6-glycidyloxynapht-1-yl oxymethyloxirane

Endpoint summary

Description of key information

One in vivo skin irritation study was performed with the substance in New Zealand White rabbits. 0.5 mL of the undiluted test substance was applied to the shaved skin under semi-occlusive dressing during 4 hours. 
One in vivo eye irritation study was performed with the substance in New Zealand white rabbits. 0.1 mL of the test substance was placed into the conjunctival sac of the left eye of each animal. 

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:

08.04.1986 to 21.04.1986

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline Study performed under GLP.

Qualifier:

according to guideline

Guideline:

EPA OTS 798.4470 (Acute Dermal Irritation)

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

-New Zealand White strain rabbits in the weight range 2.3 to 2.8 kg, prior to treatement on Day 1 and approximately 10 to 12 weeks of age were obtained fromFroxfield rabbits, Petersfield, Hamshire, England.
-The rabbits selected for the study were all acclimated to the laboratory environment.
-Each animal was identified by a numbered aluminium tag placed through the edge of one ear. This number was unique within the HRC Industrial Toxicology Departmentthroughout the duration of the study.
-The rabbits were individually housed in metal cages with perforated floors in Building R14 Room1. They had free access to tap water and SDS Standard Rabbit Diet.
-Animal room temperature was maintained at approximately 19°C and relative humidity at 30-70%.
-Air exchange was maintained at approximately 19 air changes per hour and lighting was controlled by means of a time switch to give 12 hours of artificial light (0700-1900) hours in each 24 hour period.
-All animals were observed daily for signs of ill health or toxic signs.

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated flank

Amount / concentration applied:

no data

Duration of treatment / exposure:

Exposure duration: 4 hours

Observation period:

-Examination of the treated skin was made on Day 1 (i.e. approximately 30 minutes after removal of the patches) and on Day 2, 3 and 4. Additional observations were made on Days 5 through 14.

Number of animals:

-Six New Zealand White strain males rabbits.

Details on study design:

TEST SITE
- Area of exposure: The dorso-lumbar region of each rabbit.
- % coverage: 10 cm square
- Type of wrap if used: Gauze pad and each treatment site was occluded with "Elastoplast" elastic adhesive.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Done using distilled water in an attempt to remove any residual test substance.
- Time after start of exposure: after 4 hours period.

SCORING SYSTEM:
Erythema and eschar formation:
-No erythema: 0
-Very slight erythema (barely perceptible): 1
-Well-defined erythema: 2
-Moderate to severe erythema: 3
-Severe erythema (beet redness) to slight eschar formation (injuries in depth: 4

Oedema formation:
-No oedema: 0
-Very slight oedema (barely perceptible): 1
-Slight oedema (edges of aera well-defined by definite raising): 2
-Moderate oedema (raised approximately 1 millimetre): 3
-Severe oedema (raised more than 1 millimetre and extending beyond the area of exposure): 4

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: day 1 to 14

Score:

>= 1 - <= 4

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: day 1 to 14

Score:

>= 1 - <= 4

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: day 1 to 14

Score:

>= 1 - <= 2

Max. score:

2

Reversibility:

fully reversible within: 12 days

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

other: day 1 to 14

Score:

>= 1 - <= 2

Max. score:

2

Reversibility:

not reversible

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

other: day 1 to 14

Score:

>= 2 - <= 3

Max. score:

3

Reversibility:

not reversible

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

other: day 1 to 14

Score:

>= 1 - <= 3

Max. score:

3

Reversibility:

not reversible

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: day 1 to 14

Score:

>= 1 - <= 2

Max. score:

2

Reversibility:

not reversible

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: day 1 to 14

Score:

>= 1 - <= 2

Max. score:

2

Reversibility:

not reversible

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: day 1 to 14

Score:

>= 1 - <= 2

Max. score:

2

Reversibility:

not reversible

Irritation parameter:

edema score

Basis:

animal #4

Time point:

other: day 4 to 14

Score:

ca. 1

Max. score:

1

Reversibility:

not reversible

Irritation parameter:

edema score

Basis:

animal #5

Time point:

other: day 1 to 14

Score:

>= 1 - <= 2

Max. score:

2

Reversibility:

fully reversible within: 12 days

Irritation parameter:

edema score

Basis:

animal #6

Time point:

other: day 1 to 14

Score:

>= 1 - <= 2

Max. score:

2

Reversibility:

not reversible

Irritant / corrosive response data:

There was no initial response to the four hours exposure to Epiclon EXA 4032, however, by Day 2 slight to well-defined reactions had developed. These increased in severity and by Day 4 necrotic lesions were observed in 2 rabbits and well-defined erythema with very slight to slight oedema in the four remaining animals. Ar this time whiote "blanched" arears also saterted to develop and by Day 7 were present in four rabbits.
Slight to well-defined or moderate reactions accompanied by desquamation of the stratum corneum were still present on Day 14.
Considerable difficulty had been experienced in trying to remove the test substance at the end.

Conclusions:

In conclusion, a single semi-occlusive application of EPICLON EXA 4032 to intact rabbit skin for four hours elicited well-defined to severe dermal irritation.

Executive summary:

This study was designed to assess skin irritation potential in the rabbit.The study was performed according Guidelines as described in the Federal Register, Vol. 50, N° 188, Part II of 27 September 1985, Section 798.4470_Primary Dermal Irritation.

For the experiment, six New Zealand White starin rabbits were used.

A 0.5 ml aliquot of EPICLON EXA 4032 was applied under a 2.5 cm square gauze pad to one intact skin site on each animal during four hours (semi-occlusive application).

Examination of the treated skin was made on Day 1 (i.e. approximately 30 minutes after removal of the patches) and on Day 2, 3 and 4. Additional observations were made on Days 5 through 14.

In conclusion, a single semi-occlusive application of EPICLON EXA 4032 to intact rabbit skin for four hours elicited well-defined to severe dermal irritation.

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:

14.04.1986 to 05.05.1986

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline Study performed under GLP.

Qualifier:

according to guideline

Guideline:

EPA OTS 798.4500 (Acute Eye Irritation)

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

-Six New Zealand White strain rabbits in the weight range 2.0 to 2.8 kg, prior to treatment on Day 1 and approximately 9 to 13 weeks were obtained from Froxfield Rabbits, Petersfield, Hampshire. The rabbits were acclimated to the laboratory environment.
-Each animal was identified by a numbered aluminium tag
-Rabbits were individually housed in metal cages.
-They had free access to tap water and SDS Standard Rabbit Diet.
-Animal room temperature was maintened at 19°C and relative humidity at 30-70%
-Air exchange was maintained at 19 air changes per hour and lighting was controlled to give 12 hours artificial light (0700-1900 hours) in each 24 hour period.

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

-A 0.1 ml aliquot of EPICLON EXA 4032.

Duration of treatment / exposure:

After application, the eyelids were then gently held together for one second before releasing.

Observation period (in vivo):

Examination of the eyes was made after 1 hour and 1, 2, 3, 4, 7, 14 and 21 Days after instillation.

Number of animals or in vitro replicates:

Six New Zealand White strain rabbits.

Details on study design:

SCORING SYSTEM:
Cornea: degree of density (area most dense taken for reading)
-No ulceration or opacity: 0
-Scattered or diffuse areas of opacity (other than slight dulling of norma lustre), details of iris cearly visible: 1*
-Easily discernible translucent areas, details of iris slightly obscured: 2*
-Nacrous areas, no details of iris visible, size of pupil barely discernible: 3*
-Opaque cornea, iris not descernible through the opacity: 4*

Iris.
-Normal: 0
-Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia or injection of any thereof, iris still reacting to light (sluggish reaction is positive): 1*
-No reaction to light, haemorrhage, gross destruction (any or all of these): 2*

Conjunctivae-redness (refers to palpebral and bulbar conjunctivae cornea and iris)
-Blood vessels normal: 0
-Some blood vessels definitely hyperaemic (injected): 1
-Diffuse, crimson colour, individual vessels not easily discernible: 3*

Chemosis (lids and/or nictitating membranes)
-No swelling: 0
-Any swelling above normal (includes nictitating membranes): 1
-Obvious swelling with partial eversion of lids: 2*
-Swelling with lids about half-closed: 3*
-Swelling with lids more then half-closed: 4*

*: Intepreted as a positive effect.

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: mean 24h - 72h

Score:

0

Max. score:

0

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: mean 24h - 72h

Score:

0

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: mean 24h - 72h

Score:

2.33

Max. score:

3

Reversibility:

fully reversible within: 14 days

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: mean 24h - 72h

Score:

2.33

Max. score:

3

Reversibility:

fully reversible within: 14 days

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

other: mean 24h - 72h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 21 days

Irritation parameter:

iris score

Basis:

animal #2

Time point:

other: mean 24h - 72 h

Score:

0.66

Max. score:

1

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

other: mean 24h - 72h

Score:

2.33

Max. score:

3

Reversibility:

fully reversible within: 14 days

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: mean 24h - 72h

Score:

2.66

Max. score:

3

Reversibility:

fully reversible within: 14 days

Irritation parameter:

cornea opacity score

Basis:

animal #4

Time point:

other: mean 24h - 72h

Score:

0.66

Max. score:

1

Reversibility:

fully reversible within: 7 days

Irritation parameter:

iris score

Basis:

animal #4

Time point:

other: mean 24h - 72h

Score:

0

Max. score:

0

Irritation parameter:

conjunctivae score

Basis:

animal #4

Time point:

other: mean 24h - 72h

Score:

2.33

Max. score:

3

Reversibility:

fully reversible within: 14 days

Irritation parameter:

chemosis score

Basis:

animal #4

Time point:

other: mean 24h - 72h

Score:

2.66

Max. score:

3

Reversibility:

fully reversible within: 14 days

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

other: mean 24h - 72h

Score:

2.66

Max. score:

3

Remarks on result:

other: Due to the severity of the reactions, this animal was killed four days after instillation

Irritation parameter:

conjunctivae score

Basis:

animal #5

Time point:

other: mean 24h - 72h

Score:

2.66

Max. score:

3

Remarks on result:

other: Due to the severity of the reactions, this animal was killed four days after instillation

Irritation parameter:

cornea opacity score

Basis:

animal #6

Time point:

other: mean 24h - 72h

Score:

1.66

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

iris score

Basis:

animal #6

Time point:

other: mean 24h - 72h

Score:

0

Max. score:

0

Irritation parameter:

conjunctivae score

Basis:

animal #6

Time point:

other: mean 24h - 72h

Score:

2.33

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal #6

Time point:

other: mean 24h - 72h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 7 days

Irritant / corrosive response data:

-All six animals gave a "positive" response.
-Due to the severity of the reactions, two animals were killed four days after instillation.
-Corneal opacities developed in five animals. Vascularisation of the cornea was seen in one animal.
-Iridial inflammation was seen in the three animals.
-A diffuse beefy red colouration of the conjunctivae was seen in all six animals accompanied by considerable swelling with the eyes about or more than half closed.
-Areas of necrosis on the eyelids were seen in one animal.
-The eyes of the remaining four animals were normal 7, 14 or 21 days after instillation.

Other effects:

Areas of necrosis on the eyelids were seen in one animal.

Interpretation of results:

irritating

Remarks:

Migrated information

Conclusions:

In conclusion, instillation of EPICLON EXA 4032 into the rabbit eye elicited a positive response in all six treated animals according to nT.S.C.A test criteria.

Executive summary:

This study was designed to assess eye irritation potential. The study was performed according Guidelines as described in the Federal Register, Vol. 50, N° 188, Part II of 27 September 1985, Section 798.4500_Primary Eye Irritation.

Six New Zealand White strain rabbits were used to perfoemed this study.

A 0.1 ml aliquot of EPICLON EXA 4032 was placed into the lower everted lid of one eye of each animal.

Examination of the eyes was made after 1 hour and 1, 2, 3, 4, 7, 14 and 21 days afetr instillation. Observation of the eyes was aided by the use of a handle torch.

In conclusion, instillation of EPICLON EXA 4032 into the rabbit eye elicited a positive response in all six treated animals according to nT.S.C.A test criteria.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Effects on skin irritation/corrosion: irritating

Effects on eye irritation: irritating

Justification for classification or non-classification

Based on the above stated assessment of the skin irritation potential of 1,6-dihydroxynaphthalene diglycidyl ether

the substance does have to be classified R38: Irritating to skin according to Council Directive 2001/59/EC and Slin corrosion / Irritation Cat 2 according to CLP (Regulation (EC) No 1272/2008 Of the European parliament and of the Council.

 

Base on the above assessment of the eye irritation potential of 1,6 -dihydroxynaphthalene diglycidyl ether

the substance does have to be classified R36: Irritating to eyes according to Council Directive 2001/59/EC and eye irritation Cat 2A according to CLP (Regulation (EC) No 1272/2008 Of the European parliament and of the Council.