Registration Dossier

Administrative data

Description of key information

Corrosive, based on results of one of two in vivo skin irritation or corrosion studies.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods
Justification for type of information:
Guideline study under GLP
Reference:
Composition 0
Qualifier:
equivalent or similar to
Guideline:
other: U.S. 49 CFR 173.136 (a) and 173.137
Principles of method if other than guideline:
A U.S. DOT standard skin corrosion method was used.
GLP compliance:
yes
Test material information:
Composition 1
Species:
rabbit
Strain:
not specified
Details on test animals and environmental conditions:
6 white rabbits were used in the test study.
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
A 1 square inch quaze patch was held to the test area (intact skin)
Duration of treatment / exposure:
3 minutes, 60 minutes, and 4 hours
Observation period:
48 hours
Number of animals:
6
Details on study design:
Six animals were treated by introducing the test substance under gauze patches measuring 1 square inch held on with non-irritating tape at 3 test sites. The test substance was kept in contact with the skin for 3 minutes, 60 minutes, and 4 hours by wrapping with an impervious bandage. After the exposure period, the test sites were washed with sterile water. Initial readings were scored for erythema, edema and /or corrosion 30-60 minutes post exposure. Readings were made again at the end of 48 hours.
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
48 h
Remarks on result:
no indication of irritation

None of the animals exhibited any signs of skin corrosion at any of the test sites. The test substance is not considered corrosive to the skin of albino rabbits according to the test study.

Interpretation of results:
GHS criteria not met
Conclusions:
The test substance is not considered corrosive to the skin of albino rabbits according to the guideline U.S. DOT corrosion test.
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods
Justification for type of information:
Guideline study under GLP
Reference:
Composition 0
Qualifier:
equivalent or similar to
Guideline:
other: U.S., FHSA, 16 CFR 1500.41
Principles of method if other than guideline:
U.S. Federal Hazardous Substances Act, skin irritation study guideline
GLP compliance:
yes
Test material information:
Composition 1
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Six healthy, young adult, 3 male and 3 female, New Zealand White rabbits
Animals were purchased from a registered commercial breeding laboratory (Eastern Rabbit Breeding laboratories, Taunton, MA)
Animals were weighed at the start of the study and all weighed in between 2.0 and 3.0 kilograms
10-12 weeks of age
Animals were quarantined for 4 days prior to initiation of treatment

Animals were individually housed using suspended stainless steel cages
Hardwood chips were used as non-contact bedding under the cages
Animal rooms were maintained at 68±F with a relative humidity at 30-70%
A minimum of 10-13 complete air exchanges per hour
12 hour light/dark cycle

Animals were supplied with a controlled dieet of a commercial rabbit ration (Agway Prolab, Waverly, NY) and municiple tap water ad libitum
Type of coverage:
occlusive
Preparation of test site:
other: intact and abraded
Vehicle:
physiological saline
Controls:
no
Amount / concentration applied:
0.5 grams
Duration of treatment / exposure:
4 hours
Observation period:
24 hours, 72 hours
Number of animals:
6
Details on study design:
The animals were treated by introducing the test substance under a gauze patch 2 single layers thick, measuring 2.5 cm x 2.5 cm, which were held in place with an impervious bandage. The patches were applied to one intact site and one abraded site per animal. The test substance was kept in contact with the skin for 4 hours. The skin was wiped following the four hour exposure period to remove remaining test substance.
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
24 h
Score:
> 8
Max. score:
8
Reversibility:
not reversible
Remarks on result:
other: necrosis in all animals
Irritant / corrosive response data:
All animals showed necrosis of the application site, both intact and abraded
Other effects:
No weight loss or signs of toxicity were observed. There was no evidence of pain or suffering by animals.

Signs of necrosis (irreversible corrosive damage to the skin) were present at the 24h and 72h observation period at all test sites. The test substance is considered a corrosive irritant to the skin of rabbits.

Interpretation of results:
Category 1C (corrosive) based on GHS criteria
Conclusions:
In a skin irritation study in rabbits with a 4-hour occlusive exposure, the test substance caused necrosis of the skin sites, but no other toxicity. The substance is considered a corrosive irritant 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 vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because the substance is classified as skin corrosion, leading to classification as serious eye damage (Category 1)
Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

There are conflicting findings in the two in vivo studies on irritation/corrosion endpoints. The outcome of a guideline corrosion study in rabbits is "non-corrosive" at any of the three timepoints (3 m, 60 m and 4 h), with no adverse effects noted. In contrast, the skin irritation study (4 h) resulted in a finding of necrosis in all animals. The current in vivo skin irritation studies were conducted under conditions which are more stringent than those of the OECD 404 protocols on which GHS evaluation is based. The current irritation study used occlusive exposures (impermeable bandage), and applied material to abraded sites as well as intact sites, in 6 rabbits, with no observation period after 72 h post administration. The conflicting results of the two in vivo 4-hour exposure suggests a weight of evidence approach is indicated. A dermal acute toxicity study was undertaken in rabbits where the test material was applied for a 24 h occlusive exposure duration, with a finding of necrosis in all animals. In a guinea pig skin sensitisation test, necrosis was also observed after 6 h of occlusive patch exposures to undiluted test material. There are no known occupational accident reports involving skin corrosion or irritation in human workers. The substance has a pH in water of greater than 7, indicating alkaline properties.  There are no known close structural analogues with relevant toxicity data. The evidence indicates that the test substance is a skin corrosive, classified as Category 1C. No in vivo eye irritation study exists, as severe damage is assumed based on corrosive properties.

Justification for classification or non-classification

A weight of evidence approach is used to interpret all known experimental data on skin irritation potential. The substance is classified as a skin corrosive, Category 1C. It is anticipated that the eye would also show severe damage after exposure, Cat 1.