In 1990 FDA proposed the conditions under which over-the-counter skin protectants for diaper rash would be generally recognised as safe and effective. The proposal classifies allantoin, calamine, cod liver oil (in combination), dimethicone, kaolin, lanolin (in combination), mineral oil, petrolatum, talc, topical starch, white petrolatum and zinc oxide as Category I. It limits zinc oxide above 25 percent to ointments. It contains no specification for lead, cadmium, arsenic, mercury or any other metal impurity.
Key numbers
A comment asked for zinc oxide up to and including 40 percent. The agency noted that the Topical Analgesic Panel had recommended 1 to 25 percent. The Miscellaneous External Panel had recommended 3 to 40 percent at its 1976 meeting but did not carry that into its report. The submitted data concerned an ointment of 40 percent zinc oxide and 13.56 percent cod liver oil in a petrolatum-lanolin base. In one unpublished study, 97 infants aged 12 months or younger used it as needed or six times a day with no increase in irritation. In a split-side study of 45 infants, the treated side was better than the untreated side on every measure. The agency concluded that “the studies discussed above support the safe use of 40 percent zinc oxide in an ointment dosage form”. Finding no data for other dosage forms, it proposed “(s) Zinc oxide, above 25 to 40 percent in an ointment dosage form”, with 1 to 25 percent in any appropriate dosage form (FR p.25226-25227 and the proposed §347.10 at p.25232).
The Miscellaneous External Panel had concluded “that zinc oxide crystals are not absorbed through the skin and pose no threat of systemic absorption with dermal application” and recommended no limit on body surface. That conclusion concerns crystal penetration of skin. It is not a measurement of zinc ion absorption through damaged infant skin.
Bismuth subnitrate, reviewed in a combination product at 5.8 percent, was placed in Category II. The agency “tentatively concludes that bismuth subnitrate is not safe for OTC use for the treatment of diaper rash”. It drew on panel findings of absorption of bismuth salts applied to open surfaces, fatalities in infants after oral ingestion, and possible nitrite toxicity. Aluminum hydroxide gel, cocoa butter, glycerin, shark liver oil, zinc acetate and zinc carbonate were placed in Category III.
Methods (brief)
This is a Federal Register proposed rule. It reviews advisory panel recommendations, public comments and submitted studies. The file is Part II of the 20 June 1990 issue, printed pages 25204 to 25232, with a scanned text layer.
Evidence fitness
The proposal supports FDA’s 1990 position on which ingredients and zinc oxide concentrations are appropriate for diaper rash products, and the evidence it relied on. It is a proposal. The 2003 skin-protectant final rule states that diaper rash products would be addressed separately. No metal-impurity requirement for zinc oxide diaper products comes from this document.
Limitations
The docket number in the machine text layer reads 73N-021D. The page image reads 78N-021D, which is used here. The clinical studies cited are unpublished submissions that were not obtained. They addressed irritation and efficacy, not metal content or systemic exposure.
Related evidence
- Diaper Cream, ZnO-Based
- Diaper Cream, Non-ZnO
- 21 CFR Part 347, Skin protectant drug products for over-the-counter human use (4-1-25 edition)
- Skin Protectant Drug Products for Over-the-Counter Human Use; Final Monograph
Update history
No substantive edit history is available in this build. The full commit record is available in git.