Registration Dossier

Administrative data

Description of key information

Moderately irritating to skin, mildly irritating to eyes, in vivo

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:
1994
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods
Qualifier:
according to
Guideline:
EPA OTS 798.4470 (Acute Dermal Irritation)
Principles of method if other than guideline:
This study was conducted at Product Safety Labs in compliance with Good Laboratory Practices as defined in 40 CFR 792; U.S. EPA Good Laboratory Practice Standards; Toxic Substances Control Act (TSCA) and in accordance with Health Effects Testing Guidelines, Subpart E: Primary Dermal Irritation, 40 CFR 798.4470
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Number of Animals: 6 (3 males and 3 females), adult rabbits
Initial bodyweights: 1.9-2.1 kg
Received from Davidson's Mill Farm, South Brunswick, NJ

The animals were single housed in suspended stainless steel caging with mesh floors which conform to size recommendations
Litter paper was placed beneath the cage and was changed at least three times per week
Room temperature was kept between 67-75 deg F
12 hour light/dark cycle

Rabbits were given pelleted purina rabbit chow and filtered tap water ad libitum
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5 ml of the test substance
Duration of treatment / exposure:
4 hours
Observation period:
1, 24, 48, and 72 hours, and 7, 10, and 14 days after patch removal
Number of animals:
6
Details on study design:
One the day before application, a group of animals was prepared by clipping the dorsal area and the trunk. After shaving and just prior to application, the animals were weighed, examined for health and the skin checked for any abnormalities. Five tenths of a millileter of the test substance was applied to one 6 cm x 6 cm intact dose site on each animal and covered with a 2 1/4 x 4'' adhesive-backed gauze patch. The patch and entire trunk of each animal were then wrapped with semiocclusive 3' micropore tape to avoid dislocation of the patch. Elizabethan collars were placed on each rabbit and they were returned to their designated cage.
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
48 h
Score:
2.5
Max. score:
8
Reversibility:
not fully reversible within: 14 days
Remarks on result:
probability of moderate irritation

Based on the scoring system used, the test material is classified as moderately irritating to the skin when applied as received.

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
Based on the scoring system used, the test material is classified as moderately irritating to the skin when applied as received.
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:
1994
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods
Qualifier:
according to
Guideline:
EPA OTS 798.4500 (Acute Eye Irritation)
Version / remarks:
according to 40 CFR Part 792
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
4 males and 2 females
Adult rabbits received from Davidson's Mill Farm, South Brunswick, NJ
All animals were housed singly in suspended stainless steel caging with mesh floors which conform to size recommendations.
Litter paper was placed beneath the cage and was changed at least three time per week.
Room temperature was kept at 68-70oF
12 hour light/dark cycles
Acclimation period of 14 days

Animals were given pelleted Purina Rabbit Chow and Filtered Water was supplied ad libitum
Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
One-tenth of a millileter
Duration of treatment / exposure:
One eye of each rabbit received the test substance and was applied to the eye for 1 second before releasing
Observation period (in vivo):
Animals were observed for 7 days for signs of eye irritation
Number of animals or in vitro replicates:
6
Details on study design:
6 rabbits recieved one-tenth of a millilter of the test substance instilled into the conjunctival sac of the right eye by pulling the lower lid away from the eyeball. The upper and lower lids were then gently held together for about 1 second before releasing, to prevent loss of the test substance. The other eye of each rabbit remained untreated to serve as a control. Elizabethan collars were placed on each rabbit and they were returned to their cages. Ocular irritation was evaluated using a high-intensity white light at 1,24, 48, and 72 hours and 4 and 7 days post instillation. Twenty four hours after instillation, collars were removed. The animals were observed for signs of toxicity, behavioral changes, and mortality at least once daily during the test period.
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
24 h
Max. score:
110
Reversibility:
fully reversible
Remarks on result:
probability of mild irritation
Irritant / corrosive response data:
Mildly irritating to eyes

Results: Eye Irritation,

Wnorowski, 1994

Time: Incidence of Irritation
Hours Corneal Opacity Iritis Conjunctival Irritation
1

0/6

2/6 5/6
24

0/6

1/6 6/6
48

0/6

1/6 6/6
72

0/6

1/6 6/6
Days    
4

0/6

1/6 6/6
7

0/6

0/6 0/6
       

Mean Scores per Timepoint

MMTS (Draize)

Time: MMTS   
Hours 5544 5545 5546 5547 5548 5549 Mean MMTS
1 17 12 15 10 8 10 12
24 12 8 17 12 14 14 12.8
48 6 4 17 8 10 8 8.8
72 8 4 17 8 10 6 8.8
Days    
4 8 4 17 8 10 6 8.8
7 0 0 0 0 0 0 0
               

According toKay and Calandra,J. Soc. Cos. Chem. 13: 281-289, 1962)

Interpretation of results:
Category 2B (mildly irritating to eyes) based on GHS criteria
Conclusions:
The test material was tested in a study for eye irritation in vivo. Mild conjunctivitis was observed in all animals through day 4, and mild iritis was observed in 2 of 6 animals through day 4. The substance is classified as mildly irritating to the eye.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The substance was tested in an in vitro corrosion study (Corrositex) and an in vivo DOT corrosion study, and found to be non-corrosive. The substance was also tested in a rabbit skin irritation study according to a U.S. DOT protocol (occlusive exposure), and found to be moderately irritating. No systemic toxicity was noted at a dose of > 2000 mg/kg bw. An eye irritation study, similar to an OECD 405, was undertaken and the substance was found to be mildly irritating, with iritis and conjuctivitis present through day 4 (of 7).

Justification for classification or non-classification

The substance is irritating to skin and eye, in in vivo testing using older but established U.S. protocols. The substance is classified as irritating to skin, Category 2, and to eye, Category 2B.