Dimethylol Dimethyl Hydantoin Research Articles

Quantitative Risk Assessment of Dermal Sensitization Potential Following Use of Shampoo Products Containing the Formaldehyde Releasing Preservative DMDM Hydantoin.

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.

Trends in formaldehyde and formaldehyde-releaser contact allergies as compared with market exposure in Thailand.

Formaldehyde and formaldehyde releasers (FRs) are common preservatives in cosmetics and household products. Their contact allergy trends are decreasing in Europe and America, but trend data for Asia are limited. The first objective was to determine the prevalences of and trends in contact allergies to formaldehyde and FRs. The second objective was to establish how often formaldehyde and FRs were mentioned on the labels of products sold in the Thai market. Twenty years of data on patch test results for formaldehyde and FRs were reviewed. Their frequency of mention on the labels of 5855 products was analysed. The trends in contact allergy to formaldehyde and FRs were decreasing. The overall prevalence of formaldehyde contact allergy was 2.5%. The most common FR to cause contact allergy was quaternium-15. Formaldehyde and FRs were identified as ingredients in 10.2% of the products surveyed. Dimethylol dimethyl hydantoin was the most common FR (5.2%). The highest use of formaldehyde and FRs (15.5%) was in hair care products. Although contact allergy trends in Thailand were decreasing, the proportion of products with FRs remained high. Comprehensive and universal legislation is needed to control the presence of formaldehyde and FRs.

In vitro skin penetration of bronidox, bronopol and formaldehyde from cosmetics

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.

Production Process of Hand Sanitizer from Vietnamese Coconut Oil

Currently, hand sanitizers are seen as an indispensable household product, which not only cleanses and protects the skin from bacteria but also confers skin-softening function. With the objective of research and development the process for producing hand-sanitizer from coconut oil, this study aimed to optimize the production conditions to provide a natural-derived and low-cost hygienic product. The two factors that characterized the standard for product evaluation are the level of foaming and durability of the emulsion, which reflects the cleansing ability of the product from the saponification reaction. Upon analysis, the coconut oil/NaOH ratio of 5.5:1, the alkaline solution concentration of 10 %, 3 h reaction, 80 ºC, stirring speed of 300 rpm, pH 8 and 1:2 dilution rate were found to be the optimal reaction conditions for the highest cleaning ability. In addition, other substances are used for finalizing the product such as moisturizing glycerol, dipropylene glycol, softener skin coca amidopropyl betaine, preservatives dimethylol dimethyl hydantoin, thickener hydroxyethyl cellulose, colour and essential oils.

Investigation on formaldehyde release from preservatives in cosmetics.

To understand formaldehyde residue in cosmetics, an investigation on formaldehyde release from eight preservatives (methenamine - MA, paraformaldehyde - PF, poly(p-toluenesulfonamide-co-formaldehyde) -PTSAF, quaternium-15 - QU, imidazolidinyl urea - IU, diazolidinyl urea - DU, dimethyloldimethyl hydantoin - DMDM and bronopol - BP) under various conditions was performed. The concentration of released formaldehyde was determined by high-performance liquid chromatography with photodiode array detection after derivatization with 2,4-dinitrophenylhydrazine. The amounts of formaldehyde release were in the order of PF>DU>DMDM≈QU≈IU>MA>BP>PTSAF. The releasing amounts of formaldehyde were the highest in the presence of aqueous matrices for the releasers except QU and IU, and the releasing effect was also relative to pH. More formaldehyde was released with longer storage time and higher temperature. Furthermore, all preservatives in cosmetic matrices released fewer amounts of formaldehyde than in pure aqueous or organic matrices, and the formaldehyde-releasing amounts were also cosmetic specific. Formaldehyde release was dependent on the matrix, pH, time and mainly temperature, and the releasing effect was also cosmetic specific.

Key Role for Efflux in the Preservative Susceptibility and Adaptive Resistance of Burkholderia cepacia Complex Bacteria

Bacteria from the Burkholderia cepacia complex (Bcc) are encountered as industrial contaminants, and little is known about the species involved or their mechanisms of preservative resistance. Multilocus sequence typing (MLST) revealed that multiple Bcc species may cause contamination, with B. lata (n = 17) and B. cenocepacia (n = 11) dominant within the collection examined. At the strain level, 11 of the 31 industrial sequence types identified had also been recovered from either natural environments or clinical infections. Minimal inhibitory (MIC) and minimum bactericidal (MBC) preservative concentrations varied across 83 selected Bcc strains, with industrial strains demonstrating increased tolerance for dimethylol dimethyl hydantoin (DMDMH). Benzisothiazolinone (BIT), DMDMH, methylisothiazolinone (MIT), a blend of 3:1 methylisothiazolinone-chloromethylisothiazolinone (M-CMIT), methyl paraben (MP), and phenoxyethanol (PH), were all effective anti-Bcc preservatives; benzethonium chloride (BC) and sodium benzoate (SB) were least effective. Since B. lata was the dominant industrial Bcc species, the type strain, 383(T) (LMG 22485(T)), was used to study preservative tolerance. Strain 383 developed stable preservative tolerance for M-CMIT, MIT, BIT, and BC, which resulted in preservative cross-resistance and altered antibiotic susceptibility, motility, and biofilm formation. Transcriptomic analysis of the B. lata 383 M-CMIT-adapted strain demonstrated that efflux played a key role in its M-CMIT tolerance and elevated fluoroquinolone resistance. The role of efflux was corroborated using the inhibitor l-Phe-Arg-β-napthylamide, which reduced the MICs of M-CMIT and ciprofloxacin. In summary, intrinsic preservative tolerance and stable adaptive changes, such as enhanced efflux, play a role in the ability of Bcc bacteria to cause industrial contamination.

North American Contact Dermatitis Group Patch Test Results

Patch testing is an important diagnostic tool for determination of substances responsible for allergic contact dermatitis. This study reports the North American Contact Dermatitis Group (NACDG) patch testing results from January 1, 2009, to December 31, 2010. At 12 centers in North America, patients were tested in a standardized manner with a screening series of 70 allergens. Data were manually verified and entered into a central database. Descriptive frequencies were calculated, and trends were analyzed using χ2 statistics. A total of 4308 patients were tested. Of these, 2614 (60.7%) had at least 1 positive reaction, and 2284 (46.3%) were ultimately determined to have a primary diagnosis of allergic contact dermatitis. Four hundred twenty-seven (9.9%) patients had occupationally related skin disease. There were 6855 positive allergic reactions. As compared with the previous reporting period (2007-2008), the positive reaction rates statistically decreased for 20 allergens (nickel, neomycin, Myroxylon pereirae, cobalt, formaldehyde, quaternium 15, methydibromoglutaronitrile/phenoxyethanol, methylchlorisothiazolinone/methylisothiazolinone, potassium dichromate, diazolidinyl urea, propolis, dimethylol dimethylhydantoin, 2-bromo-2-nitro-1,3-propanediol, methyl methacrylate, ethyl acrylate, glyceryl thioglycolate, dibucaine, amidoamine, clobetasol, and dimethyloldihydroxyethyleneurea; P < 0.05) and statistically increased for 4 allergens (fragrance mix II, iodopropynyl butylcarbamate, propylene glycol, and benzocaine; P < 0.05). Approximately one quarter of tested patients had at least 1 relevant allergic reaction to a non-NACDG allergen. Hypothetically, approximately one quarter of reactions detected by NACDG allergens would have been missed by TRUE TEST (SmartPractice Denmark, Hillerød, Denmark). These results affirm the value of patch testing with many allergens.

North American Contact Dermatitis Group Patch Test Results for 2007–2008

The North American Contact Dermatitis Group (NACDG) tests patients with suspected allergic contact dermatitis to a broad series of screening allergens and publishes periodic reports. The aims of this study were to report the NACDG patch-testing results from January 1, 2007, to December 31, 2008, and to compare results to pooled test data from the previous 2 and 10 years to analyze trends in allergen sensitivity. Standardized patch testing with 65 allergens was used at 13 centers in North America. χ analysis was used for comparisons. A total of 5085 patients were tested; 11.8% (598) had an occupationally related skin condition, and 65.3% (3319) had at least 1 allergic patch test reaction, which is identical to the NACDG data from 2005 to 2006. The top 15 most frequently positive allergens were nickel sulfate (19.5%), Myroxylon pereirae (11.0%), neomycin (10.1%), fragrance mix I (9.4%), quaternium-15 (8.6%), cobalt chloride (8.4%), bacitracin (7.9%), formaldehyde (7.7%), methyldibromoglutaronitrile/phenoxyethanol (5.5%), p-phenylenediamine (5.3%), propolis (4.9%), carba mix (4.5%), potassium dichromate (4.1%), fragrance mix II (3.6%), and methylchloroisothiazolinone/methylisothiazolinone (3.6%). There were significant increases in positivity rates to nickel, methylchloroisothiazolinone/methylisothiazolinone, and benzophenone-3. During the same period of study, there were significant decreases in positivity rates to neomycin, fragrance mix I, formaldehyde, thiuram mix, cinnamic aldehyde, propylene glycol, epoxy resin, diazolidinyl urea, amidoamine, ethylenediamine, benzocaine, p-tert-butylphenol formaldehyde resin, dimethylol dimethyl hydantoin, cocamidopropyl betaine, glutaraldehyde, mercaptobenzothiazole, tosylamide formaldehyde resin, budesonide, disperse blue 106, mercapto mix, and chloroxylenol. Twenty-four percent (1221) had a relevant positive reaction to a non-NACDG supplementary allergen; and 180 of these reactions were occupationally relevant. Periodic analysis, surveillance, and publication of multicenter study data sets document trends in allergen reactivity incidence assessed in the patch test clinic setting and provide information on new allergens of relevance.

Survey of Formaldehyde (FA) Concentration in Cosmetics Containing FA-donor Preservatives

We measured the amount of formaldehyde (FA) in cosmetics containing FA-donor preservatives [imidazolidinyl urea (IU), dimethyloldimethyl hydantoin (DM), diazolidinyl urea (DU), quaternium-15 (QU), and bronopol (BP)] and explored the factors affecting FA release. FA was detected in all the 89 cosmetic products tested. FA concentrations of cosmetics declared to contain DM and DU were significantly higher than those of cosmetics declared to contain IU and BP. Detected FA concentration of samples produced in the U.S.A. was significantly higher than thatof samples produced in European countries. A weak proportional relationship was observed between the pH value and the released FA concentration of the cosmetic products containing DM and DU. There were no significant differences in the FA concentrations of various categories of cosmetics (lotion, gel, conditioner, shampoo, body wash, and others). Cosmetics containing a blend of amines, amides, or hydrolyzed proteins together with FA-donor preservatives had a lower FA concentration than the others.

Sensitivity of Petrolatum and Aqueous Vehicles for Detecting Allergy to Imidazolidinylurea, Diazolidinylurea, and DMDM Hydantoin: A Retrospective Analysis from the North American Contact Dermatitis Group

To determine whether petrolatum or aqueous vehicles are more sensitive for detecting allergy to imidazolidinylurea (IU), diazolidinylurea (DU), and dimethylol dimethyl hydantoin (DM). The relationship of these allergens to formaldehyde sensitivity was also explored. Retrospective analysis of patients patch-tested by the North American Contact Dermatitis Group. All patients were simultaneously tested to seven allergens (formaldehyde, IU in petrolatum [pet], IU aqueous [aq], DU pet, DU aq, DM pet, and DM aq). Data were analyzed in pairs with various "gold standard" definitions of "true allergy" and adjusting for correlated data. Reaction to at least one of the seven allergens occurred in 2,398 patients. In all cases except one (which just approached statistical significance), the petrolatum-based allergen was statistically significantly more sensitive than the same allergen in an aqueous base. Most of the patients allergic to the three preservatives were also allergic to formaldehyde, but most formaldehyde-allergic patients were not allergic to the IU, DU, or DM. Of these two vehicles, petrolatum is significantly more sensitive than an aqueous vehicle is for detecting allergy to IU, DU, and DM.

Evaluation of Neutralizing Efficacy and Possible Microbial Cell Toxicity of a Universal Neutralizer Proposed by the CTPA

The purpose of this research was to study the neutralization efficacy of a universal neutralizer proposed by the CTPA on a range of antimicrobial agents and its potential toxicity for microorganisms that are used for antimicrobial preservation testing. Several types of antimicrobial agents including a mixture of methylisothiazolinone and its 5-chloro derivative, dimethylol dimethyl hydantoin, Quaternium-15 ® , Bronopol ® , benzalkonium chloride, phenoxyethanol, methyl and propyl paraben, chlorhexidine, imidazolidinyl urea, triclosan and thiomersal built-in pharmaceutical, cosmetic or health care products, as well as 6 types of these antimicrobials, i.e. a combination of methyl paraben (0.18% w/v) and propyl paraben (0.02%), imidazolidinyl urea (0.3%), chlorhexidine (0.01%), benzalkonium chloride (0.02%), Bronopol ® (0.1%) and thiomersal (0.02%) in their pure and soluble form were tested. Validation of microbial recovery was carried out according to the US Pharmacopeia 27 guidelines. The universal neutralizer could inactivate all the studied antimicrobial agents against different strains tested except Staphylococcus aureus. With regards to this microorganism, only seven preservative chemicals consisting of parabens, dimethylol dimethyl hydantoin, Quaternium-15 ® , Bronopol ® , benzalkonium chloride, Phenonip ® and imidazolidinyl urea were effectively inactivated. In addition, a pure solution of 0.02% thiomersal retained its antimicrobial properties against all studied microorganisms. The neutralizer solution showed no toxicity on any of the test organisms. In conclusion, CTPA proposed neutralizing solution is not an inclusive neutralizer. Moreover, each organism to be used in the test must be included in the validation study.

Durable and Regenerable Antibacterial Finishing of Fabrics with a New Hydantoin Derivative

Durable and regenerable antibacterial fabrics were prepared by using an innovative chemical technology employing a precursor biocidal agent, dimethylol dimethylhydantoin (DMDMH), in a chemical finishing process. The method resulted in significant add-on rates of hydantoin groups on cellulose and established a durable antimicrobial functionality, once the grafted heterocyclic compounds were chlorinated by diluted chlorine bleaching. Both cotton fabrics and polyester/cotton fabrics exposed to treatment baths containing from 2 to 10% of DMDMH acquired a powerful inactivating capacity against a wide range of food-borne and water-borne infectious disease agents. The biocidal functions are regenerable by regular laundry exposure to chlorine bleach and can withstand over 50 standard machine washes without appreciable deterioration. In addition to their powerful antimicrobial efficacy, the fabrics exhibited improved wrinkle resistance and maintained appropriate mechanical properties, making them ideal for medical and hygienic textile applications. In this article we report the results from biocidal tests and durability evaluations and provide data characterizing physical attributes of the treated fabrics.

Release of formaldehyde from dimethylol dimethylhydantoin, a possible antiseptic agent.

Dimethylol dimethylhydantoin (abbreviated as DMDMH), a water-soluble, stable, colorless and odorless hydantoin derivative, was investigated with various microorganisms for its potential applicability as an antiseptic agent. The possible mechanism of its action was elucidated. DMDMH inhibits bacterial and fungal growth at 15.6 to 250 µg/ml, and HeLa S3 cells at 13.7 µg/ml by its continuous presence. Its removal after 1-hr incubation at 5,000 µg/ml reversed the bacterial growth, thus indicating bacteriostatic action. The mechanism of action, in a study using a proton nuclear magnetic resonance, revealed a release of formaldehyde from DMDMH when pH was increased. Effect of DMDMH on antigen-antibody reaction in agar gel showed no adverse effect at moderate concentration. Since its toxicity to animal was much less than that of mercurials or phenol, it can be useful as an antiseptic agent.