1. The document proposes a biological occupational exposure limit (BOEL) for polycyclic aromatic hydrocarbons (PAH) of 1.0 μmol/mol creatinine for 1-hydroxypyrene in urine. This limit is based on the lowest observed level without genotoxic effects found in a meta-analysis of studies.
2. The limit accounts for different PAH profiles by adjusting the limit based on the pyrene to benzo(a)pyrene ratio, with a default ratio of 2.5 corresponding to the proposed limit of 1.0 μmol/mol creatinine.
3. While an occupational exposure limit of 200 ng/m3 for benzo(a)py
Guar Gum Originating from India - Contamination with PCP & Dioxins - Resources for Healthy Children www.scribd.com/doc/254613619 - For more information, Please see Organic Edible Schoolyards & Gardening with Children www.scribd.com/doc/254613963 - Gardening with Volcanic Rock Dust www.scribd.com/doc/254613846 - Double Food Production from your School Garden with Organic Tech www.scribd.com/doc/254613765 - Free School Gardening Art Posters www.scribd.com/doc/254613694 - Increase Food Production with Companion Planting in your School Garden www.scribd.com/doc/254609890 - Healthy Foods Dramatically Improves Student Academic Success www.scribd.com/doc/254613619 - City Chickens for your Organic School Garden www.scribd.com/doc/254613553 - Huerto Ecológico, Tecnologías Sostenibles, Agricultura Organica www.scribd.com/doc/254613494 - Simple Square Foot Gardening for Schools - Teacher Guide www.scribd.com/doc/254613410 - Free Organic Gardening Publications www.scribd.com/doc/254609890 ~
Guar Gum Originating from India - Contamination with PCP & Dioxins - Resources for Healthy Children www.scribd.com/doc/254613619 - For more information, Please see Organic Edible Schoolyards & Gardening with Children www.scribd.com/doc/254613963 - Gardening with Volcanic Rock Dust www.scribd.com/doc/254613846 - Double Food Production from your School Garden with Organic Tech www.scribd.com/doc/254613765 - Free School Gardening Art Posters www.scribd.com/doc/254613694 - Increase Food Production with Companion Planting in your School Garden www.scribd.com/doc/254609890 - Healthy Foods Dramatically Improves Student Academic Success www.scribd.com/doc/254613619 - City Chickens for your Organic School Garden www.scribd.com/doc/254613553 - Huerto Ecológico, Tecnologías Sostenibles, Agricultura Organica www.scribd.com/doc/254613494 - Simple Square Foot Gardening for Schools - Teacher Guide www.scribd.com/doc/254613410 - Free Organic Gardening Publications www.scribd.com/doc/254609890 ~
Our objective is to demonstrate how Total Organic Carbon (TOC) analysis is a quick, accurate screening alternative for critiquing cleaning validation samples.
Typical laboratory testing includes the development and implementation of analytical methods that test for residues of previously manufactured products, cleaning detergents, chemicals, solvents, byproducts, degradants, and microbial contaminates (from wet environments after the cleaning validation). TOC analysis has become one of a series of analytical methods used to assess the effectiveness of a cleaning validation. Almost any residual compound can be detected if three non-specific analytical (screening) tests are applied to a cleaning validation: TOC (for organics characteristics– carbon), pH (for acid/base characteristics) and conductivity (for ionic characteristics).
Analytical precision and analyte recovery for cleaning agents (detergents) and other possible contaminates that may be found in clean in place (CIP) solutions will be investigated for TOC. TOC analysis demonstrated equivalent or better correlation to cleaning validation compounds in comparison to traditional analytical methods. Some qualities that make TOC a viable part of a cleaning validation includes: high sensitivity, high recovery of samples, non-specific measurement, ease of use (little method development), minimal interferences and cost effectiveness.
This presentation will focus on the characteristics and benefits of TOC with general implementation guidelines for performing cleaning validation. By taking a proactive approach to one’s cleaning validation program, one can guarantee effective performance while minimizing downtime.
Remediation of Volatile Organics in Groundwater Using In Situ Carbon (ISC) In...Antea Group
Presented at this year's Battelle Conference by Jack Sheldon, this presentation includes information comparing various forms of groundwater remediation tactics using In Situ Carbon (ISC) injections.
Marike Kolossa-Gehring: The Chemical Challenge - How HBM4EU Can HelpTHL
Marike Kolossa-Gehring, Coordinator of HBM4EU, German Environment Agency, at Europe That Protects - Safeguarding Our Planet, Safeguarding Our Health EU side event, 3-4 Dec 2019, THL, Helsinki
Early Phase Pharmacodynamic Models For Respiratory Drug CandidatesSGS
The prevalence of respiratory diseases is increasing worldwide. The most common types are asthma and chronic obstructive pulmonary disease (COPD). Enlarged exposure to certain risk factors and the aging population are responsible for this increase. The large majority of treatments in this therapeutic area consist of inhalation therapy. One of the causes of the rising cost for development of new drugs and the high failure rate is the lack of sensitivity of pharmacodynamics techniques used in translational medicine. In this presentation an overview of current techniques in early development will be given. There will be a special attention for the study of drug disposition in the bronchial tree with techniques like local bronchial pharmacokinetics. Bronchoalveolar lavage may be a promising technique for evaluating drug concentrations and biomarkers in alveolar lining fluid.
Contact Us: clinicalresearch@sgs.com
Visit our Website: http://www.sgs.com/cro
Follow Us on LinkedIn: http://bit.ly/SGSLifeSciences
Enzyme based Biosensor for pesticide DetectionSubhasis Sarkar
The biosensors could be used for pesticides rapid detection with a good stability and repeatability. As a new analytical method, biosensor could be widely used in the determination of food contamination. Biosensor techniques based on the principle of specific biological-recognition have shown satisfactory results for environmental control, food quality monitoring and toxicity detection in recent years. All these detection methods based on biosensors were shorter time response and lower cost comparing with the traditional method, but these methods were not enough convenient to use, moreover, complex detection procedures make them unsuitable for commercial and industrial applications.
Glyphosate research papers - Compiled by Dr.Alex Vasquez and Dr Eva Sirinaths...João Soares
Uma compilação de resumos de artigos científicos sobre os malefícios do glifosato sobre o ambiente, os animais e a saúde pública. Esta compilação foi efectuada pelo Dr. Alex Vasquez e a Dr. Eva Sirinathsinghji, do Instituto de Ciências na Sociedade e contém 245 páginas.
«Glyphosate Research Compilation – Abstracts of studies: Glyphosate’s adverse effects on the environment & on animal & human health - by Dr. Alex Vasquez & Dr. Eva Sirinathsinghji, Institute of Science in Society (245 pages)»
EU REACH regulation changed the way to do chemical risk assessment. All chemicals marketed or manufactured in the EU must have its own dossier. Non standard methods including alternatives to animal testing are accepted.
Half Italian, half English
Our objective is to demonstrate how Total Organic Carbon (TOC) analysis is a quick, accurate screening alternative for critiquing cleaning validation samples.
Typical laboratory testing includes the development and implementation of analytical methods that test for residues of previously manufactured products, cleaning detergents, chemicals, solvents, byproducts, degradants, and microbial contaminates (from wet environments after the cleaning validation). TOC analysis has become one of a series of analytical methods used to assess the effectiveness of a cleaning validation. Almost any residual compound can be detected if three non-specific analytical (screening) tests are applied to a cleaning validation: TOC (for organics characteristics– carbon), pH (for acid/base characteristics) and conductivity (for ionic characteristics).
Analytical precision and analyte recovery for cleaning agents (detergents) and other possible contaminates that may be found in clean in place (CIP) solutions will be investigated for TOC. TOC analysis demonstrated equivalent or better correlation to cleaning validation compounds in comparison to traditional analytical methods. Some qualities that make TOC a viable part of a cleaning validation includes: high sensitivity, high recovery of samples, non-specific measurement, ease of use (little method development), minimal interferences and cost effectiveness.
This presentation will focus on the characteristics and benefits of TOC with general implementation guidelines for performing cleaning validation. By taking a proactive approach to one’s cleaning validation program, one can guarantee effective performance while minimizing downtime.
Remediation of Volatile Organics in Groundwater Using In Situ Carbon (ISC) In...Antea Group
Presented at this year's Battelle Conference by Jack Sheldon, this presentation includes information comparing various forms of groundwater remediation tactics using In Situ Carbon (ISC) injections.
Marike Kolossa-Gehring: The Chemical Challenge - How HBM4EU Can HelpTHL
Marike Kolossa-Gehring, Coordinator of HBM4EU, German Environment Agency, at Europe That Protects - Safeguarding Our Planet, Safeguarding Our Health EU side event, 3-4 Dec 2019, THL, Helsinki
Early Phase Pharmacodynamic Models For Respiratory Drug CandidatesSGS
The prevalence of respiratory diseases is increasing worldwide. The most common types are asthma and chronic obstructive pulmonary disease (COPD). Enlarged exposure to certain risk factors and the aging population are responsible for this increase. The large majority of treatments in this therapeutic area consist of inhalation therapy. One of the causes of the rising cost for development of new drugs and the high failure rate is the lack of sensitivity of pharmacodynamics techniques used in translational medicine. In this presentation an overview of current techniques in early development will be given. There will be a special attention for the study of drug disposition in the bronchial tree with techniques like local bronchial pharmacokinetics. Bronchoalveolar lavage may be a promising technique for evaluating drug concentrations and biomarkers in alveolar lining fluid.
Contact Us: clinicalresearch@sgs.com
Visit our Website: http://www.sgs.com/cro
Follow Us on LinkedIn: http://bit.ly/SGSLifeSciences
Enzyme based Biosensor for pesticide DetectionSubhasis Sarkar
The biosensors could be used for pesticides rapid detection with a good stability and repeatability. As a new analytical method, biosensor could be widely used in the determination of food contamination. Biosensor techniques based on the principle of specific biological-recognition have shown satisfactory results for environmental control, food quality monitoring and toxicity detection in recent years. All these detection methods based on biosensors were shorter time response and lower cost comparing with the traditional method, but these methods were not enough convenient to use, moreover, complex detection procedures make them unsuitable for commercial and industrial applications.
Glyphosate research papers - Compiled by Dr.Alex Vasquez and Dr Eva Sirinaths...João Soares
Uma compilação de resumos de artigos científicos sobre os malefícios do glifosato sobre o ambiente, os animais e a saúde pública. Esta compilação foi efectuada pelo Dr. Alex Vasquez e a Dr. Eva Sirinathsinghji, do Instituto de Ciências na Sociedade e contém 245 páginas.
«Glyphosate Research Compilation – Abstracts of studies: Glyphosate’s adverse effects on the environment & on animal & human health - by Dr. Alex Vasquez & Dr. Eva Sirinathsinghji, Institute of Science in Society (245 pages)»
EU REACH regulation changed the way to do chemical risk assessment. All chemicals marketed or manufactured in the EU must have its own dossier. Non standard methods including alternatives to animal testing are accepted.
Half Italian, half English
Bisphenol A is an additive used in the production of polycarbonate plastics and epoxy resins. These synthetic materials are widely used in food packaging to protect the safety and integrity of foods and beverages. BPA has been discovered to be an endocrine disruptor which can mimic the body's own hormones and may lead to negative health effects and this has generated concern over the leaching of the compound from packaging into food. This presentation describes the analysis of BPA and related compounds in baby food and infant formula using UPLC and tandem quadrupole mass spectrometry.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
For Better Surat #ℂall #Girl Service ❤85270-49040❤ Surat #ℂall #Girls
Limit value for urinary 1-hydroxypyrene as marker of occupational exposure to PAH
1. 1
Limit value of 1-hydroxypyrene in urine
for occupational PAH exposure
Frans Jongeneelen
IndusTox Consult
ISBM Manchester 2013
2. 2
Take home message
1-Hydroxypyrene in urine (µmol/mol)
1,5
1,0
LOL-GEB = Lowest observed level without genotoxic effects in the body
0,5
Non-occupational background
0,0
3. 3
Updated proposal for BOEL of PAH
Reason for new proposal
– New occupational exposure limit (OEL) in
Netherlands for PAH has been proposed
OEL of PAH = 200 ng/m3 as benzo(a)pyrene
– Companies and employees have a positive
experience and a positive attitude to biological
monitoring of PAH, however, a biological limit
was not proposed
– Employers and Unions requested us to derive
an equivalent biological occupational exposure
limit (BOEL)
5. 5
Introduction
Biological monitoring of PAH
Working environment
Gaseous and particulate PAH
Worker
Uptake of PAH by:
inhalation
dermal absorption
ingestion
6. 6
Introduction
Occupational PAH-exposure
PAH are present as complex mixtures
In gasphase and particulate matter
Dermal exposure may be significant
PAH-profile varies in between industries
and sometimes within industries
Carcinogenic potency of PAH varies: 4-6
ring components have highest potency
–
–
–
–
–
–
–
Benzo(a)pyrene = carcinogenic PAH with high potency
Pyrene = non-carcinogenic PAH
7. 7
Introduction
Biological indicator of PAH
PAH are metabolized in all tissues of the body
Each PAH has different metabolite pattern with
various toxic and non-toxic metabolites
Hydroxylated-PAH metabolites are rapidly
excreted in urine. Examples:
–
–
–
1- OH-pyrene
OH-phenantrenes
3- OH-b(a)p
8. 8
Biological indicator of PAH
Most experience: 1-hydroxypyrene in
urine
In humans, pyrene is metabolized
to the main metabolite 1hydroxypyrene, conjugated and
excreted in urine
First proposed as indicatormetabolite in 1985
Often used in scientific studies
and field testing of exposure
9. 9
Biological indicator of PAH
Other hydroxylated PAH-metabolites
as biological indicator
∑ OH-Phenantrenes
–
–
Series of up to 10 hydroxylated-PAH metabolites
–
–
Indicator of volatile PAH
Example: Germany
Not widely used
Example: US NHANES-study
3-OH-B(a)P
–
–
–
B(a)P is indicator of risk of PAH
Low concentrations in urine
Little experience, few labs
10. Biological indicator of PAH
Present status of monitoring of
PAH-metabolites in urine
– 3-OH-B(a)P has potential as bioindicator
Metabolite of B(a)P, the PAH with high carcinogenic
potency, but:
– Few labs, limited experience
– Excretion kinetics?
– Rubustness analytical method?
– 1-Hydroxypyrene is sound bioindicator
Many studies from various industries & countries
shows that it is a valuable tool for controlling exposure
Analytical method has proven to be solid
Elimination rate is known => end-of-workweek post
shift urine sampling
– However, pyrene content varies, adjustment is needed for
health risk assessment
10
11. 11
Biological occupational exposure limit of urinary 1-hydroxypyrene
Existing biological limits (1)
HSE - UK 2004: Biological monitoring guidance value
Control-based biological monitoring guidance value
Based on 90th-percentile of urine levels of workers in
‘good hygiene practice’ industries
Benchmark value: 4.0 μmol/mol creat
ACGIH - USA 2005: Biological exposure index
Health-based biological exposure index of 1hydroxypyrene in urine scientifically not justified, due to
insufficient data: No BEI!
However, measurement of 1-hydroxypyrene is valuable
tool for controlling exposure
Recommendation: control exposure towards the level in
general population
Reference level as 99-percentile of general
population = 1.0 μg/L = 0.5 μmol/mol creaat
12. 12
Biological occupational exposure limit of urinary 1-hydroxypyrene
Existing biological limits (2)
In a table:
Organisation
Country
HSE
UK
Type
BMGV – not health based, but
based on good hygiene practice
BEI
ACGIH
Limit level
(mol/mol)
4.0
Nq = nonquantitative
USA
Level that warrants occupational
exposure
0.5
13. 13
How to derive the biological limit that is
equal to health risk of exposure to 200
ng/m3 b(a)p?
Two indirect approaches are possible:
1.
Estimate urine level in workers equal to airborne
exposure at 200 ng/m3 b(a)p from meta-analysis of
cross-sectional exposure studies
2.
Derive urine level in workers without early genotoxic
effects from meta-analysis of cross-sectional early
effect studies
14. Updated biological exposure limit of PAH
14
Procedure for derivation of level of 1hydroxypyrene in urine without genotoxic
effects
1.
Search in scientific literature for cross-sectional studies
of PAH-exposed workers with:
One or more genotoxic effect markers (in lymphocytes)
Determination of 1-hydroxypyrene in urine as exposure
indicator
2.
Analyse each study and estimate the level of 1hydroxypyrene in urine at which no genotoxic effect was
observed.
3.
Select study with lowest effect level as key-study. This
key-study holds: ‘Lowest observed level without
genotoxic effect`in the body (= LOL-GEB)’
15. 15
Updated biological exposure limit of PAH
Search for relevant studies
Various
bibliographic databases were consulted
Studies from 1990 – 2012
Cross-sectional studies of PAH-exposed
workers
– with genotoxic effects in lymphocytes
– with 1-hydroxypyrene in urine
– threshold of genotoxic effect(s) can be derived
9 Studies were found, that met the criteria
16. 16
Updated biological exposure limit of PAH
Biomarkers of genotoxicity in studies of
PAH-exposed workers
Endpoint
Name of test
In short
Chromosomal disorders
in structure or number
Chromosomal aberrations
CA
Breaks in and
exchanges of DNAstrands
Sister chromatid exchange frequency
SCE
High frequency sister chromatid
exchange frequency
HFC-SCE
Chromosomal disorders
during replication
Micronucleus-test
MN
Cytokinesis Block Micronucleus-test
CBMN
NucleoPlasmic bridges
NPB
Nuclear Buds
NBUD
Single Cell Gel Electrophoresis assay
Comet
DNA-damage
(strand breaks)
17. 17
Updated biological exposure limit of PAH
Characteristics of studies of PAH-exposed
workers with 1-OH-pyrene and genotoxic effects
Nr
Study subjects
Genotoxic
endpoints
1
Belgian coke ovenworkers + graphite
anode plant workers
Dutch primary
aluminum workers
SCE
HFC-SCE
MN
DNA-adducts
German coke oven
workers
Swedish potroom
workers
5
Dutch coke oven
workers
6
Polish coke ovenworkers.
7
Polish non-smoking
coke oven workers
Chinese coke oven
workers
Chinese coke oven
workers
2
3
4
8
9
Level of 1Pyrene/hydroxypyrene in b(a)p ratio
urine without
genotoxic effects
(mol/mol)
1.3
1.5 – 4.5
Controlled
for smoking
(Y/N)
Reference
Y
Buchet et al,
1995;
3.8
2 - 30
Y
van Schooten
et al, 1995.
SCE
Comet-assay
DNA-adducts
1.9
2.2
Y
4.3
2.8
Y
Popp et al,
1997
Carstensen et
al, 1999
SCE
HFC-SCE
MN
SCE
HFC-SCE
MN
Comet-assay
MN
DNA-adducts
MN, NPB’s and
NBUDs
CBMN
1.1
?
Y
Van Delft et al,
2001
1.0
?
Not needed
Siwinska et al,
2004
3.1
?
1.3
?
2.4
?
Only nonsmokers
Not needed,
no effect
No
Pavanello et al,
2008
Duan et al,
2009
Guan et al,
2010 (abstract)
18. 18
Updated biological exposure limit of 1-hydroxypyrene
Key study: Siwinska et al (2004)
Probability of increased SCE is < 5% at < 1.0 μmol/mol
19. 19
Updated biological exposure limit of PAH
Proposed biological occupational
exposure limit (as 1-hydroxypyrene in urine)
Biological
parameter
Valid as
Reference value
(as upper bound of nonoccupational exposure)
1-hydroxypyreen in urine
End of shift at
end of
workweek
0.5 mol/mol creatinine
Biological limit
(as lowest observed level
without genotoxic effects
in the body)
1.0 mol/mol creatinine
20. 20
Updated biological exposure limit of PAH
PAH-profile adjustment of biological
occupational exposure limit
Biological occupational exposure limit is valid at
coke oven type exposure with a pyrene/benzo(a)pyrene ratio of 2.5
Adjust limit for deviating pyrene/benzo(a)pyrene
ratios. Linear adjustment results in:
pyrene/benz(a)pyrene
ratio
1.5
2.5 (default)
5
10
limit 1-hydroxypyrene
(mol/mol cr)
0,7
1.0
1.8
3.3
Type
Adjusted
Basis
Adjusted
Adjusted
21. 21
Updated biological exposure limit for 1-hydroxypyrene
Discussion
Is risk level of OEL of 200 ng/m3 B(a)P
equal to risk level of updated BOEL?
Nowadays carcinogens often have risk-based limits
OEL of 200 ng/m3 B(a)P is based on annual cancer
risk between 1: 10.000/year and 1:1.000.000/year
Cancer risk of BOEL of 1.0 mol/mol is ??????
Interference of smoking?
BOEL derived form group of non-smoking workers
Legal status of proposal?
Proposal will be discussed in advisory counsel SER
of Netherlands
– Representatives of employers & unions
Expected result
– No legal status, supplemental industry-adopted limit
22. 22
Take home message
Proposal for occupational exposure limit of 1hydroxypyrene in urine:
1-Hydroxypyrene in urine (µmol/mol)
1,5
1,0
LOL-GEB = Lowest observed level without genotoxic effects in the body
0,5
Non-occupational background
0,0
23. 23
Biological monitoring of PAH
More info?
E-mail: frans.jongeneelen@industox.nl
Voice: +31.24.3528842
Internet: www.industox.nl
Thank you!