Zinc oxide

Endpoint summary

Description of key information

The skin sensitising potential of zinc oxide (purity 99.69%) was investigated in female Dunkin Hartley guinea pigs in two well-performed maximisation tests, conducted according to Directive 96/54/EC B.6 and OECD guideline 406. Based on the results of a preliminary study, in the main studies experimental animals (10 in each test) were intradermally injected with a 20% concentration and epidermally exposed to a 50% concentration (i. e. the highest practically feasible concentration). Control animals (5 in each test) were similarly treated, but with vehicle (water) alone. Approximately 24 hours before the epidermal induction exposure all animals were treated with 10% SDS. Two weeks after the epidermal application all animals were challenged with a 50% test substance concentration and the vehicle. In the first study, in response to the 50% test substance concentration skin reactions of grade 1 were observed in 4/10 experimental animals 24 hours after the challenge (40% sensitisation rate), while no skin reactions were evident in the controls. In contrast, in the second study no skin reactions were evident in the experimental animals (0% sensitisation rate), while a skin reaction grade 1 was seen in one control animal. The skin reaction observed in one control animal is probably a sign of non specific irritation (Van Huygevoort, 1999b1, 1999b2).

In a third well-performed maximisation test, conducted according to the same guidelines and with the same experimental design, another analytical grade zinc oxide was tested (Zincweiß Pharma A; purity 99.9%). The only difference with the studies described above was the intradermal induction concentration, which was 2% as for Zincweiß Pharma A this was considered the highest concentration that could reproducibly be injected. In this test no skin reactions were evident in both experimental and control animals, hence a 0% sensitisation rate for Zincweiß Pharma A. White staining of the treated skin by the test substance was observed in some animals 24 and 48 hours after challenge (Van Huygevoort, 1999a).

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

The metals industry has historical data to indicate that metals can induce false positives/negatives in LLNA studies; this is confirmed from experiences in test labs.

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

see reference

Route:

intradermal

Vehicle:

water

Concentration / amount:

2%

Adequacy of induction:

not specified

Route:

epicutaneous, occlusive

Vehicle:

water

Concentration / amount:

50%

Day(s)/duration:

24h

Adequacy of induction:

highest technically applicable concentration used

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

water

Concentration / amount:

50%

Adequacy of challenge:

not specified

No. of animals per dose:

10 in each test in main study
5 controls in each test

Details on study design:

In a third well-performed maximisation test, conducted according to the same guidelines and with the same experimental design, another analytical grade zinc oxide was tested (Zincweiß Pharma A; purity 99.9%). The only difference with the studies described for purity ZnO 99.69% was the intradermal induction concentration, which was 2% as for Zincweiß Pharma A this was considered the highest concentration that could reproducibly be injected. In this test no skin reactions were evident in both experimental and control animals, hence a 0% sensitisation rate for Zincweiß Pharma A. White staining of the treated skin by the test substance was observed in some animals 24 and 48 hours after challenge

Challenge controls:

see details on study designs

Positive control substance(s):

yes

Positive control results:

The sensitivity and reliability of the experimental procedure is assessed regularly a year in the lab by use of items which are known to have moderate skin sensitisation properties

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

2 %

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

no indication of skin sensitisation

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

2%

No. with + reactions:

0

Total no. in group:

5

Remarks on result:

no indication of skin sensitisation

Group:

positive control

Remarks on result:

not measured/tested

Interpretation of results:

GHS criteria not met

Conclusions:

Not sensitising

Executive summary:

In a third well-performed maximisation test, conducted according to the same guidelines and with the same experimental design, another analytical grade zinc oxide was tested (Zincweiß Pharma A; purity 99.9%). The only difference with the previous studies described for zinc oxide of purity 99.69% was the intradermal induction concentration, which was 2% as for Zincweiß Pharma A this was considered the highest concentration that could reproducibly be injected. In this test no skin reactions were evident in both experimental and control animals, hence a 0% sensitisation rate for Zincweiß Pharma A. White staining of the treated skin by the test substance was observed in some animals 24 and 48 hours after challenge.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Human data:

In a human patch test performed with 100 selected leg-ulcer patients, 11/100 patients gave an allergic reaction with zinc ointment (60% ZnO and 40% sesame oil). However, 14/81 patients gave a positive response when treated with sesame oil alone. This study does not give any indication for a skin sensitizing potential of zinc oxide in humans (Malten and Kuiper, 1974). The effect of zinc oxide on contact allergy to colophony was investigated. With 14 patients with earlier history of moderate patch test reactions to colophony (a patch test) with 10% ZnO (2.3 mg Zinc/cm²) with and without colophony was performed. No positive response was observed in the 14 patients when only a 10% solution of zinc oxide was used. The addition of zinc oxide to colophony decreased the allergic reaction induced by colophony (Söderberg et al., 1990). 

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information:

While there is no particular study addressing respiratory sensitisation in experimental animals, there is no information suggesting zinc compounds to cause such effects in animals. Taking into account the complete absence of skin sensitization potential of zinc compounds, respiratory sensitisation is not expected to be of concern for zinc oxide.

Considering the absence of evidence of respiratory sensitization responses in humans, this endpoint is not expected to be of concern for zinc oxide

Justification for classification or non-classification

The data on slightly soluble zinc oxide indicated no skin sensitising potential (negative in animal and human studies) therefore classification for skin sensitisation is not required according to EC criteria.