Zinc di(acetate)

Endpoint summary

Description of key information

Skin irritation: Weight of evidence: Zinc Acetate is considered to be not irritating for skin after a single application of test substance. Experimental data on Zinc Acetate on rabbits, mice, and rats, and read-across approach from experimental data on Calcium Acetate and Zinc Stearate.
Eye irritation/corrosion: 
Key study: Test method OECD 437, GLP study: The test item was determined to be ocular corrosive or a severe irritant.
Key study: Test method OECD 438, GLP study: The test item was considered to belong to a group of substances which cause eye corrosion/irritation.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation / corrosion

Remarks:

other: read-across from in vivo experimental test with an analogue

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The analogue Calcium Acetate which shares the same functional group with Zinc Acetate, also has comparable values for the relevant molecular properties for the skin irritation endpoint.

Reason / purpose for cross-reference:

reference to other study

Principles of method if other than guideline:

Read-across approach from Letter of Access experimental data (test method similar to OECD 404) on the analogue Calcium Acetate.

GLP compliance:

no

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: 24 h

Score:

0

Max. score:

0

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: 24 h

Score:

0

Max. score:

0

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: 24 h

Score:

0

Max. score:

0

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: 48 h

Score:

0

Max. score:

0

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: 48 h

Score:

0

Max. score:

0

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: 48 h

Score:

0

Max. score:

0

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: 9 days

Score:

0

Max. score:

0

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: 9 days

Score:

0

Max. score:

0

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: 9 days

Score:

0

Max. score:

0

Irritation parameter:

other: redness

Basis:

animal #1

Time point:

other: 24 h

Score:

0

Max. score:

0

Irritation parameter:

other: redness

Basis:

animal #2

Time point:

other: 24 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 48 h

Irritation parameter:

other: redness

Basis:

animal #3

Time point:

other: 24 h

Score:

0

Max. score:

0

Irritation parameter:

other: redness

Basis:

animal #1

Time point:

other: 48 h

Score:

0

Max. score:

0

Irritation parameter:

other: redness

Basis:

animal #2

Time point:

other: 48 h

Score:

0

Max. score:

0

Irritation parameter:

other: redness

Basis:

animal #3

Time point:

other: 48 h

Score:

0

Max. score:

0

Irritation parameter:

other: redness

Basis:

animal #1

Time point:

other: 9 days

Score:

0

Max. score:

0

Irritation parameter:

other: redness

Basis:

animal #2

Time point:

other: 9 days

Score:

0

Max. score:

0

Irritation parameter:

other: redness

Basis:

animal #3

Time point:

other: 9 days

Score:

0

Max. score:

0

Other effects:

Based on the experimental results obtained with the analogue Calcium Acetate, which is considered to be not irritating for Vienna White rabbits skin, and applying the read-across approach, the substance Zinc Acetate is also considered as not irritating under test conditions.

The analogue Calcium Acetate, which shares the same functional group with Zinc Acetate, also has comparable values for the relevant molecular properties. These properties are:
- a low log Pow value which is -1.38 for Calcium Acetate and -1.28 for Zinc Acetate,
- a similar water solubility which is 1.0 g/mL at 25 ºC for Calcium Acetate and 434.78 g/L at 25 ºC for Zinc Acetate, and
- molecular weights which are 158.166 for Calcium Acetate and 183.497 for Zinc Acetate.

The substance Zinc Acetate is considered as not irritating under test conditions.

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The substance Zinc Acetate is considered as not irritating under test conditions.

Executive summary:

Based on the experimental results (reported under the endpoint record 07.03.01_05 CaAc) with the analogue Calcium Acetate, which is considered to be not irritating for Vienna White rabbits skin, and applying the read-across approach, the substance Zinc Acetate is also considered as not irritating under test conditions.

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:

29 January 2013 - 28 March 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Test method according to OECD Guideline 437, GLP study.

Qualifier:

according to guideline

Guideline:

OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying Ocular Corrosives and Severe Irritants)

GLP compliance:

yes (incl. QA statement)

Species:

other: Bovine cattle (in-vitro test)

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Bovine eyes were obtained from freshly slaughtered cattle at the abattoir. EVA, Saint-Pierre-sur-Dives - France.
- Age at study initiation: Up to 12 months old.

TRANSPORT FROM SUPPLIER TO CITOXLAB: The eyes were transported in a specific container to avoid corneal damage, at ambient temperature, immerged in buffered Hanks medium containing an antibiotic.

Upon arrival, the selection and preparation of corneas was performed as soon as possible.

Vehicle:

water

Controls:

yes

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 750 µL ± 8 µL
- Concentration (if solution): 20% (w/v) in water solution.

VEHICLE
- Drinkingn water treated by reverse osmosis using a ELIX 5 apparatus.

Duration of treatment / exposure:

4 hours ± 5 min.

Number of animals or in vitro replicates:

3 corneas were used for each treated series: test item 20% in water, vehicle control (water), positive control 20% imidazole solution in 0.9% NaCl.

Details on study design:

STUDY DESIGN:
Corneas (without defects) were mounted in corneal holders. Both chambers of the corneal holders were filled with complemented MEM culture medium (cMEM) and pre-incubated for 1 hour and 5 minutes ± minutes at 32 ºC. Before the treatment, the eyes were macroscopically observed and a first opacity measurement was performed using a opacitometer (OPT0). Then, the of the anterior chamber was removed and the test item applied using a micropipette onto the epithelium of the cornea for 4 hours. At the completion, the test item was removed from the opening of the anterior chamber and the epithelium was rinsed with cMEM (32 ºC). A second opacity measurement was then performed (OPT2). Afterwards, the medium of the anterior chamber was removed and filled with a fluorescein solution. The holders were then incubated vertically in water for 90 minutes at 32 ºC. At the end of the incubation, the optical density at a wavelength of 490 nm of the solution from the posterior chamber of each holder was measured in order to determine the permeability of the cornea. Then, each cornea was observed for opaque spots and other irregularities.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes
- Time after start of exposure: 4 hours

SCORING SYSTEM:
Opacity: Change in opacity = OPT2 - OPT0, corrected with the change of the vehicle control.
Permeability: Corrected permeability = OD490 nm - control OD490 nm
In-vitro irritancy score: IVIS = corrected opacity + (15 x cOD490)
IVIS >= 55.1 = ocular corrosive/severe irritant.
IVIS < 55.1 = not ocular corrosive or severe irritant

TOOL USED TO ASSESS SCORE: lamp, opacitometer, fluorescein

Irritation parameter:

other: IVIS

Basis:

mean

Time point:

other: 4 h

Score:

69.5

Irritant / corrosive response data:

Test item treatment: The in-vitro irritancy score (IVIS) was 69.5.

Other effects:

No notable opaque spots or irregularities were observed on vehicle control corneas following the treatment, while opacity, residual test item and fluorescein fixation were observed on the corneas treated with the test item.

Results:

GROUP		OPACITY				PERMEABILITY		SCORE
Vehicle control	Holder	OPT0	OPT2	OPT2-OPT0		OD490 nm
	11 15 28	2 2 2	1 9 7	-1 7 5		0.020 0.021 0.020
	Mean SD			3.7 4.2		0.020 0.001
Test item	Holder	OPT0	OPT2	OPT2-OPT0	cOPT	OD490 nm
	32 4 17	0 1 1	87 65 70	87 64 69	83.3 60.3 65.3	0.008 0.012 0.006	-0.012 -0.008 -0.014	83.1 60.2 65.1
	Mean SD				69.7 12.1		-0.012 0.003	69.5 12.1
Positive control	Holder	OPT0	OPT2	OPT2-OPT0	cOPT	OD490 nm
	3 44 37	1 1 3	71 61 89	70.0 60.0 86.0	66.3 56.3 82.3	1.464 1.652 3.508	1.444 1.632 3.488	88.0 80.0 134.6
	Mean SD				68.3 13.1		2.188 1.130	101.1 29.2

As the test item induces an IVIS > 55.1, it was considered to be an ocular corrosive or a severe irritant.

Interpretation of results:

Category 1 (irreversible effects on the eye)

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test item was considered to be corrosive or severely irritant to the eye.

Executive summary:

A Bovine Corneal Opacity and Permeability Test was performed with the test item according to OECD Guideline 437 in order to assess whether the substance is an ocular corrosives or severe irritant. The test item was evaluated using a treatment time of 4 hours. Three corneas per test (test item, vehicle control and positive control) were used in the present assay. Corneas were exposed to 20% of aqueous solution of test item for 4 hours. Then the corneas were rinsed. The opacity of the corneas were measured using a opacitometer before and after treatment in order to assess the change of opacity. After treatment, the corneas were exposed to a fluorescein solution of 5 mg/ml and the permeability determination was performed by measuring the density of the incubation solution media at a wavelength of 490 nm. Afterwards the in-vitro irritancy scores (IVIS) were calculated. No notable opaque spots or irregularities were observed on vehicle control corneas following the treatment, while opacity, residual test item and fluorescein fixation were observed on the corneas treated with the test item. The IVIS for the test item was 69.5. Since the IVIS was >= 55.1, it was considered to be an ocular corrosive or a severe irritant.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Additional information

SKIN IRRITATION:

Weight of evidence: Experimental data on Zinc Acetate on rabbits, mice, and rats, and read-across approach from experimental data on Calcium Acetate and Zinc Stearate.

Experimental data on Zinc Acetate:

An exposure/dermal irritancy test (open patch test) of Zinc Acetate was performed using 4 rabbits, 6 mice and 8 guinea pigs. Doses of 0.5 mL/day of a 20 % solution (w/v) in deionized water were applied during 5 days (30 min. of application). Results of the test showed slightly irritating effect in 3 of 4 rabbits, a moderate irritation in all tested mice, and no irritation in guinea pigs.

An exposure/dermal irritancy test (occlusive patch test) of Zinc Acetate was performed using 4 rabbits. 0.5 mL of 20 % solution (w/v) applied on the skin of rabbits during 5 days caused severe irritancy in all tested animals.

The studies were not realized according to official guidelines so the results are not conclusive.

Read-across from experimental data on Calcium Acetate:

The irritation and corrosive effects of Calcium Acetate acid was studied on Vienna White rabbits (two males and one female). Animals were exposed for 4 hours to a 50 % aqueous solution and observed for 9 days. Calcium Acetate did not produce any irritation effect on the rabbit skin.

Based on these results, and applying the read-across approach, the substance Zinc Acetate is also considered as not irritating under test conditions.

Read-across from experimental data on Zinc Stearate:

The irritation effects of Zinc Stearate was studied on rabbits by Draize's method. Test material was applied under occlusive conditions to abraded and intact skin for 24 h exposure period. Zinc Stearate was not irritating for rabbits.

The irritation effects of Zinc Stearate was studied on rabbits by Draize's method. Test material (0.5 g) was applied in a single dose under occlusive conditions for four hours. Zinc Stearate was not corrosive for rabbits.

Based on these results, and applying the read-across approach, the substance Zinc Acetate is also considered as not irritating under test conditions.

EYE IRRITATION:

Key study: Experimental data on Zinc Acetate (in-vitro):

A Bovine Corneal Opacity and Permeability Test was performed with the test item according to OECD Guideline 437 in order to assess whether the substance is an ocular corrosives or severe irritant. The in-vitro irritation score (IVIS) for the test item was 69.5. Since the IVIS was >= 55.1, it was considered to be an ocular corrosive or a severe irritant.

Key study: Experimental data on Zinc Acetate (in-vitro):

The Isolated Chicken Eye Test for Identifying Ocular Corrosives and Severe Irritants was performed according to OECD Guideline 438 in order to obtain information on health hazards resulting from the possibility of a superficial influence of the test item on the eye. The obtained results were as follow: Fluorescein retention: IV ICE Class; Corneal capacity: IV-III ICE Class; Corneal swelling: I-III ICE Class. On the ground of the study results, the test item belongs to a group of substances which cause eye corrosion/irritation.

In-vivo eye irritation study: Data waiving: In accordance with Column 2, the in-vivo eye irritation test does not need to be conducted since the substance causes serious damage to eyes.

Justification for selection of eye irritation endpoint:
No study was selected since both available in-vitro key studies (Klimisch = 1) showed that the substance was corrosive to the eye.

Effects on eye irritation: corrosive

Justification for classification or non-classification

Skin irritation: Based on the available data, the substance is not classified for skin irritation according to CLP Regulation (EC) no. 1272/2008.

Eye irritation: Based on the available data, the substance is classified as Eye Damage Category 1, H318 according to CLP Regulation (EC) no. 1272/2008.