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Toxicological information

Neurotoxicity

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Description of key information

There is some data available for cyclopentane. This is supported by data available for structural analogues, Light alkyl naphtha distillate and pentane and presented in the dossier. This data is read across to cyclopentane based on analogue read across and a discussion and report on the read across strategy is provided as an attachment in IUCLID Section 13. 

Four studies were identified that examined neurotoxicity endpoints.  These studies were comprised of 90-day inhalation toxicity studies (n-pentane; 2-methylbutane; cyclopentane) and a test on nerve conduction velocity and distal latency (n-pentane).  

Key value for chemical safety assessment

Effect on neurotoxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no study available

Effect on neurotoxicity: via inhalation route

Link to relevant study records

Referenceopen allclose all

Endpoint:
neurotoxicity: sub-chronic inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study is classified as reliable without restriction because it is in compliance with OECD guidelines, as well as U.S. EPA/FIFRA, U.S. EPA/TSCA, and EU guidelines.
Qualifier:
according to guideline
Guideline:
other: U.S. EPA/FIFRA Guidelines §82-4
Qualifier:
according to guideline
Guideline:
other: U.S. EPA/TSCA Guidelines 40 CFR §798.2450
Qualifier:
according to guideline
Guideline:
other: U.S. EPA/TSCA Guidelines 40 CFR §798.6059, and §798.6059, 798.6200, 798.6400
Qualifier:
according to guideline
Guideline:
other: EU Guideline 87/302/EEC
GLP compliance:
not specified
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
not reported
Route of administration:
inhalation: vapour
Vehicle:
not specified
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Analytical verification of concentrations was determined using gas chromatography.
Frequency of treatment:
Rats were exposed for 6 hours per working day for 90 days.
Remarks:
Doses / Concentrations:

Basis:

No. of animals per sex per dose:
15 male and 15 female per dose
Observations and clinical examinations performed and frequency:
General observation was performed twice on working days and once on holidays an weekends. Clinical examination was performed once each working day during the preflow period and on the day following exposure.
Neurobehavioural examinations performed and frequency:
Neurofunctional tests were performed in 10 animals per sex once before the exposure period and 3 times during the exposure period at monthly intervals.

5 animals per sex, of those subject to neurofunctional testing were sacrificed by perfusion fixation, to be examined neuropathologically.
Sacrifice and (histo)pathology:
A complete necropsy, which included weighing of selected organs, and a gross pathological evaluation was preformed in 10 animals per sex. Histopathology was performed on several tissues and organs as required by testing guidelines.
Other examinations:
Hematological and clinicochemical examination of numerous parameters was performed in 10 animals per sex post-exposure.

Body weight measurements were determined weekly and ophthamology was carried out prior to and at the end of the exposure period.
Positive control:
no data
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Behaviour (functional findings):
no effects observed
Gross pathological findings:
no effects observed
Neuropathological findings:
no effects observed
Details on results:
No abnormalities were detected during clinical, neurofunctional, and clinico-pathological examinations in any of the test groups. No changes were found during necropsy or in the histo- and neuropathological examinations.
Conclusions:
Only summary information on the study’s methodology was presented. Minimal animal data were given (no information on age, weight, treatment, husbandry, experimental set up). The dose levels were not adjusted for appropriate toxicity (i.e., no toxic effects observed at highest dose). A description of the physical environment during exposure was not given. Details on types of observations were not provided (e.g., types of “clinical examinations” or “neurofunctional tests” were not explained).
Executive summary:

Fifteen male and fifteen female Wistar rats per test group were exposed to cyclopentane vapour (pure) at concentrations of 5, 10, 30 mg/L and cyclopentane vapour (technical grade) at a concentration of 30mg/L for 6 hours per weekday for 90 days. A concurrent control group was exposed to clean air. General observations were performed twice during weekdays and once during weekends and holidays. Clinical examinations were performed once every weekday and on the day following exposure. Neurofunctional test were performed in 10 animals per sex, once before the exposure period and 3 times during the exposure period. A hematological and clinicochemical examination was performed in 10 animals per sex at the end of the exposure period. A complete necropsy was performed on 10 animals per sex, which included weighing of selected organs and gross pathological evaluation. 5 animals per sex, of those subject to neurofunctional testing, were sacrificed by perfusion fixation and examined neuropathologically. Subchronic inhalation exposure to up to 30 mg/L of cyclopentane vapour (technical grade or high purity) did not cause a substance related toxic effect. The NOAL concentration is 30 mg/L under the conditions of this study.

This study was given a Kilimsh score of 1, reliable without restriction. The study had minor discrepancies that are listed in the overall remarks/attachments comment box in this robust summary. It is anticipated that the results will influence the DNEL.

Endpoint:
neurotoxicity: sub-chronic inhalation
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study is classified as reliable without restriction because it was conducted according to OECD guideline 413 and was GLP compliant.
Justification for type of information:
A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.
Reason / purpose for cross-reference:
read-across: supporting information
Qualifier:
according to guideline
Guideline:
other: OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day)
GLP compliance:
yes
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Kingston, NY
- Age at study initiation: 7 weeks
- Weight at study initiation: Not reported
- Housing: Individual
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: 2 weeks


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 26 °C
- Humidity (%): 40 to 70%
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light
Route of administration:
inhalation: vapour
Vehicle:
other: nitrogen
Details on exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: 1000 litre exposure chamber
- Method of holding animals in test chamber: Cages
- Source and rate of air: 5-gallon container, flushed with nitrogen using laboratory pump
- Method of conditioning air: System of coarse filter, HEPA filter, charcoal filter
- System of generating particulates/aerosols: Volatilization chamber
- Temperature, humidity, pressure in air chamber: Monitored every half hour during exposure; 20 to 24 degrees C, 40 to 60% relative humidity
- Air flow rate: 200 litres per minute
- Method of particle size determination: TSI Aerodynamic Particle Sizer, once each exposure

TEST ATMOSPHERE
- Brief description of analytical method used: Gas chromatography
- Samples taken from breathing zone: yes

VEHICLE (if applicable)
- Composition of vehicle: Nitrogen
- Purity of vehicle: 99.98%
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Samples for determination of analytical exposure levels were withdrawn by vacuum pump from the breathing zone in the exposure chambers three times per exposure for treated groups, and once per exposure for controls. Samples were analyzed using gas chromatography using a flame ionization detector.
Duration of treatment / exposure:
13 weeks
Frequency of treatment:
6 hours per day, 5 days per week
Remarks:
Doses / Concentrations:
6646 ppm (24.3 mg/m3)
Basis:
analytical conc.
Remarks:
Doses / Concentrations:
2220 ppm (8.1 mg/m3)
Basis:
analytical conc.
Remarks:
Doses / Concentrations:
668 ppm (2.4 mg/m3)
Basis:
analytical conc.
No. of animals per sex per dose:
12
Control animals:
yes, concurrent no treatment
Details on study design:
- Dose selection rationale: Highest concentration approximately 75% of the lower explosive limit
- Post-exposure recovery period in satellite groups: 28 days

An extra 12 rats per sex for the high dose and control recovery groups were maintained untreated for 28 days after termination of exposure, to assess reversibility of effects.

Observations and clinical examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Twice daily

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Twice pretest, weekly during the study period

BODY WEIGHT: Yes
- Time schedule for examinations: Twice pretest, weekly during the study period, prior to sacrifice

FOOD CONSUMPTION: Yes
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data

OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: Pretest and prior to sacrifice
- Dose groups that were examined: All

HAEMATOLOGY: Yes
- Time schedule for collection of blood: Prior to sacrifice
- Anaesthetic used for blood collection: Yes (carbon dioxide/oxygen)
- Animals fasted: Yes
- How many animals: 12 per sex per group
- Parameters checked in table 1 were examined.

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: Prior to sacrifice
- Animals fasted: Yes
- How many animals: 12 per sex per group
- Parameters checked in table 2 were examined.

URINALYSIS: No
Specific biochemical examinations:
No data reported.
Neurobehavioural examinations performed and frequency:
NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: Pretest, weeks 5, 9, 14, and 18 (recovery groups)
- Dose groups that were examined: All
- Battery of functions tested: sensory activity / grip strength / motor activity / handling / open-field behaviour / reflexes
Sacrifice and (histo)pathology:
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes
Organs weighed: adrenals, brain, heart, kidneys, liver, lung, ovaries, prostate, spleen, testes (with epididymides), thymus, and uterus
Tissues histopathologically examined: 39, preserved, not reported
Other examinations:
No data reported.
Positive control:
No
Statistics:
Statistical evaluations to determine variance and significance were performed on the following parameters: body weights, body weight change from week 0, food consumption, haematology, clinical chemistry, organ weights, organ/terminal body weight ratio, and organ/brain weight ratio.
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
no effects observed
Clinical biochemistry findings:
effects observed, treatment-related
Behaviour (functional findings):
effects observed, treatment-related
Gross pathological findings:
no effects observed
Neuropathological findings:
not examined
Other effects:
not examined
Description (incidence and severity):
Migrated information from 'Further observations for developmental neurotoxicity study'



Details on results (for developmental neurotoxicity):Not examined. (migrated information)
Details on results:
CLINICAL SIGNS AND MORTALITY: No treatment-related effects were observed.

BODY WEIGHT AND WEIGHT GAIN: No treatment-related effects were observed.

FOOD CONSUMPTION: No treatment-related effects were observed.

OPHTHALMOSCOPIC EXAMINATION: No treatment-related effects were observed.

HAEMATOLOGY: Statistically significant decreases in haemoglobin, hematocrit, and erythrocytes in blood of high-dose males when compared to controls were not found to be toxicologically relevant, as the values were within the historical range for control animals.

CLINICAL CHEMISTRY: Statistically significant decreases in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in blood of high-dose females when compared to controls were not found to be toxicologically relevant, as several control female rats had elevated AST and ALT as well.

NEUROBEHAVIOUR -Motor Activity: There were statistically significant differences in the number and relative pattern of motor activity among the dose groups over the treatment testing periods, but overall, these differences did not occur in a dose-related pattern. The magnitudes of the differences were not large, and none of the treatment-group differences were larger than differences seen during the predose period.
-Functional Operational Battery: No treatment-related effects were observed.

ORGAN WEIGHTS: At terminal sacrifice, there were statistically significant dose-related increases in absolute and relative kidney weights in males of all three treatment groups. High-dose male kidney weights remained elevated after the recovery period. This correlated with microscopic observations indicating light hydrocarbon nephropathy. At terminal sacrifice, there were also statistically significant increases in absolute and relative liver weights in high-dose male and female rats. Liver weights did not remain elevated after the recovery period. There was no microscopic correlation for this condition, so this was considered a functional adaptation to treatment. There were no differences in lung and brain weights when compared to controls.

GROSS PATHOLOGY: No treatment-related effects were observed.

HISTOPATHOLOGY: NON-NEOPLASTIC: Microscopic observations included hyaline droplet formation in the proximal convoluted tubules, considered to contain an alpha2-microglobulin-hydrocarbon complex, and increase in incidence and severity of nephropathy and dilated tubules at the cortico-medullary junction.
Key result
Dose descriptor:
NOEC
Remarks:
(Subchronic toxicity)
Effect level:
> 2 220 ppm
Sex:
male/female
Basis for effect level:
other: Organ weights
Remarks on result:
other:
Key result
Dose descriptor:
NOEC
Remarks:
(Neurotoxicity)
Effect level:
>= 6 646 ppm
Sex:
male/female
Basis for effect level:
other: Organ weights
Remarks on result:
other:
Conclusions:
The NOEC of the test substance was found to be > 2220 ppm for subchronic toxicity, and >= 6646 ppm for neurotoxicity. The test substance did not cause neurobehavioral or neuropathologic effects in rats after 13 weeks of inhalation exposure at a maximum concentration of 6646 ppm (24.3 mg/m^3). The test substance did induce "light hydrocarbon nephropathy", characterized by increased organ weight and microscopic effects of the kidney (increased incidence of hyaline droplets) in male rats, but since this syndrome is species and sex specific, it is not considered relevant to humans for risk assessment purposes.
Executive summary:

 In a 90-day inhalation toxicity study, light alkylate naphtha distillate-2 was administered to 12 Sprague-Dawley rats/sex/concentration by dynamic whole body exposure at concentrations of 0, 668, 2220, or 6646 ppm (0, 2.4, 8.1, and 24.3 mg/m^3) for 6 hours per day, 5 days/week for a total of 13 weeks.

 

There were no treatment-related effects inmortality, clinical signs, neurotoxicity, body weight, or food consumption. Significant effects noted in haematology and clinical chemistry were not determined to betoxicologically relevant, and kidney weight increases found in high-dose males were not determined to be relevant to human toxicity risk assessments. The LOEC for subchronic toxicity is >= 6646 ppm, based on haematology, clinical chemistry and organ weights. The NOEC is > 2220 ppm for subchronic toxicity and >= 6646 ppm for neurotoxicity.

 

This study received a Klimisch score of 1 and is classified asreliable without restriction because it was conducted according to OECD guideline 413 and was GLP compliant.

Endpoint:
neurotoxicity: sub-chronic inhalation
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
not reported
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study is classified as reliable with restrictions because while there is no statement regarding whether this study was conducted according to GLP or equivalent, the full study protocol was provided, including test materials and methods.
Justification for type of information:
A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.
Reason / purpose for cross-reference:
read-across: supporting information
Qualifier:
no guideline followed
Principles of method if other than guideline:
This study is not a typical repeated dose, neurotoxicity study (OECD 424 guideline). It did not examine behavioral changes through functional observations, but instead examined nerve conduction velocity and distal latency. Only seven male rats were exposed for 16 weeks to a single dose of 3000 ppm without clinical exams, hematology, clinical chemistry, ophthalmology, or standard histopathology.
GLP compliance:
not specified
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 308±18

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23.5 to 24.5 °C
- Humidity (%): 41 to 61%
Route of administration:
inhalation: vapour
Vehicle:
unchanged (no vehicle)
Details on exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
No specifics were provided.

TEST ATMOSPHERE
- Brief description of analytical method used: The study report states that the vapour concentration in the exposure chamber was measured faily by gas detector and twice a week by gas liquid chromatography.
- Samples taken from breathing zone: no data


Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
The mean n-pentane concentration in the exposure chamber was 3080±200 ppm.
Duration of treatment / exposure:
12 hours a day
Frequency of treatment:
16 weeks
Remarks:
Doses / Concentrations:
3000 ppm
Basis:
other: This concentration was thought to be most likely to yield effects for the n-hexane group from results of previous experiments.
No. of animals per sex per dose:
seven males
Control animals:
yes, sham-exposed
Details on study design:
- Dose selection rationale: Other compounds were also tested. The concentration selected was thought to be likely to cause an effect with n-heptane and all compounds had the same concentration for comparison.
- Rationale for animal assignment (if not random): no data
Observations and clinical examinations performed and frequency:
CAGE SIDE OBSERVATIONS: No data

DETAILED CLINICAL OBSERVATIONS: No data

BODY WEIGHT: Yes
- Time schedule for examinations: before exposure, and after 4, 8, 12, and 16 weeks of exposure

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): no

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): no

OPHTHALMOSCOPIC EXAMINATION: no
Specific biochemical examinations:
NEUROPATHY TARGET ESTERASE (NTE) ACTIVITY: no


CHOLINESTERASE ACTIVITY: No


Neurobehavioural examinations performed and frequency:
FUNCTIONAL OBSERVATIONAL BATTERY: no

LOCOMOTOR ACTIVITY: no

AUDITORY STARTLE REFLEX HABITUATION: no

LEARNING AND MEMORY TESTING: no

OTHER: The conduction velocity of the peripheral nerve was measured in the rat's tail. Rats were immobilised in a towel and electrodes were inserted in the tail. The tail was immersed in a parafin bath maintained at 37 to 38°C. The following parameters were measured: motor nerve conduction velocity, distal latency, and mixed nerve conduction velocity.
Sacrifice and (histo)pathology:
- Time point of sacrifice: after 16 weeks
- Number of animals sacrificed: one
- Procedures for perfusion: Under anaesthesia, rats were perfused from the left ventricle with a fixative containing paraformaldehyde and glutaraldehyde. Tissues were fixed in the same fixative, then postfixed with osmium tetroxide.
- Number of animals perfused: one
- Tissues evaluated: gastrocnemius and soleus muscles, the dorsal trunk of the tail nerve at the proximal and distal portions, and the tibial nerve
- Type of staining: For electron microscopy, tissues were stained with uranyl acetate and lead citrate. For light microscopy, tissues were stained with hemalaun and eosin.
- Number of animals evaulated from each sex and treatment group: one
Other examinations:
The conduction velocity of the peripheral nerve was measured in the rat's tail. Rats were immobilised in a towel and electrodes were inserted in the tail. The tail was immersed in a parafin bath maintained at 37 to 38°C. The following parameters were measured: motor nerve conduction velocity, distal latency, and mixed nerve conduction velocity.
Statistics:
Specifics of statistical analyses were not provided, but significance at the 5% and 1% level were reported.
Clinical signs:
not specified
Mortality:
not specified
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Clinical biochemistry findings:
not examined
Behaviour (functional findings):
not examined
Gross pathological findings:
not examined
Neuropathological findings:
no effects observed
Details on results:
CLINICAL SIGNS AND MORTALITY: While there is no specific data on this endpoint for n-pentane, mention of abnormal gait in n-hexane rats indicates that these were examined and no effects were noted in the n-pentane group.

BODY WEIGHT AND WEIGHT GAIN: No significant changes were observed.

NEUROPATHOLOGY: There were no abnormal observations in the peripheral nerve, neuromuscular junction, or the muscle fibre by either light or electron microscopy in the rat examined.

OTHER FINDINGS: n-Pentane did not disrupt the conduction velocity of the motor nerve or the mixed nerve or prolong the distal latency.
Key result
Dose descriptor:
NOAEC
Effect level:
3 000 ppm (nominal)
Sex:
male
Basis for effect level:
other: absence of any effect on the specific parameters measured
Remarks on result:
other:
Conclusions:
n-Pentane did not cause neurotoxicity as measured by conduction velocity and distal latency.
Executive summary:

The nerve conduction velocity and distal latency was measured in rats that were exposed to n-pentane for 16 weeks via inhalation. While the study did not comply with typical OECD 424 repeated dose, neurotoxicity guidelines, the methods seemed appropriate for the purpose of this study. However, only males were examined. Statistical methods used were not detailed; however, p-values at the 5% and 1% level were provided for some of the data. N-pentane did not prolong distal latency or disturb the conduction velocity of the motor nerve and mixed nerve in the rat's tail. No changes were observed in the peripheral nerve, the neuromuscular junction, and muscle fiber of rats exposed to n-pentane at 3000 ppm for 16 weeks. No changes in body weight or behavior were observed in n-pentane exposed rats when compared with control animals. This study is classified as reliable with restrictions because while there is no statement regarding whether this study was conducted according to GLP or equivalent, the full study protocol was provided, including test materials and methods.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Study duration:
subacute
Species:
rat
Quality of whole database:
Three key (one substance specific and two read across) and two supporting read across studies from structural analogues available for assessment.

Effect on neurotoxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

There is key data available for cyclopentane. This is supported by data available for structural analogues, Light alkyl naphtha distillate and pentane and presented in the dossier. This data is read across to cyclopentane based on analogue read across and a discussion and report on the read across strategy is provided as an attachment in IUCLID Section 13.

Potential neurotoxic effects of pentanes were evaluated in three select subchronic repeated dose studies via inhalation, each of which contained a neurotoxicity screening component (Takeuchi et al., 1981;Schreiner, 1998;Gamer, 1998). No treatment-related effects related to neurotoxicity were reported in any of these studies. Additionally,nerve conduction velocity and distal latency was measured in rats exposed to n-pentane for 16 weeks via inhalation (Takeuchi et al., 1980). N-pentane did not prolong distal latency or disturb the conduction velocity of the motor nerve and mixed nerve in the rat's tail. No changes were observed in the peripheral nerve, the neuromuscular junction, and muscle fibre of rats exposed to n-pentane at 3000 ppm for 16 weeks. No changes in body weight or behaviour were observed in n-pentane exposed rats when compared with control animals. 

Additionally, a relevant and useful supporting study also was available for n-pentane (Stoughton, 1936). This information is also presented in the Acute Toxicity section under inhalation. In this study,the anaesthetic activity of n-pentane on mice. In the first test series, referred to as the "light anesthesia" test, two mice were placed in a 2 liter bottle containing the n-pentane gas mixture. During this test, mice were dosed at concentrations of 3.0, 3.5, and 4.2 mmol/L. If animals were unable to maintain their upright posture after spinning the bottle then they were said to be lightly anaesthetized. For the three concentration levels tested, the time it took for mice to become lightly anaesthetized ranged from 1.3 to 10 minutes. No mice died during the first test series. In the second test series, referred to as the "complete anaesthesia" test, five mice were placed in a 20 liter bottle containing the n-pentane gas mixture. During this test, mice were dosed at concentrations of 4.2, 4.5, and 4.9 mmol/L. If animals were unable to regain their upright positioning after shaking then they were said to be anaesthetized. After two hours, the mice were removed from the bottle and the number of mortalities was noted. No mortalities occurred at 4.2 mmol/L, 8 mortalities occurred at 4.5 mmol/L, and 7 mortalities occurred at 4.9 mmol/L. The average recovery time for the survivor test mice ranged from 4 to 8 minutes.The LC50 was not calculated. Based on this study, it can be inferred that cyclopentane should be classified and labelled for drowsiness and dizziness under CLP EU Regulation 1272/2008.

Justification for classification or non-classification

Based on the information presented in the read across study on anaesthetic activity of n-pentane, cyclopentane is classified as as STOT Single Exp. 3 (H336: May cause drowsiness or dizziness) in accordance with CLP EU Regulation 1272/2008.