The Antidumping Act: Proposals for Change

The Antidumping Act is in great trouble. Most of its troubles flow from a basic misconception about the role of an antidumping proceeding. A dumping case is sometimes looked on as analogous to private party litigation in which domestic producers seek to vindicate rights being injured by foreign exporters. In another view, it is sometimes regarded as analogous to a criminal proceeding in which the United States condemns and punishes certain methods of foreign price competition as unfair. In my view, it is preferable to look at an antidumping proceeding as a method of resolving a conflict in the execution of the economic foreign policy of the United States. It is not feasible to attempt to characterize most methods of price competition as fair or unfair, depending on the price charged in the home market. While egregious sales below home market prices are readily apparent, in many cases it is not known to anyone, including the foreign producer itself, whether sales are at less than fair value (hereinafter LTFV) under the American law until an exhaustive investigation has taken place. Even then, the decision is frequently arbitrary and capricious, because it depends so much upon the skill and pertinacity with which the data are presented on both sides and with which they are evaluated by the Customs Service and the Treasury Department

Urinary 8-OHdG as a Biomarker for Oxidative Stress: A Systematic Literature Review and Meta-Analysis.

Oxidative stress reflects a disturbance in the balance between the production and accumulation of reactive oxygen species (ROS). ROS are scavenged by the antioxidant system, but when in excess concentration, they can oxidize proteins, lipids, and DNA. DNA damage is usually repaired, and the oxidized products are excreted in urine. 8-hydroxy-2-deoxyguanosine is considered a biomarker for oxidative damage of DNA. It is needed to define background ranges for 8-OHdG, to use it as a measure of oxidative stress overproduction. We established a standardized protocol for a systematic review and meta-analysis to assess background ranges for urinary 8-OHdG concentrations in healthy populations. We computed geometric mean (GM) and geometric standard deviations (GSD) as the basis for the meta-analysis. We retrieved an initial 1246 articles, included 84 articles, and identified 128 study subgroups. We stratified the subgroups by body mass index, gender, and smoking status reported. The pooled GM value for urinary 8-OHdG concentrations in healthy adults with a mean body mass index (BMI) ≤ 25 measured using chemical methods was 3.9 ng/mg creatinine (interquartile range (IQR): 3 to 5.5 ng/mg creatinine). A significant positive association was observed between smoking and urinary 8-OHdG concentrations when measured by chemical analysis. No gender effect was observed

Challenges in Quantifying 8-OHdG and 8-Isoprostane in Exhaled Breath Condensate

Exhaled breath condensate (EBC) has attracted substantial interest in the last few years, enabling the assessment of airway inflammation with a non-invasive method. Concentrations of 8-Hydroxydesoxyguanosine (8-OHdG) and 8-isoprostane in EBC have been suggested as candidate biomarkers for lung diseases associated with inflammation and oxidative stress. EBC is a diluted biological matrix and consequently, requires highly sensitive chemical analytic methods (picomolar range) for biomarker quantification. We developed a new liquid chromatography coupled to tandem mass spectrometry method to quantify 8-OHdG and 8-isoprostane in EBC simultaneously. We applied this novel biomarker method in EBC obtained from 10 healthy subjects, 7 asthmatic subjects, and 9 subjects with chronic obstructive pulmonary disease. Both biomarkers were below the limit of detection (LOD) despite the good sensitivity of the chemical analytical method (LOD = 0.5 pg/mL for 8-OHdG; 1 pg/mL for 8-isoprostane). This lack of detection might result from factors affecting EBC collections. These findings are in line with methodological concerns already raised regarding the reliability of EBC collection for quantification of 8-OHdG and 8-isoprostane. Precaution is therefore needed when comparing literature results without considering methodological issues relative to EBC collection and analysis. Loss of analyte during EBC collection procedures still needs to be resolved before using these oxidative stress biomarkers in EBC

Reference ranges of oxidative stress biomarkers selected for non-invasive biological surveillance of nanotechnology workers: Study protocol and meta-analysis results for 8-OHdG in exhaled breath condensate

In the field of engineered nanomaterials (ENMs) and other airborne particulate exposure biomonitoring, circulating oxidative stress biomarkers appear promising. These biomarkers could be monitored in different biological matrices. Exhaled breath condensate (EBC) enables their measurements in the respiratory tract, without affecting airway function or creating inflammation. The 8-hydroxy-2-deoxyguanosine (8-OHdG) was found increased in the EBC of ENM-exposed workers. Our objectives were to assess the reference range of 8-OHdG in the EBC and to identify determinants of its inter- and intra-individual variability. The meta-analysis was stratified by analytical method (chemical versus immunochemical analysis) and resulted in a between-study variability over 99 % of the total variability. The between-study variability completely dominated the within-studies variability. By using a mixed model with study ID as a random effect rather than a meta-regression, only smoking was evidenced as a potential determinant of 8-OHdG inter-individual variability, and only when immunochemical analysis was used. To our knowledge, this is the first meta-analysis aimed at estimating reference values for 8-OHdG in the EBC. The estimated values should be considered preliminary, as they are based on a limited number of studies, mostly of moderate to low quality of evidence. Further research is necessary to standardize EBC sampling, storage and analytical methods. Such a standardization would enable a more accurate estimation of the reference ranges of the 8-OHdG and potentially other biomarkers measurable in the EBC, which are essential for a meaningful interpretation of the biomonitoring results

Towards Reference Values for Malondialdehyde on Exhaled Breath Condensate: A Systematic Literature Review and Meta-Analysis.

Many pathological conditions and certain airway exposures are associated with oxidative stress (OS). Malondialdehyde (MDA) is an end-product of the oxidation of lipids in our cells and is present in all biological matrices including exhaled breath condensate (EBC). To use MDA as a biomarker of OS in EBC, a reference interval should be defined. Thus, we sought to summarize reference values reported in healthy adult populations by performing a systematic review and meta-analysis using a standardized protocol registered in PROSPERO (CRD42020146623). Articles were retrieved from four major databases and 25 studies with 28 subgroups were included. Defining the distribution of MDA measured in reference populations with a detection combined with a separation technique still represents a challenge due to the low number of studies available, different analytical methods used, and questionable methodological qualities of many studies. The most salient methodological drawbacks have been in data collection and reporting of methods and study results by the researchers. The lack of compliance with the recommendations of the European Respiratory Society and American Thoracic Society was the major limitation in the current research involving EBC. Consequently, we were unable to establish a reference interval for MDA in EBC

Metal and oxidative potential exposure through particle inhalation and oxidative stress biomarkers: a 2-week pilot prospective study among Parisian subway workers.

In this pilot study on subway workers, we explored the relationships between particle exposure and oxidative stress biomarkers in exhaled breath condensate (EBC) and urine to identify the most relevant biomarkers for a large-scale study in this field. We constructed a comprehensive occupational exposure assessment among subway workers in three distinct jobs over 10 working days, measuring daily concentrations of particulate matter (PM), their metal content and oxidative potential (OP). Individual pre- and post-shift EBC and urine samples were collected daily. Three oxidative stress biomarkers were measured in these matrices: malondialdehyde (MDA), 8-hydroxy-2'deoxyguanosine (8-OHdG) and 8-isoprostane. The association between each effect biomarker and exposure variables was estimated by multivariable multilevel mixed-effect models with and without lag times. The OP was positively associated with Fe and Mn, but not associated with any effect biomarkers. Concentration changes of effect biomarkers in EBC and urine were associated with transition metals in PM (Cu and Zn) and furthermore with specific metals in EBC (Ba, Co, Cr and Mn) and in urine (Ba, Cu, Co, Mo, Ni, Ti and Zn). The direction of these associations was both metal- and time-dependent. Associations between Cu or Zn and MDA <sub>EBC</sub> generally reached statistical significance after a delayed time of 12 or 24 h after exposure. Changes in metal concentrations in EBC and urine were associated with MDA and 8-OHdG concentrations the same day. Associations between MDA in both EBC and urine gave opposite response for subway particles containing Zn versus Cu. This diverting Zn and Cu pattern was also observed for 8-OHdG and urinary concentrations of these two metals. Overall, MDA and 8-OHdG responses were sensitive for same-day metal exposures in both matrices. We recommend MDA and 8-OHdG in large field studies to account for oxidative stress originating from metals in inhaled particulate matter

Malondialdehyde and anion patterns in exhaled breath condensate among subway workers.

Underground transportation systems can contribute to the daily particulates and metal exposures for both commuter and subway workers. The redox and metabolic changes in workers exposed to such metal-rich particles have yet to be characterized. We hypothesize that the distribution of nitrosative/oxidative stress and related metabolic biomarkers in exhaled breath condensate (EBC) are modified depending on exposures. Particulate number and size as well as mass concentration and airborne metal content were measured in three groups of nine subway workers (station agents, locomotive operators and security guards). In parallel, pre- and post-shift EBC was collected daily during two consecutive working weeks. In this biological matrix, malondialdehyde, lactate, acetate, propionate, butyrate, formate, pyruvate, the sum of nitrite and nitrate (ΣNO <sub>x</sub> ) and the ratio nitrite/nitrate as well as metals and nanoparticle concentrations was determined. Weekly evolution of the log-transformed selected biomarkers as well as their association with exposure variables was investigated using linear mixed effects models with the participant ID as random effect. The professional activity had a strong influence on the pattern of anions and malondialdehyde in EBC. The daily number concentration and the lung deposited surface area of ultrafine particles was consistently and mainly associated with nitrogen oxides variations during the work-shift, with an inhibitory effect on the ΣNO <sub>x</sub> . We observed that the particulate matter (PM) mass was associated with a decreasing level of acetate, lactate and ΣNO <sub>x</sub> during the work-shift, suggestive of a build-up of these anions during the previous night in response to exposures from the previous day. Lactate was moderately and positively associated with some metals and with the sub-micrometer particle concentration in EBC. These results are exploratory but suggest that exposure to subway PM could affect concentrations of nitrogen oxides as well as acetate and lactate in EBC of subway workers. The effect is modulated by the particle size and can correspond to the body's cellular responses under oxidative stress to maintain the redox and/or metabolic homeostasis