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

Endpoint summary

Description of key information

Skin irritation in vitro: Irritating (OECD 439, GLP, Rel.1, K).
Skin irritation in vivo: Irritating (OECD 404, GLP, read-across, Rel.2, K).
Eye irritation: Irritating (OECD 405, GLP, read-across, Rel. 2, K).

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

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

Adequacy of study:

key study

Study period:

From June 10 to June 25, 1996

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

GLP study conducted according to OECD test Guideline No. 405 with minor deviations that does not affect the reliability of the study: 6 animals tested instead of 3. The study was reliable and of good quality (Klimisch score = 2). The supporting substance is considered adequate for read-across purpose (see IUCLID section 13 for additional justification). Some environmental conditions were not reported but they were assumed to be adequate because iti s 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 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

some details missing on test animals and environmental conditions but they were assumed to be adequate because it is a GLP study.

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Gingrich Animal Suply, Frdricksbury, PA. USDA # 23-B-007.
- Age at study initiation: no data.
- Weight at study initiation: no data.
- Housing: individually housed.
- 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

IN-LIFE DATES: no data

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eye served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL

Duration of treatment / exposure:

Eyes were not rinsed after instillation

Observation period (in vivo):

Observations at 1, 24, 48, 72 and on days 4, 7 and 14 after exposure.

Number of animals or in vitro replicates:

6 (Male and Female)

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not done

SCORING SYSTEM: according to OECD 405

TOOL USED TO ASSESS SCORE: evaluated by using the "Illustrated Guide for Grading Eye Irritation by Hazardous Substances".

Irritation parameter:

cornea opacity score

Remarks:

(opacity)

Basis:

animal: #1, #2, #3 & #5

Time point:

other: mean 24, 48, 72 hours

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

cornea opacity score

Remarks:

(opacity)

Basis:

animal #4

Time point:

other: mean 24, 48, 72 hours

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 3 days

Irritation parameter:

cornea opacity score

Remarks:

(opacity)

Basis:

animal #6

Time point:

other: mean 24, 48, 72 hours

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 2 days

Irritation parameter:

iris score

Basis:

animal: #1, #2, #3, #5 & #6

Time point:

other: mean 24, 48, 72 hours

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #4

Time point:

other: mean 24, 48, 72 hours

Score:

0.33

Max. score:

2

Reversibility:

fully reversible within: 4 days

Irritation parameter:

conjunctivae score

Basis:

animal: #1 & #5

Time point:

other: mean 24, 48, 72 hours

Score:

1.33

Max. score:

3

Reversibility:

fully reversible within: 14 days

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

other: mean 24, 48, 72 hours

Score:

2.67

Max. score:

3

Reversibility:

fully reversible within: 14 days

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

other: mean 24, 48, 72 hours

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 14 days

Irritation parameter:

conjunctivae score

Basis:

animal #4

Time point:

other: mean 24, 48, 72 hours

Score:

2.33

Max. score:

3

Reversibility:

fully reversible within: 14 days

Irritation parameter:

conjunctivae score

Basis:

animal #6

Time point:

other: mean 24, 48, 72 hours

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 4 days

Irritation parameter:

chemosis score

Basis:

animal: #1& #5

Time point:

other: mean 24, 48, 72 hours

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 4 days

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: mean 24, 48, 72 hours

Score:

2.67

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

chemosis score

Basis:

animal: #3 & #4

Time point:

other: mean 24, 48, 72 hours

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

chemosis score

Basis:

animal #6

Time point:

other: mean 24, 48, 72 hours

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 2 days

Irritant / corrosive response data:

The test material produced minimal conjunctival irritation (6/6) and chemosis (4/6) one hour post-instillation.
24 hours post instillation, corneal opacity in 6/6 animals and positive conjunctival irritation in 5/6 and positive chemosis in 3/6 animals. Iritis was observed in 1/6 animals on day 3 of the study.
On study day 7, there were no corneal opacities observed. Four animals had minimal conjunctival irritation. Three animals had minimal chemosis. No iritis was observed. All irritation cleared by day 14, therefore the study was terminated at that point.

Other effects:

None

Table 7.3.2/1: Eye irritation response data for each animal at each observation time

Score at time point	Cornea		Iris (/2)	Conjunctivae
	Opacity (/4)	Area (/4)		Redness (/3)	Chemosis (/4)	Discharge (/3)
24 h (Day 1)	1 / 1 / 1 / 1 / 1 / 1	3 / 3 / 3 / 3 / 3 / 1	0 / 0 / 0 / 0 / 0 / 0	2 / 2 / 2 / 2 / 2 / 1	1 / 2 / 2 / 2 / 1 / 1	2 / 2 / 2 / 2 / 1 / 1
48 h (Day 2)	1 / 1 / 1 / 1 / 1 / 0	1 / 3 / 2 / 2 / 1 / 0	0 / 0 / 0 / 0 / 0 / 0	1 / 3 / 2 / 3 / 1 / 1	1 / 3 / 2 / 2 / 1 / 0	1 / 3 / 2 / 2 / 1 / 1
72 h (Day 3)	1 /1 / 1 / 0 / 1 / 0	1 / 3 / 1 / 0 / 1 / 0	0 / 0 / 0 / 1 / 0 / 0	1/ 3 / 2 / 2 / 1 / 1	1 / 3 / 2 / 2 / 1 / 0	1 / 3 / 2 / 2 / 1 / 0
Average 24h, 48h, and 72h	1 / 1 / 1 / 0.67 / 1 / 0.33	1.67 / 3 / 2 / 1.67 / 1.67 / 0.33	0 / 0 / 0 / 0.33 / 0 / 0	1.33 / 2.67 / 2 / 2.33 / 1.33 / 1	1 / 2.67 / 2 / 2 / 1 / 0.33	1.33 / 2.67 / 2 / 2 / 1 / 0.67
Reversibility	Completely reversible	Completely reversible	Completely reversible	Completely reversible	Completely reversible	Completely reversible
Average time (unit) for reversion	7 days	7 days	4 days	14 days	14 days	14 days

Interpretation of results:

irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the test conditions, the test material is classified as irritating to eyes (category 2) according to the criteria of the Annex VI of the Regulation (EC) No 1272/2008 (CLP) based on 4/6 animals having a cornea score of 1 which fully reverses within 7 days.

Executive summary:

In an eye irritation study performed according to the OECD guideline No. 405, 0.1 mL of undiluted test material was instilled into the eye of 6 New Zealand White Rabbit. The eyes were not rinsed after the instillation of the test item.The contralateral eye of each rabbit served as control. Animals were observed at 1, 24, 48 and 72 hours, and 4, 7 and 14 days after dosing. The reactions in the conjunctiva (redness, chemosis and discharge), the iris and the cornea (opacity and area involved) were scored according to the Draize scale. 

 

The calculated mean score for each animal within 3 scoring times (24, 48 and 72 h) were 1.33 / 2.67 / 2 / 2.33 / 1.33 / 1 for redness, 1 / 2.67 / 2 / 2 / 1 / 0.33 for chemosis, 0 / 0 / 0 / 0.33 / 0 / 0 for iris lesions and 1 / 1 / 1 / 0.67 / 1 / 0.33 for corneal opacity. 4/ 6 rabbits show a mean score per animal ≥ 1 for corneal opacity. All the reactions were fully reversible within 14 days. 

Under the test conditions, the test material is classified as irritating to eyes (category 2) according to the criteria of the Annex VI of the Regulation (EC) No 1272/2008 (CLP) based on 4/6 animals having a cornea score of 1 which fully reverses within 7 days.

This study is considered as acceptable and satisfies the requirement for eye irritation endpoint.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation:

Since no key study was identified on the registered substance, the testing and assessment strategy, as described in ECHA R.7a Endpoint specific guidance (July 2015), was used to evaluate the skin corrosion/irritation potential of the registered substance:

	Element	Information	Conclusion	Comments
Existing data on physico - chemical properties	1a	Is the substance spontaneously flammable in contact with air (pyrophoric) or water at room temperature?	NO
	1b	Is the substance an organic hydroperoxide or an organic peroxide?	NO
	1c	Is the pH of the substance ≤ 2.0 or ≥ 11.5?	NO
	1d	Are there other physical or chemical properties that indicate that the substance is corrosive/irritant?	NO
Existing human data	2	Are there adequate existing human data which provide evidence that the substance is a corrosive or irritant?	NO	No irritation was observed in existing human patch test. However, the substance was not applied undiluted, and therefore these results were not considered adequate
Existing animal data from corrosion/irritation studies	3	Are there data from existing studies on corrosion and irritation in laboratory animals, which provide sound conclusive evidence that the substance is a corrosive, irritant or non-irritant?	YES
Existing data from general toxicity studies via the dermal route and from sensitisation studies	4a	Is the substance classified as fatal in contact with skin (LD50 ≤ 50 mg/kg bw, CLP hazard statement H310)	NO	Read-across to CAS 84560-00-9, mixture of cis+trans isomer, containing more than 50% of cis-isomer which is the registered substance. Dermal LD50 > 2000 mg/kg bw
	4b	Has the substance proven to be a corrosive, irritant or non-irritant in a suitable acute dermal toxicity test?	NO	Dermal irritation was reported in the acute dermal toxicity test on CAS 84560-00-9): On day 1, erythema and edema (score 2) were observed in all animals. On day 7, all animals had very slight erythema with flaking skin. There was no edema noted. On day 14, there was no erythema or edema noted. However, 4 females and the 5 males had flaked skin. But scores were not reported, therefore a conclusion was not possible
	4c	Has the substance proven to be a corrosive or an irritant in sensitisation studies or after repeated exposure?	NO
Existing/new (Q)SAR data and read -across	5a	Are there structurally related substances (suitable “read-across” or grouping), which are classified as corrosive to the skin (Skin Corrosive Cat. 1), or do suitable (Q)SAR methods indicate corrosion potential of the substance?	NO
	5b	Are there structurally related substances (suitable “read-across” or grouping), which are classified as irritant to the skin (Skin Irritant Cat. 2), or indicating that the substance is non-irritant, or do suitable (Q)SAR methods indicate irritant or non-irritant potential of the substance?	YES	In the study on CAS 84560-00-9 (OECD 404, GLP) , the scores calculated for each animal tested within 3 scoring times (24, 48 and 72 hrs) were 2.0/2.0/2.0 for erythema and 1.0/2.0/1.0 for edema. Under the test conditions, the test material induced irritation being reversible within 14 days of dosing. The scores were lower than the CLP threshold however all 3 animals had flaking skin on Day 14 therefore the test substance was considered to be irritant to skin.
Existing in vitro data	6a	Has the substance demonstrated corrosive properties in an EU/OECD adopted in vitro test? Data from in vitro test methods that have been validated and are considered scientifically valid but are not yet adopted by EU and/or OECD may also be used if the provisions defined in Annex XI are met	NO
	6b	Has the substance demonstrated irritant or non-irritant properties in an EU/OECD adopted in vitro test? Data from in vitro test methods that have been validated and are considered scientifically valid but are not yet adopted by EU and/or OECD may also be used if the provisions defined in Annex XI are met.	NO
	6c	Are there data from a non-validated suitable in vitro test(s), which provide sound conclusive evidence that the substance is corrosive/ irritant?	NO	(at the initiation of the dossier, no test was available)
Weight-of- Evidence analysis	7	The “elements” described above may be arranged as appropriate. Taking all available existing and relevant data mentioned above (Elements 1-6) into account, is there sufficient information to make a decision on whether classification/labelling is necessary, and –if so –how to classify and label?	NO
New in vitro test for corrosivity	8	Does the substance demonstrate corrosive properties in (an) EU/OECD adopted in vitro test(s) for skin corrosion?	NO	Based on all available data on CAS 84560-00-9 for ATD & in vivo skin irritation test (404)), the substance is not considered as a skin corrosive => a skin corrosion assay was not required
New in vitro test for irritation	9	Does the substance demonstrate irritating or non-irritating properties in (an) EU/OECD adopted in vitro test(s) for skin irritation?	YES	=> an Episkin test for irritation was initiated to confirm that CAS 84560-00-9 was a suitable read-across candidate, i.e. to check if cis- and trans- isomers have similar skin irritation properties. The conclusion of this Episkin test is sufficient to conclude on C&L (viability = 5.76% for 25 µL and 7,54% for 10 µL <=> skin irritant)
New in vivo test for corrosion/irritation	10	To be used only as a last resort	NO	In vivo testing should not be conducted in this case since the results of the in vitro test is sufficient to conclude on C&L and confirm that CAS 84560-00-9 is a suitable read-across candidate. The in vivo study on CAS 84560-00-9 is included in the dossier to justify the non-performance of an in vitro skin corrosion test.

 

The purposes of the newly performed in vitro test (WIL Research Europe BV, 2014) were:

- to evaluate the skin irritation potential of the test item using the EPISKIN reconstructed human epidermis model after a treatment period of 15 minutes followed by a post-exposure incubation period of 42 hours.

- to confirm that CAS 84560-00-9 is a suitable read-across candidate, i.e. to check if cis- and trans- isomers have similar skin irritation properties.

The Episkin test was performed in compliance with GLP. The quality criteria required for acceptance of results in the test were satisfied. The relative mean tissue viability obtained after 15-minutes treatment with test item compared to the negative control tissues was 5.76% and 7.54% for 25 μL and 10 μL, respectively. With a tissue viability < 50%, the test material was considered to be irritant to skin. This result confirms that CAS 84560-00-9 is a suitable read-across candidate.

In addition, since the in vitro skin irritation test does not provide adequate information on skin corrosion, the in vivo study on CAS 84560-00-9 is included in the dossier to justify the non-performance of an in vitro skin corrosion test.

 

Eye irritation:

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, 1996, K, Rel.2). In this study performed according to the OECD guideline No. 405, undiluted test material was instilled into the eye of 6 New Zealand White Rabbit. The eyes were not rinsed after the instillation of the test item.  

The calculated mean score for each animal within 3 scoring times (24, 48 and 72 h) were 1.33 / 2.67 / 2 / 2.33 / 1.33 / 1 for redness, 1 / 2.67 / 2 / 2 / 1 / 0.33 for chemosis, 0 / 0 / 0 / 0.33 / 0 / 0 for iris lesions and 1 / 1 / 1 / 0.67 / 1 / 0.33 for corneal opacity. 4/ 6 rabbits show a mean score per animal ≥ 1 for corneal opacity. All the reactions were fully reversible within 14 days. 

Therefore, the test material is irritating to eyes based on 4/6 animals having a corneal opacity score of 1 which fully reverses within 7 days.

Justification for selection of skin irritation / corrosion endpoint:
No study was selected since the in vitro and in vivo studies performed respectively on the registered substance and on the supporting substance were complementary. The in vitro skin irritation study on the registered substance is GLP-compliant and of high quality (Klimisch score = 1). However, since the results of this test was positive, a read-across approach to an in vivo skin irritation study on a supporting substance (see Iuclid section 13 for additional justification) was included to justify the non-performance of a skin corrosion test. The in vivo study was fully reliable (Klimisch score = 1), however the reliability score was lowered to 2 which is the maximum score for read-across.

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

Effects on skin irritation/corrosion: irritating

Effects on eye irritation: irritating

Justification for classification or non-classification

Harmonized classification:

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

Self-classification:

Based on the available information on the substance and on the supporting substance, the registered substance should be classified as Skin irr. Category 2 (H315: Causes skin irritation) according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP).

Based on the available information on the supporting substance, the registered substance should be classified as Category 2: Causes serious eye irritation according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP).

 

No information was available regarding respiratory irritation.