Cyclopentanol, 2-pentyl-, (1R,2S)-rel-

Endpoint summary

Description of key information

Acute toxicity: oral: LD50 > 2000 mg/kg bw (OECD 423 in rats, K, rel.1);
Acute toxicity: dermal: LD50 > 2000 mg/kg bw (OECD 402 in rabbits, read-across, K, rel. 2);
Acute toxicity: inhalation: waiver. 

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 March 11 to April 03, 2008

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study conducted according to OECD test Guideline No. 423 without any deviation.

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

(inspected on April 22, 25-29, 2005; May 09-13, 2005 / signed on November 2005)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

other: HanRcc:WIST (SPF)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd, Laboratory Animal Services, Wölferstrasse 4, 4414 Füllinsdorf, Switzerland.
- Age at study initiation: 11 weeks
- Weight at study initiation: 185-207 g
- Housing: in groups of three in Makrolon type-4 cages with wire mesh tops and standard softwood bedding.
- Fasting period before study: 16.5 to 18 hours (access to water was permitted). Food was provided again approximately 4 hours after dosing.
- Diet: pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, batch no 77/07 (Provini Kliba AG, CH-4303 Kaiseraugst/Switzerland) ad libitum. Not contaminated.
- Water: community tap water from Füllinsdorf ad libitum. Not contaminated.
- Acclimation: 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ±3
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From 2008-03-11 to 2008-04-03

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Details on oral exposure:

VEHICLE: PEG 300
- Concentration in vehicle: : 0.2 g/mL
- Justification for choice of vehicle: The vehicle was chosen after a non-GLP solubility trial which was performed before the study initiation.
- Lot/batch no. (if required): 1310049
- Source: FLUKA Chemie GmbH, CH-9471 Buchs.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

2 groups, each of 3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 day
- Clinical signs: 30 minutes, 1, 2, 3 and 5 hours after treatment on Day 1 and once daily during test days 2-15.
- Mortality/viability: 30 minutes, 1, 2, 3 and 5 hours after treatment on Day 1 and twice daily during test days 2-15.
- Frequency of weighing: recorded on Day 1(just prior to administration) and on day 8 and 15.
- Necropsy of survivors performed: yes, macroscopic examination. No organ or tissues were retained.

Statistics:

None

Preliminary study:

Not applicable

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occurred during the study.

Clinical signs:

other: Shortly after dosing or at the 1-hour observation, a slight sedation was recorded in the 6 females which persisted up to the 5-hour observation. In 2 females, the sedation progressed into moderate at the 5-hour reading. Additionally, 5 females were found

Gross pathology:

No macroscopic findings were recorded at necropsy.

Other findings:

None

None

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Oral LD50 (Female rat) > 2000 mg/kg bw

Executive summary:

In a limit acute oral toxicity study performed according to the OECD test guideline No. 423 and in compliance with GLP, two groups, each of three fasted female HanRcc:WIST (SPF) rats were treated with a single oral gavage administration of 2000 mg/kg bw. The test material was diluted in PEG 300 at a concentration of 0.2 g/mL and administered at a dosing volume of 10 mL/kg.The animals were observed for mortality, clinical signs and body weight for 14 days and then necropsied for macroscopic observations.

 

No deaths occurred during the study.

Shortly after dosing or at the 1-hour observation, a slight sedation was recorded in the 6 females which persisted up to the 5-hour observation. In 2 females, the sedation progressed into moderate at the 5-hour reading. Additionally, 5 females were found to express a slightly poor coordination 20 minutes post-dose, or at the 1- or 5 hour reading. This symptom persisted up to the 1-, 2-, 3- or 5-hour reading. Furthermore, 5 females were found with a slightly ruffled fur shortly after treatment or at the 1-hour evaluation which persisted up to the 5-hour evaluation. Otherwise, no clinical signs were observed in any animal at any observation.

The body weight of the animals was within the range commonly recorded for this strain and age.

No macroscopic findings were recorded at necropsy.

 

Oral LD50 (Female rat) > 2000 mg/kg bw

 

Under the test conditions, the test material is not classified according to the annex VI of the Regulation EC No. 1272/2008 (CLP).

This study is considered as acceptable and satisfies the requirement for acute oral toxicity endpoint.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The key study is GLP-compliant and of high quality (Klimisch score = 1)

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

other justification

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

From June 13 to June 27, 1996

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

GLP study conducted according to OECD test Guideline No. 402. The study was fully reliable (Klimisch score = 1), however the reliability score was lowered to 2 which is the maximum score for read-across. The supporting substance is considered adequate for read-across purpose (see IUCLID section 13 for additional justification). The ennvironmental conditions were not reported but assumed to be adequate because it is a GLP study.

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

Environmental conditions not reported, but GLP study so assumed to be adequate.

Principles of method if other than guideline:

not applicable

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Trevanor Farm, Mainesburg, PA. USDA # 23-A-055.
- Age at study initiation: no data.
- Weight at study initiation: 2-3 kg bw
- Housing: individually housed in suspended stainless steel wire-mesh cages.
- Diet: Agway Prolab High Fiber Rabbit feed and Alfalfa cubes, ad libitum.
- Water: city water ad libitum.
- Acclimation period: at least 7 days.


ENVIRONMENTAL CONDITIONS
No data

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal area of the trunk
- % coverage: 10%
- Type of wrap if used: 15 cm² porous gauze patch overwrapped with a gauze strip and held in place with Elastikon tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, no details
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): Dose volume = [Animal Weight (kg) x Limit Dose (2 g/kg)] / density (0.91 g/mL).
- Constant volume or concentration used: no

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5/sex/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: daily, 7 days a week. Observations included the following: skin and fur, and eyes and mucous membranes, circulatory, autonomic and central nervous systems and behaviour patterns.
- Necropsy of survivors performed: yes, gross necropsy after sacrifice by sodium pentobarbital.
- Other examinations performed: body weight, recorded just prior to administration and on day 7 and 14.

Statistics:

none

Preliminary study:

not applicable

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality.

Clinical signs:

other: No clinical observations.

Gross pathology:

No gross abnormalities.

Other findings:

Dermal observation: on day 1, 5/5 females and 5/5 males had well-defined erythema. 3 females and 1 male had well-defined oedema; 2 females and 3 males had very slight oedema; 1 male had no oedema. On day 7, all animals had very slight erythema with flaking skin. There was no oedema noted. On day 14, there was no erythema or oedema noted. However, 4 females and the 5 males had flaked skin.

None

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Dermal LD50 Combined > 2000 mg/kg bw

Executive summary:

In a limit acute dermal toxicity study performed according to the OECD guideline No. 402, groups of New Zealand White rabbit (5/sex)were semi-occlusively exposed to undiluted test material for 24 hours to 10% of the body surface at dose of 2000 mg/kg bw. The animals were observed for mortality, clinical signs including dermal reactions and body weight for 14 days and then necropsied for macroscopic observations.

 

No mortality occurred during the study. There were no signs of systemic reaction to treatment. No abnormality was revealed at autopsy. On day 1, erythema and oedema (score 2) were observed in all animals. On day 7, all animals had very slight erythema with flaking skin. There was no oedema noted. On day 14, there was no erythema or oedema noted. However, 4 females and the 5 males had flaked skin.

 

Dermal LD₅₀Combined > 2000 mg/kg bw

 

Under the test conditions, the test material is not classified according to the annex VI of the Regulation EC No. 1272/2008 (CLP).

This study is considered as acceptable and satisfies the requirement for acute dermal toxicity endpoint.

The supporting substance is considered adequate for read-across purpose (see IUCLID section 13 for justification).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The key study was fully reliable (Klimisch score = 1), however the reliability score was lowered to 2 which is the maximum score for read-across.

Additional information

Acute toxicity: oral

A key study was identified (RCC, 2008, rel.1). In this limit acute oral toxicity study performed according to the OECD test guideline No. 423 and in compliance with GLP, 6 female rats were treated with a single oral gavage administration of 2000 mg/kg bw of test material in PEG 300.The animals were observed for mortality, clinical signs and body weight for 14 days and then necropsied for macroscopic observations.

 

No deaths occurred during the study. Shortly after dosing or at the 1-hour observation, a slight sedation was recorded in the six females which persisted up to the 5-hour observation. In two females, the sedation progressed into moderate at the 5-hour reading. Additionally, five females were found to express a slightly poor coordination 20 minutes post-dose, or at the 1- or 5 hour reading. This symptom persisted up to the 1-, 2-, 3- or 5-hour reading. Furthermore, five females were found with a slightly ruffled fur shortly after treatment or at the 1-hour evaluation which persisted up to the 5-hour evaluation. Otherwise, no clinical signs were observed in any animal at any observation. All those observed effects were slight and transient at a high dose of 2000 mg/kg bw of the test substance. Therefore, they are not considered as narcotic effects.

 

Oral LD50 (Female rat) > 2000 mg/kg bw.

Acute toxicity: dermal

No study was available on the substance itself, therefore a read-across approach was used. The supporting substance is considered adequate for read-across purpose (see IUCLID section 13 for additional justification). A key study was identified on the supporting substance (Leberco-Celcis testing, 1996, rel.2). In this limit acute dermal toxicity study performed according to the OECD guideline No. 402, groups of rabbits (5/sex) were exposed under semi-occlusive conditions to the undiluted test material for 24 hours at dose of 2000 mg/kg bw. The animals were observed for mortality, clinical signs including dermal reactions and body weight for 14 days and then necropsied for macroscopic observations.

No mortality occurred during the study. There were no signs of systemic reaction to treatment. No abnormality was revealed at autopsy. On day 1, erythema and oedema (score 2) were observed in all animals. On day 7, all animals had very slight erythema with flaking skin. There was no oedema noted. On day 14, there was no erythema or oedema noted. However, 4 females and the 5 males had flaked skin.

 

Dermal LD₅₀Combined > 2000 mg/kg bw.

Justification for selection of acute toxicity – oral endpoint
Only one study available

Justification for selection of acute toxicity – inhalation endpoint
In accordance with Column 2 of REACH Annex VIII, in addition to the oral route (8.5.1), for substances other than gases, the information mentioned under 8.5.2 (acute toxicity by inhalation) and 8.5.3 (acute toxicity by the dermal route) shall be provided for at least one other route. The choice for the second route will depend on the nature of the substance and the likely route of human exposure.
In the present case, inhalation exposure will be lower than dermal exposure because the registered substance has a low vapour pressure (4.9 Pa at 25°C) and a low freezing point (< -20°C), so the potential for the generation of inhalable forms is low. Dermal exposure is the more likely route of exposure based on physico-chemical properties (Log Kow = 3.7 at 30°C, WS = 210.4 mg/L at 20°C).

Justification for selection of acute toxicity – dermal endpoint
No study was available on the substance itself, therefore a read-across approach was used. The supporting substance is considered adequate for read-across purpose (see section 13 for additional justification).

Justification for classification or non-classification

Harmonized classification:

The substance has no harmonized classification according to the Regulation (EC) No. 1272/2008.

Self-classification:

Acute toxicity via Oral route:

Based on the available data, the substance is not classified according to the Regulation (EC) No. 1272/2008 as the LD50 is greater than 2000 mg/kg bw.

Acute toxicity via Dermal route:

Based on the available data, the substance is not classified according to the Regulation (EC) No. 1272/2008 as the LD50 is greater than 2000 mg/kg bw.

Acute toxicity (Inhalation):

No data was available.

Specific target organ toxicity: single exposure (Oral):

The classification criteria according to the Annex VI of the Regulation (EC) No. 1272/2008 as specific target organ toxicant (STOT) – single exposure, oral are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value (oral) for a Category 1 classification (C≤ 300 mg/kg bw) and at the guidance value (oral) for a Category 2 classification (2000 mg/kg bw≥C > 300 mg/kg bw). No classification is required.

The criteria for Transient Organ effects (STOT-SE Category 3) according to Annex VI of the Regulation (EC) No. 1272/2008 are not met since narcotic effects were not observed in the acute oral toxicity study.

Specific target organ toxicity: single exposure (Dermal):

The classification criteria according to the Annex VI of the Regulation (EC) No 1272/2008 as specific target organ toxicant (STOT) – single exposure, dermal are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value (dermal) for a Category 1 classification (C≤ 1000 mg/kg bw) and at the guidance value (dermal) for a Category 2 classification (2000 mg/kg bw≥C > 1000 mg/kg bw). No classification is required.

The criteria for Transient Organ effects (STOT-SE Category 3) according to Annex VI of the Regulation (EC) No. 1272/2008 are not met since narcotic effects were not observed in the acute dermal toxicity study.

Specific target organ toxicity: single exposure (Inhalation):

No data was available.