RLS-0071, a novel anti-inflammatory agent, significantly reduced inflammatory biomarkers in a randomised human evaluation of mechanisms and safety study.

Background: This study was a randomised, double-blind, placebo-controlled study intended to establish the translatability of the RLS-0071 mechanisms of action from animal disease models to humans by inhibiting neutrophil-mediated inflammation at the tissue level and major inflammatory biomarkers. We hypothesised that RLS-0071 inhibits a temporary neutrophil-mediated inflammation in the lungs induced by inhalation of low-dose lipopolysaccharide (LPS) in healthy participants.

Methods: Participants were randomised to one of three arms to receive inhaled LPS followed by three doses of either low-dose (10 mg·kg) or high-dose (120 mg·kg loading dose followed by two doses of 40 mg·kg) RLS-0071 or placebo (saline) every 8 h.

Range of the perfluorooctanoate (PFOA) safe dose for human health: An international collaboration.

Many government agencies and expert groups have estimated a dose-rate of perfluorooctanoate (PFOA) that would protect human health. Most of these evaluations are based on the same studies (whether of humans, laboratory animals, or both), and all note various uncertainties in our existing knowledge. Nonetheless, the values of these various, estimated, safe-doses vary widely, with some being more than 100,000 fold different.

Can Incorrect Analysis of Time-Dependent Exposure Explain Associations between PM2.5 Exposure and Risk of Dementia?

Background: Epidemiological studies have reported positive associations between long-term exposure to particulate matter of 2.5 microns or less in diameter (PM2.5) and risk of Alzheimer's disease and other clinical dementia.

Integration of Evidence on Community Cancer Risks from Elongate Mineral Particles in Silver Bay, Minnesota.

The potential for cancer-related risks to community members from ambient exposure to elongate mineral particles (EMPs) in taconite processing has not been formally evaluated. We evaluated 926 ambient air samples including 12,928 EMPs (particle structures with length-to-width ratio ≥3:1) collected over 26 years near a taconite processing facility in Silver Bay, Minnesota. Eighty-two percent of EMPs were ≤3 μm in length and 97% of EMPs had an average aspect ratio <20:1.

Peak Exposures in Epidemiologic Studies and Cancer Risks: Considerations for Regulatory Risk Assessment.

We review approaches for characterizing "peak" exposures in epidemiologic studies and methods for incorporating peak exposure metrics in dose-response assessments that contribute to risk assessment. The focus was on potential etiologic relations between environmental chemical exposures and cancer risks. We searched the epidemiologic literature on environmental chemicals classified as carcinogens in which cancer risks were described in relation to "peak" exposures.

Six years after the NRC review of EPA's Draft IRIS Toxicological Review of Formaldehyde: Regulatory implications of new science in evaluating formaldehyde leukemogenicity.

Shortly after the International Agency for Research on Cancer (IARC) determined that formaldehyde causes leukemia, the United States Environmental Protection Agency (EPA) released its Draft IRIS Toxicological Review of Formaldehyde ("Draft IRIS Assessment"), also concluding that formaldehyde causes leukemia. Peer review of the Draft IRIS Assessment by a National Academy of Science committee noted that "causal determinations are not supported by the narrative provided in the draft" (NRC 2011). They offered recommendations for improving the Draft IRIS assessment and identified several important research gaps.

Cancer Risk Associated With Exposure to Bitumen and Bitumen Fumes: An Updated Systematic Review and Meta-Analysis.

Objective: To evaluate whether cancer risks are increased among bitumen (asphalt) workers.

Methods: Systematic review and meta-analysis of cancer risks (lung, upper aerodigestive tract (UADT), esophagus, bladder, kidney, stomach, and skin) and bitumen exposure. Certainty in the epidemiological evidence that bitumen-exposed workers experience increased cancer risks was rated using Grading of Recommendations Assessment, Development and Evaluation criteria.

Quantitative estimated exposure to vinyl chloride and risk of angiosarcoma of the liver and hepatocellular cancer in the US industry-wide vinyl chloride cohort: mortality update through 2013.

Objective: To evaluate mortality risks of angiosarcoma of the liver (ASL), primary hepatocellular carcinoma (HCC) and other cancers among 9951 men employed between 1942 and 1972 at 35 US vinyl chloride (VC) or polyvinyl chloride plants followed for mortality through 31 December 2013.

Methods: SMR and time-dependent Cox proportional hazards analyses were used to evaluate mortality risks by cumulative VC exposure.

Results: Liver cancer mortality was elevated (SMR=2.

Does occupational exposure to formaldehyde cause hematotoxicity and leukemia-specific chromosome changes in cultured myeloid progenitor cells?

Several cross-sectional studies of a single population of workers exposed to formaldehyde at one of two factories using or producing formaldehyde-melamine resins in China have concluded that formaldehyde exposure induces damage to hematopoietic cells that originate in the bone marrow. Moreover, the investigators interpret observed differences between groups as evidence that formaldehyde induces myeloid leukemias, although the mechanisms for inducing these diseases are not obvious and recently published scientific findings do not support causation. Our objective was to evaluate hematological parameters and aneuploidy in relation to quantitative exposure measures of formaldehyde.

Meta-Analysis of Cardiac Mortality in Three Cohorts of Carbon Black Production Workers.

Epidemiological studies have demonstrated associations between airborne environmental particle exposure and cardiac disease and mortality; however, few have examined such effects from poorly soluble particles of low toxicity such as manufactured carbon black (CB) particles in the work place. We combined standardised mortality ratio (SMR) and Cox proportional hazards results from cohort studies of US, UK and German CB production workers. Under a common protocol, we analysed mortality from all causes, heart disease (HD), ischemic heart disease (IHD) and acute myocardial infarction (AMI).

Assessment of blood lead level declines in an area of historical mining with a holistic remediation and abatement program.

Unlabelled: Lead exposure and blood lead levels (BLLs) in the United States have declined dramatically since the 1970s as many widespread lead uses have been discontinued. Large scale mining and mineral processing represents an additional localized source of potential lead exposure in many historical mining communities, such as Butte, Montana. After 25 years of ongoing remediation efforts and a residential metals abatement program that includes blood lead monitoring of Butte children, examination of blood lead trends offers a unique opportunity to assess the effectiveness of Butte's lead source and exposure reduction measures.

Cohort Study of Carbon Black Exposure and Risk of Malignant and Nonmalignant Respiratory Disease Mortality in the US Carbon Black Industry.

Objective: To evaluate lung cancer and respiratory disease mortality associations with cumulative inhalable carbon black exposure among 6634 US carbon black workers.

Methods: This analysis was performed using standardized mortality ratio (SMRs) and Cox regression analyses.

Results: Lung cancer mortality was decreased overall (SMR = 0.

Formaldehyde Exposure and Mortality Risks From Acute Myeloid Leukemia and Other Lymphohematopoietic Malignancies in the US National Cancer Institute Cohort Study of Workers in Formaldehyde Industries.

Objectives: To evaluate associations between cumulative and peak formaldehyde exposure and mortality from acute myeloid leukemia (AML) and other lymphohematopoietic malignancies.

Methods: Cox proportional hazards analyses.

Results: Acute myeloid leukemia was unrelated to cumulative exposure.

Exposure Reconstruction and Risk Analysis for Six Semiconductor Workers With Lymphohematopoietic Cancers.

Objective: To investigate whether workplace exposures to recognized lymphohematopoietic carcinogens were possibly related to cancers in six semiconductor-manufacturing workers.

Methods: A job-exposure matrix was developed for chemical and physical process agents and anticipated by-products. Potential cumulative occupational exposures of the six cases were reconstructed.

Comparative Risks of Cancer from Drywall Finishing Based on Stochastic Modeling of Cumulative Exposures to Respirable Dusts and Chrysotile Asbestos Fibers.

Sanding joint compounds is a dusty activity and exposures are not well characterized. Until the mid 1970s, asbestos-containing joint compounds were used by some people such that sanding could emit dust and asbestos fibers. We estimated the distribution of 8-h TWA concentrations and cumulative exposures to respirable dusts and chrysotile asbestos fibers for four worker groups: (1) drywall specialists, (2) generalists, (3) tradespersons who are bystanders to drywall finishing, and (4) do-it-yourselfers (DIYers).

A model to systematically employ professional judgment in the Bayesian Decision Analysis for a semiconductor industry exposure assessment.

Bayesian Decision Analysis (BDA) uses Bayesian statistics to integrate multiple types of exposure information and classify exposures within the exposure rating categorization scheme promoted in American Industrial Hygiene Association (AIHA) publications. Prior distributions for BDA may be developed from existing monitoring data, mathematical models, or professional judgment. Professional judgments may misclassify exposures.

State-of-the-science assessment of non-asbestos amphibole exposure: is there a cancer risk?

The distinction between amphibole asbestos fibers and non-asbestos amphibole particles has important implications for assessing potential cancer risks associated with exposure to amphibole asbestos or amphibole-containing products. Exposure to amphibole asbestos fibers can pose a cancer risk due to its ability to reside for long periods of time in the deep lung (i.e.

A cohort mortality study of employees in the U.S. carbon black industry.

Objectives: The objectives of this study are to evaluate historical mortality patterns, especially due to cancers, among employees of the U.S. carbon black industry and to address the methodological shortcomings of previous U.

Lung cancer mortality in the German chromate industry, 1958 to 1998.

Objectives: We conducted a mortality study of two German chromate production facilities and evaluated possible dose-response relationships between hexavalent chromium exposure and lung cancer.

Methods: Mortality was followed-up through 1998 and limited to those employed since each plant converted to a no-lime production process. More than 12,000 urinalysis results of chromium levels were available, as was smoking information.

Low-level hexavalent chromium exposure and rate of mortality among US chromate production employees.

Objective: Although numerous studies have reported an elevated lung cancer risk among chromium chemical production employees, few studies have focused on employees hired after major process changes and enhanced industrial hygiene controls were implemented.

Methods: This study examines the mortality experience of two post-change cohorts of chromate production employees constituting the current US chromium chemical industry.

Results: Mortality among chromium chemical workers generally was lower than expected on the basis of national and state-specific referent populations.

Meta-analysis of studies of occupational exposure to vinyl chloride in relation to cancer mortality.

Objective: A meta-analysis was made of studies addressing occupational exposure to vinyl chloride in relation to cancer mortality.

Methods: Two recently updated multicenter cohort studies and six smaller studies were identified. For selected neoplasms, standardized mortality ratios (SMR) and 95% confidence intervals (95% CI) were abstracted (or calculated from raw data).