Brent D Kerger

Exponent Health and Environmental · Center for Toxicology and Mechanistic Biology

This chapter is intended to provide a detailed weight of evidence scientific review on polychlorinated biphenyls (PCBs) and polybrominated biphenyls (PBBs). Notably, PCBs are among the most thoroughly studied chlorinated persistent organic pollutants to date; despite their discontinued commercial production in the 1970s, their environmental persist...

Objective To characterize personal exposures and measures of eye and respiratory tract irritation in controlled environmental chamber studies of 44 healthy adult volunteers simulating upper-bound use of peracetic acid (PAA)–based surface disinfectant for terminal cleaning of hospital patient rooms. Design Experimental, within-subject, double-blind...

Airborne and surface Pb concentrations were measured inside a glovebox chamber with controlled inflow rate at 1.0 L/min of ultrapure air over a 4-hour period while an operator completed 1,680 solder connections using Sn63:Pb37 solder with rosin flux core. Chamber atmosphere showed released mean Pb mass of 0.0238 ± 0.011 μg and mean airborne concent...

Objective This study investigates the hypothesis that an increasing fraction of incident pleural mesothelioma (PM) in the US population may be related to longevity, i.e., to expansion of the population over age 75 years with an age-related elevation in risk. An age-period-cohort analysis of the SEER 9 cancer registries (1973–2013) was conducted usi...

Toxaphene is a liver tumor promoter in B6C3F1 mice but not in F344 rats or hamsters. Recent studies demonstrate that key events leading to the mouse liver tumor response for toxaphene are mediated by activation of the constitutive androstane receptor (CAR). Benchmark dose modeling was conducted on available data for five endpoints in B6C3F1 mouse l...

Technical toxaphene (TT) is a liver tumor promoter in B6C3F1 mice but not in F344 rats. To further evaluate dose-response relationships for weathered toxaphene, B6C3F1 mouse hepatocytes were treated with TT alone, five selected persistent congeners (p-26, p-50, p-62, Hx-Sed, and Hp-Sed), or two selected congener mixtures (simulating weathered toxap...

Background Negative news media reports regarding potential health hazards of implanted medical devices and pharmaceuticals can lead to a ‘negative halo effect,’ a phenomenon whereby judgments about a product or product type can be unconsciously altered even though the scientific support is tenuous. To determine how a ‘negative halo effect’ may impa...

Bronchiolitis obliterans (BO) is a rare disease involving concentric bronchiolar fibrosis that develops rapidly following inhalation of certain irritant gases at sufficiently high acute doses. While there are many potential causes of bronchiolar lesions involved in a variety of chronic lung diseases, failure to clearly define the clinical features...

Inductively coupled plasma with mass spectrometric detection (ICP-MS) has been used for clinical analysis of cobalt (Co) due to its sensitivity and specificity; however, media-specific validation studies are lacking. This study provides data on performance variables affecting differences between selected analytical platforms (Perkin Elmer and Agile...

Laboratory studies were conducted to evaluate airborne release of diacetyl from selected mixtures simulating butter flavorings added to foods. The test materials included diacetyl (97% purity); 0.015%, 0.15%, 1.5%, and 3.0% diacetyl in a water/propylene glycol mixture; 1.5% diacetyl in deionized water or soybean oil; and 3% or 6% diacetyl in a comm...

Cobalt (Co) can stimulate erythropoietin production in individuals at doses exceeding 25 mg CoCl2/day. Co has also been shown to exert effects on the thyroid gland, heart and nervous system at sufficient doses. The biological activity of Co is dictated by the concentration of free (unbound) ionic Co(2+). Blood concentrations, as well as, urinary ex...

Toll-like Receptor-4 (TLR-4) activity is upregulated in persons with fibrotic lung diseases secondary to chronic inflammatory conditions like Crohn's disease and rheumatoid arthritis. We hypothesized that α-diketones associated with fixed obstructive lung disease may activate TLR-4. We utilized a human embryonic kidney cell assay (HEK293) with huma...

The diagnosis of mesothelioma is not always straightforward, despite known immunohistochemical markers and other diagnostic techniques. One reason for the difficulty is that extrapleural tumors resembling mesothelioma may have several possible etiologies, especially in cases with no meaningful history of amphibole asbestos exposure. When the diagno...

Concerns have recently been raised about the presence of metals in apple juices. As such, the concentration of aluminum (Al), arsenic (As), cadmium (Cd), chromium (Cr), copper (Cu), lead (Pb), manganese (Mn), mercury (Hg), and zinc (Zn) were measured in six commercially available brands of apple juice and three organic brands. The concentrations of...

An updated biokinetic model for human exposures to cobalt (Co) was developed based on a comprehensive set of human pharmacokinetics data collected from five male and five female volunteers who ingested ∼1.0 mg Co/day of a Co supplement for three months. Three key experimental observations from the human dosing studies were incorporated into the mod...

The United Kingdom Expert Group on Vitamins and Minerals concluded that ingesting cobalt (Co)-containing supplements up to 1400 μg Co/d is unlikely to produce adverse health effects. However, the associated blood Co concentrations and safety of Co-containing dietary supplements have not been fully characterized. Thus, blood Co kinetics and a toxico...

The presence of benzene in motor gasoline has been a health concern for potential increased risk of acute myelogenous leukemia and perhaps other lymphatic/hematopoietic cancers for approximately 40 years. Because of the widespread and increasing use of gasoline by consumers and the high exposure potential of occupational cohorts, a thorough underst...

A method utilizing size exclusion liquid chromatography (SEC) was developed to separate and quantify large molecular cobalt (Co) (e.g., albumin-Co) from cyanocobalamin (vitamin B12) and small molecular Co (e.g., glutathione-Co and free Co) in human serum. Highly selective and sensitive detection using inductively coupled plasma–mass spectrometry wa...

Abstract Cobalt (Co) is an essential element with ubiquitous dietary exposure and possible incremental exposure due to dietary supplements, occupation and medical devices. Adverse health effects, such as cardiomyopathy and vision or hearing impairment, were reported at peak blood Co concentrations typically over 700 µg/L (8-40 weeks), while reversi...

A new analytical method for determining cobalt (Co) species in human serum by size exclusion chromatography with inductively coupled plasma mass spectrometry (SEC-ICP-MS) was applied to serum samples collected from 12 human volunteers who participated in a Co(II) chloride supplement study involving ingestion of 1 mg Co/day for up to 90 consecutive...

The University of Michigan Dioxin Exposure Study provides extensive data on elevated residential soil and house dust concentrations of polychlorinated dioxins and dibenzofurans (PCDD/Fs) and adult body burdens among residents near a chemical manufacturing plant in Midland, Michigan. Recent reports found no significant contribution of residential so...

A physiologically-based pharmacokinetic (PBPK) model of benzene inhalation based on a recent mouse model was adapted to include bone marrow (target organ) and urinary bladder compartments. Empirical data on human liver microsomal protein levels and linked CYP2E1 activities were incorporated into the model, and metabolite-specific conversion rate pa...

Airborne benzene concentrations were measured in a room with controlled air exchange during surface cleaning with two petroleum-based solvents (a paint thinner and an engine degreaser). The solvents were spiked with benzene to obtain target concentrations of 0.001, 0.01, and 0.1% by volume in the liquid. Personal samples on the worker and area samp...

A dose-response relationship between serum 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin) and adult diabetes risk has been reported among U.S. Vietnam veterans in the Ranch Hand (RH) cohort. We examine the hypothesis that diabetes progression leads to higher serum dioxin (reverse causation) rather than higher serum dioxin leading to diabetes (causati...

This study evaluates how equilibrium vapor concentrations above petroleum solvent mixtures are affected by liquid aromatic content and the implications for estimating benzene vapor exposures. Headspace vapor concentrations over mixtures with liquid benzene content ranging from 0.001 to 1.0% and varied percentages of 1,2,4-trimethylbenzene in n-nona...

The 1976 trichlorophenol reactor explosion led to the most massive acute airborne release of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) into a densely populated area that has been documented to date. This industrial accident caused a persistent skin disease, chloracne, in nearly 200 individuals and led to some of the highest body doses of TCDD ever...

Persistent organic chemicals, such as perfluorooctanoic acid (PFOA), perfluorooctanesulfonate (PFOS), dioxins, and polychlorinated biphenyls, pose investigative challenges because they are found in virtually everyone (there is no unexposed control group). To overcome this problem, outcome data in some studies are sorted by chemical dose level and f...

We address two errors in the paper by Beaumont et al.1 that reanalyzes the data of the late Dr. Zhang2,3,4 which in 1995 we (SL) co-authored and helped him submit for publication (BK, WB, TY). First, among the five exposed villages, there is no consistent pattern of association of cancer rates with the gradient of exposure to Cr6+ as noted earlie...

This report is a further characterization of data from an ecological cancer mortality study of a population (about 10,000) exposed to groundwater contaminated by hexavalent chromium [Cr(VI)] up to 20 mg/L near JinZhou City in the LiaoNing Province of China between 1960 and 1978. Prior reports showed an elevation in all-cancer mortality from 1970 to...

Abstract Some of the most significant advances and refinements in human health risk assessments for environmental and occupational chemicals have come from investigations in the area of exposure assessment. This presentation summary describes three previously published examples of continuing advances in this process.

An adaptable model is presented for assessing the blood lipid concentrations of polychlorodibenzodioxins and polychlorodibenzofurans (PCDD/Fs) from dietary (breast milk, formula, milk, and other foods) and soil pathway exposures (soil ingestion and dermal contact) utilizing age-specific exposure and intake estimates for young children. The approach...

Half-life estimates of three polychlorodibenzofurans (PCDFs) were calculated using serial blood samples collected over a 15 to 19-year period. Blood fat PCDFs were modeled in eight individuals who were exposed to contaminated rice oil in Japan (Yusho, n = 5) and in Taiwan (Yucheng, n = 3). The elimination kinetics of PCDFs were concentration-depend...

We modified our prior age-dependent half-life model to characterize the range of child (ages 0-7) body burdens associated with dietary and environmental exposure to polychlorodibenzodioxins and furans (PCDD/Fs). Several exposure scenarios were evaluated. Infants were assumed to be either breast-fed or formula-fed from birth to 6 months of age. They...

Pharmacokinetic and statistical analyses are reported to elucidate key variables affecting 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) elimination in children and adolescents. We used blood concentrations to calculate TCDD elimination half-life. Variables examined by statistical analysis include age, latency from exposure, sex, TCDD concentration an...

This article reviews the scientific evidence and methodologies that have been used to assess the risks posed by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and presents a probabilistic analysis for identifying virtually safe concentrations of TCDD toxicity equivalents (TEQ) in residential soils. Updated data distributions that consider state-of-the-...

Elimination half-life estimates for several polychlorinated dibenzodioxins/furans (PCDD/F) were calculated by modeling the blood and breast milk concentrations in two breast-fed human infants as reported by Abraham et al. (1996, 1998). Our analysis differs from that of other investigators in that we analyzed individual dioxin and furan congeners wh...

There is scant information pertaining to airborne ammonia exposures from either spills or common household uses of ammonia-containing floor and tile cleaners or from spray-on glass cleaners. We assessed instantaneous and event-specific time-weighted average (TWA) exposures to airborne ammonia during spills and use (per label directions) of a househ...

This study evaluates airborne concentrations of common trihalomethane compounds (THM) in selected living spaces of homes supplied with chlorinated tap water containing >85 ppb total THM. Three small homes in an arid urban area were selected, each having three bedrooms, a full bath, and approximately 1000 square feet; two homes had standard (refrige...

Rodent cancer bioassays indicate that substantial differences exist among PCB mixtures in terms of tumorigenic response, although no bioassay has been conducted with Aroclor 1268. The USEPA has used data from these studies to develop three sets of PCB cancer slope factors (CSFs) ranging from 0.07 to 2.0(mg/kg-day)(-1). Selection of the appropriate...

This study examines benzene emissions from the use of a metal parts washer ("degreaser") supplied with a mineral spirits solvent containing either 9 or 58 ppm benzene. Air samples were obtained during a one-hour session of relatively vigorous parts cleaning activity using a degreaser station equipped with wet brush and sprayer attachments and a com...

Hexavalent chromium [Cr(VI)] has been detected in groundwater across the United States due to industrial and military operations, including plating, painting, cooling-tower water, and chromate production. Because inhalation of Cr(VI) can cause lung cancer in some persons exposed to a sufficient airborne concentration, questions have been raised abo...

Hexavalent chromium [Cr(VI)] has been detected in groundwater across the United States due to industrial and military operations, including plating, painting, cooling-tower water, and chromate production. Because inhalation of Cr(VI) can cause lung cancer in some persons exposed to a sufficient airborne concentration, questions have been raised abo...

The objective of the current study was to evaluate the types and concentrations of volatile organic compounds (VOCs) in the passenger cabin of selected sedan automobiles under static (parked, unventilated) and specified conditions of operation (i.e., driving the vehicle using air conditioning alone, vent mode alone, or driver's window half open). D...

This analysis addresses the health risks to residents exposed to chromium(VI)-containing groundwater at concentrations up to 4,000 ppb. Although a number of studies have shown that high levels of airborne chromium(VI) produced an increased incidence of lung cancer in workers exposed during the 1940s-1960s, little toxicology information was availabl...

A physiologically based model of human chromium kinetics has been developed, based on an existing physiologically based model of human body and bone growth (O'Flaherty, 1993, Toxicol. Appl. Pharmacol. 118, 16-29; 1995a, Toxicol. Appl. Pharmacol. 131, 297-308; 2000, Toxicol. Sci. 55, 171-18) and an existing physiologically based model of chromium ki...

This study evaluates airborne concentrations of common trihalomethane (THM) compounds in bathrooms during showering and bathing in homes supplied with chlorinated tap water. Three homes in an urban area were selected, each having three bedrooms, a full bath, and approximately 1,000 square feet of living area. THMs were concurrently measured in tap...

This study examines time- and concentration-dependent changes in distribution of hexavalent chromium [Cr(VI)] and total chromium [Cr-(TOT)] in reconstituted human blood following addition of potassium dichromate. Fresh human blood stabilized with EDTA was obtained from human volunteers soon after meal ingestion and at 2.5 h after a light meal (here...

This study examined the systemic uptake of chromium in four human volunteers following three hours of contact with water containing hexavalent chromium [Cr(VI)] at a concentration of 22 mg/L. Volunteers were immersed below the shoulders in water at 91 +/- 2.5 degrees F. On the day prior to the experiment and for five days afterwards, samples of uri...

Estimates of the overall reducing capacity of hexavalent chromium(VI) in some human body compartments were made by relating the specific reducing activity of body fluids, cell populations or organs to their average volume, number, or weight. Although these data do not have absolute precision or universal applicability, they provide a rationale for...

Regulatory agencies have established safe drinking water concentrations for hexavalent chromium [Cr(VI)] based in part on the presumed capability of human gastric juices to rapidly reduce Cr(VI) to nontoxic trivalent chromium [Cr(III)] prior to systemic absorption. This study examines dose-related pharmacokinetics in humans following repeated oral...

This study examines the magnitude of hexavalent chromium [Cr(VI)] absorption, distribution, and excretion following oral exposure to 5 and 10 mg Cr(VI)/L in drinking water administered as a single bolus dose (0.5 L swallowed in 2 min) or for 3 d at a dosage of 1 L/d (3 doses of 0.33 L each day, at 6-h intervals). Adult male volunteers ingested deio...

The uptake and elimination of Cr(VI) in a male volunteer who ingested 2 L/d of water containing 2 mg/L for 17 consecutive days was measured. Total chromium was measured in urine, plasma, and red blood cells (RBCs) for 4 d prior to and 2 wk after dosing (34 d total). The estimated bioavailability (2%) and the plasma elimination half-life (36 h) were...

These studies investigate the magnitude and valence state of chromium absorbed following plausible drinking water exposures to chromium(VI). Four adult male volunteers ingested a single dose of 5 mg Cr (in 0.5 liters deionized water) in three choromium mixtures: (1) Cr(III) chloride (CrCl3), (2) potassium dichromate reduced with orange juice (cr(II...

Increased DNA-protein cross-linking (DPX) in circulating leukocytes has been proposed as a potential biomarker for exposure and genotoxic damage caused by inhalation of certain reactive chemicals, such as hexavalent chromium [Cr(VI)]. This study was designed to determine whether ingestion of a single dose of potassium dichromate alone [Cr(VI)] or p...

Laboratory studies were conducted to determine how rapidly and completely chromium (VI) [Cr(VI)] is reduced upon contact with common beverages mixed with tapwater. Studies were performed for five common beverages (coffee, tea, orange juice, Kool Aid, and powdered lemonade) spiked with either 10 or 50 mg Cr(VI)/l. The concentrations of Cr(VI) were m...

Field studies were conducted to estimate the plausible uptake of hexavalent chromium [Cr(VI)] aerosols inhaled during indoor residential use of a shower or an evaporative cooler supplied with water containing Cr(VI). In the evaporative cooler study, water concentrations of 20 mg Cr(VI)/L did not produce an increased concentration of airborne Cr(VI)...

This study examines the potential in vivo genotoxicity of Chromium(VI) in drinking water at concentrations ranging from the relevant human exposure level of 1 mg/l to the upper limit of palatability in rodents (20mg/l).

A recent study from our laboratory revealed that cotreating mice with the alpha-adrenoreceptor antagonists phentolamine and idazoxan markedly diminished bromobenzene-induced hepatotoxicity. Subsequent studies also revealed that such cotreatment does not alter the pharmacokinetic disposition of bromobenzene in mice nor its bioactivation to reactive...

Bromobenzene is metabolized by hepatic microsomes to two different epoxide intermediates, which then rearrange to form either ortho- or para-bromophenol. A rapid and sensitive technique utilizing HPLC with electrochemical detection is presented for the quantitation of these primary bromobenzene metabolites. This analytical procedure allows selectiv...

The coadministration of phentolamine, an alpha-adrenoreceptor antagonist, was found to be effective in antagonizing the hepatotoxicity produced by bromobenzene in B6C3F1 mice. Multiple doses of phentolamine, administered in dosages of 10 mg/kg, attenuated almost completely the acute lethality resulting from a 0.5 ml/kg dosage of bromobenzene. Consi...

A previous study has revealed that phentolamine markedly antagonizes the bromobenzene-induced hepatotoxicity and lethality in B6C3F1 mice. One potential mechanism by which phentolamine may diminish the bromobenzene-induced hepatotoxicity is by a direct or indirect interference with the metabolism of bromobenzene to toxic metabolites. In the present...

A new method is presented for the detection of phentolamine by high performance liquid chromatography with electrochemical detection. The electrochemical detector was used in the oxidative mode at +900 mV potential versus Ag/AgCl reference. The on-column detection limit for phentolamine using this method was 3 ng, and detector response was linear f...

Fatty acids of twelve strains of budding bacteria (Planctomyces and Pirellula spp.), which have atypical 16S rRNA and do not contain peptidoglycan cell walls, were shown to contain typical diacyl polar lipids with no indication of isoprenoid ether lipids suggestive of a relationship with the archaebacteria. The major ester-linked fatty acids of the...

The acid-producing thiobacilli contain fatty acid components in the polar lipids and lipopolysaccharide lipid A that are sufficiently unusual that they can be utilized as signature lipid biomarkers for these organisms in environmental samples. Studies in microcosms have shown correlations between activity of these organisms, measured by recovery an...

The polar lipids of 5 species of Thiobacillus were extracted and purified. An analysis of the fatty acid composition of the polar lipids documented the presence of methoxy, cyclopropyl, monounsaturated and hydroxycyclopropyl fatty acids of sufficiently unusual structure to serve as ‘signatures’ for the presence of these organisms in environmental s...

Application of quantitative methods for microbial biomass, community structure, and nutritional status to the subsurface samples collected with careful attention to contamination reveals the presence of a group of microbes. The microbiota is sparse by several measures of biomass compared with that present in surface sediments and soils. The communi...

The technique of Fourier transforming in infra red spectroscopy provides a nondestructive technique for examining biofilms on the surface of metals on a scale approaching the size of microcolonies of bacteria. Research suggests that the inohomogeneous distribution of microbial biofilms in an extracellular polymer matrix containing calcium hydroxide...

Half-life estimates of three polychlorodibenzofurans (PCDFs) were calculated using serial blood samples collected over a 15-19 year period. Blood fat PCDFs were modeled in 8 individuals who were exposed to contaminated rice oil in Japan (Yusho, n = 5) and in Taiwan (Yucheng, n = 3). The elimination kinetics of PCDFs were concentration-dependent, wi...