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Administrative data

Description of key information

A single 4-hour, semi-occluded application of the test item to the intact skin of three rabbits produced reactions indicative of dermal corrosion. The reactions included dermal necrosis, slight to severe edema and scabbing (SafePharm, 1992). A Corrositex test with test item resulted in a mean breakthrough time of 70.58 min, and assignment of GHS Category 1C skin corrosivity (Ryan, 2014).

The eye irritation test was terminated after three days since signs of necrosis were observed (Huntington, 1975).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin corrosion: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
2014-08-18 to 2014-08-29
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 435 (In Vitro Membrane Barrier Test Method for Skin Corrosion)
Deviations:
no
GLP compliance:
yes
Test system:
other: Synthetic biobarriers
Justification for test system used:
The test articles were qualified and found to be compatible with the Corrositex® test system. The test articles were categorized by pH.
Qualification:
For each test article, 150 µL of the test article were added to the CDS reagent in a Qualify vial, and the vial was observed for any notable color change. An observable color change indicates that the test article is compatible with the Corrositex" system.
Details on test system:
Corrositex" (InVitro International, Placentia, CA)
- Test item: 500 μL of the test item were dispensed directly atop the bio-barrier.
- Positive control: 1.0 N Sodium Hydroxide.
- Negative control: Citric acid (1% (w/v)
- Vehicle for negative control: Tissue Culture Water,
METHOD
- The test articles were qualified and found to be compatible with the Corrositex® test system.
- The test articles were categorized by pH.
- For each test article, 500 µl of the test article were added to the Corrositex® test vials containing biobarriers and the time required for each test article to destroy the biobarrier was recorded.
- A Positive Control (1.0 N Sodium Hydroxide) and a
- Negative Control (1 % Citric Acid) were tested concurrently.
The mean breakthrough lime, which predicts the in vivo corrosive potential of each test article, was used to designate the United Nations (U.N.) Packing Group classifications.

CLASSIFICATION
Test article was classified by adding 500 µI of the test article to four test vials containing biobarriers to determine the packing group. lf the test article permeates through the biobarrier, it will come in contact with the CDS reagent in the vial and induce a color change similar to that observed in the Qualify tube. The amount of time required for the test article to destroy each biobarrier was recorded and the mean time of the four replicates is used to designate the United Nations (U.N.) Packing Group classification (Table 1). Classifications are as follows: Packing Group 1 (severe corrosivity), Packing Group II (moderate corrosivity), Packing Group III (mild corrosivity), or Non-Corrosive. A Positive Control was performed using 1.O N Sodium Hydroxide. The result for the Positive Control is considered valid if it falls within the range of the MB Research historical mean ± 2 standard deviations. A Negative Control was performed using 1% Citric Acid; the result is considered valid if the breakthrough time is greater than 60 minutes.

Amount/concentration applied:
500 µL
Duration of treatment / exposure:
see above
Duration of post-treatment incubation (if applicable):
see above
Number of replicates:
4
Duration of treatment / exposure:
Barrier breakthrough time for the replicates (min) 66.75, 71.75, 71.75, and 72.08
Irritation / corrosion parameter:
penetration time (in minutes)
Value:
70.58
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other:
Remarks:
Basis: membrane break through. Time point: 70.58 minutes. Reversibility: not applicable. Remarks: Corrositex test observed mean breakthrough time of 70.58 minutes. Category I material resulting in a packaging group III corrosive rating.

Designation of U.N. Packing Groups

 

Breackthrough Time (minutes)

 

Category 1

0 – 3 min

 

> 3 – 60 min

 

> 60 – 240 min

 

> 240 min

 

 Category 2

 

0 – 3 min

 

> 3 – 30 min

 

> 30 – 60 min

 

> 60 min

 

 

 

Packing Group I

Severe Corroivity

Packing Group II

Moderate Corroivity

Packing Group III

Mild Corroivity

Non corrosive

 

Conclusions:
A Corrositex test with test item resulted in a mean breakthrough time of 70.58 min, and assignment of GHS Category 1C skin corrosivity and UN packaging group III classifications.
Executive summary:

The test articles were analyzed using the Corrositex® test method to determine their dermal corrosivity potential and Packing Group designations.

The 1.0 N Sodium Hydroxide Positive Control had a breakthrough lime of 17.75 minutes, which fell within the range allowed (>13.5 and <22.4 minutes).

The 1% Citric Acid Negative Control had a breakthrough time of >80.00 minutes, which met the acceptance criterion of >60 minutes.

The results of this study indicated that the test articles were compatible with the Corrositex® system. The mean times required to destroy the synthetic biobarriers and the Packing Group classifications of these test articles are listed in Tables below.

Categorization Results

 

Test Article ldentity

Conc. Tested

pH of

10% (v/v) solution

pH in

Tube B

Category

 

Test item

10%

11.0

10.5

1

Classification Results

Test Article ldentity

BreakthroulhTime (minutes)

Packing Group

Corrosivity

Mild

1

2

3

4

Mean

Test item

66.75

71 .75

71.75

72.08

70.58

Packing Group III

 

 

Conclusion:

A Corrositex test with test item resulted in a mean breakthrough time of 70.58 min, and assignment of GHS Category IC skin corrosivity and UN packaging group III classifications.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1992-01-16 to 1992-02-12
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes
Specific details on test material used for the study:
For the purpose of this study the test material was used as supplied.
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd., Moston, Sandbach, Cheshire, U.K.
- Strain: New Zealand White rabbits
- Age: approximately twelve to sixteen weeks old
- Weight at study initiation: 2.10 - 2.32 kg
- Housing: single
- Diet: (Spillers Rabbit Diet, Dalgety Agriculture Ltd., Almondsbury, Bristol), ad libitum
- Water (e.g. ad libitum): tap water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 23 °C
- Humidity (%): 42 - 59 %
- Air changes (per hr): approximately 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours daily
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 mL test item
Duration of treatment / exposure:
4 hour and 3 minutes
Observation period:
7 days
Number of animals:
3 and 3
Details on study design:
ADMINISTRATION/EXPOSURE 
- Area of exposure: ca. 6 cm2
- Total volume applied: 0.5 ml
- Type of wrap: The patch was secured in position with a strip of surgical adhesive tape, the trunk o f each rabbit was wrapped in an elasticated corset
- Postexposure period: 7 days
- Removal of test substance: test material removed by gentle swabbing with cotton wool soaked indistilled water.
EXAMINATIONS
- Scoring system: Draize J.H. (1959) Association of Food and Drug Officials of the United States, Austin, Texas, "The Appraisal o f the Safety o f Chemicals in Foods, Drugs and Cosmetics
- Examination time points: 1; 24; 48; 72 hours and 6; 8; 10; 14 days  after removal of patch and test substance
Irritation parameter:
other: signs of necrosis observed
Basis:
other: all animals
Reversibility:
not fully reversible within: 7 days
Remarks on result:
other: scores are not relevant since the material produced dermal necrosis
Irritant / corrosive response data:
4-Hour Exposure Period
Green-coloured dermal necrosis and very slight to severe oedema were noted at all treated skin sites one and 24 hours after patch
removal. Well-defined erythema surrounding other skin reactions was also noted at two treated skin sites at the 24-hour observation. A
hardened, dark brown/black-coloured scab was noted at two treated skin sites at the 48 and 72-hour and 7-day observations. Well -
defined erythema surrounding the scab was also noted a t the 48 and 72-hour observations. Scattered sunken, scabs around the edge of
the treatment site with well-defined erythema over the treatment site was noted at one treated skin site at the 48 and 72-hour observations.
A sunken, hardened, dark brown/bl ack-coloured scab was noted at this treated skin site at the 7-day observation. Adverse reactions prevented accurate evaluation of erythema and oedema at all treated skin sites at the 48 and 72-hour and 7-day observations. The treatment sites were assigned a grade 4 for erythema on the Draize scale due to injuries in depth.
The animals were killed for humane reasons immediately after the 7-day observation i n accordance with current U.K. Home Office guidelines.

3-Minute Exposure Period

Very slight erythema was noted at all treated skin sites one and 24 hours after patch removal and persisted at two treated skin sites at the 48 and 72-hour observations.

Very slight oedema was noted at one treated skin site at the 24-hour observation.

Desquamation was confined to one treated skin site seven days after treatment.

Conclusions:
Test item is corrosive following a 4-hour semi-occluded exposure.
Executive summary:

The study was performed to assess the irritancy potentia l of the test item following single , semi-occluted applications to the intact rabbit skin for exposure periods o f 4 hours and 3 minutes (Safepharm Standard Method Number OECD 4). The method used followed the recommendations of the OECD Guidelines for Testing of Chemicals (1981) No. 404.

The results may be used as a basis for classification and labeling under Commission Directive 83/467/EEC and the UK Approved Code of Practice " Classification and Labeling of Substances Dangerous for Supply".

The test system was chosen because the rabbit has been shown to be a suitable model for this type of study and is recommended in the test method. The results o f the study are believed to be of value in predicting the likely skin irritancy potential of the test material to man

A single 3-minute, semi-occluded application of the test material to the skin of three rabbits produced very slight erythema. Very slight edema was confined to one treated skin site at the 24-hour observation. Desquamation was confined to one treated skin site seven days after treatment. A single 4-hour, semi-occluded application of the test material to the intact skin of three rabbits produced reactions indicative of dermal corrosion. The reactions included dermal necrosis, slight to severe edema and scabbing.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Referenceopen allclose all

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: Study pre-dates GLPs
Qualifier:
according to
Guideline:
other: CPSC guidelines in CFR 16
Principles of method if other than guideline:
The procedure employed was that prescribed by THE CONSUMER PRODUCT SAFETY COMMISSION OF THE U.S.A. in the CODE OF FEDERAL REGULATIONS, TITLE 16, SECTION 1500.42, and in THE JOURNAL DE LA REPUBLIQUE FRANCAISE, APRIL 21, 1971. Only three animals were used instead of six.
GLP compliance:
no
Species:
rabbit
Strain:
not specified
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
Albino rabbits
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.1 ml test item
Duration of treatment / exposure:
1 time
Observation period (in vivo):
3 days
Number of animals or in vitro replicates:
3
Details on study design:
The eyes are examined and the grade of ocular reaction i s recorded at 24, 48 and 72 hours. Reading of reaction i s facilitated by use of a binocular loupe, hand slit-lamp, or other expert means.
After the recording of observations at 24 hours, any or all eyes may be further examined after applying fluorescein. For this optional test, one drop of fluorescein sodium ophthalmic solution U.S.P. or equivalent is dropped directly on the cornea. After flushing out the excess fluorescein with sodium chloride solution U.S.P. or equivalent, injured areas of the cornea appear yellow; this is best visualized in a darkened room under ultra-violet illumination. Any or all eyes may be washed with sodium chloride solution U.S.P. or equivalent after the 24 hour reading.
Irritation parameter:
other: totality of effects
Basis:
other: all animals
Time point:
other: Day 3
Score:
39 - 78
Max. score:
78
Reversibility:
not reversible
Remarks on result:
other: test was terminated after three days since signs of necrosis were observed
Irritant / corrosive response data:
see below
Other effects:
CORNEAL OPACITIES WERE OBSERVED IN ALL THREE ANIMALS (TWO HAD COMPLETE CORNEAL OPACITY AND GROSS DESTRUCTION OF THE CORNEA WAS OBSERVED IN THE THIRD ANIMAL). IRITIS WAS OBSERVED IN ALL THREE ANIMALS. A DIFFUSE CRIMSON TO BEEFY AND COLORATION OF THE CONJUNCTIVA AND CONSIDERABLE SWELLING WITH THE EYELIDS ABOUT HALF CLOSED WERE OBSERVED IN ALL THREE ANIMALS. THE NICITATING MEMBRANE SHOWED AREAS OF NECROSIS IN ALL THREE ANIMALS. THE MAXIMUM AVERAGE SCORE (MM) = 58.
Conclusions:
Test item was extremely irritating to the rabbit eye and is probably corrosive.
Executive summary:

  WITHIN THE LIMITATIONS OF THE ABOVE ABBREVIATED TEST PROCEDURE TEST ITEM GAVE A POSITIVE TEST FOR EYE IRRITATION. FINAL CLASSIFICATION ACCORDING TO THE PROCEDURE IN THE OFFICIAL JOURNAL WAS NOT POSSIBLE, AS ONLY THREE ANIMALS WERE USED, AND THE TEST WAS TERMINATED ON DAY THREE.

Endpoint:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study need not be conducted because the available information indicates that the criteria are met for classification as corrosive to the skin or irritating to eyes
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

Based on the results of the in vivo and in vitro skin and eye irritation studies and according to the criteria of EC Regulation 1272/2008 and subsequent regulations on classification, labelling and packaging of substances and mixtures, the test item has to be classified into subcategory 1C of hazard class skin corrosion as well as category 1 of hazard class eye damage.