Saturday, May 19, 2012

dioxin testing in Israel not 05


What is CALUX?

The CALUX Bioassay

The chemically activated luciferase gene expression (CALUX) in vitro cell bioassay is a bioanalytical tool increasingly used by research and commercial laboratories for screening of dioxins and dioxin-like compounds in sample extracts. The assay is based on aromatic hydrocarbon receptor (AhR)-mediated firefly luciferase expression in genetically modified rat or mouse hepatoma cell lines that express firefly luciferase upon exposure to dioxins or dioxin-like compounds. Since CALUX analyses provide a biological response to all Ah-receptor active compounds present in a sample extract, interpretation of results is much more complex than that of chemical analyses, as an array of parameters affects the results. The Bioassay Research Laboratory at EU-RL for Dioxins and PCBs examines critical methodological parameters and aspects of the CALUX bioassay that can affect quality and accuracy of the analyses.

CALUX technology comprises various fields of work and attention: Cell culturing and maintenance, sample fat extraction, followed by selective clean-up techniques, exposure of cultured cells to cleaned-up sample extracts containing dioxins and/or dioxin-like compounds, measurement of luciferase activity and statistical evaluation and interpretation of results.

Performance Evaluation of the CALUX Technology
Biologically based techniques hold the promise of screening large numbers of samples and greatly decreasing the time and cost of analyses. These techniques are based on the measurement of cellular response produced by enzyme activation. As one of the tasks assigned by the European Commission, the performance of bioassay technology available on the European market is evaluated with regard to their suitability for routine use by European official laboratories, namely, the DR-CALUX [BioDetection Systems (BDS), Netherlands], involving genetically modified H4IIe rat hepatoma cells, and the XDS-CALUX [Xenobiotic Detection Systems, USA] technologies, the latter originating from the research laboratories of Prof. M.S.Denison, University of California Davis (USA), involving genetically modified H1L6.1c3 mouse hepatoma cells. Included in the scope of EU-RL’s activities were also H1L6.1c3 mouse hepatoma cells directly obtained from Prof. M.S.Denison, for research purposes. 
So there are two companies selling CALUX.  BDS was the first to present in Israel at a seminar held at Bactochem, Nes Ziona.  However, it was felt their price structure was too expensive so contacts were made with the US company XDS which had a much more reasonable licensing procedure.


Here are some illustrations from XDSI site
XDS-CALUX® cell mechanism


The AhR receptor complex is capable of binding dioxins, furans, PCBs and other dioxin-like compounds. Once these chemicals bind to the AhR, the complex migrates into the nucleus where it specifically binds to the ARNT protein. The resulting chemical: AhR:ARNT complex then binds to a specific DNA sequence, the Dioxin Responsive Element (DRE), which is present upstream from many genes including that of CYP1A1, and this binding stimulates expression of the adjacent gene.
Dose response curves of the XDS-CALUX® assay to
various PCDH


Diagram of XDS’s separation scheme and the activity



Comparison of XDS-CALUX® to HR GC/MS









Full method at


4435 - 1 Revision 0
September 2007
METHOD 4435

METHOD FOR TOXIC EQUIVALENTS (TEQS) DETERMINATIONS FOR DIOXIN-LIKE CHEMICAL ACTIVITY WITH THE CALUX® BY XDS BIOASSAY
SW-846 is not intended to be an analytical training manual. Therefore, method procedures are written based on the assumption that they will be performed by analysts who are formally trained in at least the basic principles of chemical analysis and in the use of the subject technology. In addition, SW-846 methods, with the exception of required method use for the analysis of method-defined parameters, are intended to be guidance methods which contain general information on how to perform an analytical procedure or technique which a laboratory can use as a basic starting point for generating its own detailed Standard Operating Procedure (SOP), either for its own general use or for a specific project application. The performance data included in this method are for guidance purposes only, and are not intended to be and must not be used as absolute QC acceptance criteria for purposes of laboratory accreditation.

1.0 SCOPE AND APPLICATION
1.1 Method 4435 is a bio-analytical procedure that is based on the mechanism of action of dioxin-like chemicals which allows for the determination of the relative toxic potential of sample extracts containing these chemicals and the resulting potency values are expressed as Toxic Equivalents (TEQs). Method 4435 is a bio-analytical method that is based on the ability of dioxin and related chemicals to activate the Ah receptor (AhR), a chemical-responsive DNA binding protein that is responsible for producing the toxic and biological effects of these chemicals. Measurement of the level of activation of AhR-dependent gene expression by a chemical or chemical extract provides a measure by which to estimate the relative potency and toxic potential of these chemicals and/or extracts with resulting values expressed as Toxic Equivalents (TEQs).
Xenobiotic Detection Systems (XDS web site: www.dioxins.com) has a commercially available genetically engineered cell line that contains the firefly luciferase gene under trans-activational control of the AhR (U.S. patent # 5,854,010). This cell line can be used for the sensitive detection and relative quantification of AhR agonists and agonist activity of complex mixtures. Our term for the in vitro assay is the XDS Chemical-Activated Luciferase Expression or CALUX® by XDS assay. The most widely studied class of compounds that activate this system is the polychlorinated diaromatic hydrocarbons (PCDH), such as 2,3,7,8-tetrachlorodibenzo-p-dioxin
(2,3,7,8-TCDD, dioxin). The relative toxic and biological potency of many PCDH compounds are quantified and expressed relative to that of 2,3,7,8-TCDD, since this is one of the most potent activators of AhR-mediated effects, including gene transcription. This relative quantification approach generates overall potency values known as Toxic Equivalents (TEQs) and the results obtained from the CALUX® by XDS assay provide a measure of TEQs in a sample. By using XDS's sample processing procedures and an affinity column (U.S. Patent # 6,720,431) polychlorinated biphenyls (PCBs) can be separated from chlorinated dioxins/dibenzofurans (PCDDs/PCDFs) making it possible to determine what portion of the total TEQs of a sample is due to each of these classes of compounds. XDS has termed this the Dioxin/Furan- and PCBspecific(DIPS) analysis or the DIPS-CALUX bioassay for dioxin-like chemicals.
The AhR-dependent mechanism of the toxic and biological effects of dioxin-like chemicals and the basis of the CALUX® by XDS bioassay measurement and estimate of TEQ is [shown above] (Denison et al., 2004). The AhR receptor complex is capable of binding dioxins, furans, PCBs and other dioxin-like compounds. Once these chemicals bind to the AhR, the complex migrates into the nucleus where it specifically binds to the ARNT protein. The resulting chemical: AhR:ARNT complex then binds to a specific DNA sequence, the Dioxin Responsive Element (DRE), which is present upstream from many genes including that of CYP1A1, and this binding stimulates expression of the adjacent gene. In the case of the CALUX® by XDS assay, a plasmid containing four DREs immediately upstream of the firefly luciferase reporter gene was stably transfected into the mouse Hepa1c1c7 cell line to produce the recombinant cell line H1L6.1c3 (6.1 cells). This transformed cell line responds to toxic PCDDs, PCDFs and PCBs, and high molecular weight polynuclear aromatic hydrocarbons (PAHs) with the dose-dependent induction of firefly luciferase (Garrison et al., 1996; Denison et al., 2002, 2004; Ziccardi et al., 2002; Han et al., 2004). Comparison of these results to a 2,3,7,8-TCDD standard curve for induction allows for determination of the TEQs in a given sample.
By using XDS sample processing methods (U.S. patent # 6,720,431) it is possible to separate polyhalogenated biphenyls from polyhalogenated dioxins/dibenzofurans present in the same sample. Using this DIPS-CALUX® bioassay it is possible to determine the portion of the total TEQ activity in a given sample that is due to each of these classes of compounds (Brown et.,al 2002).
NOTE: The bioassay testing product listed in this method has been submitted to EPA, evaluated by the Agency, and found to meet the performance specifications necessary for inclusion in SW-846. As additional testing products are evaluated by EPA and found to provide equivalent performance, information will be made available by the Office of Solid Waste regarding those testing products that are capable of meeting the performance specifications in this method
 (See http://www.epa.gov/epaoswer/hazwaste/test/pdfs/kits.pdf).  However, this procedure will not be revised solely to include information on additional testing products. Descriptions and materials lists for products relevant to this method are provided in Table 3 and are given in the manufacturer’s literature.
1.2 The CALUX® by XDS method for TEQ estimation of dioxin-like chemicals. The CALUX® by XDS method is a relatively rapid screening method capable of estimating the Toxic Equivalents (TEQs) concentration for dioxin-like chemicals in a sample.  The sample is extracted in an organic solvent and fractionated through the sample processing procedure. An extract that contains the halogenated dioxins/furans is separated from an extract containing the halogenated biphenyls. These extracts are applied to monolayers of our H1L6.1c3 cells and the amount of luciferase induction is measured after 20 to 24 hours. A standard dilution series of 2,3,7,8-TCDD is included on each plate of cells.
Estimation of dioxin/2,3,7,8-TCDD-like TEQ activity present in the sample extract is performed by extrapolation to the 2,3,7,8-TCDD standard curve by least squares estimates with the 4 parameter Hill Equation.
There are three modes by which the DIPS-CALUX bioassay is performed. These are the screening mode with historical recovery, screening mode surrogate recovery, and the semiquantitative mode. The screening mode involves the analysis of a single aliquot of the sample and recovery is estimated from the mean of historical recoveries that have been obtained for soils/sediment samples. This is considered to be acceptable as the variability of recoveries for soils/sediment samples has been relatively small (76.2 +/- 8.5%). Using this mode would indicate whether a sample needed to be further analyzed by either the semi-quantitative mode or by chemical analysis. The screening mode surrogate recovery, involves processing two aliquots of the sample, the first for analysis in the DIPS-CALUX bioassay and the second used for the surrogate spike with radiolabeled 2,3,7,8- TCDD to estimate recovery. The semiquantitative mode involves analyzing three aliquots of the sample in the DIPS-CALUX bioassay and a fourth aliquot of the sample used for determination of recovery with radiolabeled 2,3,7,8- TCDD. The cost of sample analysis is dependent upon which mode of the DIPS-CALUX bioassay is used for estimation of the levels of sample contamination.

1.3 Toxic Equivalents (TEQs):
The concept of Toxic Equivalents (TEQs) has been promulgated by the World Health
Organization to provide a means of quantifying for risk assessment purposes the toxicity of a family of chemicals with a similar overall mechanism of toxicity (Van den Berg, 1998). The family of dioxin-like chemicals (PCDHs) within this group includes 7 chlorinated dibenzo-p-dioxin congeners with 4 to 8 chorines on the molecule, 10 chlorinated dibenzofuran congeners with 4 to 8 chlorines on the molecule, and 12 chlorinated biphenyls with 4 to 10 chlorines on the molecule.

16.0 REFERENCES
Brown, D. J., Nakamura, M., Chu, M.D., Denison, M.S., Murata, H., and Clark, G.C.
(2002). "Recovery determinations for bioassay analysis: Condierations and results."
Organohalogen Compounds 58: 357-360.
Brown, D. J., Van Overmeire, I., Goeyens, L., Chu, M.D., Denison, M.S., and Clark, G.C.(2002). "Elimination of interfering compounds in preparation for analysis by an Ah receptor based bioassay." Organohalogen Compounds 58: 401-404.
Clark, G., V. Garry, et al. (2002). "Relationships between exposure to dioxin-like
chemicals, testosterone levels, and sex of the children of pesticide applicators."
Organohalogen Compounds 56: 73-76.
Clark, G. C., Brown, D.J., Seidel, S.D., Phelan, D., Denison, M.S. (1999).
"Characterization of the CALUX and GRAB bioassays for sensitivity and specificity in
detection of phamacological agents that activate the Ah Receptor signaling system."
Organohalogen Compounds 42: 309-312.
Clark, G. C., Chu, M., Touati, D., Rayfield, B., Stone, J., Cooke, M. (1999). "A Novel
Low-Cost Air Sampling Device (AmbStack Sampler) and Detection System (CALUX
Bioassay) for Measuring Air Emissions of Dioxin, Furan, and PCB on a TEQ Basis
Tested With a Model Industrial Boiler." Organohalogen Compounds 42: 309-312.
Denison, M. S., Nagy, S.R., Clark, G.C., Chu, M., Brown, D.J., Murata, H., Shan, G.,
Sanborn, J.R., and Hammock, B.D. (2001). "Bioanalytical approaches for the Detection
of Dioxin and Related Halogenated Aromatic Hydrocarbons." Organohalogen
Compounds 45.
Denison, M. S., Seidel, S.D., Ziccardi, M., Rogers, W.J., Brown, D.J., and Clark, G.C.
(1999). "Ah receptor-based bioassays for dioxins and related chemicals: Applications
and limitations." Organohalogen Compounds 40: 27-30.
Denison, M.S., Zhao, B., Baston, D.S., Clark, G.C., Murata, H. and Han, D.-H. (2004)
Recombinant Cell Bioassay Systems for the Detection and Relative Quantitation of
Halogenated Dioxins and Related Chemicals, Talanta 63: 1123-1133.
Denison, M.S. Nagy, S.R., Ziccardi, M., Clark, G.C., Chu, M., Brown, D.J., Shan, G.,
Sugawara, Y., Shirley J. Gee, S.J., James Sanborn, J. and Hammock, B.D. (2002)
Bioanalytical approaches for the detection of dioxin and related halogenated aromatic
hydrocarbons, in: Technology-Driven Biomarkers Development and Application in
Environmentally-Associated Diseases, Wilson, D. and W. Suk, W., eds., pp. 483-494,
Lewis Press, Boca Raton, FL.
Garrison, P.M., Tullis, K., Aarts, J.M.M.J.G., Brouwer, A. and Giesy, J.P. and Denison,M.S. (1996) Species-specific recombinant cell lines as bioassay systems for the detection of 2,3,7,8-tetrachlorodibenzo-p-dioxin-like chemicals, Fund. Appl. Toxicol. 30,194-203.
Han, D.-H., Nagy, S.R. and Denison, M.S. (2004) Comparison of recombinant cell Bioassays for the detection of Ah receptor agonists, Biofactors 20, 11-22.
Han, D., Nagy, S.R., and Denison, M.S. (2002). "Recombinant cell lines for the detection of dioxins and Ah Receptor ligands- Not all assays are created equal." Organohalogen Compounds 58: 421-424.
Ziccardi, M.H., Gardner, I.A. and Denison, M.S. (2002) Application of the luciferase
recombinant cell culture bioassay system for the analysis of polycyclic aromatic
hydrocarbons, Environ. Toxicol. & Chem. 21, 2027-2033.
Windal, I., Dennison, M. S, Birnbaum L. S., Van Wouwe, N., Baeyens, W. Goeyens L.
(2005). “Chemically Activated Luciferase Gene Expression (CALUX) Cell Bioassay
Analysis for the Estimation of Doxin-Like Activity: Critical Parameters of the CALUX
Procedure that Impact Assay Results, Environ.” Sci. Technol., 3, 7357-7364.
Van den Berg et al (2006). “The 2005 World Health Organization Reevaluation of
Human and Mammalian Toxic Equivalency Factors for Dioxins and Dioxin-Like
Compounds.” Toxicological Sciences 93(2):223-241.










www.dioxins.com/pdf/environment/environment09.pdf

How to measure dioxins in a smokestack using CALUX


Analysis P006
ORGANOHALOGEN COMPOUNDS


Vol.40 (1999) pp. 79-82
A Novel Low-Cost Air Sampling Device (AmbStack Sampler) and Detection System (CALUX Bioassay) for Measuring Air Emissions of Dioxin, Furan, and PCB on a TEQ Basis Tested With a Model Industrial Boiler
George C. Clark 1, Michael Chu 1, Dahman Touati 2, Barry Rayfield 3, Jon Stone 4, and Marcus Cooke 5
Affilitations: 1 Xenobiotic Detection Systems, Durham, NC, 2 Arcadis, Durham, NC, 3 Kilkelly Associates, Raleigh, NC, 4 URG, Chapel Hill, NC, 5 Cooke Companies International, Chapel Hill, NC

Introduction

The analysis of polychlorinated dibenzo-p-dioxin (PCDD) and polychlorinted dibenzofuran (PCDF) in gaseous samples is very labor intensive, and expensive. Regulatory reporting usually requires a sampling team and several days collect multiple samples. Shipping too is complicated by the use of organic solvent rinses and numerous subsamples that require complex and expensive shipping.Sample analysis, after collection, is also expensive. Multiple clean up steps are needed, and expensive instrumentation is used, such as high resolution gas chromatography (HRGC) coupled to high resolution mass spectrometry (HRMS). A low cost unitized sampling system, the "AmbStack Sampler" was designed by our group, and combined with a reporter gene bioassay system, the "CALUX" method, to give accurate PCDD/PCDF analyses with much simpler techniques than are currently in use. The AmbStack/CALUX system provides reliable air emission data at a fractional cost of conventional emission methods.This system has been demonstrated for ambient sampling, low temperature stack emissions, and simulated industrial boiler discharges. The sampling unit, called the "AmbStack Sampler”, is commercially available, and uses a polyurethane plug (PUF) insert in a glass sampling cartridge for ambient and stack sampling. AmbStack samples can be directly analyzed for PCDD, PCDF, PCB or polycyclic aromatic hydrocarbons (PAH). The AmbStack Sampler contains a glass probe-cartridge unit, and Teflon® connections a dry gas meter and air pump. After sampling, the probe-cartridge unit is sealed with Teflon®-lined end caps, and shipped directly to the laboratory for analysis. Sample extraction is done by in situ solvent extraction and clean up, followed by CALUX reporter gene bioassay.
Xenobiotic Detection Systems, Inc. (XDS) has a genetically engineered cell line which contains the firefly luciferase gene under trans-activational control of the aryl hydrocarbon receptor. This cell line can be used for the detection and quantification of AhR agonists. Exposure of this patented cell line to AmbStack sample extracts yields a direct measure of total TEQ since response of these cells is based on the mechanistic basis by which biologically active PCDD, PCDF, and PCB express their toxicity (1,2).
In the current experiments we demonstrate the sensitivity and performance of the AmbStack Sampler for PCDD/PCDF quantification on a TEQ basis, using the CALUX bioassay and a simulated industrial boiler discharge.

Materials and Methods

Incinerator Conditions

The combustion system used to perform this test was a North American Package Boiler (NAPB), which is capable of firing natural gas or #2 through #6 fuel oils. The boiler is a three pass firetube “Scotch” marine-type design fitted with a North American burner rated at 2.5 x106 Btu/hr. A dopant (a mixture of 1,2 dichlorobenzene and copper naphthenate) was injected through a separate injection system to the main fuel injection system prior to the burner. The dopant flow rate was adjusted to yield a HCl concentration at the stack of approximately 500 ppm at 7% O2. A Method 23 sampling train and the AmbStack sampler were placed at the same location in the stack. The flue gas stream for this experiment was stable at a temperature of about 140 oC with a mo isture level of about 11 %. Prior to testing the Boiler unit experienced a thermal decontamination process of about 400 hours.

AmbStack sampling and CALUX bioassay

The PUF insert was removed from the cartridge, and the flow direction noted. The forward or "front end" section of the PUF cartridge was separated from the remaining PUF and analyzed separately with the probe rinse, to determine an Apparent Collection Efficiency, ACE. The front 2/3 of the PUF insert was extracted using toluene , and combined with the toluene rinsate from the probe and the cartridge holder. The remaining back 1/3 section of the PUF insert was extracted separately.The front and back extracts were analyzed separately to determine if any sample breakthrough had occurred.
Sample extracts were split into equal aliquots , the first aliquot was prepared by our Method 1 cleanup procedure to measure TEQ activity of chlorinated species (PCDD, PCDF, and PCB). The second aliquot was prepared using our Method 2 Procedure which provides separate extracts to estimate TEQ for PCB and PCDD/PCDF individually. These proprietary clean up processes involve differential chromatography. All extracts were solvent exchanged into DMSO before analysis.
Sample extracts were suspended in cell culture medium. This media was applied to H1.1C2 mouse hepatoma cells (Patent # 5,854,010 ) grown in 96 well culture plates. In addition to sample dilutions a standard curve of 2,3,7,8-tectrachloro dibenzo-p-dioxin (TCDD) was assayed. All assays of standards and unknowns were run in duplicate. Plates were incubated for 4 hours in a humidified C02 incubator. Following incubation media was removed and cells observed microscopically for viability. Luciferase response, the induction of luciferase activity, was measured optically as total light emission using a BMG Luminometer.

Results

Cell viability: Microscopic examination of the cells following exposure to sample extracts did not reveal any indication of toxicity. Samples were analyzed and compared to a clean PUF blank.

Results of CALUX measurements of TEQ activity from the simulated industrial boiler extracts are presented in Table I.

TABLE I. CALUX RESULTS (NANOGRAM TEQ ACTIVITY PER SAMPLE)
Method 1
Total TEQ(PCDD/PCDF/PCB)A

Front End (2/3 PUF/Rinsate)
13.7 ± 3.6

Back End (1/3 PUF)
2.8 ± 0.6


PCDD/PCDFB
PCBC
SumD
Method 2
TEQ
TEQ
Total TEQs
Front End
12.1 ± 2.07
2.01 ± 0.44
14.1
Back End
2.2 ± 0.47
0.91 ± 0.11
3.1




___________________________________________________________________
A. Data are Mean ± Standard Deviation of 5 independent determinations in the CALUX assay for total TEQ activity.
B. Data are Mean ± Standard Deviation of 3 independent determinations in the CALUX assay for TEQ activity in a sample fraction purified for dioxins and furans.
C. Data are Mean ± Standard Deviation of 3 independent determinations in the CALUX assay for TEQ activity purified for planar PCB.
D. Data are the sum of TEQ determinations from PCDD/PCDF and PCB fractions.
Relative emission levels found in collected PUF samples are presented in Table II based on 3.58 M
3 air sampled during the 3 hour test period.

TABLE II. ANALYSIS OF AIR SAMPLES (NANOGRAM /METER3 TEQ ACTIVITY)

Method 1
Total TEQs
Front End
3.8
Back End
0.78
Apparent Collection Efficiency
83%


Method 2
TEQ                     TEQ                       Total TEQ

PCDD/PCDF       PCB                           Sum
Front End
   3.4                     0.56                             3.9



A comparison HRMS analysis was performed by collecting a parallel U.S. Environmental Protection Agency, Method 23 sample. The results of that analysis were 2.75 ng/dscm (7% O2) versus 1.9 ng/dscm (7% O2) by AmbStack and CALUX. The comparison analysis of AmbStack/CALUX showed excellent agreement with HRMS.

Discussion
The comparison analysis of AmbStack/CALUX showed excellent agreement with HRMS. The AmbStack Sampler, combined with CALUX TEQ quantification, gives a rapid and cost effective method to measure PCDD/PCDF emissions. The method was sensitive at concentrations found in a simulated industrial boiler emission. The CALUX screen proved to be rugged in analyzing this complex sample type. The clean up procedure was rapid and data reports were generated in two working days after sampling was complete.
Performance in this study suggests that the AmbStack/CALUX system, using PUF, is suitable for many ambient and industrial applications, such as post control emissions testing. This technique is especially useful as a low cost diagnostic tool to quickly measure dioxin emissions from thermal combustion systems.

References

1) Garrison, P.M., et al. Fund. Appl. Toxicol. 1996. 30, 194-203.
2) Denison, M.S., A. Brouwer, and G.C. Clark. U.S. patent # 5,854,010.

Acknowledgement

The authors would like thank Dr. Brian K. Gullet of the U.S. Environmental Protection Agency for
his assistance in arranging the boiler test, and facilitating sampling at the EPA Combustion
Research Facility at Research Triangle Park, NC.



Japanese analysis for ash and soil using CALUX

Full paper at:
http://www.dioxins.com/pdf/environment/environment10.pdf

Validation study for the use of the dioxin responsive CALUX assay for analysis of Japanese ash and soil samples
Brown D; Kishimoto Y; Ikeno O; Chu M; Nomura J; Murakami T; Murata H
Organohalogen Compounds 45:200, 2000
In Japan incineration is a common method for disposing of municipal waste and it is estimated that more than 10,000 incinerators of various capacities are currently in operation. In the past couple of years there has been an increased concern regarding the emission from these incinerators and other the emissions of other industries. In particular the concern has focused on the inadvertent production and release of chlorinate aromatic compounds such as polychlorinated biphenyls (PCBs), polychlorinated dibenzo--p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs). In August 1997 the Japanese government addressed these concerns by amending the cabinet orders of the Air Pollution Control Law and Waste Management and PubIic Cleansing Law. These amendments implemented stricter regulations on incinerators and other Industries that emit PCBs, PCDDs and PCDFs. These amendments pIaced an immediate limit on emissions from new facilities that will emit these compounds and provided for gradually more strict limits for existing facilities over a five-year period. In order to comply with these new limits it was expected that monitoring by chemical analysis would have to increase. This raised concerns that the chemical analysis by HRGCMS for compliance might be an economic hardship for some of the regulated industries and that the increased demand might outstrip the capacity of the existing analytical laboratories. Based on these concerns the Japanese government and private corporations began to examine the possibility of using alternative testing methods to monitor for the presence of these compounds. In this article we report the results from a preliminary validation study conducted by Hiyoshi Corporation and Xenobiotic Detection Systems, Inc (XDS). This study used a blinded format to compare the results from the dioxin  responsive CALUX  assay with HRGCMS data.
  The samples were extracted using a modification of the EPA 8290 extraction method
Briefly, the dried samples were ground and one gram aliquots were placed in solvent cleaned glass vials with PTFE lined caps.  The sample was extracted with a 20% solution of methanol in toluene then twice with toluene.  During each extraction step the samples were incubated in an ultrasonic water bath.  The three extracts from each sample were filtered, pooled and concentrated by vacuum centrifugation.  The sample extract was suspended in hexane and prepared for the bioassay by a proprietary clean up method.  The eluate from the clean up method was concentrated under vacuum into dimethyl sulfoxide (DMSO).  The DMSO solution was used to dose the genetically engineered cells in the CALUX assayPrior to dosing the cells, the sample extracts in DMSO were suspended in cell culture medium.  This medium was then used to expose monolayers of the H1L1 cell line grown in 96 well culture plates.  In addition to the samples, a standard curve of 2,3,7,8-tetrachlorodibenzo-p-dioxin )TCDD) was assayed (161, 80.5, 40.2, 20.1, 10.1, 5.0, 2.5, 1.2 and 0.6 parts per trillion (ppt TCDD).  The plates were incubated for a time to produce optimal expression of the luciferase activity in a humidified CO2 incubator.  Following incubation, the medium was removed and the cells were examined microscopically for viability.  The induction of luciferase activity was  quantified using the luciferase assay kit from Promega.
Results and Discussion
From the GC/MS analysis of the samples, the I-TEQs were calculated using the TEF values for the individual congeners.  The sample I-TEQs were estimated by the CALUX assay by comparing the response of the sample extract to the standard curve for 2,3,7,8-TCDDThe correlation coefficient between the results is acceptable, (r = 0.94). 









How the Japanese do an air sample






Sampling

  Sample should be taken by a high volume air sampler with which a sampling tube with 2 pieces of polyurethane foam is attached below filter paper.  For obtaining a 24-hour average concentration, sample should be collected at a high flow rate of 700 L/min for 24 hours.  For obtaining a weekly average concentration, samples should be collected 7 times at a high flow rate of 700 L/min for 24 hours or collected continuously at a medium flow rate of 100 L/min for consecutive 7 days.  Glass fiber filter shall be used as the filter paper for a high-volume air sampler.

Solvent Extraction

Sample is extracted from glass fiber filter by Soxhlet extractor with toluene for 16 to 24 hours.  
For the polyurethane foam, sample is extracted by a Soxhlet extractor with acetone for 16 to 24 hours.