DMDM HYDANTOIN

Facial makeup cosmetics are commonly used products that are applied to the skin, and their ingredients come into contact with it for many years. Consequently, they should only contain substances that are considered safe or used within an allowable range of established concentrations. According to current European laws, all cosmetics approved for use should be entirely safe for their users, and the responsibility for this lies with manufacturers, distributors, and importers. However, the use of cosmetics can be associated with undesirable effects due to the presence of certain chemical substances. An analysis of 50 random facial makeup cosmetics commercially available on the European Union market and manufactured in six European countries was carried out, concerning the presence of substances with potential carcinogenic properties, as described in recent years in the literature. Nine types of facial makeup cosmetics were selected, and their compositions, as declared on the labels, were analyzed. The carcinogens were identified with information present in the European CosIng database and according to the Insecticide Resistance Action Committee's (IRAC) classification. As a result, the following potential carcinogens were identified: parabens (methylparaben, propylparaben, butylparaben, and ethylparaben), ethoxylated compounds (laureth-4, lautreth-7, or ethylene glycol polymers known as PEG), formaldehyde donors (imidazolidinyl urea, quaternium 15, and DMDM hydantoin), and ethanolamine and their derivatives (triethanolamine and diazolidinyl urea), as well as carbon and silica. In conclusion, all of the analyzed face makeup cosmetics contain potential carcinogenic substances. The literature review confirmed the suppositions regarding the potential carcinogenic effects of selected cosmetic ingredients. Therefore, it seems necessary to carry out studies on the long-term exposure of compounds present in cosmetics and perhaps introduce stricter standards and laws regulating the potential presence of carcinogens and their activity in cosmetics.

Consumer products and topical medications today contain many allergens that can cause a reaction on the skin known as allergic contact dermatitis. This review looks at various allergens in these products and reports current allergic contact dermatitis incidence and trends in North America, Europe, and Asia. First, medication contact allergy to corticosteroids will be discussed along with its five structural classes (A, B, C, D1, D2) and their steroid test compounds (tixocortol-21-pivalate, triamcinolone acetonide, budesonide, clobetasol-17-propionate, hydrocortisone-17-butyrate). Cross-reactivities between the steroid classes will also be examined. Next, estrogen and testosterone transdermal therapeutic systems, local anesthetic (benzocaine, lidocaine, pramoxine, dyclonine) antihistamines (piperazine, ethanolamine, propylamine, phenothiazine, piperidine, and pyrrolidine), topical antibiotics (neomycin, spectinomycin, bacitracin, mupirocin), and sunscreen are evaluated for their potential to cause contact dermatitis and cross-reactivities. Finally, we examine the ingredients in the excipients of these products, such as the formaldehyde releasers (quaternium-15, 2-bromo-2-nitropropane-1,3 diol, diazolidinyl urea, imidazolidinyl urea, DMDM hydantoin), the non-formaldehyde releasers (isothiazolinones, parabens, methyldibromo glutaronitrile, iodopropynyl butylcarbamate, and thimerosal), fragrance mixes, and Myroxylon pereirae (Balsam of Peru) for contact allergy incidence and prevalence. Furthermore, strategies, recommendations, and two online tools (SkinSAFE and the Contact Allergen Management Program) on how to avoid these allergens in commercial skin care products will be discussed at the end.

Preservatives represent one of the main causes of skin irritation and contact allergies. To comprehensively evaluate the skin irritation potential of phenoxyethanol, methylparaben, propylparaben, imidazolidinyl urea, and DMDM hydantoin under regulatory acceptable concentrations. A patch test and repeated open application test (ROAT) were applied to evaluate skin irritation in vivo. In vitro alternative methods consisting of the keratinocyte cytotoxicity assay, red blood cell (RBC) test, and hen's egg test-chorioallantoic membrane (HET-CAM) were performed to elucidate the mechanism of preservative-induced irritation responses. The patch test showed that all test substances showed a weak erythema response. Propylparaben had the highest occlusive irritancy potential in the patch test, owing to damage to the cell membrane. The two formaldehyde releasers showed noticeable skin irritation potential in the ROAT through their cytotoxicity to keratinocytes, while a visible response was observed after applying phenoxyethanol and the two parabens. No filtration was noticed in the in vivo tests, which might be attributed to the failure of subcutaneous vessel alteration by the preservatives. Commonly used cosmetic preservatives have minor skin irritation potential with mild erythema reaction under practical use, especially formaldehyde releasers and propylparaben.

Our recent tissue cross-linking studies using formaldehyde releasers (FARs) suggest that corneal and scleral tissue strengthening may be possible without using ultraviolet irradiation or epithelial removal, two requirements for the photochemical method in widespread clinical use. Thus, the present study was carried out in order to better understand these potential therapeutic solutions by studying the effects of concentration, pH, buffer, time, and tissue reactivity on formaldehyde release of these FARs. Three FARs, sodium hydroxymethyl glycinate (SMG), DMDM, and diazolidinyl urea (DAU) were studied using a chromotropic acid colorimetric FA assay. The effects of concentration, pH, and buffer were studied as well as the addition of corneal and scleral tissues. The main determinant of release was found to be dilution factor (concentration) in which maximal release was noted at the lowest concentrations studied (submillimolar). In time dependent studies, after 60 min, FA levels decreased by 38% for SMG, 30% for DMDM, and 19% for DAU with corneal tissue added; and by 40% for SMG, 40% for DMDM, and 15% for DAU with scleral tissue added. We conclude that concentration (dilution factor) was found to be the most important parameter governing the percent of FA released.

Historically, formaldehyde was used as a preservative in personal care products to extend product shelf-life; however, given its skin sensitization potential it has been phased out of use and replaced with formaldehyde-releasing preservatives, such as Dimethyloldimethyl hydantoin (DMDMH). A relationship has been established between positive patch test results following exposure to DMDMH and previous sensitization to formaldehyde. Upon direct contact with the skin, formaldehyde can react with skin proteins and cause an acute inflammatory reaction, which may progress to skin sensitization following repeated exposure. This quantitative risk assessment (QRA) aimed to assess the risk of skin sensitization induction following use of shampoo products containing the maximum allowable concentrations of DMDMH in formulation (1% w/v), translating to a free formaldehyde concentration of 0.02%. To determine a margin of safety (MOS) for exposure to DMDMH from use of shampoo products, consumer exposure levels (CEL) were estimated based on typical use scenarios and then benchmarked against an acceptable exposure level (AEL). The AEL was derived using a weight of evidence approach where a range of no expected sensitization induction levels (NESILs) was utilized. The MOS values for a shampoo product containing 1% DMDMH (.02% formaldehyde) was above 1 for the typical use scenario indicating a low likelihood of skin sensitization induction among healthy individuals. Thus, it can be concluded that shampoo products containing DMDMH at or below current allowable concentrations are not expected to increase the risk of skin sensitization induction.

Formaldehyde and its releasers are common preservatives and potent sensitizers. This meta-analysis aimed to estimate the prevalence of formaldehyde contact allergy and allergy to its five most common releasers among dermatitis patients. Two authors independently searched PubMed, Embase, and Web of Science from inception to 30th September 2025. A proportion meta-analysis was conducted using a random-effects model. A total of 158 studies involving 1 347 638 dermatitis patients were included. The pooled prevalence of formaldehyde contact allergy was 2.88% (95% CI 2.55-3.24) with clinical relevance at 41.57%. The pooled prevalence for releasers was 2.76% for 2-bromo-2-nitropropane-1,3-diol, 1.89% for quaternium-15, 1.42% for diazolidinyl urea, 1.37% for DMDM hydantoin, and 1.20% for imidazolidinyl urea. Quaternium-15 showed the highest clinical relevance at 55.67%. Significant sensitization rates were observed in different geographic regions, with the highest prevalence found in North America (6.8%). The prevalence rate was 2.96% among children and 2.61% among adults, with no significant difference. The prevalence rate was 2.65% among patients with atopic dermatitis (AD) and 2.85% among patients without AD, with no significant difference. The profound geographic disparities suggest that regulatory interventions, such as the EU's prohibition of formaldehyde and quaternium-15 in cosmetics, are highly effective public health measures.

Formaldehyde (FA) and formaldehyde-releasers (FRs) are well-known causes of allergic contact dermatitis (ACD). Following the 2019 EU ban on FA and Quaternium-15 in cosmetics, stable or slightly decreasing sensitisation rates have been reported. In Turkey, both were banned in 2021. To assess FA/FR sensitisation and ACD rates before and after the ban, and evaluate the role of FA as a marker for FR allergy. A single-centre retrospective cohort of 2592 patients patch tested with FA 1% or 2% aq. and at least one FR between 1996 and 2024. FA/FRs sensitisation prevalence was 1.9% (48/2592), mostly in patients > 40 years old. The most frequent sensitisers were hexahydro-1,3,5-tris-(2-hydroxyethyl)triazine (0.7%) and Quaternium-15 (0.6%). ACD occurred in 37.5% (18/48), mainly as hand eczema from non-occupational rinse-off cosmetics, while 16.7% were occupational (hairdressers/barbers/metalworkers). FA 1%-2% aq. failed to detect FR sensitisation in 31.9% (n = 15/47) of patients, including nine missed with FA 1% aq. and six with FA 2% aq. No cases occurred after the 2021 ban. 2-bromo-2-nitropropane-1,3-diol and DMDM-hydantoin showed no co-reactivity with FA, but were important inducers of FR-related ACD. The 2021 ban in Turkey appears to have reduced ACD due to FA and FRs. Continued FR testing remains essential, as FA 2% aq. is complementary but not a fully reliable marker.

Personal care products (PCPs), such as shampoos, conditioners and body washes, can contain ingredients that may cause allergic contact dermatitis (ACD). Hotels commonly offer complimentary toiletries; however, there is limited data regarding the allergen content of these products. This study aims to identify allergens within PCPs that may cause ACD in hotels across Canada, the United States (US) and Europe. A cross-sectional analysis was conducted to identify American Contact Dermatitis Society (ACDS) core allergens listed in the ingredients of PCPs sampled from 90 hotels across Canada, the US and Europe. Hotels were stratified equally into luxury, mid-scale and budget-friendly categories. Methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) was found in 4.4% of hotel products in Europe, which is significantly lower than its prevalence in Canada (47.8%) and the US (40.0%) (p < 0.0001). In Canada and the US, DMDM hydantoin, a formaldehyde-releasing preservative, was detected in approximately one in seven products but was absent in the toiletries from European hotels (Canada vs. Europe: p = 0.01; US vs. Europe: p = 0.02). A higher percentage of multiple ACDS core allergens were identified in complimentary hotel toiletries in Canada and the US than in Europe. This study underscores the importance of patient and clinician awareness of the potential risk of ACD resulting from exposure to hotel products.

Consumer exposure to cosmetic ingredients is estimated in a tiered manner. Simple Tier1 deterministic aggregate exposure modelling generates a worst case estimate of exposure. Tier1 assumes that a consumer uses all cosmetic products concomitantly daily, at maximum frequency, and products always contain the ingredient at the maximum allowed % w/w concentration. Refining exposure assessment from worst case to more realistic estimates uses evidence from surveys of actual use levels of ingredients and Tier2 probabilistic models, where distributions of consumer use data can be applied. In Tier2+ modelling, occurrence data provides evidence of products on the market actually containing the ingredient. Three case studies are presented using this tiered approach to illustrate progressive refinement. The scale of refinements from Tier1 to Tier2+ modelling for the ingredients, propyl paraben, benzoic acid and DMDM hydantoin were: 0.492 to 0.026; 1.93 to 0.042 and 1.61 to 0.027 mg/kg/day exposure dose. For propyl paraben, moving from Tier1 to Tier2+ represents a refinement from 49-fold to 3-fold overestimate of exposure when compared to a maximum estimate of 0.01 mg/kg/day exposure seen in human studies. Such refinements from worst case to realistic levels of exposure estimation can be critical in the demonstration of consumer safety.

This review aims to provide a clinically useful update regarding the role of formaldehyde (FA) and its five main releasers (FRs) quaternium-15, diazolidinyl urea, DMDM hydantoin, imidazolidinyl urea, and 2-bromo-2-nitropropane-1,3-diol (bronopol) in contact allergy and allergic contact dermatitis. These ubiquitous preservatives are still often present, and sometimes undeclared, in cosmetics, pharmaceuticals, medical devices, household detergents, and chemical (industrial) products. In Europe, the use of free FA and quaternium-15 in cosmetics is forbidden and contact allergy rates have been found to be stable to decreasing. However, FA/FRs still readily provoke localized (eg, facial/hand), airborne, and generalized dermatitis, and may also complicate atopic and stasis dermatitis, or result in nummular dermatitis. Seborrheic-, rosacea- and impetigo-like dermatitis have recently been reported. For a correct diagnosis, FA 2% aq. (0.60 mg/cm 2 ) should be used, and particularly the FRs bronopol 0.5% pet. and diazolidinyl urea 2% pet. should be patch tested separately in a baseline series. If sensitization to FA occurs, both FA and FRs should preferably be avoided, except perhaps for bronopol in case it tests negatively. If a patient reacts to one or more FRs (such as bronopol or diazolidinyl/imidazolidinyl urea), but not to FA, then the specific FR(s) should be avoided.

The objective was to evaluate the influence of the formulation in the in vitro transdermal absorption through pig ear skin of three preservatives, bronopol, bronidox and formaldehyde as well as the absorption of formaldehyde from bronopol and dimethyloldimethyl hydantoin (DMDM hydantoin). An aqueous solution, an O/W emulsion and a hydrogel were assayed. Bronidox and bronopol absorption depends on the formulation. The O/W emulsion was the system that least promoted absorption of bronidox while the absorption of bronopol was lower from the hydrogel. The aqueous solution provided maximal transdermal absorption of both preservatives. Moreover, the transdermal absorption of formaldehyde released from bronopol also depends on the formulation, being the aqueous solution the system that allowed greater absorption. Transdermal absorption of formaldehyde, applied directly or released from DMDM hydantoin, is not conditioned by the excipients. The degree of transdermal absorption of all the preservatives tested is low and therefore the concentrations allowed by regulations are safely used. Nonetheless, since formaldehyde was detected in the receptor compartment after a long time exposure to bronopol and DMDM hydantoin it would be important to consider the possibility of limiting the use of these two preservatives to rinse off products as is the case of bronidox.

Studies suggest that patch testing with formaldehyde releasers (FRs) gives significant additional information to formaldehyde 1% aq. and should be considered for addition to the European baseline series (EBS). It is not known if this is also true for formaldehyde 2% aq. To determine the frequency of sensitization to formaldehyde 2% aq. and co-reactivity with FRs. To establish whether there is justification for including FRs in the EBS. A 4-year, multi-center retrospective analysis of patients with positive patch test reactions to formaldehyde 2% aq. and five FRs. A maximum of 15 067 patients were tested to formaldehyde 2% aq. and at least one FR. The percentage of isolated reactions to FR, without co-reactivity to, formaldehyde 2% aq. for each FR were: 46.8% for quarternium-15 1% pet.; 67.4% imidazolidinyl urea 2% pet.; 64% diazolidinyl urea 2% pet.; 83.3% 1,3-dimethylol-5, 5-dimethyl hydantoin (DMDM) hydantoin 2% pet. and 96.3% 2-bromo-2-nitropropane-1,3-diol 0.5% pet. This demonstrates that co-reactivity varies between FRs and formaldehyde, from being virtually non-existent in 2-bromo-2-nitropropane-1,3-diol 0.5% pet. (Cohen's kappa: 0, 95% confidence interval [CI] -0.02 to 0.02)], to only weak concordance for quaternium-15 [Cohen's kappa: 0.22, 95%CI 0.16 to 0.28)], where Cohen's kappa value of 1 would indicate full concordance. Formaldehyde 2% aq. is an inadequate screen for contact allergy to the formaldehyde releasers, which should be considered for inclusion in any series dependant on the frequency of reactions to and relevance of each individual allergen.

Patch testing for multiple cross-reactive allergens for allergic contact dermatitis (ACD) may not be necessary because of copositivity. We evaluated the formaldehyde group allergens to determine the optimal, most cost-effective allergens to test. A retrospective analysis of Mayo Clinic (1997-2022) examined the well-established copositive formaldehyde group: formaldehyde, quaternium 15, hexahydro-1,3,5-tris(2-hydroxyethyl)triazine, diazolidinyl urea, imidazolidinyl urea, toluenesulphonamide formaldehyde resin, DMDM hydantoin, and ethyleneurea melamine formaldehyde mix. Patch Optimization Platform identified which single formaldehyde-related allergen optimally captures patients with clinically relevant ACD. Next, Patch Optimization Platform determined the optimal additional 1, 2, 3, etc. allergens. Cost per patch test was $5.19 (Medicare 2022). A total of 9832 patients were tested for all listed allergens, with 830 having positive patch test results. Patch Optimization Platform determined that quaternium 15 alone captures 53% of patients with ACD to the formaldehyde group; adding the optimal second allergen (formaldehyde 1%) captures 78%; the optimal 5 top allergens capture >94% of patients. The incremental cost per additional diagnosis increased up to 44-fold as the number of allergens tested increased. Data are from a single institution, and the cost per test was fixed according to Medicare Part B in 2022. For diagnosing ACD, we recommend considering an optimized allergen selection algorithm.