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Toxicological information

Skin irritation / corrosion

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Administrative data

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
Justification for data waiving:
other:
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1991

Materials and methods

Test guideline
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 the test material were observed after 5 d application of test material to skin using both open and occlusive patch method.
GLP compliance:
not specified

Test material

Constituent 1
Reference substance name:
Zinc chloride
EC Number:
231-592-0
EC Name:
Zinc chloride
Cas Number:
7646-85-7
IUPAC Name:
zinc dichloride
Details on test material:
- Name of test material (as cited in study report): Zinc chloride
- Analytical purity: 98 % (minimum)
- Storage condition of test material: Test solution in deionized water was prepared 24 h before use and stored at 4 °C.

Test animals

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


Test system

Type of coverage:
other: Both open and occlusive in two different tests
Preparation of test site:
other: Clipped
Vehicle:
water
Controls:
yes, concurrent vehicle
Amount / concentration applied:
TEST SOLUTION
- Amount(s) applied (volume): 0.5 mL
- Concentration (if solution): 1 % w/v zinc chloride solution in deionized water
- pH: 5.6
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 in both open and occlusive patch test
Details on study design:
Open patch test: Eight test sites (5 x 5 cm) were designated, four on each side of the mid-dorsal line. Test solution or vehicle was applied daily for 5 successive days. The animals were restrained for 30 min to allow the 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 solution 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 period.

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

Results and discussion

In vivo

Results
Irritation parameter:
other: not reported
Irritant / corrosive response data:
Severe irritation was observed in all the animals of test group in both open and occlusive patch test after 5 d exposure. Macroscopic observations of animals exposed for 3 d resembled those observed after 5 d in occlusive patch test. No reactions were observed in the control group.

Other effects:
Histological changes: Profound epidermal hyperplasia with parakeratosis and ulceration was observed in the open patch test. Similar and more severe changes were observed in the occlusive patch test.

Morin fluorescence for zinc on skin: Very prominent blue-green fluorescence was observed indicating high binding of zinc to epidermal keratin.



Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:
highly irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the test conditions, 1 % w/v zinc chloride was found to be severely irritating to rabbit skin.
Executive summary:

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

In the open patch test, 0.5 mL of 1 % w/v zinc chloride solution 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 the occlusive patch test, groups of four animals were treated similarly to open patch test, but the test solution or vehicle was applied to the skin under occlusive dressing for 3 d. After 3 d, 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 gauzes and then re-examined and killed after a further 2 d period.

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.

Severe irritation was observed in all the animals of the test group in both open and occlusive patch test after 5 d exposure. Macroscopic observations of animals exposed for 3 d resembled those seen after 5 d in occlusive patch test. Profound epidermal hyperplasia with parakeratosis and ulceration was observed in open patch test upon histological examination. Similar and more severe changes were observed in occlusive patch testbe more severe. No reactions observed in control group. Very prominent morin fluorescence was observed in skin sections indicating high binding of zinc to epidermal keratin.

Under the test conditions, 1 % w/v zinc chloride was found to be severely irritating to rabbit skin.

 

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