Tetrahydrofurfuryl acrylate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1998

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

1992

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Tetrahydrofurfuryl acrylate

EC Number:

219-268-7

EC Name:

Tetrahydrofurfuryl acrylate

Cas Number:

2399-48-6

Molecular formula:

C8H12O3

IUPAC Name:

tetrahydrofuran-2-ylmethyl acrylate

Test material form:

liquid

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Ace Animals, Boyertown, PA
- Age at study initiation: 4/5 weeks
- Weight at study initiation: 2.2-2.4 kg
- Housing: 1/cage
- Diet (e.g. ad libitum): Fresh purina rabbit chow, provided daily
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no details but temperature controlled
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.5 ml by site

Duration of treatment / exposure:

3 minutes, 1 hour or 4 hours

Observation period:

-3 minute and 1 hour of exposure: observation at 60 minute after patch removal
-4 hour of exposure: observation at 60 minute after patch removal, then 24, 48, 72 hours, day 7 and day 14.

Number of animals:

3 (one male and two females)

Details on study design:

Initially, one rabbit was dosed on sites #1, 2 and 3 with 0.5 ml of the test article. the test article was placed under a 2.5x2.5 cm, 4 ply, surgical gauze patch. Gentle pressure was applied to the gauze to aid in the distribution of the tes substance over the prepared site. Each patch was secured with non-irritating tape. The torso was wrapped with two pieces of plastic, one covering site #1 only, and one covering sites # 2 and #3. This method allowed partial removal of the wrapping to expose site #1 at 3 minutes postdose without disturbing sites #2 and #3. The plastic was applied in a semi-occlusive manner and secured with non-irritating tape. This method of wrapping aids in retaining the test patch in position and retards evaporation of volatile substances.
The wrapping and test article patch covering site #1 was removed at 3 minutes postdose and the site was gently washed with distilled water. A window was cut in the wrapping over site #2 at 1 hour after dosing. The patch was removed and the site gently washed with distilled water. At 4 hours post dose, the torso wrappings and patch covering site #3 were removed and the site gently washed with distilled water.
Since no evidence of a corrosive or severely irritating effect was observed in the initial animal, additional animals were added to the study. Both animals were dosed with 0.5 ml of the test article at site #3. After an exposure period of 4 hours, the wrappings and patches were removed and the sites gently washed with distilled water.

The test sites of all animals were scored for dermal irritation at 1 hour after removal of wrappings. Since no evidence of corrosion or severe irritation was noted on sites #1 or#2, no further scoring was required. Site #3 was scored at 24, 48 and 72 hours. Reactions were scored again on days 7 and 14 following patch removal. Erythema and edema were scred according to the numerical Draize technique. The skin was also evaluated for ulceration and necrosis or any evidence of tissue destruction. Additional signs were described.
The general health of the animals was monitored at each observation time. Body weights of all animals were recorded pre test adn at study termination.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

(3 min exposure)

Time point:

other: 60 minutes

Score:

0

Max. score:

4

Reversibility:

other: n/a

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

(3 min exposure)

Time point:

other: 60 minutes

Score:

0

Max. score:

4

Reversibility:

other: n/a

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

(1h exposure)

Time point:

other: 60 minutes

Score:

0

Max. score:

4

Reversibility:

other: n/a

Remarks on result:

no indication of irritation

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

(1 hr exposure)

Time point:

other: 60 minutes

Score:

0

Max. score:

4

Reversibility:

other: n/a

Remarks on result:

no indication of irritation

Results 5

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

(4 hr exposure)

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Results 6

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

(4hr exposure)

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Results 7

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

(4hr exposure)

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

positive indication of irritation

Remarks:

brown area observed at 1h and 24h. Moderate and severe eschar observed from 48h to day 7, cleared at day 14. Poor hair regrowth at day 14.

Results 8

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

(4 hr exposure)

Time point:

24/48/72 h

Score:

2.33

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

positive indication of irritation

Results 9

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

(4 hr exposure)

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

positive indication of irritation

Remarks:

poor hair regrowth observed at day 14.

Results 10

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

(4 hr exposure)

Time point:

24/48/72 h

Score:

2.67

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

After 3 minute exposure, erythema and edema were absent at 60 minutes after patch removal. After 1 hour of exposure, erythema was absent and edema was very slight at 60 minutes following patch removal. After 4 hour exposure, the first animal showed a very slight erythema at 60 minutes following patch removal, and well defined erythema from 24 -72 hours and cleared erythema by day 7. Edema was moderate at 60 minutes, slight at 24 and 48 hours, very slight at 72 hours and cleared by day 7. In additional animal (4 hour exposure), erythema was very slight to well defined at 60 minutes following patch removal, well defined to severe from 24 hours through day 7 and cleared by day 14. Brown areas were noted in 1 animal at 60 minutes and 24 hours, progressing to moderate eschar by 48 hours, and moderately severe eschar at 72 hours and day 7. By day 14, shiny areas were observed on one animal and poor hair regrowth was noted in both. Edema, severe at 60 minutes following patch removal, was moderate at 24 hours, slight to moderate at 48 hours, slight at 72 hours, very slight on day 7 and cleared by day 14.

Other effects:

Body weight changes were within normal limits and no abnormal physical signs were observed.

Applicant's summary and conclusion

Interpretation of results:

Category 1C (corrosive) based on GHS criteria

Conclusions:

In conclusion, the test article is corrosive after a dermal exposure of 4 hours in rabbits.

Executive summary:

The objective of this study was too determine the irritant or corrosive effects if any, of a test article when applied dermally. Since the test article was suspected to be corrosive, one rabbit was dosed dermally with the test article (0.5 ml) to three intact sites for an exposure period of 3 minutes on site #1, one hour on site #2 and 4 hours on site #3. Dermal reaction were scored at 60 minutes after each patch removal on all three sites. Site #3 was scored again at 24, 48 and 72 hours and on days 7 and 14 following the patch removal. The skin was also evaluated for ulceration and necrosis or any evidence of tissue destruction at these time periods. Since the reaction of the initial animal did not produce a corrosive or severe irritating effect, additional animals (females) were added to the study. The animals were doses at site #3 for a 4 hour exposure. Dermal reaction were scored at 1, 24, 48 and 72 hours and on days 7 and 14 following patch removal. Bodyweights for all animals were recorded pretest and termination.

After 3 minute exposure, erythema and edema were absent at 60 minutes after patch removal. After 1 hour of exposure, erythema was absent and edema was very slight at 60 minutes following patch removal. After 4 hour exposure, the first animal showed a very slight erythema at 60 minutes following patch removal, and well defined erythema from 24 -72 hours and cleared erythema by day 7. Edema was moderate at 60 minutes, slight at 24 and 48 hours, very slight at 72 hours and cleared by day 7. In additional animal (4 hour exposure), erythema was very slight to well defined at 60 minutes following patch removal, well defined to severe from 24 hours through day 7 and cleared by day 14. Brown areas were noted in 1 animal at 60 minutes and 24 hours, progressing to moderate eschar by 48 hours, and moderately severe eschar at 72 hours and day 7. By day 14, shiny areas were observed on one animal and poor hair regrowth was noted in both. Edema, severe at 60 minutes following patch removal, was moderate at 24 hours, slight to moderate at 48 hours, slight at 72 hours, very slight on day 7 and cleared by day 14.

Body weight changes were within normal limits and no abnormal physical signs were observed.

In conclusion, the test article is corrosive after a dermal exposure of 4 hours in rabbits.