Cyclopentane

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1992-11-18 to 1992-12-10

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study is classified as reliable without restrictions because it is in compliance with international guidelines for acute inhalation toxicity studies.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Cyclopentane

EC Number:

206-016-6

EC Name:

Cyclopentane

Cas Number:

287-92-3

Molecular formula:

C5H10

IUPAC Name:

cyclopentane

Details on test material:

- Name of test material (as cited in study report): cyclopentane
- Physical state: liquid
- Analytical purity: 98.6% a.i.
- Lot/batch No.: Z0002 00132
- Storage condition of test material: 4 degrees celcius in the dark
- Other: clear, colourless liquid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, UK Limited
- Age at study initiation: male: 6 weeks; female: 8 weeks
- Weight at study initiation: ~200 grams
- Fasting period before study: not reported
- Housing: Stainless steel cages (size 35 cm x 53 cm x 25 cm height) suspended on a movable rack
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 24⁰C
- Humidity (%): 27 to 65%
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light):not reported

IN-LIFE DATES: From: 1992-11-18 To: 1992-12-10

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: Air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: square perspex chambers with pyramidal tops attached to a vapour generator placed in a water bath maintained at 30 degrees celcius
- Exposure chamber volume: 120 Litres
- Method of holding animals in test chamber: wire mesh partitions to hold 10 animals at a time
- Source and rate of air: dried, filtered, oil free air supplied at 25 litres per minute
- Method of conditioning air: not reported
- System of generating particulates/aerosols: atomiser with PTFE tubing fitted with a syringe pump
- Method of particle size determination: not reported
- Treatment of exhaust air: exhaust to atmosphere through a carbon scrubbing system
- Temperature, humidity, pressure in air chamber: 23 to 24 degrees celcius, humidity and pressure not reported

TEST ATMOSPHERE
- Brief description of analytical method used: 5 samples were drawn through a gas absorption trap containing acetone chilled to -70⁰C. Samples were diluted with methanol and then 3µL aliquots of sample solution were inject onto a Gas Chromatography column. Concentration of cylcopentane was calculated using expression:
Cx = (Ax - I)/S where:
Cx = Concentrationof cyclopentane in aliquot (mg/mL)
Ax = Peak area due to cyclopentane
S = Gradient of standard curve
I = Intercept of standard curve
- Samples taken from breathing zone: yes

VEHICLE
- Composition of vehicle (if applicable): air
- Concentration of test material in vehicle (if applicable):25.30 mg/L
- Justification of choice of vehicle: not reported
- Lot/batch no. (if required): not reported
- Purity: not reported

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution:not reported
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): not reported

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: not provided

Analytical verification of test atmosphere concentrations:

yes

Remarks:

25.30 ± 0.76 mg/L

Duration of exposure:

ca. 4 h

Concentrations:

25.30 mg/L (26.4 mg/L - nominal concentration)

No. of animals per sex per dose:

5 rats/sex/dose

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical signs monitored at 0.25, 0.50, 1.0 hours and then hourly during exposure and once daily during the 14-day post-expsoure observation period.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, food and water consumption

Statistics:

Mean and standard deviation (SD) computed for body weight, concentration analysis, food and water consumption, and lung to body weight ratios.

Results and discussion

Preliminary study:

The 4-hour inhalation LC50 of cyclopentane is >25.3 mg/L.

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 25.3 mg/L air

Exp. duration:

4 h

Mortality:

No deaths were observed.

Clinical signs:

other: Hunched posture was observed in all rats (male and female) during hours 1 to 4 of the expsoure period.

Body weight:

A few male rats exhibited reduction in bodyweight gain on the day following exposure. Subsequently though, bodyweight gain was similar to that observed in control rats. One male rat also exhibited wet fur around the snout and jaws immediately following exposure period.

Gross pathology:

No macroscopic abnormalities were noted in rats exposed to cyclopentane and individual findings such as basophilic cortical tubules in kidneys, macophage aggregates, alveolar hemorrhage and pneumonitis in the lungs were considered spontaneous in origin and not treatment-related.

Other findings:

- Organ weights: Lung to body-weight ratios were found to be within normal limits for all male and female rats.
- Other observations: Food consumption was found to be slightly reduced in male rats for a single day while water consumption seemed unaffected following exposure to cyclopentane.

Any other information on results incl. tables

Table 1. Clinical signs during observation period

Group	Signs	Number of animals showing sings
		Day of observation period post-exposure
		0	1	2	3	4	5	6	7	8	9	10	11	12	13	14
Control Males	Normal behaviour and appearance	5	5	5	5	5	5	5	5	5	5	5	5	5	5	5
Control Females	Normal behaviour and appearance	5	5	5	5	5	5	5	5	5	5	5	5	5	5	5
Males (25.3 mg/L)	Normal behaviour and appearance	4	5	5	5	5	5	5	5	5	5	5	5	5	5	5
	Wet fur around snout and jaws	1
Females (25.3 mg/L)	Normal behaviour and appearance	5	5	5	5	5	5	5	5	5	5	5	5	5	5	5

Table 2. Mean body weight during study period.

Group	Day of Observation and Mean weight in grams
	-5	-4	-3	-2	-1	0	1	2	3	4	5	6	7	8	9	10	11	12	13	14
Male Control	175	185	194	201	207	213	221	230	239	248	257	264	272	278	283	288	298	303	308	315
Female Control	189	195	202	207	211	214	216	220	220	225	227	233	231	238	235	238	239	246	248	251
Male (25.3 mg/L)	177	183	194	202	208	217	233	231	238	248	256	265	271	279	284	291	299	305	309	316
Female (25.3 mg/L)	189	191	198	202	201	205	208	214	215	218	223	227	226	228	232	234	236	240	247	248

Rats exposed at Day 0. Bodyweight recorded before exposure.

Table 3. Microscopic pathology incidence summary.

	Control Males	Males (25.3 mg/L)	Control Females	Females (25.3 mg/L)
Animals on study	5	5	5	5
Animals completed	5	5	5	5
Lungs
Examined	5	5	5	5
No abnormalities detected	2	2	3	4
Penumonitis (Total)	0	0	0	1
Minimal	0	0	0	1
Alveolar collapse	1	0	0	0
Moderate	1	0	0	0
Macrophage aggregates (Total)	2	3	0	0
Minimal	2	2	0	0
Bronchiolar associated lymphoid tissue (Total)	1	0	0	0
Moderate	1	0	0	0
Recent alveolar haemorrhage (Total)	0	1	2	0
Minimal	0	1	2	0
Liver
Examined	5	5	5	5
No abnormalities detected	5	5	5	5
Kidneys
Examined	5	5	5	5
No abnormalities detected	1	1	4	3
Basophilic cortical tubules (Total)	4	4	1	2
Minimal	4	4	1	2

Applicant's summary and conclusion

Interpretation of results:

other: Not classified

Remarks:

Not classified because LC50 is greater than the requirements for a Category 4 vapour toxicant (20 mg/L) Criteria used for interpretation of results: EU

Conclusions:

4-hour acute inhalation toxicity LC50 >25.3 mg/litre

Executive summary:

In an acute inhalation toxicity study, 5 albino Sprague-Dawley rats/sex were administered 25.30 mg/L (nominal concentration of 26.40 mg/L) of cyclopentane via the inhalation route (whole body exposure) for a period of 4 hours. The rats were observed constantly for signs of reaction during the exposure period and twice daily during the 14-day observation period that followed. Clinical signs were recorded at the end of chamber equilibration period, at 0.25, 0.50, and 1 hours and then at hourly intervals during the exposure period. Clinical signs were recorded once in the morning and then as necessary through the observation period. Bodyweight, food, and water consumption determinations were made daily. At termination, rats were killed and subjected to a detailed macroscopic examination. The liver and kidneys of each rat were evaluated histopathologically under light microscope.

There were no observed mortalities and hunched posture was observed in all rats (male and female) during hours 1 to 4 of the exposure period. A few male rats exhibited reduction in bodyweight gain on the day following exposure. Subsequently though, bodyweight gain was similar to that observed in control rats. Food consumption was found to be slightly reduced in male rats for a single day while water consumption seemed unaffected following exposure to cyclopentane. One male rat also exhibited wet fur around the snout and jaws immediately following the exposure period.

No macroscopic abnormalities were noted in rats exposed to cyclopentane and individual findings such as basophilic cortical tubules in kidneys, macophage aggregates, alveolar hemorrhage and pneumonitis in the lungs were considered spontaneous in origin and not treatment-related. Lung to body-weight ratios were found to be within normal limits for all male and female rats.

Based on the results discussed above, the 4-hour inhalation LC₅₀ for cyclopentane is >25.30 mg/L. Cyclopentane is practically non-toxic in the acute inhalation toxicity test in rats. This study received a Kilmisch score of 1 and is classified as reliable without restrictions because it is in compliance with international guidelines for acute.