Distinct Species-Specific and Toxigenic Metabolic Profiles for 6PPD and 6PPD Quinone by P450 Enzymes: Insights from In Vitro and In Silico Studies.

The tire rubber antioxidant N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) and its quinone product (6PPDQ) are prevalent emerging contaminants, yet their biotransformation profiles remain poorly understood, hampering the assessment of environmental and health risks. This study investigated the phase-I metabolism of 6PPD and 6PPDQ across aquatic and mammalian species through in vitro liver microsome (LM) incubations and in silico simulations. A total of 40 metabolites from seven pathways were identified using the highly sensitive nano-electrospray ionization mass spectrometry. Notably, 6PPDQ was consistently detected as a 6PPD metabolite with an approximate 2% yield, highlighting biotransformation as a neglected indirect exposure pathway for 6PPDQ in organisms. 6PPDQ was calculated to form through a facile two-step phenyl hydroxylation of 6PPD, catalyzed by cytochrome P450 enzymes. Distinct species-specific metabolic kinetics were observed, with fish LM demonstrating retarded biotransformation rates for 6PPD and 6PPDQ compared to mammalian LM, suggesting the vulnerability of aquatic vertebrates to these contaminants. Intriguingly, two novel coupled metabolites were identified for 6PPD, which were predicted to exhibit elevated toxicity compared to 6PPDQ and result from C-N oxidative coupling by P450s. These unveiled metabolic profiles offer valuable insights for the risk assessment of 6PPD and 6PPDQ, which may inform future studies and regulatory actions.

Tissue Accumulation and Biotransformation of 6PPD-Quinone in Adult Zebrafish and Its Effects on the Intestinal Microbial Community.

The pronounced lethality of N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6PPD-quinone or 6PPDQ) toward specific salmonids, while sparing other fish species, has received considerable attention. However, the underlying cause of this species-specific toxicity remains unresolved. This study explored 6PPDQ toxicokinetics and intestinal microbiota composition in adult zebrafish during a 14-day exposure to environmentally realistic concentrations, followed by a 7-day recovery phase. Predominant accumulation occurred in the brain, intestine, and eyes, with the lowest levels in the liver. Six metabolites were found to undergo hydroxylation, with two additionally undergoing O-sulfonation. Semiquantitative analyses revealed that the predominant metabolite featured a hydroxy group situated on the phenyl ring adjacent to the quinone. This was further validated by assessing enzyme activity and determining in silico binding interactions. Notably, the binding affinity between 6PPDQ and zebrafish phase I and II enzymes exceeded that with the corresponding coho salmon enzymes by 1.04-1.53 times, suggesting a higher potential for 6PPDQ detoxification in tolerant species. Whole-genome sequencing revealed significant increases in the genera Nocardioides and Rhodococcus after exposure to 6PPDQ. Functional annotation and pathway enrichment analyses predicted that these two genera would be responsible for the biodegradation and metabolism of xenobiotics. These findings offer crucial data for comprehending 6PPDQ-induced species-specific toxicity.

A Dual-Signal Sensing for the Visual and Luminescent Detection of p-Phenylenediamine Based on Cerium-Nitrogen-Co-Doped Carbon Dots.

Herein, a visual and luminescent dual-mode (colorimetric and fluorometric) method for the detection of P-phenylenediamine (PPD) in hair dye was successfully established based on cerium-nitrogen co-doped carbon dots (Ce, N-CDs) that displayed remarkable luminescence and peroxidase activity. Ce, N-CDs catalyzed H2O2 to produce superoxide anion, which then oxidized the colorless 3,3,5,5-tetramethylbenzidine (TMB) into blue oxidized TMB (oxTMB), capable of quenching the fluorescence through fluorescence resonance energy transfer (FRET) between Ce, N-CDs and oxTMB. The reducing properties of PPD could reduce oxTMB back to TMB, leading to a decrease in the absorption intensity of oxTMB and a fluorescence recovery of Ce, N-CDs. As a result, the quantitative detection of PPD could be achieved by measuring the absorption values of oxTMB and the fluorescence signal of Ce, N-CDs. The detection limits for PPD were calculated as 0.36 µM and 0.10 µM for colorimetry and fluorimetry, respectively. Furthermore, smartphone application (ColorPicker) capable of measuring the RGB value of the color was utilized in the detection system, facilitating on-site quantitative detection. This approach effectively shortens the detection time and simplifies the operation, offering a powerful and convenient tool for real-time monitoring of PPD.

Need for new strategies to improve the recall and avoidance rates of contact allergens: A retrospective cohort study from Turkey.

BACKGROUND: Previous studies reported a low-to-moderate benefit from patch testing regarding allergen recall and avoidance. OBJECTIVES: To determine the allergen recall and avoidance rates of patients with allergic contact dermatitis (ACD) in Turkey. METHODS: This was a retrospective cohort study based on a phone questionnaire of 465 patients diagnosed with ACD from major allergen groups, that is, metals, preservatives, rubber, fragrances (ubiquitous allergens) and hair dye/black henna, topical drug and resins (nonubiquitous allergens), at our tertiary referral centre between 1996 and 2018. RESULTS: Among 176 responders, allergen groups were remembered better (53.4%) than the individual allergens (36.9%). Age <40 years and keeping the allergy pass had a significantly positive impact on the recall rate of methylchloroisothiazolinone/methylisothiazolinone and nickel, particularly non-occupational nickel allergy from metal jewellery in females, respectively. Exacerbations of ACD (56.3%) were mainly due to reexposures to ubiquitous allergens. 42.9% of patients with occupational ACD changed or quit their job, most of them being construction workers and hairdressers, showing a high share (83.3%) of benefit. CONCLUSIONS: The overall rates of allergen recall and avoidance were moderate. New strategies are needed to improve the recall and avoidance rates of contact allergens, such as increased use of allergy pass, smartphone applications and legal precautions.

Construction of a Colorimetric and Fluorescence Dual-Mode Immunoassay Detection of Alpha-Hemolysin in Milk.

Alpha-hemolysin (Hla) is a major virulence factor secreted by Staphylococcus aureus (S. aureus), which can lyse a variety of mammalian cells and help bacteria evade the host immune system or antibiotics, posing a safety hazard to human health. Therefore, it is critical to establish a quick-responsive and sensitive method for Hla detection to ensure food safety. In this work, a dual-mode immunoassay was developed with both colorimetric and fluorescent readouts for discriminative detection of Hla. The proposed sensing system consists of p-phenylenediamine (PPD) and fluorescein, where fluorescein functions as a fluorescent reporter, and PPD serves a dual function as a colorimetric reporter and fluorescence quencher. Subsequently, the reaction system of this method was optimized, and the detection limit, sensitivity, and specificity were evaluated. Under optimal conditions, the proposed method possesses excellent analytical performance in the range from 0.5 to 500 ng/mL with a limit of detection as low as 0.5 ng/mL. Noteworthy, this method was successfully employed for the detection of Hla in milk with good selectivity and high accuracy. Overall, the dual-mode immunoassay provides a superior platform for the on-site, quantitative, and accurate detection of Hla in food samples.

Fluorescent and colorimetric dual-mode detection of Cu2+ based on carbon dots.

A fluorescent and colorimetric dual-mode strategy based on carbon dots (CDs) was rationally designed for sensitive determination of Cu2+. Green fluorescent CDs with high absolute quantum yield of 72.9% were synthesized by facile one-step hydrothermal treatment of triethylenetetramine and Rose Bengal. Cu2+ could trigger the oxidative and chromogenic reaction of p-phenylenediamine (PPD) to generate chromogenic PPDox, accompanied by the fluorescence quenching of the CDs. The quenching mechanism was identified as the inner filter effect between PPDox and CDs. Therefore, a colorimetric/fluorescent dual-mode detection method for Cu2+ recognition was constructed. The limits of detection for Cu2+ were 4.14 µM and 1.28 µM for colorimetric and fluorescent mode, respectively. In addition, this method had achieved satisfactory results in the detection of Cu2+ in real serum samples.

Ratiometric fluorescence probe based on carbon dots and p-phenylenediamine-derived nanoparticles for the sensitive detection of manganese ions.

A ratiometric fluorescence probe based on carbon quantum dots with 420 nm emission (bCQDs) and a p-phenylenediamine-derived fluorescence probe with 550 nm emission (yprobe) is constructed for the detection of Mn2+. The presence of Mn2+ results in the enhanced absorption band at 400 nm of yprobe, and the fluorescence of yprobe is significantly enhanced based on the chelation-enhanced fluorescence mechanism. The fluorescence of bCQDs is then quenched based on the inner filtration effect. The ratio (I550/I420) linearly increases with the increase of Mn2+ concentration within 2.00 × 10-7-1.50 × 10-6 M, and the limit of detection is 1.76 × 10-9 M. Given the fluorescence color changing from blue to yellow, the visual sensing of Mn2+ is feasible based on bCQDs/yprobe coupled with RGB value analysis. The practicability of the proposed method has been verified in tap water, lake water, and sparkling water beverage, indicating that bCQDs/yprobe has promising application in Mn2+ monitoring.

Presentations to emergency departments in Melbourne, Australia diagnosed as allergic contact dermatitis.

BACKGROUND: This study investigated cases diagnosed as allergic contact dermatitis (ACD) in emergency departments (EDs) and management. METHODS: A multisite retrospective study of patients attending EDs in metropolitan Melbourne between July 2017 and June 2018 was performed. Using International Statistical Classification of Disease-10 (ICD-10) codes, the Victorian Agency for Health Information generated a list of cases of contact dermatitis (CD). Demographic and clinical data were analysed. RESULTS: Two hundred twenty-eighty patients from 14 different sites were diagnosed with ACD. Hair dyes caused the most cases, and one such case was admitted to hospital. It was apparent from the specified causes that cases of irritant CD were misdiagnosed as ACD. There were significant differences in management with dermatology input, with dermatologists more often advising oral corticosteroids (33.3% vs. 14.5%, P = 0.004) topical corticosteroids (92.9% vs. 38.7%, P < 0.01), emollients (38.1% vs. 20.4%, P = 0.01) and less often advising antihistamines (16.7% vs. 44.6%, P < 0.001). With dermatology input, potent or very potent steroids were more likely to be prescribed (69.3% vs. 11.1%, P < 0.001); without, a mild potency steroid was more likely to be prescribed (63.9% vs. 4%, P = 0.01). CONCLUSION: Improved understanding, diagnosis and management of CD are needed in EDs.

Participation of Lattice Oxygen in Perovskite Oxide as a Highly Sensitive Sensor for p-Phenylenediamine Detection.

The harmful effects on the human body from p-phenylenediamine (PPD) in hair dyes can cause allergies and even cancer. Therefore, it is particularly important to accurately control and detect the content of PPD in our daily products and environment. Here, a small amount of non-metallic elemental P doped in perovskite oxide of SrCoO3-δ (SC) forms a good catalytic material, SrCo0.95P0.05O3-δ (SCP), for PPD detection. The improved performance compared with that of the parent SC can be attributed to three contributing factors, including a larger amount of highly oxidative oxygen species O22-/O-, better electrical conductivity, and more active sites on the P5+-oxygen bonds of SCP. Moreover, the lattice oxygen mechanism (LOM) with highly active species of lattice O vacancies and adsorbed -OO for electrocatalytic oxidation of PPD by the SCP/GCE (glass carbon electrode) sensor is proposed in our work. More importantly, the SCP/GCE sensor exhibits good stability, a low limit of detection, and high reliability (error < 5.78%) towards PPD determination in real samples of hair dyes, suggesting the substantial research potential for practical applications.

A Novel Spectrophotometric Method for Determination of Percarbonate by Using N, N-Diethyl-P-Phenylenediamine as an Indicator and Its Application in Activated Percarbonate Degradation of Ibuprofen.

Sodium percarbonate (SPC) concentration can be determined spectrophotometrically by using N, N-diethyl-p-phenylenediamine (DPD) as an indicator for the first time. The ultraviolet-visible spectrophotometry absorbance of DPD•+ measured at 551 nm was used to indicate SPC concentration. The method had good linearity (R2 = 0.9995) under the optimized experimental conditions (pH value = 3.50, DPD = 4 mM, Fe2+ = 0.5 mM, and t = 4 min) when the concentration of SPC was in the range of 0-50 µM. The blank spiked recovery of SPC was 95-105%. The detection limit and quantitative limit were 0.7-1.0 µM and 2.5-3.3 µM, respectively. The absorbance values of DPD•+ remained stable within 4-20 min. The method was tolerant to natural water matrix and low concentration of hydroxylamine (<0.8 mM). The reaction stoichiometric efficiency of SPC-based advanced oxidation processes in the degradation of ibuprofen was assessed by the utilization rate of SPC. The DPD and the wastewater from the reaction were non-toxic to Escherichia coli. Therefore, the novel Fe2+/SPC-DPD spectrophotometry proposed in this work can be used for accurate and safe measurement of SPC in water.