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Administrative data

Description of key information

Skin irritation- corrosive
Eye irritation- severely irritating

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study
Qualifier:
according to guideline
Guideline:
other: 49CFR, Section 173.240(a)(2)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Hazelton Dutchland, Denver, Pennsylvania
- Age at study initiation: 13-18 weeks
- Weight at study initiation: not reported
- Housing: not reported
- Diet (e.g. ad libitum): not reported
- Water (e.g. ad libitum): not reported
- Acclimation period: not reported


ENVIRONMENTAL CONDITIONS- not reported



IN-LIFE DATES: From: June 26, 1984 To: July 31, 1984
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
undiluted
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): not applicable


VEHICLE no vehicle
Duration of treatment / exposure:
4 hour(s)
Observation period:
14 days
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: clipped intact skin on the back
- % coverage: not reported
- Type of wrap if used: entire trunk of each animal was wrapped with a polyethylene sheet and an impervious cuff secured with adhesive tape for 4 hr.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): application sites were wiped gently with paper towels moistened with 80% (v/v) ethanol in water
- Time after start of exposure: 24 hours


SCORING SYSTEM: Draize
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 72-hr
Score:
7.3
Reversibility:
not reversible
Irritant / corrosive response data:
AVERAGE SCORE - Erythema: 4.0 - Edema: 3.3 REVERSIBILITY: no
Other effects:
On Day 21, severe erythema with eschar (in all rabbits) and eschar sloughing off with hair growth beneath it (in 5 of the 6 rabbits) was observed. Desiccation was also observed. On Day 28, no erythema or edema was observed. Three rabbits had hair growth over entire site with a small area that was hard to the touch. The other rabbits had possible scar formation. The one remaining rabbit's skin site appeared normal. On Day 35, no erythema or edema was observed. One rabbit had a white linear striation on the application site and possible scar formation. Four of the six rabbits had a small area that was hard to the touch and hair growth covering the entire application site.
Interpretation of results:
Category 1B (corrosive) based on GHS criteria
Conclusions:
Based on the severe and persisting dermal reactions, and the possible scar formation underneath the skin, the test substance is considered corrosive to the 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: Acceptable, well-documented study report which meets basic scientific principles
Qualifier:
no guideline followed
Principles of method if other than guideline:
The purpose of this study was to evaluate whether washing with distilled water or 0.85% saline would diminish or enhance the eye irritation caused by the test material in the rabbit. One-tenth milliliter of undiluted test material was applied to the cornea of the left eye of male New Zealand White rabbits (2 rabbits per group). The treated eyes of one group of rabbits received no further treatment after dosing. The treated eyes of the remaining four groups of rabbits were irrigated with either distilled water or 0.85% saline beginning either 4 or 30 seconds after dosing. The degree of eye irritation for each animal was scored according to Draize's procedure at 24, 48, and 74 hr and at 7, 14, and 21 days.
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Hazelton Research Animals, Denver, pennsylvania, USA
- Age at study initiation: not reported
- Weight at study initiation: not reported
- Housing: 1/cage in stainless steel cages
- Diet (e.g. ad libitum): ad libitum; Purina laboratory rabbit chow high fiber
- Water (e.g. ad libitum): ad libitum
- Acclimation period: approximately 13 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.3 degrees C
- Humidity (%): not reported, but was monitored continuously
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hours light / 12 hours dark


IN-LIFE DATES: From: March 19, 1986 To: May 6, 1986
Vehicle:
unchanged (no vehicle)
Controls:
other: Only one eye of each animal was treated; the other eye served as the control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): none


VEHICLE not applicable, no vehicle
Duration of treatment / exposure:
Group 6 remained unwashed; groups 7 to 10: 4 or 30 seconds
Observation period (in vivo):
24, 48 and 72 hours and at 7, 14 and 21 days post exposure
Number of animals or in vitro replicates:
10
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): The treated eye of group 6 was unwashed. The treated eyes of groups 7 and 8 were irrigated with distilled water for 60 seconds beginning 4 or 30 seconds after dosing. The treated eyes of groups 9 and 10 were irrigated with 0.85% saline for approximately 60 seconds beginning 4 or 30 seconds after dosing.
- Time after start of exposure: 4 or 30 seconds after dosing in groups 7 to 10


SCORING SYSTEM: Draize

TOOL USED TO ASSESS SCORE: fluorescein- 2% sodium fluorescein
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 72 h
Score:
37
Max. score:
80
Remarks on result:
other: unwashed eyes
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 72 h
Score:
4.2
Max. score:
10
Remarks on result:
other: unwashed eyes
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 72 h
Score:
19
Max. score:
20
Remarks on result:
other: unwashed eyes
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 72 h
Score:
19.2
Max. score:
80
Remarks on result:
other: washed for 30 sec with distilled water
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 72 h
Score:
4.2
Max. score:
10
Remarks on result:
other: Washed for 30 sec with distilled water
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 72 h
Score:
18.3
Max. score:
20
Remarks on result:
other: washed for 30 sec with distilled water
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 72 h
Score:
33.3
Max. score:
80
Remarks on result:
other: washed for 30 sec with 0.85% saline
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 72 h
Score:
4.2
Max. score:
10
Remarks on result:
other: washed for 30 sec with 0.85% saline
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 72 h
Score:
17
Max. score:
20
Remarks on result:
other: washed for 30 sec with 0.85% saline
Irritant / corrosive response data:
In rabbits dosed with the test material and receiving no further treatment (i.e., unwashed eyes), both rabbits exhibited corneal, iridal, and conjunctival effects at 24 hr. Conjunctival and iridal effects were no longer present at Day 14. Corneal effects were still present by Day 21. In addition, blood vessels extending onto the cornea, blanched nictitating membrane, eschar on eyelids, bulging of the cornea, and hair loss around the treated eye were observed during the 21-day observation period. In groups receiving a distilled water or saline wash 4 seconds after treatment with the test material, both animals in each group exhibited corneal, iridal, and conjunctival effects at 24 hr. Iridal and conjunctival effects in animals washed with distilled water 4 seconds after dosing were recovered by Day 7 and 14, respectively. Iridal and conjunctival effects in animals washed with saline 4 seconds after dosing were recovered by 72 hr and Day 14, respectively. Corneal effects were present at 21 days in both groups. In addition, blood vessels extending onto the cornea, blanched nictitating membrane, hair loss around the treated eye and eyelids pinched together at corners were observed during the 21-day observation period. In groups receiving a distilled water or saline was 30 seconds after treatment with the test material, both animals in each group exhibited corneal, iridal, and conjunctival effects at 24 hr. Iridal and conjunctival effects in animals washed with distilled water 30 seconds after dosing were recovered by Day 7 and 14, respectively. Iridal and conjunctival effects in animals washed with saline 30 seconds after dosing were recovered by Day 7 and Day 21, respectively. Corneal effects were present at 21 days in both groups. In addition, circumcorneal blood vessels, blanched nictitating membrane, hair loss around eye, eschar on eyelids, bulging of the cornea, and eyelids pinched together at corners were observed during the 21-day observation period
Other effects:
In rabbits dosed with the test material and receiving no further treatment (i.e., unwashed eyes), blood vessels extending onto the cornea, blanched nictitating membrane, eschar on eyelids, bulging of the cornea, and hair loss around the treated eye were observed during the 21-day observation period. In groups receiving a distilled water or saline wash 4 seconds after treatment with the test material, blood vessels extending onto the cornea, blanched nictitating membrane, hair loss around the treated eye and eyelids pinched together at corners were observed during the 21-day observation period. In groups receiving a distilled water or saline was 30 seconds after treatment with the test material, circumcorneal blood vessels, blanched nictitating membrane, hair loss around eye, eschar on eyelids, bulging of the cornea, and eyelids pinched together at corners were observed during the 21-day observation period
  Group  10  10 
Time  Structure  Unwashed  Unwashed  4 seconds distilled water  4 seconds distilled water  30 seconds distilled water  30 seconds distilled water  4 seconds 0.85% saline  4 seconds 0.85% saline  30 seconds 0.85% saline  30 seconds 0.85% saline 
24 hours  Cornea  20  40  20  20  20  20  20  20  20  20 
24 hours  Iris 
24 hours  Conjunctivae  20 a  20 a  20 a  20 a  20 a  16 a  14 a  20 a  18 a  18 a 
48 hours  Cornea  40  40  20  20  20  20  10  20  40  40 
48 hours  Iris  2.5  2.5  2.5  2.5 
48 hours  Conjunctivae  20 a  20 a  18 a  20 a  20 a  18 a  12  16  14 a  20 a 
72 hours  Cornea  40  40  20  20  20   15  10  20  40  40 
72 hours  Iris  2.5  2.5  2.5 
72 hours  Conjunctivae  18 a  18 a  18 a  18  18 a  18  16  14 a  20 a 
7 day  Cornea  40 b  40 b  40 b  20 b  40 b  0 bf  0 k  10  15 bce  60 j 
7 day  Iris  2.5 
7 day  Conjunctivae  8.0 cd  8 cd  8 e  4 cd  12 acd  4 cd  10  16 acde 
14 day  Cornea  30 bh  15 b  10 b  10 b  10 bh  0 bi  0 m  0 kb  0 bm  60 j 
14 day  Iris 
14 day  Conjunctivae  0 c  0 c  0 c  0 c  0 c  0 c  0 d  0 c  6 c 
21 day  Cornea  20 bh  0 f  0 f  10  10 b  0 i  0 m  0 m  0 bm  40 l 
21 day  Iris 
21 day  Conjunctivae  0 c  0 c  0 c  0 c 

a a) Nictating membrane blanched b) Blood vessels approximately 1 -3 mm in length extended onto the cornea c) Hair loss around the treated eye d) Eschar on eyelids e) Eyelids pinched together at corners f) After application of 2.0% sodium fluorescein the entire cornea appeared hazy. This finding was judged to be treatment related. h) Cornea appears to bulge above the surface approximately 3 mm. i) After application of 2.0% sodium fluorescein, a 2 x 3 mm area appeared hazy in the center of the cornea. This finding was judged to be treatment related. j) Circumcorneal blood vessels approx. 1 -3 mm in length on cornea. k) After application of 2.0% sodium fluorescein a slight haze appeared on the cornea. This finding was judged to be treatment related. l) Circumcorneal blood vessels approx. 4 -6 mm in length on cornea. m) After application of 2.0% sodium fluorescein, 50% of the cornea appeared hazy. This finding was judged to be treatment related.

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Remarks:
Criteria used for interpretation of results: expert judgment
Conclusions:
The test material produced severe eye irritation. When compared to unwashed treated eyes, washing with either water or saline 4 or 30 seconds after treatment resulted in no significant increases or decreases in the corneal, iridal, or conjunctival effects.
Executive summary:

The purpose of this study was to evaluate whether washing with distiled water or 0.85% saline would diminish or enhance the eye irritation caused by the test material in the rabbit. One-tenth milliliter of undiluted test material was applied tot he cornea of the left eye of male New Zealand White rabbits (2 rabbits per group). The treated eyes of one group of rabbits received no further treatment after dosing. The treated eyes of one group of rabbits received no further treatment after dosing. The treated eyes of the remaining four groups of rabbits were irrigated with either distilled water or 0.85% saline beginning either 4 or 30 seconds after dosing. The degree of eye irritation for each animal was scored according to Draize procedure at 24, 48 and 72 hr and 7, 14 and 21 days after dosing.

The test material produced severe eye irritation. When compared to unwashed treated eyes, washing with either water or saline 4 or 30 seconds after treatment resulted in no significant increase or decrease in the corneal, iridal or conjunctival effects.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The test material was evaluated for its potential to produce dermal irritation in New Zealand White rabbits.  In the study, 0.5 ml of the undiluted test material was held under a patch covered with an impervious cuff in continuous 4-hour contact with the skin of six rabbits from which the hair had been closely clipped. Readings for irritation (erythema and edema) were made after patch removal and through either 48 hours or 14 days post application using the method of Draize, et al., 1944. Results indicate that the test material is corrosive to skin.

The test material was evaluated for its potential to produce irritation in the eyes of New Zealand White rabbits.  In the study, one-tenth ml of the undiluted test material was placed into the eye of each rabbit. The ocular reactions were graded at 24 hr intervals after dosing through 7 or 21 days. In the study, satellite groups of 2 animals each received a four or 30 second wash with either distilled water or 0.85% saline solution. Irritation evaluations were made following the method of Draize et al., 1944.  The test material produced severe eye irritation.

The potential of the test material to irritate skin as well as eyes and gastrointestinal mucosa upon contact indicates that this material is also likely to be irritating to the mucosa of the upper respiratory tract. Repeat-dose inhalation exposure results in irritation of the upper respiratory tract as discussed in 5.6.1.


Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: highly irritating

Justification for classification or non-classification

The test material is classified as corrosive based on the skin irritation/corrosion results. Severe erythema with eschar (in all rabbits) and eschar sloughing off with hair growth beneath it (in 5 of the 6 rabbits) was observed. Desiccation was also observed. Three rabbits had hair growth over entire site with a small area that was hard to the touch. The other rabbits had possible scar formation. The one remaining rabbit's skin site appeared normal. One rabbit had a white linear striation on the application site and possible scar formation. Four of the six rabbits had a small area that was hard to the touch and hair growth covering the entire application site.