29-6)) is conducted in accordance with Regulation (EC) No 1907/2006, Annex XI, 1.5. in order to fulfil the standard data requirements defined in Regulation (EC) No 1907/2006, Annex VII, 8.5. Common functional groups, structural similarities and comparable toxicological properties (according to the joint consideration in Annex VI to CLP) of the source and target substance are the basis of read-across. A detailed justification for the analogue read-across approach is provided in the technical dossier (see IUCLID Section 13).

 

Acute oral toxicity

CAS 75-29-6

Acute toxicity of 2-chloropropane was tested in Crl:(WI) BR rats according to OECD TG 401 (reference 7.2.1-1). Based on the results of a range finding study, the test substance was administered in a limit test at a concentration of 2000 mg/kg bw in oleum arachidis via gavage to groups of 5 males and females. No concurrent control group was included in the study. No mortality and no abnormal clinical signs were observed. Weight gains appeared normal until the end of the observation period and gross pathology did not reveal test-substance specific findings Based on these results of the conducted study, a LD50 > 2000 mg/kg bw was derived for males and females.

Based on the results of the conducted study, 2-chloropropane does not meet the classification criteria according to Regulation (EC) No 1272/2008. However, according to the harmonised classification, 2-chloropropane is considered to meet the classification criteria for Acute toxicity, Cat. 4, H302 according to Regulation (EC) No 1272/2008.

 

CAS 540-54-5

Limited data on the toxic potential of 1-chloropropane are available for the oral route (Dow et al., 1946). Administration of 1000 mg/kg bw to guinea pigs did not result in mortalities, whereas doses of 3000 mg/kg bw caused death. As no further information are available, the data are considered as supporting data in regard to the hazardous properties of 1-chloropropane following oral exposure but are not taking into consideration for hazard assessment.

Overall conclusion

Based on the analogue approach and considering the harmonized classification, 1-chloropropane is considered to meet the classification criteria for Acute toxicity, Cat. 4, H302 according to Regulation (EC) No 1272/2008.

Inhalation.

CAS 75-29-6

An acute inhalation toxicity study was performed according to OECD TG 403 and in compliance with GLP (reference 7.2.2-1). In this study, groups of 5 male and 5 female Sprague-Dawley rats were exposed to single doses of 1.94 and 6.54 mg 2-chloropropane/L air (analytical concentration) for 4 h via nose only inhalation. Based on a vapour pressure of 0.49 bar at 20°C, an almost complete gas phase was achieved in the inhalation chamber after the test substance air mixture escaped from the spray-jet. Animals were observed for 14 days after test material exposure. No mortality occurred during the entire study period and no clinical signs of toxicity were observed. Macroscopic inspection revealed no pathological findings. The acute inhalation LC50 value is considered to be > 6.54 mg/L air.

Further, supporting data on the acute toxic potential following inhalation are available for 2-chloropropane (reference 7.2.2-2). Whole body exposure to 133g/m3 for 1 h resulted in deeply narcotized test animals within ten minutes. All animals died after 1 hour of exposure, when the test was terminated. Final gross necropsy revealed hyperemic lungs in all test animals.

Based on the available data, 2-chloropropane does not meet the classification criteria according to Regulation (EC) No 1272/2008. However, according to the harmonised classification, 2-chloropropane is considered to meet the classification criteria for Acute toxicity, Cat. 4, H332 according to Regulation (EC) No 1272/2008.

Overall conclusion

Based on the analogue approach and considering the harmonized classification, 1-chloropropane is considered to meet the classification criteria for Acute toxicity, Cat. 4, H332 according to Regulation (EC) No 1272/2008.

 

Acute dermal toxicity

CAS 75-29-6

An acute dermal toxicity study was performed with 2-chloropropane according to OECD TG 402 (reference 7.2.3-1). In this study, groups of 5 female and 5 males Wistar rats were exposed to a single dose of 2000 mg/kg bw test substance for 24 hours. The observation period was 14 days. 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. Thus, a LD50 value of > 2000 mg/kg bw was determined for male and female rats. 

Based on the results of the conducted study, 2-chloropropane does not meet the classification criteria according to Regulation (EC) No 1272/2008. However, according to the harmonised classification, 2-chloropropane is considered to meet the classification criteria for Acute toxicity, Cat. 4, H312 according to Regulation (EC) No 1272/2008.

Overall conclusion

Based on the analogue approach and considering the harmonized classification, 1-chloropropane is considered to meet the classification criteria for Acute toxicity, Cat. 4, H312 according to Regulation (EC) No 1272/2008.

Justification for classification or non-classification

1-chloropropane (CAS 540-54-5) and the analogue substance 2-chloropropane (CAS 75-29-6) are classified as Acute Tox. 4, H302, H312 and H332 according to Annex VI of Regulation (EC) No 1272/2008. Although the available data on acute toxicity do not meet the classification criteria according to Regulation (EC) No 1272/2008, the registrant follows the harmonised classification.