Calcium sulphidoacetate

Endpoint summary

Description of key information

CaTG is not irritating to the skin, but is considered irritating to eyes (Eye Irrit 2). 

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:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

French Republic, Prime Minister, Interministerial Group on Chemicals (GIPC)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system 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:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

not specified

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:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

not specified

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:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Remarks:

4 -hour exposure

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Remarks:

4 -hour exposure

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Remarks:

4 -hour exposure

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Remarks:

4 -hour exposure

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: Day 7

Remarks on result:

other: Residual test item

Irritation parameter:

edema score

Remarks:

4 -hour exposure

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: Day 7

Remarks on result:

other: Residual test item

Interpretation of results:

GHS criteria not met

Conclusions:

Under the experimental conditions, the test item CaTG is not irritating 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:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vitro / ex 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:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

equivalent or similar to guideline

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. QA statement)

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:

cornea opacity score

Value:

0

Vehicle controls validity:

not specified

Negative controls validity:

not specified

Positive controls validity:

not specified

Irritation parameter:

other: Corneal Epithelium Condition

Value:

0

Vehicle controls validity:

not specified

Negative controls validity:

not specified

Positive controls validity:

not specified

Other effects / acceptance of results:

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:

Category 2 (irritating to eyes) based on GHS criteria

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

Effects on skin irritation/corrosion: not irritating

Effects on eye irritation: irritating (Eye Irrit 2)

Justification for classification or non-classification

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

EU GHS:

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