3-ethyloxetane-3-methanol

Endpoint summary

Description of key information

Studies of skin and eye irritation are available for the submission substance.

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:

20 April 1998 to 30th April 1998.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

not specified

Qualifier:

according to guideline

Guideline:

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

Deviations:

not specified

Principles of method if other than guideline:

Not applicable.

GLP compliance:

yes

Specific details on test material used for the study:

- Name of test material (as cited in study report): TMP oxetane
- Physical state: Colourless liquid.
- Analytical purity: No information provided.
- Purity test date: No information provided.
- Lot/batch No.: JNS 980121 F 1-3
- Expiration date of the lot/batch: No information provided.
- Storage condition of test material: Stored in a refrigerator at 2 - 8°C in the dark.

Species:

rabbit

Strain:

other: SPF albino rabbits of the stock Mol:Russian.

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Møllegaard Breeding and Research Centre A/S. Ejby, DK-4623, Lille Skensved.
- Age at study initiation: No information provided.
- Weight at study initiation: 2.5 - 2.6kg
- Housing: The animals were housed individually in PPO/HIPS cages with a perforated floor and floor area of 2576cm2.
- Diet (e.g. ad libitum): A pelleted complete rabbit diet "Altromin 2123" available ad libitum.
- Water (e.g. ad libitum): Free access to bottles with domestic quality drinking water acidified with hydrochloric acid to pH 2.5 to prevent microbial growth.
- Acclimation period: At least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3°C
- Humidity (%): 55 ± 15%
- Air changes (per hr): 10 air changes per hour.
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark.

IN-LIFE DATES: From: To: No information provided.

Type of coverage:

not specified

Preparation of test site:

shaved

Vehicle:

not specified

Controls:

yes, concurrent no treatment

Amount / concentration applied:

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

Duration of treatment / exposure:

4 hours exposure.

Observation period:

Observation period was 72 hours, with readings made at 24, 48 and 72 hours after exposure.

Number of animals:

Three animals.

Details on study design:

TEST SITE
- Area of exposure: Four shaved areas (2.5cm x 2.5cm) on the backs of the rabbits. The test material was applied to 2 sites, one on the left posterior and one on the right posterior.
- Type of wrap if used: Test material was applied to gauze patches which were applied to the shaved areas and secured with 2.5cm wide adhesive tape and fixed with Scanpor tape (5cm wide). Nobifix (6cm width) was then loosely wound round the trunk.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Following the 4 hour exposure period, the treated skin was cleaned with lukewarm water.
- Time after start of exposure: 4 hours after start of exposure.

SCORING SYSTEM: Readings made according to numerical scale.

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 72 hours

Score:

0

Max. score:

1

Reversibility:

fully reversible

Remarks on result:

other: Only the scores from the 3 readings (24, 48, 72 hours) are included in the calculation of the individual values. 

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 72 hours

Score:

0

Max. score:

0

Reversibility:

fully reversible

Remarks on result:

other: Only the scores from the 3 readings (24, 48, 72 hours) are included in the calculation of the individual values. 

Irritant / corrosive response data:

Very slight erythema was observed in two animals 1 hour from termination of exposure. Apart from that, no erythema was observed in any of the animals at the other observations. No oedema was observed in any of the animals at any of the observations.

Other effects:

No information provided.

Individual scores and mean values:

Rabbit No./Weight (kg)	Site	Erythema-Eschar observed at hours				Individual mean values*	Oedema observed at hours				Individual mean values*
		1	24	48	72		1	24	48	72
1116/2.5	LP	0	0	0	0	0.0	0	0	0	0	0.0
	RP	0	0	0	0		0	0	0	0
2888/2.5	LP	1	0	0	0	0.0	0	0	0	0	0.0
	RP	1	0	0	0		0	0	0	0
2102/2.6	LP	1	0	0	0	0.0	0	0	0	0	0.0
	RP	1	0	0	0		0	0	0	0

LP: Left posterior test field

RP: Right posterior test field.

* Only the scores from the 3 readings (24, 48, 72 hours) are included in the calculation of the individual values. 

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study, TMP oxetane was not found to be irritating to skin and does not meet the criteria for classification for skin irritation.

Executive summary:

The primary skin irritant effect of TMP oxetane was investigated in accordance with OECD Guideline 404 and EEC Guideline B.4. Three rabbits were exposed to the test article at 2 skin sites on the back, under an occlusive dressing. After 4 hours of exposure, the patches and tape were removed and the skin washed to remove test article with lukewarm water. Skin was examined at 1, 24, 48 and 72 hours after termination of exposure. No skin reactions or only very slight skin reactions were observed in all three animals from 1 to 72 hours after the termination of exposure. Under the experimental conditions described in the report, the mean score for erythema was 0.0 and for oedema was 0.0. Under the conditions of this study, TMP oxetane was not found to be irritating to skin.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

not specified

Qualifier:

according to guideline

Guideline:

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

Deviations:

not specified

Principles of method if other than guideline:

Not relevant

GLP compliance:

yes

Specific details on test material used for the study:

- Name of test material (as cited in study report): TPM oxetane, 2-ethyl-2-hydroxylmethyl oxetane
-CAS 3047-32-3
- Physical state: Colourless liquid.
- Analytical purity: No information provided.
- Purity test date: No information provided.
- Lot/batch No.: No information provided. JNS 980121 F 1-3
- Stability under test conditions: No information provided.
- Storage condition of test material: Stored in a refrigerator at 2 - 8°C in the dark.

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland GmbH, Stolzenseeweg 32-36, D-88353 Kisslegg, Germany.
- Age at study initiation: No information provided.
- Weight at study initiation: 2.8kg
- Housing: Individually housed in PPO/HIPS cages (floor area of 2576 cm2) with perflorated floor.
- Diet (e.g. ad libitum): A pelleted complete rabbit diet (Altromin 2123) was available ad libitum.
- Water (e.g. ad libitum): Free access to bottles with domestic quality drinking water acidified with hydrochloric acid to pH 2.5 to prevent microbial growth.
- Acclimation period: At least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3°C
- Humidity (%): 55% ± 15%
- Air changes (per hr): 10 air changes per hour.
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark.

IN-LIFE DATES: From: 4th May 1998 To: 18th May 1998

Vehicle:

not specified

Controls:

other: Untreated eye acted as control.

Amount / concentration applied:

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

Duration of treatment / exposure:

Single exposure.

Observation period (in vivo):

14 days.

Number of animals or in vitro replicates:

One

Details on study design:

0.1ml of the test article was placed in the left eye of the rabbit by gently pulling the lower lid away from the eyeball to form a cup into which the article was dropped. The lids were then gently held together for 1 second. The eye was examined and the grade of ocular reaction was recorded 1 and 24 hours later. After the 24 hour reading, Fluorescein was instilled. After rinsing with 20ml 0.9% sodium chloride solution the eye was examined again using UV light to detect possible corneal damage. The eye was also examined 48 and 72 hours as well as 7 and 14 days after treatment. Because of the corneal damage observed at the 24 hour examination, fluorescein was also used at subsequent examinations.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No information provided.
- Time after start of exposure: No information provided.

SCORING SYSTEM: Scored between 1 and 4.

TOOL USED TO ASSESS SCORE: fluorescein

Irritation parameter:

cornea opacity score

Remarks:

opacity

Basis:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 14 days.

Irritation parameter:

iris score

Remarks:

lesion

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: Not applicable.

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

fully reversible within: 14 days.

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 14 days.

Irritant / corrosive response data:

Marked signs of conjunctival irritation (chemosis, redness and discharge) were observed 1 hour to 7 dys after termination of exposure. Cornea showed diffuse opacity during the same period. From 1 to 72 hours after termination of exposure, superficial damage to more that 2/3 of the cornea was observed when oculoguttae fluoresceini was installed. At the 7 day reading, the suoperficial damage only involved 1/4 of the eye.

Other effects:

No other abnormalities were observed after 14 days.

No additional information.

Interpretation of results:

irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study, TPM oxetane was found to be irritating to the eyes and meets the criteria for clasification as an eye irrtant.

Executive summary:

The eye irritant effect of TMP oxetane was investigated in rabbit eye. One albino rabbit was exposed to 0.1ml of the test material in the left eye. The eye was examined and the changes were graded according to a numerical scale 1, 24, 48 and 72 hours as well as 7 and 14 days after dosing. Marked signs of corneal and conjunctival irritation were observed in the rabbit 1 hour to 7 days after termination of exposure. On day 14, no abnormalities were observed in the rabbit. The following mean values based on the 24, 48 and 72 hour readings are 1.0 for corneal opacity, 0 for iris lesions, 3.0 for conjunctiva oedema and 3.0 for conjunctival redness. Under the conditions of this study, TMP oxetane was found to be irritating to the eyes and meets the criteria for classification as an eye irritant.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation/corrosion

The skin irritation potential of 3-ethyloxetane-3-methanol was investigated in rabbits in a GLP study conducted according to OECD Test Guideline 404 (Kaaber, 1998a). In the study, three rabbits were exposed to the test substance, TMP oxetane, at two skin sites on the back, under an occluded dressing. After 4 hours of exposure, tape and patches were removed and the treated areas were washed with lukewarm water to remove the test substance. Skin reactions were observed 1, 24, 48 and 72 hours after the termination of exposure. No skin reactions or only very slight skin reactions were observed in all three animals from 1 to 72 hours after the termination of exposure. Mean scores of 0 were reported for erythema and oedema respectively. Under the conditions of the study, 3-ethyloxetane-3-methanol was not found to be irritating to skin.

Eye irritation

The eye irritation potential of 3-ethyloxetane-3-methanol was investigated in rabbits in a GLP study conducted according to OECD Test Guideline 405 (Kaaber, 1998b). In the study, one albino rabbit was exposed to 0.1 ml of the test material, TMP oxetane in the left eye. The eye was examined and any changes were graded according to a numerical scale, 1, 24, 48 and 72 hours as well as 7 and 14 days after dosing. Marked signs of corneal and conjuctival irritation were observed in the treated eye of the rabbit 1 hour to 7 days after termination of exposure. No abnormalities were observed on the 14 th day after treatment. The following mean scores were obtained based on 24, 48 and 72 hour readings: 1.0 for corneal opacity; 0 to iris lesions, 3.0 for conjunctiva oedema and 3.0 for conjuctival redness. It was concluded that 3-ethyloxetane-3-methanol is irritating to the eyes and the substance meets the criteria for classification as an eye irritant.

Justification for classification or non-classification

Based on the results of skin and eye irritation, TMPO is classified as an eye irritant (Cat 2) according to the CLP Regulation. Classification for skin irritation is not required.