Registration Dossier

Administrative data

Description of key information

CaTG is considered to be irritating to the skin and the eyes. 

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:
04-Mar-2003 - 09-Mar-2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP Guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
French Republic, Prime Minister, Interministerial Group on Chemicals (GIPC)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: CEGAV, Saint Mars d'Egrenne, France
- Age/weight: on the day of treatment, the animals were 2 to 4 months old and had a mean body weight ± standard deviation of 2.6 ± 0.2 kg.
- Food and water: ad libitum
- Acclimation: at least 5 days before the beginning of the study.
ENVIRONMENTAL CONDITIONS
- temperature: 18 ± 3°C
- relative humidity: 30 to 70%
- light/dark cycle: 12 h/12 h
- ventilation: approximately 12 cycles/hour of filtered, non-recycled air.
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
Doses of 500 mg of the test item were placed on a dry gauze pad which was then applied to the right flank (application for 4 hours) or the left flank (application for 3 minutes) of the animals. The gauze pad was used dry and not moistened with water because the pH of the test item in water is 12. The OECD Guideline No. 404 recommends to use water or another suitable vehicle (if necessary) to moisten the test item and ensure a good contact with the skin. However, as the skin of the rabbit may be sensitive to many vehicles, it was chosen not to use a moistening agent rather than a non well-tolerated vehicle (such as corn oil). Furthermore, this condition of application reflects more accurately the condition of a possible accidental exposure.
Duration of treatment / exposure:
As possible irritant effects were anticipated, the test item was evaluated on a single animal in the first instance. The duration of exposure was 3 minutes on one flank and 4 hours on the other flank.
Since the test item was not severely irritant on this first animal, it was then applied for 4 hours to two other animals.
Observation period:
The skin was examined approximately 1, 24, 48 and 72 hour(s) after removal of the dressing.
Since there was persistent irritation reactions at 72 hours, the observation period was extended. In the absence of complete reversibility of skin reactions on day 15, the study was ended.
Number of animals:
3
Irritation parameter:
erythema score
Remarks:
3-minute exposure
Basis:
animal #1
Time point:
other: 1, 24, 48, 72 h
Score:
1
Max. score:
1
Remarks on result:
other: dryness of the skin on day 1 and 2
Irritation parameter:
edema score
Remarks:
3-minute exposure
Basis:
animal #1
Time point:
other: 1, 24, 48, 72 h
Score:
0
Max. score:
0
Remarks on result:
other: dryness of the skin on day 1 and 2
Irritation parameter:
erythema score
Remarks:
4 -hour exposure
Basis:
animal #1
Time point:
other: 24, 48, 72, 96 h
Score:
0
Max. score:
0
Irritation parameter:
edema score
Remarks:
4 -hour exposure
Basis:
animal #1
Time point:
other: 1, 24, 48, 72 h
Score:
0
Max. score:
0
Irritation parameter:
erythema score
Remarks:
4 -hour exposure
Basis:
animal #2
Time point:
other: 1, 24, 48, 72 h
Score:
0
Max. score:
0
Irritation parameter:
edema score
Remarks:
4 -hour exposure
Basis:
animal #2
Time point:
other: 1, 24, 48, 72 h
Score:
0
Max. score:
0
Irritation parameter:
erythema score
Remarks:
4 -hour exposure
Basis:
animal #3
Time point:
other: 1, 24, 48, 72 h
Score:
2
Max. score:
2
Remarks on result:
other: Residual test item
Irritation parameter:
edema score
Remarks:
4 -hour exposure
Basis:
animal #3
Time point:
other: 1, 24, 48, 72 h
Score:
1
Max. score:
1
Remarks on result:
other: Residual test item
Interpretation of results:
moderately irritating
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
Under the experimental conditions, the test item CaTG is irritant when applied topically to rabbits.
Executive summary:

After a 3-minute exposure (one animal), a very slight erythema (grade 1) was noted from day 1 up to day 4. Dryness of the skin was recorded on day 2 and 3 then between day 5 and day 10.

After a 4-hour exposure (three animals), a very slight or well-defined erythema (grade 1 or 2), together with a very slight oedema (grade 1) between day 2 and day 5, was noted in 1 of 3 animals from day 2 up to day 7. Dryness of the skin was recorded in the same animal from day 6 up to the end of the observation period (day 15).

Mean scores over 24, 48 and 72 hours for each animal were 0.0, 0.0 and 2.0 for erythema and 0.0, 0.0 and 1.0 for oedema.

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:
05 Mar 2003 - 10 July 2003
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: non-GLP study, alternative ex vivo screeening study.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
ex vivo study
Principles of method if other than guideline:
The rabbit enucleated eye test is used at SPL as a first stage in the assessment of ocular irritancy potential. The preferred species of choice is the rabbit. The assay has undergone interlaboratory validation and has been shown to reliably detect test materials that are negligible, or moderate to severe ocular irritants compared to the OECD 405 guideline study.
GLP compliance:
yes (incl. certificate)
Remarks:
Dept. of Health, UK
Species:
other: ex vivo rabbit eyes
Strain:
not specified
Vehicle:
water
Controls:
yes, concurrent no treatment
Amount / concentration applied:
A volume of 0.1 ml of the test material, which was found to weigh approximately 55 mg (as measured by gently compacting the required volume into an adapted syringe) was sprinkled as evenly as possible over the surface of the cornea. After ten seconds the test material was washed off the cornea using a minimum of 20 ml of saline solution (approximately 32°C). After washing, some of the test material was found to have adhered to the cornea, this did not affect the assessment of irritation or swelling.
Duration of treatment / exposure:
Immediately following washing of the corneal surface, the treated eye was returned to the superfusion chamber and the saline drip repositioned to irrigate the eye. The untreated eyes were similarly washed and used for control purposes.
Observation period (in vivo):
Assessment of corneal cloudiness was made pre-enucleation, post equilibration and approximately 60, 120, 180 and 240 minutes following treatment, according to the numerical evaluation adopted from Advances in Modern Toxicology: Dermatoxicology, 4th Ed, (F Marzulli and H Maibach, eds) Hemisphere Publishing Corporation, Washington DC, 1991, pp 749-815.
Number of animals or in vitro replicates:
Three eyes were treated with test material, two additional eyes remained untreated for control purposes. The treatment eye was removed from thesuperfusion apparatus whilst still being held in the perspex clamp. The clamp/eye was then placed horizontally into a petri dish.
Irritation parameter:
other: Corneal Opacity
Basis:
mean
Time point:
other: 1, 2, 3 and 4 hours
Score:
0
Max. score:
0
Reversibility:
fully reversible
Irritation parameter:
other: Corneal Epithelium Condition
Basis:
mean
Time point:
other: 1, 2, 3 and 4 hours
Score:
0
Max. score:
0
Reversibility:
not specified
Remarks on result:
other: normal compared to control eyes
Irritant / corrosive response data:
Corneal Opacity: No corneal effects were noted in the test eyes or control eyes during the study period.
Corneal thickness and Condition: Corneal swelling of the test eyes during the study period was slightly greater than that observed in the control eyes over the same period. The condition of the corneal epithelium of the test eyes and control eyes appeared normal during the study period.
Fluorescein Uptake: No fluorescein uptake was noted in the test eyes or control eyes 240 minutes after treatment.
Interpretation of results:
moderately irritating
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
Under the conditions of the test and following assessment of data for all end points, the test material is considered to have the potential to cause ocular irritancy in vivo. The test material is also likely to cause severe ocular irritancy in vivo in respect of its extreme alkalinity in aqueous solution.
Executive summary:

A screening study was performed to assess the ocular irritancy potential of the test material in the rabbit following application onto the cornea of the enucleated eye. The results of the study are believed to be of value in predicting the ocular irritation potential of the test material in man.

For that purpose 0.1 ml of the test material, which was found to weigh approximately 55 mg, was applied onto the cornea of each of three enucleated eyes which had been maintained at a temperature of 32°C ± 1.5°C within a superfusion chamber. A further two enucleated eyes were treated, for control purposes, with saline solution (0.9% Sodium Chloride).

 

Maximal ocular irritation observations recorded for the test eyes were as follows:

Corneal Opacity

Fluorescein Uptake

Corneal Swelling (%)

Condition of Corneal Epithelium

Test Eyes a [min]

Control Eyes b [min]

Cldy

Area

Int

Area

60

120

240

60

120

240

0

0

0

0

11.2

12.5

20.0

3.4

3.6

3.7

Normal

a          = For each time point the swelling recorded is the mean of three eyes

b         = For each time point the swelling recorded is the mean of two eyes

Cldy = Corneal cloudiness

Int = Intensity of fluorescein uptake

[min] = Minutes following treatment

It can be concluded that under the conditions of the test, the test material is considered to have the potential to cause ocular irritancy in-vivo. The test material is also likely to cause severe ocular irritancy in-vivo in respect of its extreme alkalinity in aqueous solution.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

CaTG is considered to be irritating to the skin and the eyes. CaTG is also likely to cause severe dermal and ocular irritancy in vivo in respect of its extreme alkalinity in aqueous solution.


Effects on skin irritation/corrosion: irritating

Effects on eye irritation: irritating

Justification for classification or non-classification

Based on the irritating properties of CaTG, CaTG should be classified as follows:

EU GHS:

Skin Irrit. 2; H315: Causes skin irritation.

Eye Irrit. 2; H319: Causes serious eye irritation.

DSD (67/548/EEC):

Xi; R37 Irritating to respiratory system

Xi; R41 Risk of serious damage to eyes.