Cyclopentanone

Endpoint summary

Description of key information

LD50 oral (rat): > 2000 mg/kg bw
LD50 dermal (rat): > 2000 mg/kg bw
LC50 inhalation (Male rats) (4h): >= 19.5 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:

from 26-NOV-1998 to 03-SEP-1999

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The test substance purity was known. The screening protocol was standard, but not validated for GLP by the quality assurance unit.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

(3 animals were used at each dose level)

Principles of method if other than guideline:

other: screening protocol similar to OECD guide-line 401 "acute oral toxicity"

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TESTS ANIMALS
- Source: Harlan Nossan S.r.l, Italy
- Age at study initiation: data not available
- Weight at study initiation: 190-203 g (males), 158-169 g (females)
- Fasting period before study: data not available
- Housing, food consumption, water consumption, acclimation period: data not available

ENVIRONMENTAL CONDITIONS (temperature , humidity, air changes, photoperiod): data not available

In-life dates: data not available

Route of administration:

oral: gavage

Vehicle:

other: maize oil

Details on oral exposure:

VEHICULE
- Concentration in vehicle: 50 and 200 mg/mL
- Amount of vehicle: 10 mL/kg
- Justification for choice of vehicle: data not available
- Purity: data not available

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION :data not available

Doses:

500 and 2000 mg/kg bw

No. of animals per sex per dose:

3 males (500 mg/kg) and 3 females (2000 mg/kg)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 day
- Frequency of observations and weighing: data not available
- Necropsy of survivors performed: yes

Statistics:

not applicable

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Remarks on result:

other: 95% Conf. limits: not applicable

Mortality:

no mortality was observed

Clinical signs:

other: Toxic effects were observed: - at 500 and 2000 mg/kg bw, reduced activity, piloerection, hunched posture were observed. - at the lower dose, hair loss was noted following dosing. - at the highest dose, lethargy, part-closed eyes and staining of skin/fu

Gross pathology:

Necropsy showed no abnormalities at 500 and 2000 mg/kg bw doses.

Table 2: body weight changes

Dose level	Animal	Body weight (g) on Day:		Change in body weight
(mg/kg)	Number	1	15	Day 1-15
	182	190	293	103
500	184	195	316	121
	186	203	315	112
	181	159	188	29
2000	183	158	201	43
	185	169	197	28

Table 1: Clinical signs and mortality

Dose level	Clinical signs	Mortality
(mg/kg)
500	Reduced activity, piloerection, hunched posture and hair loss noted following dosing. Recovery within 14 days. Necropsy showed no abnormalities.	0/3
2000	Reduced activity/lethargy, piloerection, hunched posture, part-closed eyes and staining of skin/fur noted following dosing. Recovery within 10 days. Necropsy after 14 days showed no abnormalities.	0/3

Interpretation of results:

GHS criteria not met

Conclusions:

In this study, no mortality were observed in rats (males and females) at the 2 administred doses
of cyclopentanone (500 and 2000 mg/kg).

Executive summary:

In an acute oral toxicity study (Nunziata A, 1999), groups of male and female Sprague-Dawley rats (3/group) were given a single oral dose of cyclopentanone (99.8% purity) in maize oil at doses of 500 and 2000 mg/kg bw and observed for 14 days.
Oral LD50 Combined > 2000mg/kg bw (no mortality was observed)

Cyclopentanone is not classified for acute oral toxicity based on the LD50 identify in male and female rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

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:

no data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Purity of the test substance was not reported even if the cyclopentanone was received from Esso Research and Engineering and was considered to be free from impurities. The study was performed before the GLP standard was established. However, the method and the results were quite well described. The exposure chamber concentrations were nominal dosage concentrations. The LC50 was estimated because mortality data were not suitable for statistical analysis.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

not specified

GLP compliance:

no

Test type:

other: no data

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: 200 - 225 g
- Housing: Animals were housed in wiremesh cages centred in the
stainless steel exposure chamber.
- Source, age at study initiation, fasting period before study, diet, water, acclimation period: data not available

ENVIRONMENTAL CONDITIONS (temperature, humidity, air changes, photoperiod): data not available.

IN-LIFE DATES: data not available.

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
inhalation exposure to vapours was carried out in a dynamic, 500 litres, stainless steel exposure chamber.
Vaporization of the cyclopentanone was achieved by means of delivering predetermined amounts of the liquid test substance by a metering pump
into a stainless steel spray nozzle tip operating under positive air pressure.
The cyclopentanone metered through the nozzle were then vaporized by the pressurized air flow directly into the exposure chamber.
Nominal dosage concentrations were calculated from the amount of liquid being metered and the total airflow through the chamber.

TEST ATMOSPHERE: data not available

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

4 h

Concentrations:

4.7, 12, 15, 17.8, 19.5 mg/L

No. of animals per sex per dose:

10 male rats per group

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: mortality and signs of toxicity were observed at half-hour intervals during the actual exposure and daily during a 14-day post-exposure observation period.
- Necropsy of survivors performed: yes

Statistics:

no data available

Sex:

male

Dose descriptor:

LC50

Effect level:

>= 19.5 mg/L air

Exp. duration:

4 h

Remarks on result:

other: 95% CL: results not suitable for statistical analysis

Mortality:

Groups of animals were exposed to test concentrations of 4.7, 12, 15, 17.8 or 19.5mg/L, resulting in the following cumulative mortality data
(no. animals dead/no. animals tested): 0/10, 1/10, 3/10, 3/10 and 4/10, respectively.
All animals survived the exposure period, with deaths occurring during the 14 day observation period.

Clinical signs:

other: During exposure, dyspnea, depression and decreased activity were observed. Moreover, ataxia and prostration were also noted at the two highest levels. These signs disappeared within 48 hours.

Body weight:

no data available

Gross pathology:

Autopsy of dead animals showed moderate congestion of the lungs, liver and kidneys. No gross findings were noted from autopsies at the end of the study.

Copy of Exxon's submission to EPA of test data on Isophorone & cyclopentanone. LC50 studies in rats were reported.

Interpretation of results:

GHS criteria not met

Conclusions:

In this study, no mortality were observed in male rats at 4.7, 12, 15 mg/L of cyclopentanone.
Three and 4 rats died respectivelly after 17.8 and 19.5 mg/L.

Executive summary:

In an acute inhalation toxicity study (Anon., 1965), groups of Wistar rats (10 males/group) were exposed by inhalation (whole body) to cyclopentanone (purity unknown) for 4 hours at concentrations of 4.7, 12, 15,n 17.8, 19.5 mg/L. 

Animals then were observed for 14 days.

No mortality were observed in male rats at 4.7, 12, 15 mg/L of cyclopentanone. Three and 4 rats died respectivelly after 17.8 and 19.5 mg/L.

Based on these results a LC50 for male rats was identified. LC50 (male rats) >= 19.5 mg/L

Cyclopentanone is classified as being of LOW Toxicity based on male results.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

19 500 mg/m³ air

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:

from 26-NOV-1998 to 03-SEP-1999

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The test substance purity was known. The screening protocol was standard, but not validated for GLP by the quality assurrance unit.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

(only 3 animals were used per dose level)

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS:
- Species: COMMON SPECIES: rat
- Strain: RAT STRAINS: Sprague-Dawley
- Sex: male/female
- Source: Harlan Nossan S.r.l., Italy
- Age at study initiation: data not available
- Weight at study initiation: 251 to 274 g (males), 208 to 212 g (females)
- Fasting period before study, housing, diet, water, acclimation period: data not available

ENVIRONMENTAL CONDITIONS (temperature, humidity, air changes, photoperiod): data not available

In-life dates: data not available

Type of coverage:

not specified

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE: (area of exposure, % coverage, type of wrap if used): data not available

REMOVAL OF TEST SUBSTANCE: data not available

TEST MATERIAL: data not available

Duration of exposure:

no data available

Doses:

400 and 2000 mg/kg bw

No. of animals per sex per dose:

3 females (400 mg/kg) and 3 males (2000 mg/kg)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: data not available
- Necropsy of survivors performed: yes

Statistics:

not applicable

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Remarks on result:

other: 95% CL not applicable

Mortality:

At the 400 and 2000 mg/kg bw doses, no mortality occurred

Clinical signs:

other: At the lower dose (400 mg/kg), no clinical signs were observed. At the highest dose (2000 mg/kg), piloerection and staining of skin/fur were observed during period of  exposure and disappeared within 24 hours (See table 1 in the attached document).

Gross pathology:

necropsy after 14 days revealed no abnormalities at the 2 doses.

CYCLOPENTANONE: dermal LD50 (Nunziata A, 1999)

Table 1: Clinical signs and mortality

Dose level	Clinical signs	Mortality
(mg/kg)
2000	Piloerection and staining of skin/fur during period of exposure. Recovery within 24 hours. Necropsy after 14 days revealed no abnormalities.	0/3
400	No clinical signs observed. Necropsy after 14 days revealed no abnormalities.	0/3

Table 2: body weight changes

Dose level	Animal	Body weight (g) on Day:		Change in body weight
(mg/kg)	Number	1	15	Day 1-15
	112	274	339	65
2000	114	269	343	74
	116	251	320	69
	111	209	221	12
400	113	208	227	19
	115	212	255	43

Interpretation of results:

GHS criteria not met

Conclusions:

At the 2 tested doses (400 and 2000 mg/kg) no mortality were observed in male and female rats after dermal exposure.

Executive summary:

In an acute dermal toxicity study (Nunziata A, 1999), groups of Sprague-Dawley male and female rats (3/group) were dermally exposed to cyclopentanone (99.8% purity) undiluted at doses of 400 and 2000 mg/kg bw. Animals then were observed for 14 days.

Dermal LD50 for male and female rats was greater than 2000 mg/kg bw. Based on this result, cyclopentanone is not classified for dermal acute toxicity.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Value:

2 000 mg/kg bw

Additional information

Oral:

Four studies were available with reliability from 2 (2 studies) to 3 (2 studies) according to Klimisch rating. One of them (internal report from RTC, 1999 - Nunziata A, 1999) with reliability 2 was selected as key study and gave a LD50 by oral route in rats (males and females) above 2000 mg/kg.

In this study, groups of male and female Sprague-Dawley rats (3/group) were given a single oral dose of cyclopentanone (99.8% purity) in maize oil at doses of 500 and 2000 mg/kg bw and observed for 14 days.

Oral LD50 Combined > 2000 mg/kg bw (no mortality was observed)

 

Cyclopentanone is not classified for acute oral toxicity based on the LD50 identify in male and female rats.

Inhalation:

Two studies were available with reliability 2 and 3 according to Klimisch scale. The study with reliability 2 during 4 hours was retained. The summary of this study is the following: In an acute inhalation toxicity study (Anonymous, 1965 - Esso, 1965), groups of male Wistar rats (10 males/group) were exposed by inhalation route to cyclopentanone (purity unknown) for 4 hours to (whole body) at concentrations of 4.7, 12, 15,n 17.8, 19.5 mg/L. Animals then were observed for 14 days.

LC50 Male rats (4h) >= 19.5 mg/L

Cyclopentanone is classified as being of LOW Toxicity based on male rat results.

Dermal:

Two studies with reliability 2 according to Klimisch rating were available, and one of them (internal report from RTC, 1999) was selected as key study.

In this study, groups of Sprague-Dawley male and female rats (3/group) were dermally exposed to cyclopentanone (99.8% purity) undiluted at doses of 400 and 2000 mg/kg bw. Animals then were observed for 14 days.

Dermal LD50 for male and female rats was greater than 2000 mg/kg bw.

Based on this result, cyclopentanone is not classified for dermal acute toxicity.

Justification for classification or non-classification

Oral: Based on the oral LD50 greater than 2000 mg/kg bw, cyclopentanone is not classified for oral acute toxicity according to 67/548/EEC Directive (Annex VI) and to CLP Annex I of the Regulation 1272/2008.

Inhalation: According to the LC50 Male rats (4h) >= 19.5 mg/L, acute inhalation toxicity of cyclopentanone is low. Therefore, no classification for this endpoint is required.

Dermal: Based on the dermal DL50 in male and female rats greater than 2000 mg/kg bw, cyclopentanone is not classified for dermal acute toxicity according to 67/548/EEC Directive (annex VI) and to CLP Annex I of the Regulation 1272/2008.