Registration Dossier

Administrative data

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:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
Not reported
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well documented, meets generally accepted scientific principles, acceptable for assessment
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
no guideline followed
Deviations:
not applicable
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 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:
other: Score not reported
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
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: well performed, reliable, GLP compliant study, used in EU risk assessment for zinc phosphate
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Principles of method if other than guideline:
none
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
see reference
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
100 mg zinc phosphate
Duration of treatment / exposure:
up to 72 hours
Observation period (in vivo):
1, 24, 48 and 72 hours after exposure
Number of animals or in vitro replicates:
3 males
Details on study design:
see reference
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24 h
Score:
0
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 48 h
Score:
0.7
Remarks on result:
other: seen as redness
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 72 h
Score:
0.3
Remarks on result:
other: seen as redness
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24 h
Score:
0
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 48 h
Score:
0.3
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 72 h
Score:
0.3
Irritant / corrosive response data:
Very slight irritation of the conjuctivae (grade 1) was seen as redness (mean scores over 24-72 hours 0, 0.7 and 0.3) and chemosis (mean scores 0, 0.3 and 0.3), which persisted up to 48 hours at the latest. No conjunctival discharge and no iris and corneal lesions were observed.
Other effects:
none
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Zinc phosphate is not irritating in an vivo rabbit study.
Executive summary:

In a well-performed eye irritation study, conducted according to Directive 92/69/EEC B.5 and OECD guideline 405, 100 mg of zinc phosphate was administered into the conjuctival sac of the left eye of three male New Zealand White rabbits. The right eye remained untreated and served as control. The eyes (unrinsed) were examined at 1, 24, 48 and 72 hours after administration.Very slight irritation of the conjuctivae (grade 1) was seen as redness (mean scores over 24-72 hours 0, 0.7 and 0.3) and chemosis (mean scores 0, 0.3 and 0.3), which persisted up to 48 hours at the latest. No conjunctival discharge and no iris and corneal lesions were observed.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

Based on the available information it appears that he 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.