The Problem of Preservation in the 1990s: II. Formaldehyde and Formaldehyde-Releasing Biocides: Incidences of Cross-Reactivity and the Significance of the Positive Response to Formaldehyde

Formaldehyde, a ubiquitous allergen with remarkable sensitization potential, finds decreasingly frequent use by pharmaceutical and cosmetic manufacturers as “safer” formaldehyde and nonformaldehyde-releasing preservatives are developed and marketed. The incidence of formaldehyde sensitivity of 9.6% at the Mayo Clinic (Rochester, MN) has remained stable for over 10 years and is represented at the upper end of the frequency spectrum reported by other investigators. Significant incidence rates are similarly found for bromo-2-nitropropane-1,3-diol (BNPD) (5.1%), quaternium-15 (4.9%), and imidazolidinyl urea (2.2%). Formaldehyde is most frequently solely reactive (57%) or concurrent with quaternium-15 sensitivity (22%); BNPD sensitivity frequently exists alone (74%); patients with quaternium-15 allergy are often formaldehyde allergic as well (43%); and imidazolidinyl urea reactors respond to the other three preservatives in roughly even distribution. These reactivity data reflect parameters of frequency of preservative use in therapeutic and cosmetic products, potential for free formaldehyde availability, and special characteristics of our patient population. The significance of the positive formaldehyde reaction when tested at 1% to 2% aqueous concentration has been questioned by many investigators; in critically analyzing information available on 300 consecutive formaldehyde-sensitive patients exhibiting a 2+ or stronger reaction or a 1+ reaction with coexistent formaldehyde-releasing biocide allergy, it is found that formaldehyde assumes a central or prominent ancillary role in dermatitis origin and propagation in the majority of cases. The formaldehyde response is a frequent and significant event with definable and explainable cross-reactivity patterns to other formaldehyde-releasing biocides.