Assessment of the eye surface and subjective symptoms after using 0.1% dexamethasone drops with and without preservatives in patients after cataract surgery.

Cataract surgery can cause dry eye symptoms. One of the many factors compromising the ocular surface is the use of benzalkonium chloride (BAC)-preserved topical eye drops administered during the postoperative period. In this open-label, prospective, randomized, comparative clinical trial, 40 patients not previously affected by dry eye disease were assigned to receive either preservative-free (PFD) or preserved (PD) dexamethasone 0.1% eye drops for two weeks after a standard phacoemulsification procedure. Fluorescein break-up time, ocular surface staining score, Schirmer test, Ocular Surface Disease Index and anterior chamber (AC) cells were evaluated at baseline prior to the surgery and 2 weeks after surgery. No statistically significant differences in baseline assessments were observed between groups. At week 2, a significant increase in corneal staining scores (p = 0.003) and foreign body sensation (p = 0.04) was observed for the PD group only. The conjunctival staining score was significantly higher in both groups. The mean AC cell grading was higher in the PFD group than in the PD group (0.28 ± 0.30 and 0.07 ± 0.18, respectively; p = 0.013). Preservative-free dexamethasone eye drops after cataract surgery caused milder dry eye symptoms as compared with preserved dexamethasone. The AC inflammation control comparison may require a larger study group. Trial registration: ClinicalTrials.gov identifier NCT05753787, 03/03/2023.

Medical devices biocompatibility assessment on HCE: Evidences of delayed cytotoxicity of preserved compared to preservative free eye drops.

A multiple endpoint analysis (MEA) approach on human reconstructed corneal epithelium (HCE) model has been applied to assess the biocompatibility (cytotoxicity and irritation potential) of medical devices (MD): ophthalmology literature clearly shows the need to better assess these products to exclude any potential chronic damage to the ocular surface. Preserved eye drops (Artelac Multidose, Optive multidose and Artelac Rebalance Multidose) and the same without preservative (Artelac Edo, Optive Unidose, Artelac Rebalance Unidose) and Thealoz Duo were tested after acute (24 h + 16 h post incubation) and repeated (2 applications/day for 72 h) exposure using BAK 0.01% as positive control on HCE. Cellular viability, trans-epithelial electrical resistance measurements, LDH release and occludin gene expression were evaluated for each product to discriminate the potential toxicity of preservatives. The BAK 0.01% toxicity on HCE was confirmed following both exposures. The analysis of the same parameters reveals that the 72 h exposure was suitable to identify toxicity and damages to the ocular surface even for 'soft' preserved MD. The results confirm the reliability, sensitivity and predictivity of the MEA on HCE in detecting subclinical signs of cellular toxicity: 'soft' preservatives resulted toxics suggesting that delayed toxicity should be integral part of the biocompatibility assessment of ophthalmic formulations intended for long-term use.

Prevalence of Contact Allergens in Personal Care Products for Babies and Children.

BACKGROUND: Personal care products marketed for babies and children are often regarded as "safe" or "gentle." However, little is known about the prevalence of contact allergens in these types of products. OBJECTIVE: This study assessed the prevalence of important sensitizers in personal care products marketed for babies and children. A secondary objective of this study was to determine whether a product's cost correlates with content of sensitizing ingredients. METHODS: The ingredient lists of 533 unique personal care products were analyzed for presence of fragrance, betaines, propylene glycol, methylchloroisothiazolinone, methylisothiazolinone, formaldehyde, lanolin, and neomycin. Price per ounce was determined for each product as well. CONCLUSIONS: Most personal care products for babies and children contain 1 or more sensitizers. Products containing more sensitizers tend to cost less than those without any sensitizing ingredients.

Risk Assessment of the Skin Sensitization Induction Potential of Kathon CG in Rinse-off and Leave-on Personal Care and Cosmetic Products.

BACKGROUND: Kathon CG is a commonly used cosmetic-grade preservative that contains active ingredients methylchloroisothiazolinone (MCI) and methylisothiazolinone (MI). OBJECTIVE: The aim of the study was to perform a skin sensitization induction risk assessment of daily exposure to Kathon CG after use of various personal care and cosmetic products. METHODS: We calculated an estimated daily consumer exposure level for rinse-off and leave-on products using the amount of product applied per application, number of applications per day, a retention factor, the MCI/MI concentration, and body surface area values. We assumed that the products contained the maximum recommended safe concentration of MCI/MI: 15 ppm in rinse-off products and 7.5 ppm in leave-on products. We compared estimated consumer exposure levels with the no expected sensitization induction level for MCI/MI and applied sensitization assessment factors to calculate product-specific margins of safety (MOSs). CONCLUSIONS: The MOSs for rinse-off products ranged from 5 to 63, whereas the MOSs for leave-on products ranged from 0.03 to 1.49. Overall, our results provide evidence that some leave-on products containing the maximum recommended safe concentration of Kathon CG may increase the risk of sensitization induction due to exposure to MCI/MI. In contrast, rinse-off products were not associated with a potential increased risk of skin sensitization induction.

Application of in vitro skin penetration measurements to confirm and refine the quantitative skin sensitization risk assessment of methylisothiazolinone.

Use of quantitative risk assessment (QRA) for assessing the skin sensitization potential of chemicals present in consumer products requires an understanding of hazard and product exposure. In the absence of data, consumer exposure is based on relevant habits and practices and assumes 100% skin uptake of the applied dose. To confirm and refine the exposure, a novel design for in vitro skin exposure measurements was conducted with the preservative, methylisothiazolinone (MI), in beauty care (BC) and household care (HHC) products using realistic consumer exposure conditions. A difference between measured exposure levels (MELs) for MI in leave-on versus rinse-off BC products, and lower MELs for MI in HHC rinse-off compared to BC products was demonstrated. For repeated product applications, the measured exposure was lower than estimations based on summation of applied amounts. Compared to rinse-off products, leave-on applications resulted in higher MELs, correlating with the higher incidences of allergic contact dermatitis associated with those product types. Lower MELs for MI in rinse-off products indicate a lower likelihood to induce skin sensitization, also after multiple daily applications. These in vitro skin exposure measurements indicate conservatism of default exposure estimates applied in skin sensitization QRA and might be helpful in future risk assessments.

Prevalence of Preservatives Across All Product Types in the Contact Allergen Management Program.

BACKGROUND: Preservatives are known causes of allergic contact dermatitis. OBJECTIVE: The aim of this study was to determine the prevalence of preservatives in each product category in the Contact Allergen Management Program and compare prevalence with reported rates of allergic contact dermatitis. METHODS: Contact Allergen Management Program product information was queried based on the 53 approved preservatives for cosmetic products by the European Union and Association of Southeast Asian Nations plus 5 additional preservatives used in US products. RESULTS: Phenoxyethanol and parabens were the most common preservatives with 23.9% of products containing phenoxyethanol and 20.75% of products containing parabens. Methylisothiazolinone (MI) was found in 12.9% of products, most commonly in hair care and household products. Preservatives like MI and methylchloroisothiazolinone (MCI) that are both common in products and have a high incidence of allergic contact dermatitis are of greatest concern as contact allergy hazards. Phenoxyethanol and parabens are common and have weak sensitizing power, making them preferred preservatives. CONCLUSIONS: Evaluating the prevalence of preservatives provides important information on allergen exposures. Using current positive reaction rates, the risk of sensitization to a given preservative can be more accurately estimated and may affect the use of certain preservatives by industry in the future.

Failures in risk assessment and risk management for cosmetic preservatives in Europe and the impact on public health.

BACKGROUND: In view of the current and unprecedented increase in contact allergy to methylisothiazolinone (MI), we characterized and evaluated two recent epidemics of contact allergy to preservatives used in cosmetic products to address failures in risk assessment and risk management. OBJECTIVE: To evaluate temporal trends of preservative contact allergy. METHODS: The study population included consecutive patch tested eczema patients seen at a university hospital between 1985 and 2013. A total of 23 138 patients were investigated for a contact allergy. RESULTS: The overall prevalence of contact allergy to at least one preservative increased significantly over the study period, from 6.7% in 1985 to 11.8% in 2013 (p < 0.001). Importantly, the preservatives methyldibromo glutaronitrile and MI rapidly resulted in high sensitization prevalence rates, which reached epidemic proportions. Although the proportion of patients with current clinical disease attributable to methyldibromo glutaronitrile contact allergy decreased significantly following the ban on its use in cosmetic products (p < 0.001), the sudden and high proportion of current sensitization to MI requires immediate attention (p < 0.001). CONCLUSIONS: The introduction of new preservatives in Europe with inadequate pre-market risk assessment has rapidly increased the overall burden of cutaneous disease caused by preservatives. We suggest that the cosmetic industry has a responsibility to react faster and replace troublesome preservatives when a preservative contact allergy epidemic is recognized, but the European Commission has the ultimate responsibility for failures in risk management after new, major sensitizing preservatives are introduced onto the market.

Timerosal en las vacunas: ¿blanco, negro, o más bien todo lo contrario? / Thimerosal in vaccines: white, black, or quite the opposite?

El presente artículo tiene por objetivo analizar la controversia ocurrida en Chile, especialmente durante los últimos meses, en relación a un proyecto de ley que busca prohibir la fabricación, importación, comercialización o distribución de vacunas que contengan dentro de sus compuestos, en cualquier nivel de concentración, timerosal o compuestos organomercúricos. Sin constituir una síntesis formal de toda la investigación existente, se analiza la evidencia científica que los distintos actores han utilizado, las razones de la controversia y las anomalías en el proceso de toma de decisión sanitaria.

This article analyzes the recent controversy regarding the introduction of a bill to Chilean Congress that aims to ban thiomersal and/or any trace of organomercurial compounds from vaccines in the country. Rather than providing a formal overview of all available evidence, this analysis focuses on the reasons behind the controversy, the scientific evidence invoked by both sides in the debate, and the anomalies in the healthcare decision-making process.

Addressing the vaccine confidence gap.

Vaccines--often lauded as one of the greatest public health interventions--are losing public confidence. Some vaccine experts have referred to this decline in confidence as a crisis. We discuss some of the characteristics of the changing global environment that are contributing to increased public questioning of vaccines, and outline some of the specific determinants of public trust. Public decision making related to vaccine acceptance is neither driven by scientific nor economic evidence alone, but is also driven by a mix of psychological, sociocultural, and political factors, all of which need to be understood and taken into account by policy and other decision makers. Public trust in vaccines is highly variable and building trust depends on understanding perceptions of vaccines and vaccine risks, historical experiences, religious or political affiliations, and socioeconomic status. Although provision of accurate, scientifically based evidence on the risk-benefit ratios of vaccines is crucial, it is not enough to redress the gap between current levels of public confidence in vaccines and levels of trust needed to ensure adequate and sustained vaccine coverage. We call for more research not just on individual determinants of public trust, but on what mix of factors are most likely to sustain public trust. The vaccine community demands rigorous evidence on vaccine efficacy and safety and technical and operational feasibility when introducing a new vaccine, but has been negligent in demanding equally rigorous research to understand the psychological, social, and political factors that affect public trust in vaccines.

Allergy to methyldibromoglutaronitrile/phenoxyethanol (Euxyl k 400): regulatory issues, epidemiology, clinical characteristics, and management.

Methyldibromoglutaronitrile/phenoxyethanol (Euxyl K 400) is a preservative found in both personal care products and industrial sources. Although Euxyl K 400 initially appeared to have low sensitizing potential, increased prevalence of contact allergy to Euxyl K 400 led to regulatory intervention. This review summarizes the history, epidemiology, and management of contact allergy to Euxyl K 400. Issues related to patch-test preparations are also discussed.

Thimerosal exposure in infants and neurodevelopmental disorders: an assessment of computerized medical records in the Vaccine Safety Datalink.

The study evaluated possible associations between neurodevelopmental disorders (NDs) and exposure to mercury (Hg) from Thimerosal-containing vaccines (TCVs) by examining the automated Vaccine Safety Datalink (VSD). A total of 278,624 subjects were identified in birth cohorts from 1990-1996 that had received their first oral polio vaccination by 3 months of age in the VSD. The birth cohort prevalence rate of medically diagnosed International Classification of Disease, 9th revision (ICD-9) specific NDs and control outcomes were calculated. Exposures to Hg from TCVs were calculated by birth cohort for specific exposure windows from birth-7 months and birth-13 months of age. Poisson regression analysis was used to model the association between the prevalence of outcomes and Hg doses from TCVs. Consistent significantly increased rate ratios were observed for autism, autism spectrum disorders, tics, attention deficit disorder, and emotional disturbances with Hg exposure from TCVs. By contrast, none of the control outcomes had significantly increased rate ratios with Hg exposure from TCVs. Routine childhood vaccination should be continued to help reduce the morbidity and mortality associated with infectious diseases, but efforts should be undertaken to remove Hg from vaccines. Additional studies should be conducted to further evaluate the relationship between Hg exposure and NDs.

Neurodevelopmental disorders, maternal Rh-negativity, and Rho(D) immune globulins: a multi-center assessment.

BACKGROUND: Many formulations of Thimerosal (49.55% mercury by weight)-containing Rho(D) immune globulins (TCRs) were routinely administered to Rh-negative mothers in the US prior to 2002. OBJECTIVES: It was hypothesized: (1) if prenatal Rho(D)-immune globulin preparation exposure was a risk factor for neurodevelopmental disorders (NDs) then more children with NDs would have Rh-negative mothers compared to controls; and (2) if Thimerosal in the Rho(D)-immune globulin preparations was the ingredient associated with NDs, following the removal of Thimerosal from all manufactured Rho(D)-immune globulin preparations from 2002 in the US the frequency of maternal Rh-negativity among children with NDs should be similar to control populations. METHODS: Maternal Rh-negativity was assessed at two sites (Clinic A-Lynchburg, VA; Clinic B-Rockville and Baltimore, MD) among 298 Caucasian children with NDs and known Rh-status. As controls, maternal Rh-negativity frequency was determined from 124 Caucasian children (born 1987-2001) without NDs at Clinic A, and the Rh-negativity frequency was determined from 1,021 Caucasian pregnant mothers that presented for prenatal genetic care at Clinic B (1980-1989). Additionally, 22 Caucasian patients with NDs born from 2002 onwards (Clinics A and B) were assessed for maternal Rh-negativity. RESULTS: There were significant and comparable increases in maternal Rh-negativity among children with NDs (Clinic: A=24.2%), autism spectrum disorders (Clinic: A=28.3%, B=25.3%), and attention-deficit-disorder/attention-deficit-hyperactivity-disorder (Clinic: A=26.3%) observed at both clinics in comparison to both control groups (Clinic: A=12.1%, B=13.9%) employed. Children with NDs born post-2001 had a maternal Rh-negativity frequency (13.6%) similar to controls. CONCLUSION: This study associates TCR exposure with some NDs in children.

Mercury, vaccines, and autism: one controversy, three histories.

The controversy regarding the once widely used mercury-containing preservative thimerosal in childhood vaccines has raised many historical questions that have not been adequately explored. Why was this preservative incorporated in the first place? Was there any real evidence that it caused harm? And how did thimerosal become linked in the public mind to the "autism epidemic"? I examine the origins of the thimerosal controversy and their legacy for the debate that has followed. More specifically, I explore the parallel histories of three factors that converged to create the crisis: vaccine preservatives, mercury poisoning, and autism. An understanding of this history provides important lessons for physicians and policymakers seeking to preserve the public's trust in the nation's vaccine system.

Update on the National Vaccine Injury Compensation Program.

The National Childhood Vaccine Injury Act of 1986, as amended, established the Vaccine Injury Compensation Program (VICP). The VICP went into effect on October 1, 1988 and is a Federal "no-fault" system designed to compensate individuals, or families of individuals, who have been injured by covered vaccines. From 1988 until July 2006, a total of 2531 non-autism/thimerosal and 5030 autism/thimerosal claims were made to the VICP. The compensation paid for the non-autism/thimerosal claims from 1988 until 2006 was $902,519,103.37 for 2542 awards. There was no compensation for any of the autism/thimerosal claims. On the basis of the deaths and extensive suffering to patients and families from the adverse reactions to vaccines, all physicians must provide detailed information in the Vaccine Information Statement to the patient or the parent or legal guardian of the child about the potential dangers of vaccines as well as the VICP.