Dermal absorption of high molecular weight parent and alkylated polycyclic aromatic hydrocarbons from manufactured gas plant soils using in vitro assessment.

An enhanced in vitro human dermal bioavailability method was developed to measure the release of twenty parent and seven alkylated high molecular weight (HMW) polycyclic aromatic hydrocarbons (PAHs) from contaminated soils collected from five former manufactured Gas Plants (MGP) in England. GC-MS/MS was used to quantify HMW PAHs in soil, Strat-M artificial membrane representing skin, and synthetic receptor solution (RS) representing systemic circulation at 1-h, 10-h, and 24-h timesteps. Fluoranthene and pyrene exhibited the highest fluxes from soils to membrane (ranging from 9.5 - 281 ng/cm2/h) and soil to RS (

Fluorene-induced stress in the benthic oligochaete Tubifex tubifex: A multi-biomarker assessment of toxicological pathways and mechanisms under acute and subchronic exposures.

This study examined the multifaceted impacts of fluorene exposure on Tubifex tubifex, encompassing acute (survival analysis and behavioral responses) and subchronic exposure regimens (antioxidant enzyme response and histopathology), molecular docking studies, and generalized read-across analysis. Survival analysis revealed concentration-dependent increases in toxicity over varying time intervals, with LC50 values decreasing from 30.072 mg/L at 24 h to 12.365 mg/L at 96 h, emphasizing the time-sensitive and concentration-responsive nature of the stressor. Behavioral responses were both concentration- and duration-dependent. While Erratic Movement and Clumping Tendency exhibited earlier responses (within 24 h) at lower concentrations, the wrinkling effect and mucus secretion) exhibited delayed onset, suggesting intricate regulatory mechanisms underlying adaptability to environmental challenges; moreover, the wrinkling effect was consistently induced at higher concentrations, indicating greater sensitivity to the toxic effects of fluorene. With sublethal environmentally relevant concentrations-1.24 mg/l and 2.47 mg/L i.e., 10% and 20% 96 h, respectively-the antioxidant enzyme response (i.e., upregulation of SOD, CAT, and GST) with increasing fluorene concentration, revealing a nonlinear, hormetic response, suggested adaptive protection at lower doses but inhibition at higher concentrations. Histopathological examination indicated that higher fluorene concentrations caused cellular proliferation, inflammation, and severe tissue damage in the digestive tract and body wall. Molecular docking studies demonstrated robust interactions between fluorene and major stress biomarker enzymes, disrupting their functions and inducing oxidative stress. Interactions with cytochrome c oxidase suggested interference with cellular energy production. Generalized Read-Across (GenRA) analysis unveiled shared toxicity mechanisms among fluorene and its analogs, involving the formation of reactive epoxides and the influence of cytochrome P450 enzymes. The diverse functional groups of these analogs, particularly chlorine-containing compounds, were implicated in toxicity through lipid peroxidation and membrane damage. Adverse outcome pathways and broader consequences for aquatic ecosystem health are discussed.

Degradation of multiple PAHs and co-contaminants by microbial consortia and their toxicity assessment.

The anthropogenic activities toward meeting the energy requirements have resulted in an alarming rise in environmental pollution levels. Among pollutants, polycyclic aromatic hydrocarbons (PAHs) are the most predominant due to their persistent and toxic nature. Amidst the several pollutants depuration methods, bioremediation utilizing biodegradation is the most viable alternative. This study investigated the biodegradation efficacy using developed microbial consortium PBR-21 for 2-4 ringed PAHs named naphthalene (NAP), anthracene (ANT), fluorene (FLU), and pyrene (PYR). The removal efficiency was observed up to 100 ± 0.0%, 70.26 ± 4.2%, 64.23 ± 2.3%, and 61.50 ± 2.6%, respectively, for initial concentrations of 400 mg L-1 for NAP, ANT, FLU, and PYR respectively. Degradation followed first-order kinetics with rate constants of 0.39 d-1, 0.10 d-1, 0.08 d-1, and 0.07 d-1 and half-life t 1 / 2  of 1.8 h, 7.2 h, 8.5 h, and 10 h, respectively. The microbial consortia were found to be efficient towards the co-contaminants with 1 mM concentration. Toxicity examination indicated that microbial-treated PAHs resulted in lesser toxicity in aquatic crustaceans (Artemia salina) than untreated PAHs. Also, the study suggests that indigenous microbial consortia PBR-21 has the potential to be used in the bioremediation of PAH-contaminated environment.

The occurrence characteristics, removal efficiency, and risk assessment of polycyclic aromatic hydrocarbons in sewage sludges from across China.

Sewage sludge is considered to be an important sink for polycyclic aromatic hydrocarbons (PAHs) in wastewater treatment plants and the potential risks from sludge contaminated with PAHs during land application has attracted attention. To identify the priority PAHs for control and enhance their removal from sludge, the occurrence characteristics, removal efficiency, and risk assessment of PAHs in sewage sludges from across China were analyzed. Data collection was from 2001 to 2023. Results showed that 16 PAHs were widely detected in Chinese sewage sludge with total amounts (∑16PAHs) between 0.06 and 34.93 mg kg dw-1. Fossil fuel, coal, and biomass combustion are main anthropogenic sources of PAHs in China. In general, phenanthrene (PHE), anthracene (ANT), fluorescein (FL), chrysene (CHR), pyrene (PYR), and benzo[b]fluoranthene (BbF) are regarded as the main components and PAHs with 3-5 rings dominate (84.01%-91.53%) sewage sludge in China. Although aerobic composting and anaerobic treatment significantly improve ∑16PAHs removal, sludge stabilization treatment only reduced the risk by a small amount, especially for high-molecular-weight (HMW) PAHs. The benzo[a]anthracene (BaA), benzo[a]pyrene (BaP), and dibenzo[a,h]anthracene (DahA) are proposed as the priority control contaminants for sewage sludge in China because they have consistently high-risk quotient (RQ) values of 2.42-7.47, 1.28-3.16, 1.06-1.83 before and after sludge stabilization, respectively. More attention should be paid to BaA, BbF, benzo[k]fluoranthene (BkF), BaP, DahA, and indeno[1,2,3-cd]pyrene (IcdP) in Beijing; ANT, BaA, and BaP in Shanghai; and BaA and BaP in Guanghzou. Although the toxic equivalent quotient (TEQ) for PAHs met the limit concentration requirements of the national standard, the potential health risks due to long-term exposure to HMW PAHs cannot be ignored because the incremental lifetime cancer risk (ILCR) was consistently in the risk threshold range (>1 × 10-6). Some suggestions on enhanced treatment approaches and land use standards are proposed to further alleviate the risk from HMW PAHs.

Interaction of fluorene and its analogs with high-density polyethylene microplastics: An assessment of the adsorption mechanism to establish the effects of heteroatoms in the molecule.

The threat of microplastics (MP) pollution in aquatic ecosystems can be even more severe for they are able to interact with organic pollutants that can migrate to adjacent environments. The presence of heteroatoms in organic pollutants can directly influence adsorption onto MP. This research evaluated the adsorption of fluorene (FLN) and its heteroatom analogs dibenzothiophene (DBT), dibenzofuran (DBF) and carbazole (CBZ) onto high-density polyethylene (HDPE) MP from residual (HDPEres) and commercial (HDPEcom) sources. The Langmuir isotherm showed a better fit, while DBT showed higher maximum adsorption capacity (19.2 and 15.8 µmol g-1) followed by FLN (13.4 and 11.7 µmol g-1), and DBF (13.5 and 10.3 µmol g-1) to the HDPEcom and HDPEres, respectively, which indicates a direct correlation with the hydrophobicity of the molecules determined by Log Kow. In contrast, CBZ showed no significant interaction with MP, due to their polar characteristic, thus, no kinetic and thermodynamic parameters could be determined. The adsorption process of all PAH was determined to be exothermic and spontaneous, with low temperatures favoring the process. The pseudo-second-order kinetic models have fitted to the adsorption onto both HDPE; intraparticle diffusion was also observed. Computational studies, physical characterization techniques and batch adsorption experiments demonstrated that the mechanism is governed by hydrophobic interactions, with van der Waals forces as a secondary effect in the adsorption of FLN, DBT and DBF onto HDPEres and HDPEcom. Thus, allowing a deeper understanding of the interactions between HDPE MP and FLN as well with its derivatives.

Biomonitoring of polycyclic aromatic hydrocarbons in Brazilian pregnant women: Urinary levels and health risk assessment.

Over the years, humans have been continuously exposed to several compounds directly generated by industrial processes and/or present in consumed products. Polycyclic aromatic hydrocarbons (PAHs) are legacy pollutants ubiquitous in the environment and represent the main chemical pollutants in urban areas. Worldwide, studies that aim to understand the impacts of exposure to these chemicals have gained increasing prominence due to their potential toxicity profile, mainly concerning genotoxicity and carcinogenicity. Human biomonitoring (HB) is an analytical approach to monitoring population exposure to chemicals; however, these studies are still limited in Brazil. Thus, this work aimed to evaluate the exposure of Brazilian pregnant women to PAHs through HB studies. Besides, the risk characterization of this exposure was performed. For this purpose, urine samples from 358 Brazilian pregnant women were used to evaluate 11 hydroxylated metabolites of PAHs employing gas chromatography coupled to mass spectrometry. The 1OH-naphthol and 2OH-naphthol were detected in 100% of the samples and showed high levels, corresponding to 16.99 and 3.62 µg/g of creatinine, respectively. 2OH-fluorene (8.12 µg/g of creatinine) and 9OH-fluorene (1.26 µg/g of creatinine) were detected in 91% and 66% of the samples, respectively. Benzo(a)pyrene (BaP) metabolites were detected in more than 50% of the samples (0.58-1.26 µg/g of creatinine). A hazard index of 1.4 and a carcinogenic risk above 10-4 were found for BaP metabolites in the risk characterization. Therefore, our findings may indicate that exposure to PAHs poses a potential risk to pregnant women's health and a high probability of carcinogenic risk due to their exposure to BaP. Finally, this work shows the need for more in-depth studies to determine the sources of exposure and the implementation of health protection measures regarding the exposure of the Brazilian population to PAHs.

Comparative assessment of soil microbial community in crude oil contaminated sites.

Petroleum refineries generate oily sludge that contains hazardous polycyclic aromatic hydrocarbons (PAH), and hence, its proper disposal is of foremost concern. Analysis of the physicochemical properties and functions of indigenous microbes of the contaminated sites are essential in deciding the strategy for bioremediation. This study analyses both parameters at two geographically distant sites, with different crude oil sources, and compares the metabolic capability of soil bacteria with reference to different contamination sources and the age of the contaminated site. The results indicate that organic carbon and total nitrogen derived from petroleum hydrocarbon negatively affect microbial diversity. Contamination levels vary widely on site, with levels of PAHs ranging from 5.04 to 1.66 × 103 µg kg-1 and 6.20 to 5.64 × 103 µg kg-1 in Assam and Gujarat sites respectively, covering a higher proportion of low molecular weight (LMW) PAHs (fluorene, phenanthrene, pyrene, and anthracene). Functional diversity values were observed to be positively correlated (p < 0.05) with acenaphthylene, fluorene, anthracene, and phenanthrene. Microbial diversity was the highest in fresh oily sludge which decreased upon storage, indicating that immediate bioremediation, soon after its generation, would be beneficial. Improvement in the bio-accessibility of hydrocarbon compounds by the treatment of biosurfactant produced by a (soil isolate/isolate) was demonstrated., with respect to substrate utilization.

Seasonal assessment of the distribution, source apportionment, and risk of water-contaminated polycyclic aromatic hydrocarbons (PAHs).

The research aims to evaluate the seasonal differences in the distribution, source, and risks of water-contaminated PAHs. The PAHs were extracted by the liquid-liquid method and analyzed with GC-MS, and a total of eight PAHs were detected. There was a percentage increase in the average concentration of the PAHs from the wet to the dry season in the range of 20 (Anthracene)-350 (Pyrene)%. Total PAHs (∑PAHs) range from 0.31 to 1.23 mg/l in the wet period and from 0.42 to 1.96 mg/l in the dry period. The distribution of the average PAHs in mg/l showed that Fluoranthene ≤ Pyrene < Acenaphthene < Fluorene < Phenanthrene < Acenaphthylene < Anthracene < Naphthalene in wet period and while Fluoranthene < Acenaphthene < Pyrene < Fluorene < Phenanthrene < Acenaphthylene < Anthracene < Naphthalene in the dry period. The children were exposed to non-carcinogenic risk through non-dietary ingestion due to the accumulative effect (HI) of the PAHs in the dry period. Furthermore, the naphthalene was responsible for ecological and carcinogenic risk in the wet period, while the fluorene, phenanthrene, and anthracene were responsible for ecological and carcinogenic risk in the dry period. However, while adults and children are both susceptible to carcinogenic risk through the oral channel during the dry period, only children are susceptible to non-carcinogenic risk through this pathway. The multivariate statistical analysis revealed the influence of physicochemical parameters on the detected PAHs and also showed the PAHs' sources to be mainly combustion, pyrolysis, and vehicular emission.

Occurrence, partition behavior, source and ecological risk assessment of nitro-PAHs in the sediment and water of Taige Canal, China.

Nitrated polycyclic aromatic hydrocarbons (NPAHs) are widespread organic pollutants that possess carcinogenic and mutagenic properties, so they may pose a risk to the environment and human health. In this study, the concentrations of 15 NPAHs and 16 polycyclic aromatic hydrocarbons (PAHs) in 30 surface water samples and 26 sediment samples were measured in 2018 from the Taige Canal, one of the main rivers flowing into Taihu Lake, China. The total NPAH concentrations in water and sediment ranged from 14.7 to 235 ng/L and 22.9 to 96.5 ng/g dw, respectively. 9-nitrophenanthrene (nd-76.3 ng/L) was the dominant compound in surface water, while 2+3-nitrofluoranthene (1.73-18.1 ng/g dw) dominated in sediment. Among PAHs, concentration ranging from 1,097 to 2,981 ng/L and 1,089 to 4,489 ng/g dw in surface water and sediment, respectively. There was a strong positive correlation between the log octanol-water partition coefficient (Kow) and log sediment-water partition coefficient due to hydrophobic interaction. The fugacity fraction value increased with the decrease of log Kow, and chrysene was transferred from water into sediment. The residual NPAHs in surface water and sediment of the Taige Canal have partial correlation. Diesel engine and coal combustion emissions were probably the principal sources of NPAHs in surface water and sediment. The results of ecological risk assessment showed that some NPAHs in water (e.g, 1-nitropyrene and 6-nitrochrysene) and sediment (e.g., 2-nitrobiphenyl, 5-nitroacenaphthene, 9-nitrophenanthrene and 2+3-nitrofluoranthene) had moderate ecological risks, which should be of concern.

Assessment of biological community in riparian zone contaminated by PAHs: Linking source apportionment to biodiversity.

Riparian zone, an important land-water interface, plays an essential role in maintaining the ecological health of rivers, whereas the effects of Polycyclic aromatic hydrocarbons (PAHs) on the health of biological communities in riparian groundwater remain undetermined. To understand the responses of multiple communities to environmental variables, the distribution and ecosystem risk of 16 PAHs have been investigated in the Beiluo River, China. The distribution of multiple communities in riparian groundwater was investigated by environmental DNA metabarcoding, including 16S rRNA, 18S rRNA, and COI gene sequencing for bacteria, microbial eukaryotes (including algae, fungi, and protozoa), and metazoan, respectively, followed by correlation analysis between multiple communities and PAH contamination levels. The concentration of PAHs in the Beiluo River ranged largely from 35.32 to 728.59 ng/L. Here, the Shannon's diversity index of bacteria (Firmicutes) decreased possibly due to the occurrence of Pyrene, which mainly derives from coal and biomass combustion. Furthermore, the reduced richness of fungi (Ascomycota, Basidiomycota) and algae (Chlorophyta, Chrysophyceae) can be attributed to the presence of medium molecular weight (MMW) PAHs (Pyrene, Benz(a)anthracene, Chrysene), and low molecular weight (LMW) PAHs (Naphthalene, Fluorene, Phenanthrene). The richness and Shannon's diversity index of metazoan (Arthropoda) were promoted owing to MMW PAHs (Chrysene, Fluoranthene) generated from coal and biomass combustion and traffic emission. The ecological risk of PAHs in the groundwater environment of the Beiluo River was characterized as low to medium, where LMW and MMW PAHs posed higher risk than the high molecular weight (HMW) compounds. Overall, this study provides insights into the structures of riparian multi-biological communities altered by PAHs.

Urinary polycyclic aromatic hydrocarbon excretion and regional body fat distribution: evidence from the U.S. National Health and Nutrition Examination Survey 2001-2016.

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants that may contribute to the etiology of obesity. However, it is unclear whether PAHs from environmental sources are associated with regional body fat distribution, and whether the association varies across racial/ethnic groups who may have differential PAH exposure patterns. OBJECTIVES: To examine correlations between PAHs and body fat distribution, and potential racial/ethnic differences among U.S. adults. METHODS: Ten PAHs were measured in spot urine samples from 2691 non-smoking adults (age ≥ 20 years) in the NHANES 2001-2016. Dual-energy X-ray absorptiometry was used to measure fat mass percent (FM%). Partial Pearson correlation coefficients (r) with multivariable adjustment were used to assess PAH-FM% associations. RESULTS: In the total population, 1-naphthalene, 3-fluorene, and 1-pyrene were inversely correlated with total FM% or trunk FM% (adjusted r ranged: - 0.06 to - 0.08), while 2-naphthalene, 9-fluorene, and 4-phenanthrene were positively correlated with the FM% measurements (r: 0.07-0.11). PAH levels are highest among non-Hispanic Blacks, followed by Hispanics and Whites and some of the correlations were different by these races/ethnicities. Among non-Hispanic Whites, no PAH was correlated with FM%. In contrast, 9-fluorene was positively correlated with total FM% (r = 0.20) and trunk FM% (r = 0.22) among Blacks, and 4-phenanthrene was positively correlated with total FM% (r = 0.23) and trunk FM% (r = 0.24) among Hispanics (P-interaction: 0.010-0.025). DISCUSSION: In this US adult population, certain PAHs are significantly associated with higher body fat contents among non-Hispanic Blacks and Hispanics but not non-Hispanic Whites, suggesting that minority groups might be particularly susceptible to PAH's obesogenic effects or the effects of other factors that determine the PAH exposure levels. Alternatively, differences in body composition may contribute to differential PAH metabolism in minority groups. Future studies are warranted to explore the racial/ethnic disparity in PAH exposures, drivers of these exposure differences, and mechanisms through which PAHs may influence body composition by races/ethnicities.

Assessment of the exposure to polycyclic aromatic hydrocarbons in users of various tobacco/nicotine products by suitable urinary biomarkers.

Polycyclic aromatic hydrocarbons (PAHs) occur naturally (bitumen and oils) and are formed during all incomplete combustions of organic materials. PAH exposure sources are manifold and include specific workplaces, ambient air, various foodstuffs, tobacco smoke and some medications. At least four members of this class of chemicals have been classified as proven or probable human carcinogens. Assessment of the exposure to PAHs with suitable methods is of importance, particularly in users of new-generation tobacco/nicotine products, which are intended to replace combustible cigarettes (CCs), a major source of non-occupational exposure to PAHs. In a clinical study comprising a period of 74 h under confinement, we investigated the exposure to naphthalene (Nap), fluorene (Flu), phenanthrene (Phe), pyrene (Pyr) and benzo[a]pyrene (BaP) by measuring urinary monohydroxy-PAH (OH-PAH) derived from these parent compounds in habitual users of CCs, electronic cigarettes (ECs), heated tobacco products (HTPs), oral tobacco (OT), and nicotine replacement therapy products (NRTs). Non-users (NU) of any tobacco/nicotine products served as (negative) control group. Smokers exhibited the highest levels for all PAH biomarkers measured, almost all of which were significantly different from the NU and user groups of all other products investigated. CC smokers were the only group which showed a significant relationship between almost all PAH biomarkers and dose markers such as daily consumption, urinary nicotine equivalents (Nequ) and plasma cotinine (CotP). The ratios in urinary OH-PAH between CC and all other groups were dependent on the biomarker and range from < 2 to > 10. These ratios could at least partly be explained by the enzymes involved, their region-selectivity and inducibility by smoking. In conclusion, cigarette smokers (CC) were the only group, which showed product use dependent exposure to PAHs, whereas users of EC, HTP, NRT and OT were not distinguishable from NU of any tobacco/nicotine products.

Exposure assessment of polycyclic aromatic hydrocarbons in refined coal tar sealant applications.

BACKGROUND: Refined coal tar sealant (RCTS) emulsions are used to seal the surface of asphalt pavement. Nine of the 22 polycyclic aromatic hydrocarbons (PAHs) evaluated in this study are classified as known, probable, or possible human carcinogens. Exposure assessment research for RCTS workers has not been published previously. OBJECTIVES: The overall objective of this study was to develop a representative occupational exposure assessment of PAH exposure for RCTS workers based on worksite surveys. The specific aims were to: 1) quantify full-shift airborne occupational exposures to PAHs among RCTS workers; 2) quantify workers' dermal exposures to PAHs; 3) quantify biomarkers of PAH exposure in workers' urine; 4) identify specific job titles associated with RCTS exposure; and 5) apply these results to a biological exposure index to assess risk of potential genotoxicity from occupational exposures. METHODS: A total of twenty-one RCTS workers were recruited from three companies. Personal and area air samples were collected using a modification of NIOSH Method 5515. Dermal exposure was assessed by hand and neck wipes before and after shifts. Twenty-two PAHs were quantified via gas chromatography-mass spectrometry selected ion monitoring. Internal dose was estimated by quantifying select PAH metabolites in pre- and post-shift urine samples using on-line solid phase extraction-high performance liquid chromatography-tandem mass spectrometry. RESULTS: PAH levels in the worker breathing zones were highest for naphthalene, acenaphthene, and phenanthrene, with geometric means of 52.1, 11.4, and 9.8 µg/m3, respectively. Hand wipe levels of phenanthrene, fluoranthene and pyrene were the highest among the 22 PAHs with geometric means of 7.9, 7.7, and 5.5 µg/cm2, respectively. Urinary PAH biomarkers for naphthalene, fluorene, phenanthrene, and pyrene were detected in all workers and were higher for post-shift samples than those collected pre-shift. Urinary concentrations of the metabolite 1-hydroxypyrene were greater than the American Conference of Governmental Industrial Hygienists (ACGIH) Biological Exposure Index (BEI) for this metabolite in 89 percent of post-shift samples collected on the final day of the work week or field survey. Statistically significances were found between concentrations of fluorene, naphthalene, and phenanthrene in the breathing zone of workers and their corresponding urinary PAH biomarkers. Workers were placed in two work place exposure groups: applicators and non-applicators. Applicators had higher total PAH concentrations in personal breathing zone (PBZ) air samples than non-applicators and were more likely to have post-shift hand wipe concentrations significantly higher than pre-shift concentrations. Concentrations of post-shift urinary biomarkers were higher, albeit not significantly, for applicators than non-applicators. CONCLUSIONS: The exposure results from RCTS worker samples cannot be explained by proximal factors such as nearby restaurants or construction. Air and skin concentration levels were substantially higher for RCTS workers than previously published levels among asphalt workers for all PAHs. PAH profiles on skin wipes were more consistent with RCTS sealant product than air samples. Last day post-shift urinary concentrations of 1-hydroxypyrene greatly exceeded the ACGIH BEI benchmark of 2.5 µg/L in 25 of 26 samples, which suggests occupational exposure and risk of genotoxicity. When pyrene and benzo[a]pyrene were both detected, concentration ratios from personal exposure samples were used to calculate the adjusted BEI. Concentrations of 1-hydroxypyrene exceeded the adjusted BEIs for air, hand wipes, and neck wipes in most cases. These results indicate the need to increase safety controls and exposure mitigation for RCTS workers.

Cost-effectiveness of a "treat-all" strategy using Direct-Acting Antivirals (DAAs) for Japanese patients with chronic hepatitis C genotype 1 at different fibrosis stages.

AIM: To evaluate the cost-effectiveness of therapeutic strategies initiated at different stages of liver fibrosis using three direct-acting antivirals (DAAs), sofosbuvir-ledipasvir (SL), glecaprevir-pibrentasvir (GP), and elbasvir plus grazoprevir (E/G), for Japanese patients with chronic hepatitis C (CHC) genotype 1. METHODS: We created an analytical decision model reflecting the progression of liver fibrosis stages to evaluate the cost-effectiveness of alternative therapeutic strategies applied at different fibrosis stages. We compared six treatment strategies: treating all patients regardless of fibrosis stage (TA), treating individual patients with one of four treatments starting at four respective stages of liver fibrosis progression (F1S: withholding treatment at stage F0 and starting treatment from stage F1 or higher, and three successive options, F2S, F3S, and F4S), and administering no antiviral treatment (NoRx). We adopted a lifetime horizon and Japanese health insurance payers' perspective. RESULTS: The base case analysis showed that the incremental quality-adjusted life years (QALY) gain of TA by SL, GP, and E/G compared with the strategies of starting treatments for patients with the advanced fibrosis stage, F2S, varied from 0.32 to 0.33, and the incremental cost-effectiveness ratios (ICERs) were US$24,320, US$18,160 and US$17,410 per QALY, respectively. On the cost-effectiveness acceptability curve, TA was most likely to be cost-effective, with the three DAAs at the willingness to pay thresholds of US$50,000. CONCLUSIONS: Our results suggested that administration of DAA treatment for all Japanese patients with genotype 1 CHC regardless of their liver fibrosis stage would be cost-effective under ordinary conditions.

The impact of public coverage of newer hepatitis C medications on utilization, adherence, and costs in British Columbia.

BACKGROUND: Sofosbuvir and ledipasvir-sofosbuvir are both newer direct-acting antiviral agents for the treatment of hepatitis C. The high list prices for both drugs have led to concern about the budget impact for public drug coverage programs. Therefore, we studied the impact of public prescription drug coverage for both drugs on utilization, adherence, and public and private expenditure in British Columbia, Canada. METHODS: We used provincial administrative claims data from January 2014 to June 2017 for all individuals historically tested for either hepatitis C and/or human immunodeficiency virus. Using interrupted time series analysis, we examined the impact of public insurance coverage on treatment uptake, adherence (proportion of days covered), and public and private expenditures. RESULTS: Over our study period, 4,462 treatment initiations were eligible for analysis (1,131 sofosbuvir and 3,331 ledipasvir-sofosbuvir, which include 19 patients initiated on both treatments). We found the start of public coverage for sofosbuvir and ledipasvir-sofosbuvir increased treatment uptake by 154%. Adherence rates were consistently high and did not change with public coverage. Finally, public expenditure increased after the policy change, and crowded out some private expenditure. CONCLUSION: Public coverage for high-cost drugs for hepatitis C dramatically increased use of these drugs, but did not reduce adherence. From a health policy perspective, public payers should be prepared for increased treatment uptake following the availability of public coverage. However, they should not be concerned that populations without private insurance coverage will be less adherent and not finish their treatment course.

Assessment of outcome for sample of Iraqi patients with chronic hepatitis C virus infection treated by Ledipasvir/sofosbuvir drug.

OBJECTIVE: To evaluate the response to treatment by the new directly acting antivirals drugs Sofosbuvir and Ledipasvir (Harvoni), on Iraqi patients diagnosed with hepatitis C infection genotype1 and genotype 4. METHODS: This prospective study was conducted in the Gastroenterology unit of Al- Yarmouk Teaching Hospital, Baghdad, Iraq, from February 2019 to February 2020. Included were one hundred patients diagnosed with hepatitis C by antibody test and viral load. All non-cirrhotic participants received a drug containing 400 mg sofosbuvir /90 mg ledipasvir once daily for 12 weeks, whereas the cirrhotics had to take it for 24 weeks. Lab. Investigations and viral load were assessed at baseline, and twelve weeks after end of treatment. RESULTS: The predominant genotype was 1 with 58 (58 %) patients whereas genotype 4 had 42 (42%) patients. Liver cirrhosis was present in 9(9%) patients and severe renal impairment in 27(27%) patients. Undetectable viral load at the end of treatment (week 12) was observed in 96 (96%) patients whereas 4 (4%) patients were reported as non-responders. CONCLUSIONS: Excellent therapeutic results were achieved with generic combination of sofosbuvir/ledipasvir. The regimen is highly effective and tolerable with the highest viral response observed in HCV patients with genotype 1and 4, inclusive of patients with chronic renal failure or cirrhosis.

Successful use of generic direct acting antiviral medications to treat hepatitis C-a New Zealand-wide study.

AIMS: Direct acting antiviral (DAA) hepatitis C (HCV) medications are funded in New Zealand since 2016 for some and since 2019 for all genotypes. The purpose of this study was to review New Zealand-wide data of the use of generic HCV DAA medications imported through Tasmanian FixHepC Buyer's Club and the associated side effect profiles. METHODS: This is a retrospective data audit on the use of generic DAAs to treat HCV; outcomes from consecutive hepatitis C patients (naïve and pre-treated) treated with generic DAAs (sofosbuvir/ledipasvir, sofosbuvir/daclatasvir, sofosbuvir/ledipasvir, ribavirin) collected from all known sites that used Buyer's club medications in eight New Zealand district health board regions were summarised. Demographic, disease characteristics, FibroScan and blood markers' (platelets, ALT, GGT, AFP) data were collected. RESULTS: Study sample was 81.8% New Zealand European, 64.8% male of median 56.0 (IQR: 48.0-60.0) years old. Three participants (4.5%) were HIV positive. 74.7% of the participants had signs of fibrosis (F1-F4); 40.5% had cirrhosis/scaring (F4). 61.7% of the patients were naïve to treatment. 42.0%, 40.1% and 12.0% received sofosbuvir/ledipasvir, sofosbuvir/daclatasvir, sofosbuvir/velpatasvir, respectively; 32.1% also received ribavirin. 80.2% of patients received treatment for 12 weeks. 95.1% (154/162) of the sample achieved sustained virological response at 12 weeks post-treatment, 2.5% relapsed, 1.2% were lost to follow-up. The main minor side effects included fatigue, headache, difficulty sleeping, experienced by 21.7%, 7.0%, 7.0%, respectively. An average total cost for medication and monitoring was 2,027 to 2,659 NZD (12 weeks), and 3,054 to 4,260 NZD (24 weeks) per patient. CONCLUSIONS: Generic DAAs to treat hepatitis C are safe, efficient and a cheaper than branded medications option.

Toxicity assessment of Fluoranthene, Benz(a)anthracene and its mixed pollution in soil: Studies at the molecular and animal levels.

An increasing amount of Fluoranthene (Fla) and Benz(a)anthracene (BaA) is being produced and used, eventually entering the soil sediments. The accumulation of Fla and BaA will cause poisoning to typical enzymes (α-Amylase) and organisms (Eisenia fetida) in soil. However, the studies about exploring and comparing the different effects of Fla, BaA and their joint effect at different levels are rarely reported. In this paper, the different effects of Fla, BaA and their mixed pollutant on α-Amylase were evaluated and compared at the molecular level, and the effect of Fla-BaA to the antioxidant system of earthworm (Eisenia fetida) was investigated from the aspects of concentration and exposure time at the animal level. The results showed that Fla-BaA had the greatest influence on the skeleton structure and the microenvironment of amino acid residue of α-Amylase compared to Fla and BaA, and in the mixed pollutant system, the joint effect mode was additive mode. The inhibitory effect of Fla-BaA on the activity of α-Amylase was also stronger than that of the system alone. The assays at the animal level showed that low concentrations (below 5 mg/kg) of Fla-BaA increased the activity of GSH-Px and SOD while high concentrations inhibited their activity. The POD that was activated throughout the experiment period suggested its key role in the earthworm antioxidant system. Changes in T-AOC and MDA showed that long-term and high-dose of Fla-BaA exposure inhibited the antioxidant capacity of Eisenia fetida, causing lipid peroxidation and damage to cells.

Development of a long-acting direct-acting antiviral system for hepatitis C virus treatment in swine.

Chronic hepatitis C virus (HCV) infection is a leading cause of cirrhosis worldwide and kills more Americans than 59 other infections, including HIV and tuberculosis, combined. While direct-acting antiviral (DAA) treatments are effective, limited uptake of therapy, particularly in high-risk groups, remains a substantial barrier to eliminating HCV. We developed a long-acting DAA system (LA-DAAS) capable of prolonged dosing and explored its cost-effectiveness. We designed a retrievable coil-shaped LA-DAAS compatible with nasogastric tube administration and the capacity to encapsulate and release gram levels of drugs while resident in the stomach. We formulated DAAs in drug-polymer pills and studied the release kinetics for 1 mo in vitro and in vivo in a swine model. The LA-DAAS was equipped with ethanol and temperature sensors linked via Bluetooth to a phone application to provide patient engagement. We then performed a cost-effectiveness analysis comparing LA-DAAS to DAA alone in various patient groups, including people who inject drugs. Tunable release kinetics of DAAs was enabled for 1 mo with drug-polymer pills in vitro, and the LA-DAAS safely and successfully provided at least month-long release of sofosbuvir in vivo. Temperature and alcohol sensors could interface with external sources for at least 1 mo. The LA-DAAS was cost-effective compared to DAA therapy alone in all groups considered (base case incremental cost-effectiveness ratio $39,800). We believe that the LA-DAA system can provide a cost-effective and patient-centric method for HCV treatment, including in high-risk populations who are currently undertreated.

Development of human health ambient water quality criteria of 12 polycyclic aromatic hydrocarbons (PAH) and risk assessment in China.

Polycyclic aromatic hydrocarbons (PAHs) are widely distributed in various environmental media and have thus attracted extensive attention worldwide. To prevent and control PAH pollution in China, the study of ambient water quality criteria (AWQC), human health risks, and aquatic ecological risk is critical. There are no reports to date on the human health AWQC of PAHs in China. Therefore, this study first derived the human health AWQC values of 12 PAHs based on exposure data and bioaccumulation factor in China. We found that local exposure parameters and other relevant factors were key during the development of AWQC in different countries and regions, which led to differences with the reference value recommended by USEPA. Based on the incremental life time cancer risk (ILCR), hazard quotients (HQ) and potentially affected fraction (PAF) methods, the health and ecological risks of 16 PAHs were assessed subsequently. And the results are as follows: the non-carcinogenic PAHs' health risks ranged from 1.01 × 10-10 to 1.60 × 10-9, and carcinogenic PAH health risks ranged from 5.03 × 10-7 to 4.74 × 10-5. The toxic effects of 8 PAHs on aquatic organisms exhibited the following order: benzo (a) pyrene (BaP) > anthracene (Ant) > pyrene (Pye) > phenanthrene (Phe) > fluoranthene (Flua) > acenaphthene (Ace) > fluorene (Flu) > naphthalene (Nap). Among these, the ecological risks posed by Ant and BaP were the highest, according to the HQ and PAF methods.