Tetrahydro-3-methylfuran

Endpoint summary

Description of key information

Corrosive to skin.  May cause irreversible damage to eyes.

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:

12/17/85-12/19/85

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: comparable to a guideline study witha acceptable restrictions (e.g. non GLP)

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Principles of method if other than guideline:

Study conducted according to The United States Deprtment of Transportation Regulations

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Animals were obtained from Buckshire Company and supplied food and water ad libitum. Rabbits were quarantined, weighed and observed for
general health for two weeks. Environmental conditions of the rooms were targeted for a temperature of 20 °C +/- 2 °C and relative humidity of 50 % +/- 10%. Excursions outside these ranges were of small magnitude and/or brief duration and did not adversely affect the validity of the study.

Type of coverage:

occlusive

Preparation of test site:

other: clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.5 ml

Duration of treatment / exposure:

4 hours

Observation period:

24 and 48 hours after application

Number of animals:

6

Details on study design:

On the day prior to study initiation, the hair of 1 male and 5 female New Zealand White rabbits were closely clipped to expose the back from the scapular to the lumbar region. The rabbits weighed from 3146 to 4126 grams on the day of treatment. A 0.5 ml aliquot of 3-methyl-tetrahydrofuran was applied to test site beneath a 1-inch gauze square that was held in place with tape. The test site was then occluded with rubber sheeting for 4 hours, wiped with paper towels and scored according to the Draize scale. The adjacent areas of the untreated skin were used for comparison.

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animal 1

Time point:

other: 4 to 48 hours

Score:

1

Max. score:

4

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animal 2

Time point:

other: 4 to 48 hours

Score:

1.5

Max. score:

4

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animal 3

Time point:

other: 4 to 48 hours

Score:

2.5

Max. score:

4

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animal 4

Time point:

other: 4 to 48 hours

Score:

4

Max. score:

4

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animal 5

Time point:

other: 4 to 48 hours

Score:

4

Max. score:

4

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animal 6

Time point:

other: 4 to 48 hours

Score:

4

Max. score:

4

Irritation parameter:

edema score

Basis:

mean

Remarks:

animal 1

Time point:

other: 4 to 48 hours

Score:

0.67

Max. score:

4

Irritation parameter:

edema score

Basis:

mean

Remarks:

animal 2

Time point:

other: 4 to 48 hours

Score:

2.33

Max. score:

3

Irritation parameter:

edema score

Basis:

mean

Remarks:

animal 3

Time point:

other: 4 to 48 hours

Score:

2.67

Max. score:

4

Irritation parameter:

edema score

Basis:

mean

Remarks:

animal 4

Time point:

other: 4 to 48 hours

Score:

3

Max. score:

4

Irritation parameter:

edema score

Basis:

mean

Remarks:

animal 5

Time point:

other: 4 to 48 hours

Score:

3.33

Max. score:

4

Irritation parameter:

edema score

Basis:

mean

Remarks:

animal 6

Time point:

other: 4 to 48 hours

Score:

3

Max. score:

4

Erythema				Edema
Response	4 hr	24 hr	48 hr	4 hr	24 hr	48 hr
Severe	1 / 6; 2 / 6 (N); 1 / 6 (SN)	1 / 6 (N); 1 / 6 (SN,B); 1 / 6 (N, B)	1 / 6 (N); 1 / 6 (N, B)	4 / 6	0 / 6	0 / 6
Moderate	0 / 6	1 / 6	0 / 6	1 / 6	5 / 6	1 / 6
Mild	0 / 6	0 / 6	2 / 6, 1 / 6 (B)	0 / 6	0 / 6	2 / 6
Slight	2 / 6	2 / 6	1 / 6	1 / 6	1 / 6	2 / 6
No Response	0 / 6	0 / 6	0 / 6	0 / 6	0 / 6	1 / 6
N=Necrosis; SN=Superficial necrosis; B = Blanching;

Interpretation of results:

Category 1C (corrosive)

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study 3 -methyl-tetrahydrofuran was a corrosive agent when applied to the clipped intact skin of rabbits.

Executive summary:

When 3-methyl-tetrahydrofuran (3-meTHhF; 0.5 ml) was placed onto the skin of clipped rabbits and left covered for 4 hrs and then wiped and covered with gauze, it produced slight erythema in 2 of 6 rabbits and severe erythema in 4 of the 6 rabbits; 2 rabbits also had necrosis and 1 had superficial necrosis within 4 hours post treatment. Slight to severe edema was observed in all rabbits at 4 hours. Approximately 24 hours post treatment, a total of 3 rabbits had severe erythema with necrosis or superficial necrosis. Slight or moderate edema was observed in all rabbits at 24 hours. At 48 hours, 4 rabbits had slight or mild erythema and 2 rabbits had severe erythema with necrosis; slight to moderate edema was observed in 5 rabbits. Blanching was observed in 2 rabbits at 24 and 48 hours post treatment. Under the conditions of this study 3 -meTHF was a corrosive agent when applied to the clipped intact skin of rabbits.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Similar to guideline method, but predates GLP. Purity of test compound not provided and observation period terminated after 14 days instead of 21. Results are sufficient in detail for evaluation.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

Purity of test substance not reported and observation terminated at 14 days instead of 21 and only two animals were tested.

GLP compliance:

not specified

Remarks:

study predates GLP

Species:

rabbit

Strain:

other: Albino

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

0.1 ml

Duration of treatment / exposure:

Single application, one eye wased after 20 seconds while other eye was unwashed.

Observation period (in vivo):

Observations made at one and four hours and at 1,2,7,and 14 days

Number of animals or in vitro replicates:

2

Details on study design:

A dose of 0.1 ml of terahydro-3-methylfuran was instilled into the right conjunctival sac of each of two albino rabbits. After 20 second, one exposed eye was washed with tap water for one minute while the other was not washed. Observation of the cornea, iris, and conjuctiva were made with a hand slit lamp at the appropriate times, 5% fluorescein stain and biomicroscope were used for these examinations.

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

of animals 1and 2 (individually), unwashed eye

Time point:

other: 24-72 hours

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Irritation parameter:

iris score

Basis:

mean

Remarks:

of animals 1 and 2 (individually), unwashed eye

Time point:

other: 24-72 hours

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 4 days

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

of animals 1 and 2 (individually), unwashed eye

Time point:

other: 24-72 hours

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 14 days

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

of animals 1 and 2 (individually), unwashed eye

Time point:

other: 24-72 hours

Score:

2.67

Max. score:

4

Reversibility:

not specified

Dose	Treatment of Eyes	Ocular Effects
		Cornea	Iris	Conjunctiva
0.1 ml of Product*	Not washed	Moderate but deep injury at 1-3 days; mild injury with superficial vascularization at 7 days; small areas of haziness under magnification at 14 days.	Minimal congestion 1-4 hours; moderate iritis 1-3 days.	Mild redness 1 hour - 3 days, minimal at 7 days; severe to moderate swelling 1-4 hours, mild 1-3 days, minimal at 7 days; copious discharge 1 hour - 3 days, minimal at 7 days**.
0.1 ml of Product*	Washed (after 20 seconds of exposure)	Moderate but deep injury 1-3 days; small area of haziness under magnification 7-14 days.	Minimal to mild congestion 1-4 hours: moderate iritis 1-2 days: mild iritis at 3 days.	Mild redness 1 hour - 3 days; moderate swelling 1-4 hours, mild 1-2 days, minimal at 3 days; copious discharge 1 hour - 2 days, mild at 3 days***.
* 3-methyl-tetrahydrofuran, stabilized with 0.025 wt. % Ionol®  **Fibrin in discharge 1-3 days. *** Fibrin in discharge 1-2 days.

Interpretation of results:

Category 1 (irreversible effects on the eye)

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

3 -Methyltetrahydrofuran produced moderate but penetrating corneal damage, moderate iritis and conjuctivitis in both rabbit eyes that were not promptly washed after dosing and in a rabbit eye that was washed 20 seconds after contact. Both corneas still had mild damage at 14 days.

Executive summary:

Tetrahydro-3-methylfuran (3meTHF) should be regarded as capable of causing irreversible effects on the eye based on in vivo administration of 0.1 ml of 3meTHF into the right conjunctival sac of each of two albino rabbits. After 20 seconds, one exposed eye was washed with tap water for one minute while the other was not washed. Observation of the cornea, iris, and conjuctiva were made with a hand slit lamp at the appropriate times, 5% fluorescein stain and biomicroscope were used for these examinations. 3meTHF produced moderate but penetrating corneal damage, and moderate iritis and conjuctivitis in both rabbit eyes that were not promptly washed after dosing and in a rabbit eye that was washed 20 seconds after contact. Both corneas still had mild damage at 14 days.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Additional information

Skin Irritation / Corrosion

Tetrahydro-3-methylfuran (3-methyl-THF) has been adequately characterized for skin irritation / corrosion using Draize scoring under occluded conditions. In the key study, 3-methyl-THF was corrosive when 0.5 ml was applied to the clipped skin of 6 rabbits and left covered for 4 hours and then wiped and observed for 48 hours (DuPont, 1987). Approximately 24 hours post treatment, a total of 3 rabbits had severe erythema with necrosis or superficial necrosis. Blanching was observed in 2 rabbits at 24 and 48 hours post treatment. In an earlier study (DuPont, 1986), 3-methyl-THF was reported to be a moderate skin irritant with reversible effects. However, these earlier results are considered unreliable since multiple substances were tested simultaneously on the same animals, leading to possible data observation / recording errors. Therefore, it is proposed that 3-methyl-THF be considered corrosive to the skin (Category 1C).

 

Eye Irritation

Tetrahydro-3-methylfuran (3-methyl-THF) is an eye irritant capable of causing irreversible effects when 0.1 ml was instilled into the conjunctival sacs of two albino rabbits (DuPont, 1969). 3-methyl-THF produced moderate but penetrating corneal damage, and moderate iritis and conjunctivitis, in both rabbit eyes that were not promptly washed after dosing and one of two rabbit eyes that was washed after contact. Corneas still had mild damage at 14 days. Evaluation of these data using Draize scoring yielded a mean cornea score of 2, Iris score of 1, conjunctive score of 2 and a chemosis score of 2.67. Since the injury was not reversible within 14-days and is considered corrosive to the skin, it is proposed that 3-methyl-THF be considered a severe eye irritant (category 1).  This conclusion is supported by read-across to a closely related substance, Tetrahydrofuran (THF; CAS# 109-99-9), in which THF caused irreversible eye irritation in rabbits (DuPont, 1971 and DuPont, 2010).

Justification for selection of skin irritation / corrosion endpoint:
Sufficiently reliable key study

Justification for selection of eye irritation endpoint:
Reliable key study

Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: corrosive

Justification for classification or non-classification

Skin irritation

Based on the results of the key study which resulted in 3 of 6 rabbits with severe erythema and necrosis, and blanching in 2 rabbits (DuPont, 1987) tetrahydro-3-methylfuran would considered corrosive to the skin (R34) under the EU DSD criteria (EU Directive 67/548/EEC) and corrosive to skin (Cat. 1C) under the EU CLP criteria (EU Regulation 1272/2008).

 

Eye irritation

Based on classification as corrosive to skin (Cat. 1C), and the results of the key study which resulted in a mean cornea score of 2, Iris score of 1, conjunctive score of 2 and a chemosis score of 2.67 and corneal injury that did not reverse within 14-days (Dupont, 1969); tetrahydro-3-methylfuran should be classified as posing a risk of serious damage to eyes (R41) under the EU DSD criteria (EU Directive 67/548/EEC) and irreversible effects on the eye (Cat. 1) under the EU CLP criteria (EU Regulation 1272/2008).