Development of a consumer product ingredient database for chemical exposure screening and prioritization.

Consumer products are a primary source of chemical exposures, yet little structured information is available on the chemical ingredients of these products and the concentrations at which ingredients are present. To address this data gap, we created a database of chemicals in consumer products using product Material Safety Data Sheets (MSDSs) publicly provided by a large retailer. The resulting database represents 1797 unique chemicals mapped to 8921 consumer products and a hierarchy of 353 consumer product "use categories" within a total of 15 top-level categories. We examine the utility of this database and discuss ways in which it will support (i) exposure screening and prioritization, (ii) generic or framework formulations for several indoor/consumer product exposure modeling initiatives, (iii) candidate chemical selection for monitoring near field exposure from proximal sources, and (iv) as activity tracers or ubiquitous exposure sources using "chemical space" map analyses. Chemicals present at high concentrations and across multiple consumer products and use categories that hold high exposure potential are identified. Our database is publicly available to serve regulators, retailers, manufacturers, and the public for predictive screening of chemicals in new and existing consumer products on the basis of exposure and risk.

Association of gastrointestinal illness and recreational water exposure at an inland U.S. beach.

Recent epidemiology studies examining U.S. recreational water exposure and illness relationships have focused primarily on coastal and Great Lakes beaches. Human-made lakes in the U.S. have received little attention in epidemiology studies despite contributing to more waterborne disease epidemics annually than coastal U.S. waters. In a comprehensive beach cohort study, we examined relationships between water quality indicators and reported adverse health outcomes among users of a beach at an inland U.S. lake. Human health data was collected over 26 swimming days during the 2009 swimming season in conjunction with water quality measurements. Adverse health outcomes were reported 8-9 days post-exposure via a phone survey. Wading, playing or swimming in the water was observed to be a significant risk factor for GI illness (adjusted odds ratio (AOR) of 3.2; CI 1.1, 9.0). Among water users, Escherichia coli density was significantly associated with elevated GI illness risk where the highest E. coli quartile was associated with an AOR of 7.0 (CI 1.5, 32). GI illness associations are consistent with previous freshwater epidemiology studies. Our findings are unique in that our observations of positive associations with GI illness risk are based upon a single daily E. coli measurement. Lastly, this study focused on an understudied issue, illness risk at inland reservoirs. Our results support the usefulness of E. coli as a health-relevant indicator of water quality for this inland U.S. beach.

Comparative analysis of passive dosimetry and biomonitoring for assessing chlorpyrifos exposure in pesticide workers.

Under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), the US Environmental Protection Agency (EPA) has the authority to regulate the use of pesticides to prevent unreasonable adverse human health effects associated with pesticide exposure. Accordingly, the EPA requires pesticide registrants to perform studies evaluating the potential for pesticide handler exposure. Data from five such studies that included exposure measurements based on both external measurements and biological monitoring were used to examine methods of assessment, routes and determinants of exposure and dose to the pesticide chlorpyrifos. Eighty workers across four job classes were included: mixer/loaders (M/L, n = 24), mixer/loader/applicators (M/L/A, n = 37), applicators (A, n = 9) and re-entry scouts (RS, n = 10). Results showed that doses were highly variable and differed by job class (P < 0.05) with median total (inhalation and dermal combined) exposure-derived absorbed doses (EDADtot) of 129, 88, 85 and 45 microg/application for A, M/L/A, M/L and RS, respectively. Doses derived from the measurement of 3,5,6-trichloro- 2-pyridinol (3,5,6-TCP) in urine were similar in magnitude but differed in rank with median values of 275, 189, 122 and 97 microg/application for A, M/L, RS, and M/L/A, respectively. The relative contribution of dermal to inhalation exposure was examined by their ratio. The median ratios of exposure-derived absorbed dermal dose (EDADderm) (assuming 3% absorption) to exposure-derived absorbed inhalation dose (EDADinh) (assuming 100% absorption) across job classes were 1.7, 1.5, 0.44 and 0.18 for RS, M/L, A and M/L/A, respectively, with an overall median of 0.6. For 34 of 77 workers (44%), this ratio exceeded 1.0, indicating the significance of the dermal exposure pathway. Different dermal absorption factor (DAF) assumptions were examined by comparing EDADtot to the biomarker-derived absorbed dose (BDAD) as a ratio where EDADtot was calculated assuming a DAF of 1, 3 and 10%. Median ratios of 0.45, 0.71 and 1.28, respectively, were determined suggesting the DAF is within the range of 3-10%. A simple linear regression of urinary 3,5,6-TCP against EDADtot indicates a positive association explaining 29% of the variability in the 3,5,6-TCP derived estimate of dose. A multiple linear regression model including the variables EDADderm, EDADinh and application type explained 46% of the variability (R2 = 0.46) in the urinary dose estimate. EDADderm was marginally significant (P = 0.066) while EDADinh was not (P = 0.57). The EDADderm regression coefficient (0.0007) exceeded the coefficient for EDADinh (0.00002) by a factor of 35. This study demonstrates the value of the pesticide registrant database for the purpose of evaluating pesticide worker exposure. It highlights the significance of the dermal exposure pathway, and identifies the need for methods and research to close the gap between external and internal exposure measures.

Evaluation of methyl tert-butyl ether (MTBE) as an interference on commercial breath-alcohol analyzers.

Anecdotal reports suggest that high environmental or occupational exposures to the fuel oxygenate methyl tert-butyl ether (MTBE) may result in breath concentrations that are sufficiently elevated to cause a false positive on commercial breath-alcohol analyzers. We evaluated this possibility in vitro by establishing a response curve for simulated breath containing MTBE in ethanol. Two types of breath-alcohol analyzers were evaluated. One analyzer's principle of operation involves in situ wet chemistry (oxidation of ethanol in a potassium dichromate solution) and absorption of visible light. The second instrument uses a combination of infrared absorption and an electrochemical sensor. Both types of instruments are currently used, although the former method represents older technology while the latter method represents newer technology.The percent blood alcohol response curve was evaluated over a breath concentration range thought to be relevant to high-level environmental or occupational exposure (0-361 microg/l). Results indicate that MTBE positively biases the response of the older technology Breathalyzer when evaluated as a single constituent or in combination with ethanol. We conclude that a false positive is possible on this instrument if the MTBE exposure is very high, recent with respect to testing, and occurs in combination with ethanol consumption. The interference can be identified on the older technology instrument by a time dependent post-reading increase in the instrument response that does not occur for ethanol alone. In contrast, the newer technology instrument using infrared and electrochemical detectors did not respond to MTBE at lower levels (0-36 microg/l), and at higher levels (>72 microg/l) the instrument indicated an "interference" or "error". For this instrument, a false positive does not occur even at high MTBE levels in the presence of ethanol.

Randomized double-blind phase II survival study comparing immunization with the anti-idiotypic monoclonal antibody 105AD7 against placebo in advanced colorectal cancer.

The cancer vaccine 105AD7 is an anti-idiotypic monoclonal antibody that mimics the tumour-associated antigen 791T/gp72 (CD55, Decay Accelerating Factor) on colorectal cancer cells. Phase I studies in patients with advanced disease confirmed that 105AD7 is non-toxic, and that T cell responses could be generated. A prospective, randomized, double-blind, placebo-controlled survival study in patients with advanced colorectal cancer was performed. 162 patients were enrolled between April 1994 and October 1996. Patients attended at trial entry, and at 6 and 12 weeks, where they received 105AD7 or placebo. Study groups were comparable in terms of patient demographics, and time from diagnosis of advanced colorectal cancer (277.1 v 278.6 days). Baseline disease was similar, with 50% of patients having malignancy in at least 2 anatomic sites. Compliance with treatment was poor, with only 50% of patients receiving 3 planned vaccinations. Median survival from randomization date was 124 and 184 days in 105AD7 and placebo arms respectively (P = 0.38), and 456 and 486 days from the date of diagnosis of advanced disease (P = 0.82). 105AD7 vaccination does not prolong survival in patients with advanced colorectal cancer. The reasons for lack of efficacy are unclear, but may reflect the high tumour burden in the patient population, and poor compliance with immunization. Further vaccine studies should concentrate on patients with minimal residual disease.

The contribution of traffic to indoor concentrations of polycyclic aromatic hydrocarbons.

A photoelectric aerosol sensor (PAS) was used to measure real-time indoor concentrations of polycyclic aromatic hydrocarbons (PAHs) at three residences. Semi-quantitative measurements of total indoor particle-bound PAH and temperature were collected continuously every minute for approximately 2 weeks at each location. The purpose of this study was to examine the effect of traffic on indoor concentrations of PAHs. This was accomplished by collecting indoor measurements at an urban, semi-urban, and suburban residential location with varying levels of, and proximity to, traffic. Since the homes were occupied, the effects of cooking, the dominant indoor source, were also examined among the three nonsmoking households. The results indicate that traffic was the main outdoor source of PAH concentrations measured indoors for all locations. In fact, a significant (p<0.001) traffic-related trend in weekday PAH concentration was detected with a geometric mean concentration at the urban location (31 ng/m3) nearly two times that at the semi-urban location (19 ng/m3) and over three times larger than the suburban location (8.0 ng/m3), once adjusted for indoor sources. Hourly average concentration profiles also revealed weekday rush hour peaks of PAHs at all locations. No pronounced peaks and significantly lower concentrations (10, 10, and 4.9 ng/m3) were seen during the weekends for all locations i.e., the urban, semi-urban and suburban locations, respectively. Indoor sources including frying/sautéing, broiling, and candle-burning were characterized by peak concentration, duration of PAH elevation, and potential dose. This analysis suggests that cooking, and especially frying/sautéing, may be an important source of indoor PAH concentrations.

The environment and asthma in U.S. inner cities.

The prevalence and severity of asthma has increased in the last 20 years, and the greatest increase has been seen among children and young adults living in U.S. inner cities. The reasons for this increase are obviously complex, but include environmental exposures to allergens and pollutants, changing patterns of medication, and the psychosocial stresses of living in poor inner-city neighborhoods. This paper presents an overview of environmental, immunologic, and genetic factors associated with asthma morbidity and mortality. This overview can be used to provide a framework for designing an interdisciplinary research program to address the complexities of asthma etiology and exacerbation. The strongest epidemiologic association has been found between asthma morbidity and the exposure of immunologically sensitive asthmatic patients to airborne allergens. Our current understanding of the process of sensitization suggests that there is a strong genetic predisposition to form IgE to allergenic proteins on airborne particles. Much of this work has been conducted with animal models, but in a number of instances, specific confirmation has been reported in humans. Sensitized individuals respond to inhaled exposure with immediate mast-cell dependent inflammation that may be augmented by pollutant particles, especially diesel exhaust particles. Relatively little is known about the methods of assessing exposure to airborne pollutants, especially biologically active particulates. However, to examine the relationship of morbidity in genetically predisposed individuals, it will be important to determine the most relevant method of making this assessment.

The effect of dust lead control on blood lead in toddlers: a randomized trial.

BACKGROUND: Contaminated household dust is believed to be a major source of exposure for most children with elevated blood lead levels. To determine if a vigorous dust clean-up effort would reduce this exposure we conducted a randomized controlled field trial. METHODS: We randomized 113 urban children between the ages of 6 and 36 months: 56 children to a lead dust intervention composed of maternal education and biweekly assistance with household cleaning and 57 children to a control group. Household cleaning was done by two trained lay workers who focused their efforts on wet mopping of floors, damp-sponging of walls and horizontal surfaces, and vacuuming with a high-efficiency particle accumulating vacuum. Household dust lead levels, child blood lead levels, and maternal knowledge of lead poisoning and sources of exposure were measured before and after the intervention. RESULTS: Ninety-nine children were successfully followed for 12 +/- 3 months: 46 children in the lead group and 53 children in the control group. Age and blood lead were similar in the two groups at baseline and averaged 20 months and 12.0 micrograms/dL, respectively. Blood lead fell 17% in the intervention group and did not change among controls. Household dust and dust lead measures also fell significantly in the intervention group. Children in homes cleaned 20 or more times throughout the year had an average blood lead reduction of 34%. CONCLUSIONS: Regular home cleaning, accompanied by maternal education, is a safe and partially effective intervention that should be recommended for the large majority of lead-exposed children for whom, unfortunately, removal to lead-safe housing is not an option.

Excision of products of oxidative DNA base damage by human NTH1 protein.

A functional human homologue of Escherichia coli endonuclease III (Nth-Eco protein) has recently been cloned and characterized [Aspinwall, R., Rothwell, D. G., Roldan-Arjona, T., Anselmino, C., Ward, C. J., Cheadle, J. P., Sampson, J. R., Lindahl, T., Harris, P. C., and Hickson, I. D. (1997) Proc. Natl. Acad. Sci. U.S.A., 94, 109-114]. This enzyme, designated hNTH1 protein, shares an extensive sequence similarity with Nth-Eco protein and a related enzyme from Schizosaccharomyces pombe (Nth-Spo protein). We investigated the substrate specificity of this human enzyme for oxidative DNA base damage, using the technique of gas chromatography/isotope-dilution mass spectrometry. Four different DNA substrates damaged by various free radical-generating systems were used. 5-Hydroxycytosine, thymine glycol, 5-hydroxy-6-hydrothymine, 5,6-dihydroxycytosine, and 5-hydroxyuracil were substrates of hNTH1 protein among 17 lesions found in DNA substrates. The substrate specificity and excision kinetics of the human enzyme were found to be significantly different from those of Nth-Spo and Nth-Eco proteins.

Approaches to environmental exposure assessment in children.

An improved understanding of the contribution made by environmental exposures to disease burden in children is essential, given current increasing rates of childhood illnesses such asthma and cancer. Children must be routinely included in environmental research. Exposure assessment, both external (e.g., air, water) and internal dose (e.g., biomarkers), is an integral component of such research. Biomarker measurement has some advantages that are unique in children. These include assessment of potentially increased absorption because of behaviors that differ from adults (i.e., hand-to-mouth activity); metabolite measurement, which can help identify age-related susceptibility differences; and improved assessment of dermal exposure, an important exposure route in children. Environmental exposure assessment in children will require adaption of techniques that are currently applied in adult studies as well as development of tools and validation of strategies that are unique for children. Designs that focus on parent-child study units provide adult comparison data and allow the parent to assist with more complex study designs. Use of equipment that is sized appropriately for children, such as small air pumps and badge monitors, is also important. When biomarkers are used, biologic specimens that can be obtained noninvasively are preferable. Although the current need is primarily for small focused studies to address specific questions and optimize research tools, the future will require establishment of large prospective cohorts. Urban children are an important study cohort because of relatively high morbidity observed in the urban environment. Finally, examples of completed or possible future studies utilizing these techniques are discussed for specific exposures such as benzene, environmental tobacco smoke, aflatoxin, volatile organic compounds, and polycyclic aromatic hydrocarbons.

Body burden measurements and models to assess inhalation exposure to methyl tertiary butyl ether (MTBE).

Biomarkers of methyl tertiary butyl either (MTBE) exposure and the partitioning of inhaled MTBE into the body were investigated in a human chamber study. Two subjects were exposed to an environmentally relevant nominal 5,011 micrograms/m3 (1.39 ppm) MTBE for 1 hour, followed by clean-air exposure for 7 hours. Breath and blood were simultaneously sampled, while total urine was collected at prescribed times before, during, and after the exposure. Mass-balance and toxicokinetic analyses were conducted based upon the time series measurement of multiple body-burden endpoints, including MTBE in alveolar breath, and MTBE and tertiary butyl alcohol (TBA) in venous blood and urine. The decay of MTBE in the blood was assessed by fitting the post-exposure data to a 2- or 3-exponential model that yielded residence times(tau) of 2-3 min, 15-50 min, and 3-13 h as measured by alveolar breath, and 5 min, 60 min, and 32 h as evaluated from venous blood measurements. Based on observations of lower than expected blood and breath MTBE during uptake and a decreasing blood-to-breath ratio during the post-exposure decay period, we hypothesize that the respiratory mucous membranes were serving as a reservoir for the retention of MTBE. The decay data suggest that 6-9% of the MTBE intake may be retained by this non-blood reservoir. The compartmental modeling was further used to estimate important parameters that define the uptake of inhaled MTBE. The first of these parameters is f, the fraction of C(air) exhaled at equilibrium, estimated as 0.60 and 0.46 for the female and male subject, respectively. The second parameter is the blood-to-breath partition coefficient (P) estimated as approximately 18. The product of these parameters provides an estimate of the blood concentration at equilibrium as 8-11 times the air concentration. Blood TBA lagged MTBE levels and decayed more slowly (tau = 1.5-3 h), providing a more stable indication of longer term integrated exposure. The concentration ranges of MTBE and TBA in urine were similar to that of the blood, ranging from 0.37 to 15 micrograms/L and 2 to 15 micrograms/L, respectively. In urine, MTBE and TBA by themselves bore little relationship to the exposure. However, the MTBE:TBA ratio followed the pattern of exposure, with peak values occurring at the end of the exposure (20- and 60-fold greater than pre-exposure values) before decaying back to pre-exposure levels by the end of the 7-h decay period. Urinary elimination accounted for a very small fraction of total MTBE elimination (< 1%).

Radiologic features of gout.

Gout is a common rheumatologic disease characterized by the deposition of monosodium urate crystals in tissue from supersaturated extracellular fluid. The deposition of crystals in the joints and periarticular soft tissue can lead to arthritis and bone destruction. The radiologic features of gout include swelling of soft tissues, tophi, normal mineralization, preservation of joint space until the later stages of disease, "punched-out" erosions with overhanging edge of cortex and sclerotic borders, and an asymmetric polyarticular distribution. The lower-extremity joints are most often affected, but the small joints of the hands, wrists and elbows may also be involved. Gout rarely occurs in the shoulders, hips, sacroiliac joints or spine.

Cancer vaccines.

In the past there was considerable evidence that cellular rather than antibody responses were more effective for tumor rejection (1). However, the task of identifying the tumor antigens recognized by T-cells was daunting technically. More recently there has been a growing optimism that the potential of tumor immunotherapy may at last be realized. This enthusiasm has been fed by a better understanding of the presentation and processing of peptides necessary for the induction of immune responses and the identification of new tumor targets. These developments will be discussed in this chapter. Because cancer vaccines are still in their infancy and largely experimental, detailed protocols for their production will not be presented.

Improved high-performance liquid chromatographic method for the determination of polycyclic aromatic hydrocarbon metabolites in human urine.

A reversed-phase HPLC method with fluorescence detection was evaluated for utility in determination of urinary metabolites of polycyclic aromatic hydrocarbons as biomarkers of environmental exposure. The method, which was developed for use in studies of high-level occupational exposure, was found to be unreliable for relatively low-level environmental exposures. The method was modified to include quantitation by standard addition in order to compensate for matrix effects at levels as low as 0.1 ng/ml. The standard addition modification increased both qualitative and quantitative performance, with recovery of 1-hydroxypyrene spikes improved from 164% to 114% at 0.36 ng/ml. The modified method was successfully applied in an environmental exposure study.

An assessment of a urinary biomarker for total human environmental exposure to benzo[a]pyrene.

Urinary banzo[a]pyrene (BaP) metabolite levels were compared to human environmental exposure to BaP through inhalation and dietary ingestion to assess the predictive validity of the exposure biomarker. These measurements were made for 14 adult volunteers over 14 consecutive days, once during summer/fall, again during winter periods. Based on personal air monitoring, median potential inhalation doses of 11.0 and 2.3 ng/day were estimated for the winter and summer/fall studies, respectively. A median potential ingested dose of 176 ng/day, estimated from "duplicate plate" sampling, exceeded inhalation by 6- and 122-fold for the winter and summer/fall studies, respectively. "Total" urinary BaP metabolites were measured using a published "reverse metabolism" (BaP) method of analysis. Median rates of urinary BaP metabolite elimination for the winter and summer/fall studies were 121 and 129 ng/day, respectively. The changes in inhaled and ingested potential doses were regressed on the change in urinary metabolite elimination from week 1 to week 2 to test the predictive validity of the biomarker measurement. The regression was statistically significant (r = 0.620, p = 0.015, n = 25) when body weight was included and two extreme values were removed. Consistent with the exposure measurements showing diet as the dominant route of exposure, most of the variation in urinary metabolite elimination was explained by the ingested dose. It is concluded that the measurement of urinary BaP by "reverse metabolism" is qualitative and of marginal predictive validity as an exposure biomarker due to the method's low recoveries and the large unexplained variance.

Enhanced cell-mediated tumor killing in patients immunized with human monoclonal antiidiotypic antibody 105AD7.

A human antiidiotypic monoclonal antibody (105AD7) has been shown to induce antitumor cellular responses in animals and appears to prolong survival in patients with metastatic colorectal cancer without associated toxicity. Proliferative leukocyte responses to the targeted tumor antigen gp72 were observed in these patients and plasma interleukin 2 levels were increased following immunization. Autologous tumor tissue was not available in these patients, so antitumor cytotoxicity could not be measured. This issue has now been addressed in an adjuvant clinical study in primary rectal cancer patients. Six patients with rectal cancer were immunized preoperatively with 105AD7. Peripheral blood lymphocytes taken prior to immunization were tested against tumor cells extracted from biopsies also obtained prior to immunization or from natural killer (NK)-sensitive target cells. Cryopreserved lymphocytes taken before and after tumor immunization, fresh peripheral blood lymphocytes taken immediately prior to surgery, and lymphocytes from tumor-draining lymph nodes were tested against autologous cells from the resected specimen or NK-sensitive target cells. Significant killing of autologous tumor cells, which was not due to NK activity, was seen with cryopreserved lymphocytes or lymph node cells of three patients at 1-2 weeks postimmunization with 105AD7 but not on pretreatment biopsies. Enhanced NK activity was seen 2-3 weeks postimmunization in 3 of 6 patients. These results indicate that 105AD7 human monoclonal antibody immunization enhances cytotoxicity in rectal cancer patients by specific and nonspecific effector mechanisms.

Gasoline-contaminated ground water as a source of residential benzene exposure: a case study.

In a private residence using gasoline-contaminated ground water (approximately 300 micrograms/l benzene), a series of experiments were performed to assess the potential benzene exposures that may occur in the shower stall, bathroom, master bedroom, and living room as a result of a single 20-min, shower. Integrated fixed site SUMMA TM-polished canister and Tenax GC air samples were collected in the target microenvironments over 20, 60, and 240 min. periods. These results were compared with the long-term personal Tenax GC samples (6 h) and grab samples collected with glass, gas-tight syringes at 0, 10, 18, 20, 25, 25.5, and 30 min. Maximum benzene concentrations occurred in the shower stall (758-1670 micrograms/m3) and bathroom (366-498 micrograms/m3) during and immediately after the shower. Inhalation exposures in the shower stall during the 20-min. shower were 2.1-4.9 times higher than corresponding 20-min, bathroom exposures. The total benzene dose resulting from the shower was estimated to be approximately 281 micrograms, with 40% via inhalation and 60% via the dermal pathway. This total is 2 to 3.5 times higher than the mean inhalation dose received during a concurrent 6 h occupation of the house. These results indicate that domestic use of gasoline-contaminated water can produce relatively high benzene exposures that vary significantly according to an individual's proximity to the water use zone. The information in this document has been funded wholly or in part by the U.S. Environmental Protection Agency. It has been subjected to Agency review and approved for publication. Mention of trade names or commercial products does not constitute endorsement or recommendation for use. The entire experiment was reviewed and approved by the Research Triangle Institute Human Subjects Review Committee.

Solid-phase extraction combined with radioimmunoassay for measurement of zalcitabine (2',3'-dideoxycytidine) in plasma and serum.

Of the antiviral agents that are currently in clinical use in the US for therapy for human immunodeficiency virus infections, zalcitabine (ddC) is the most potent and is effective at the lowest plasma concentrations. The two reported procedures for measuring these low concentrations involve a chromatographic technique coupled with mass spectrometry. We have developed a procedure combining solid-phase extraction with a strong cation-exchange resin and commercially available RIA reagents for the quantification of ddC in plasma or serum. The method demonstrates good linearity, specificity, and precision, with overall CVs of < 10% from 2-20 micrograms/L and 17% at 0.8 microgram/L (the lower limit of quantitation). No significant cross-reactivity with nucleoside analogs other than ddC analogs was noted. The major advantages of this assay are its efficiency and relative simplicity, which should facilitate its performance in many laboratories.

An examination of the time course from human dietary exposure to polycyclic aromatic hydrocarbons to urinary elimination of 1-hydroxypyrene.

The significance of diet as an exposure route for polycyclic aromatic hydrocarbons (PAHs) and the associated kinetics of urinary 1-hydroxypyrene (1-OHPY) elimination were examined through a controlled human exposure study. Results showed that a 100 to 250-fold increase in a dietary benzo(a)pyrene (BaP) dose paralleled a four to 12-fold increase in urinary 1-OHPy elimination. Mean elimination rates during minimal exposure periods ranged from 6 to 17 ng/h whereas peak elimination rates of 60 to 189 ng/h were seen after a meal high in PAHs. A biexponential model fitted to a limited number of urinary 1-OHPY elimination points gave mean kinetic parameter estimates for t1/2 of 4.4 hours and tmax of 6.3 hours. It is concluded that dietary exposure to PAHs is potentially as substantial as some occupational exposures and therefore requires consideration in studies of exposure to PAHs. The dietary control strategies and the kinetic parameters defined in this investigation provide data for the control of this exposure route when examining other sources of exposure.

High Precision Microcalorimetry: Apparatus, Procedures, and Biochemical Applications.

Apparatus and procedures used for high-precision microcalorimetric measurements are described. The calorimeter is of the heat-conduction type and utilizes semi-conductor thermoelectric modules. The bicompartmental reaction vessel is made of high-density polyethylene and holds about 0.5 mL of solution in each compartment. Imprecision of heat measurement is 0.2 percent when measuring 300 mJ of heat produced by a rapid chemical reaction. Three microcalorimeters are operated simultaneously using a microcomputer and a data acquisition system. Thermochemical and kinetic applications are described. The acquisition of data from an isoperibol solution calorimeter is also described.