Zinc

Endpoint summary

Description of key information

key studies demonstrate a lack of irritation/corrosion potential

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:

Not reported

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Qualifier:

no guideline followed

Principles of method if other than guideline:

Macroscopic skin reactions, skin histological changes and epidermal keratin binding of test material were observed in New Zealand White rabbits after 5 d application of test material to skin using both open and occlusive patch methods.

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Sex: Male
- Source: Charing Cross and Westminster Medical School, London, UK
- Weight at study initiation: 2.5-4.0 kg
- Housing: Housed singly
- Diet: R14 pellets (Biosure) (zinc content 74 mg/kg, w/w)
- Water: Tap water
- Acclimation: Acclimatized to conventional restraining boxes before open patch test


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18±2
- Humidity (%): 45
- Photoperiod (h dark/h light): 12/12

Type of coverage:

other: Both open and occlusive in two different tests

Preparation of test site:

other: Clipped

Vehicle:

other: 0.1 % Tween 80

Controls:

yes, concurrent vehicle

Amount / concentration applied:

TEST SOLUTION
- Amount(s) applied (volume): 0.5 mL
- Concentration (if solution): 20 % (w/v) zinc oxide suspension in 0.1 % Tween 80
- pH: 7.4

Duration of treatment / exposure:

5 d

Observation period:

Open patch test: Observed during and after 5 d exposure period
Occlusive patch test: On Day 3 and Day 5

Number of animals:

Four animals each for control and test groups in both open and occlusive patch test

Details on study design:

Open patch test: Eight test sites (5 cm2) were designated, four on each side of the mid-dorsal line. Test suspension or vehicle was applied daily for 5 successive days. The animals were restrained for 30 min to allow test sites to dry. Skin sites were observed during and after 5 d exposure period. Rabbits were killed 24 h after the fifth daily treatment.

Occlusive patch test: Animals were prepared similar to open patch test. Test suspension or vehicle was applied to the skin on a sterile gauze pad that was secured by a hypoallergenic adhesive tape. The trunks of these animals were wrapped in rubberized fabric and impermeable dressing for 3 d. At this stage, dressings were removed and skin sites were evaluated for irritancy. Two rabbits were killed at this stage. The remaining animals were redressed with freshly impregnated gauze pads and then re-examined and killed after a further 2 d.

In both tests, representative samples of each test and control skin sites of killed animals were preserved in 10 % phosphate buffered formalin for histology. Thin sections cut along the anterior-posterior axis were stained with haematoxylin and eosin, or with morin dye, which fluoresces blue-green in the presence of zinc ions and ultraviolet light (to demonstrate zinc binding to epidermal keratin histologically).

SCORING SYSTEM: Not reported

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 5 d

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: 5 d

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: 5 d

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

other: 5 d

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Time point:

24 h

Remarks on result:

not measured/tested

Irritation parameter:

erythema score

Time point:

48 h

Remarks on result:

not measured/tested

Irritation parameter:

erythema score

Time point:

72 h

Remarks on result:

not measured/tested

Irritation parameter:

edema score

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Irritant / corrosive response data:

No obvious reactions were observed in both control and treatment groups in any of the performed tests after 5 d exposure.

Other effects:

Histological changes: No evidence of damage was observed.

Morin fluorescence for zinc on skin: No obvious reaction was observed.

None

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based on these results, 20 % w/v zinc oxide was found to be non-irritating to rabbit skin.

Executive summary:

A study was conducted to evaluate the skin irritation potential of zinc oxide in New Zealand White rabbits by both open and occlusive patch methods.

In open patch test, 0.5 mL of 20 % w/v zinc oxide suspension in 0.1 % Tween 80 or vehicle was applied to clipped sites (5 cm²) of groups of four animals for 5 d. Skin sites were observed during and after 5 d exposure period. Animals were killed 24 h after the fifth daily treatment.

In occlusive patch test, groups of four animals were treated similarly to open patch test, but the test suspension or vehicle was applied to the skin using occlusive dressing for 3 d. After 3 d, dressings were removed and skin sites evaluated for irritancy. Two rabbits were killed at this stage. The remaining animals were redressed with freshly impregnated gauzes and then re-examined and killed after a further 2 d.

In both tests, representative samples of each test and control skin site of killed animals were analysed histologically and stained with morin dye to study epidermal keratin binding of zinc.

No obvious reactions were observed in both control and treatment groups in any of the performed tests after 5 d exposure. No evidence of damage was observed upon histological examination. No morin fluorescence was observed in skin sections.

Based on these results, 20 % w/v zinc oxide was found to be non-irritating to rabbit skin.

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

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:

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

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

none

Vehicle:

not specified

Controls:

yes, concurrent no treatment

Amount / concentration applied:

100 mg of test substance

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

1, 24, 48 and 72 hours

Number of animals or in vitro replicates:

3

Details on study design:

three male New Zealand White rabbits were treated by instillation of approximately 100 mg of the substance into the conjuctival sac of one eye. The other eye remained untreated and served as control. After 24 hours, both eyes of two animals were rinsed with water. The eyes were examined at 1, 24, 48 and 72 hours after instillation.

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

>= 0.7 - < 1

Max. score:

3

Reversibility:

fully reversible

Remarks:

in 72 h

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Slight irritation of the conjuctivae, which was seen as redness (grade 1-2; mean scores over 24-72 hours 1, 1 and 0.7) that had completely resolved at 72 hours in all animals. Chemosis (grade 1-2) was also observed in all animals at 1 hour only, while discharge (grade 1) was observed at 1 (two animals) and 24 hours (one animal).

Other effects:

no symptoms of systemic toxicity and no mortality occured. No iridial irritation and no corneal opacity or epithelial damage was observed in any of the animals.

none

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the eye irritation data, zinc dust is not irritating/corrosive to the eyes. Hence, according to EU criteria, metallic zinc does not have to be classified/labelled for irritating properties.

Executive summary:

A well-performed eye irritation/corrosion studie, conducted according to Directive 92/69/EEC B.5 and OECD guideline 405, was carried out with metallic zinc dust (median particle diameter 4mm).

Three male New Zealand White rabbits were treated by instillation of approximately 100 mg of the substance into the conjuctival sac of one eye. The other eye remained untreated and served as control. After 24 hours, both eyes of two animals were rinsed with water. The eyes were examined at 1, 24, 48 and 72 hours after instillation.

No symptoms of systemic toxicity were observed and no mortality occurred. Also, no iridial irritation and no corneal opacity or epithelial damage was observed in any of the animals. Zinc dust caused slight irritation of the conjuctivae, which was seen as redness (grade 1-2; mean scores over 24-72 hours 1, 1 and 0.7) that had completely resolved at 72 hours in all animals. Chemosis (grade 1-2) was also observed in all animals at 1 hour only, while discharge (grade 1) was observed at 1 (two animals) and 24 hours (one animal).

Reference 2

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:

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

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

none

Vehicle:

not specified

Controls:

yes, concurrent no treatment

Amount / concentration applied:

100 mg of test substance

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

1, 24, 48 and 72 hours

Number of animals or in vitro replicates:

3

Details on study design:

three male New Zealand White rabbits were treated by instillation of approximately 100 mg of the substance into the conjuctival sac of one eye. The other eye remained untreated and served as control. The eyes were examined at 1, 24, 48 and 72 hours after instillation.

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Time point:

24/48/72 h

Score:

>= 0.3 - <= 0.7

Max. score:

3

Reversibility:

fully reversible within: 48 hours in two animals; 72 hours in one animal

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Redness of the conjuctivae (grade 1; mean scores over 24-72 hours 0.7, 0.3 and 0.3) had completely resolved within 48 hours in two animals and within 72 hours in the other animal. Chemosis (grade 1-2 in all animals) and discharge (grade 1 in two animals) were also observed, but only at 1 hour.

Other effects:

No symptoms of systemic toxicity and no mortality occured. No iridial irritation and no corneal opacity or epithelial damage was observed in any of the animals.

none

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the eye irritation data, zinc powder is not irritating/corrosive to the eyes. Hence, according to EU criteria, metallic zinc does not have to be classified/labelled for irritating properties.

Executive summary:

A well-performed eye irritation/corrosion studies, conducted according to Directive 92/69/EEC B.5 and OECD guideline 405, was carried out with metallic zinc powder (median particle diameter 150mm).

Three male New Zealand White rabbits were treated by instillation of approximately 100 mg of the substance into the conjuctival sac of one eye. The other eye remained untreated and served as control. The eyes were examined at 1, 24, 48 and 72 hours after instillation.

No symptoms of systemic toxicity were observed and no mortality occurred. Also, no iridial irritation and no corneal opacity or epithelial damage was observed in any of the animals. Redness of the conjuctivae (grade 1; mean scores over 24-72 hours 0.7, 0.3 and 0.3) had completely resolved within 48 hours in two animals and within 72 hours in the other animal. Chemosis (grade 1-2 in all animals) and discharge (grade 1 in two animals) were also observed, but only at 1 hour.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Based on the available information it appears that the slightly soluble zinc oxide and insoluble zinc sulphide are not skin irritants and therefore slightly soluble zinc hydroxide, zinc phosphate, zinc carbonate and zinc metal are also expected to be not irritating to skin. Zinc oxide, zinc phosphate, zinc metal and zinc sulphide are not eye irritants and therefore zinc carbonate and zinc hydroxide are also expected to be not irritating to eyes. None of the slightly soluble or insoluble zinc compounds appear to cause respiratory tract irritation.

The slightly soluble and insoluble zinc compounds (zinc oxide, zinc hydroxide, zinc phosphate, zinc carbonate, zinc metal and zinc sulphide) are not corrosive based on the available irritation data.

Justification for classification or non-classification

The slightly soluble and insoluble zinc compounds ( zinc oxide, zinc hydroxide, zinc phosphate, zinc carbonate, zinc metal and zinc sulphide)

are not irritating or corrosive based on the available irritation data and therefore no classification is required according to EC criteria either for irritation or corrosion.