Zinc chloride

Endpoint summary

Description of key information

Zinc chloride is corrosive based on animal skin irritation studies.

0.5 ml ZnCl₂(1% solution in deionized water) was applied on the dorsal skin (5 cm²) for 5 consecutive days in open patch tests with mice, rabbits and guinea pigs and in an occlusive test with rabbits. In the open patch test 4/4 rabbits and 6/6 mice had severe irritancy and 3/8 guinea pigs had moderate irritancy (scoring from slight (+) to severe (+++)). In the occlusive patch test 4/4 rabbits had severe irritancy. The severe skin effects in the open patch tests were characterized by parakeratosis, hyperkeratosis and inflammatory changes in the epidermis and superficial dermis and acanthosis of the follicular epithelia. In the occlusive patch test similar, but more severe, effects were observed, and in addition erythema and ulceration (Lansdown, 1991).

Due the corrosive nature of zinc chloride to skin, eye irritation studies do not need to be conducted and hence no animal eye irritation data is available on zinc chloride.

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 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

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:

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

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 5 d

Reversibility:

not specified

Remarks on result:

probability of severe 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:

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.

None

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.

 

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the substance is classified as skin corrosion, leading to classification as serious eye damage (Category 1)

Endpoint conclusion

Endpoint conclusion:

no study available

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Justification for classification or non-classification

Zinc chloride is classified as Skin Corr 1B; H314 according to EC criteria due to severe skin irritancy seen in animals at concentrations of 1% solution and irreversible damage to eyes caused by zinc chloride after accidental exposure in humans. Zinc chloride has also shown signs of respiratory tract irritation in single exposure studies (see acute inhalation toxicity).