Cyclopentane, methoxy-

Endpoint summary

Description of key information

Skin irritation (Rabbit, 4 Hour exposure) - Irritating

Eye irritation (Rabbit) - Irritating (CLP Criteria)

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

12 February 2002 - 04 March 2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to EC, OECD and US EPA test guidelines and in compliance with GLP; on this basis the study is considered reliable without restriction.

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

- Analytical purity: 99.8%
- Lot/batch No.: 010912

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: At least 11 weeks
- Weight at study initiation: 3.1 - 3.4 kg
- Housing: Housed individually in stainless steel cages with perforated floors
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: 21 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19±2°C
- Humidity (%): 30 to 70%
- Photoperiod (hrs dark / hrs light): 12 hours light / 12 hours dark

IN-LIFE DATES: From: 12 February 2002 To: 04 March 2002

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): Approximately 0.5 mL

Duration of treatment / exposure:

First animal - 3 minutes, 60 minutes, and 4 hours (three treatment sites)
Second and third animals - 4 hours

Observation period:

14 days

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 25 x 25 mm
- Type of wrap if used: Gauze pad held in place using an elasticated adhesive dressing

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Washed with warm (32 - 34°C) water At the end of the exposure period (4 minutes, 60 minutes, or 4 hours)
- Time after start of exposure:

SCORING SYSTEM:
Refer to tables under "Any other information on materials and methods incl. tables".

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 12 days

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.7

Max. score:

4

Reversibility:

fully reversible within: 12 days

Irritant / corrosive response data:

Well-defined to moderate to severe erythema with very slight to slight oedema was seen in all animals following the four hour exposure. Dermal reactions gradually ameliorated, resolving completely in one animal by Day 14, however, very slight erythema with or without very slight oedema was still evident in the two remaining animals at study termination on Day 14. Thickening of the skin was observed in all animals from Day 3 or 4, resolving in two animals by Day 12 or 14 but persisting in the remaining animal through to the final observation on Day 14. In addition, desquamation (characterised by dryness of the skin) was noted in one animal from Day 8 through 11 and in two further animals from Day 12 through to the final observation on Day 14. Also noted during the study were areas of ulceration on the edge of the dose site (thought to be caused by removal of the bandage) in two animals from Day 9 through 11 and cracking of the skin in one animal from Day 12 through 14.

Other effects:

There were no signs of toxicity or ill health in any rabbit during the observation period.

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

The substance was concluded to have been irritating to skin following 4 hours' exposure.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

02 March 2002 - 19 March 2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to OECD, EC, and US EPA test guidelines, and in compliance with GLP; on this basis the study is considered reliable without restrictions.

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

- Analytical purity: 99.8%
- Lot/batch No.: 010912

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Age at study initiation: At least 13 weeks
- Weight at study initiation: 2.8 to 3.1 kg
- Housing: Metal cages with perforated floors
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: At least 16 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19±2°C
- Humidity (%): 30 to 70%
- Photoperiod (hrs dark / hrs light): 12 hours light / 12 hours dark

IN-LIFE DATES: From: 02 March 2002 To:19 March 2002

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.1 mL

Duration of treatment / exposure:

N/A (following instillation of the test material, the eye lids were held together for 1 second before release).

Observation period (in vivo):

14 days

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Not performed

SCORING SYSTEM: Refer to tables below.

TOOL USED TO ASSESS SCORE: handheld light

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 14 Days

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 14 days

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.7

Max. score:

3

Reversibility:

fully reversible within: 14 days

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 2 days

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

(All animals)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: No corneal damage observed in any animal

Irritation parameter:

iris score

Basis:

mean

Remarks:

(All animals)

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

other: No iridial observed in any animal

Other effects:

There were no signs of toxicity or ill health in any rabbit during the observation period.

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

A single instillation of the substance into the eye of the rabbit elicited well-defined to considerable conjunctival irritation.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

A Skin Irritation study (Huntingdon Life Sciences, 2002, study code ZCE089) was conducted to determine the skin irritation potential of the substance. The study was performed according to OECD test guideline 404, EC method B4, and US EPA guideline OPPTS 870.2500; the study was performed in compliance with GLP.

The effects of 3-minute, 60-minute, and 4-hour dermal exposure to the substance were initially investigated in one New Zealand White rabbit; the effects of 4-hour exposure were subsequently investigated in two further rabbits.

3-minute and 60-minute exposure produced well defined dermal irritation; the effects ameliorated during the 14 -day post-exposure recovery period, however slight signs of irritation remained at the end of the observation period. A single semi-occlusive application of the substance for four hours elicited a dermal reaction ranging from well defined to moderate to severe in all three animals tested. Over the course of the 14 -day observation period the signs of irritation ameliorated, recovering fully in one animal, however slight signs of irritation remained in the other two animals. In addition, thickening of the skin and desquamation were seen in all animals, with ulceration near the edge of the dose site in two animals, and cracking of the skin in one animal.

On the basis on the mean irritation scores from 24, 48 and 72 -hour measurements following the end of exposure, the substance is considered to be irritating to skin.

An Eye Irritation study (Huntingdon Life Sciences, 2002, ZCE090) was conducted to assess the effect of the instillation of the substance into the eyes of New Zealand White rabbits. The study was performed according to OECD test guideline 405, EC method B5, and US EPA guideline OPPTS 870.2400; the study was performed in compliance with GLP.

Three rabbits were each administered a single ocular dose of 0.1 mL of the substance, then observed for 14 days.

Well-defined conjunctival irritation was observed in all animals, however these had resolved in all animals by the end of the observation period. No Corneal or Iridial damage was observed.

The mean scores at 24, 48, and 72 hours following administration, the substance is considered an eye irritant under the current legislation.

Justification for classification or non-classification

Skin irritation:

Mean value of erythema/oedema scores at 24, 48 and 72 hours is <2.3 (actual value erythema 2.1, odema 1.6), but irritating were persisted to the end of observation period 14 days in 2 of 3 animals.

Based on these results, the substance meets the criteria for classification as a skin irritant. According to Commission Regulation 1272/2008 table 3.2.2, the substance is classified as Skin Irritant, Category 2.

Eye irritation:

Mean conjunctival redness score at 24, 48 and 72 hours in 2 of 3 animals is equal 2 (actual value: conjunctival redness 2, 2, 1.7; chemosis mean 0.1; corneal opacity 0; iritis 0).

Based on these results, the substance is classified as Eye Irritant Category 2, according to Commission Regulation 1272/2008 table 3.3.2.