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Biomedical subjects

R I Krieger

Publications and source records attributed to R I Krieger.

At least 19 recordsLinked to original sources

Perchlorate and nitrate in leafy vegetables of North America.

In previous studies trace levels of perchlorate were found in lettuce (Lactuca sativa L.) irrigated with Colorado River water, which is contaminated with low levels of perchlorate from aerospace and defense related industries. In this paper, we report the results of a survey conducted across North America to evaluate the occurrence of perchlorate in leafy vegetables produced outside the lower Colorado River region, and evaluate the relative iodide uptake inhibition potential to perchlorate and nitrate in these leafy vegetables. Conventionally and organically produced lettuce and other leafy vegetable samples were collected from production fields and farmers' markets in the central and coastal valleys of California, New Mexico, Colorado, Michigan, Ohio, New York, Quebec, and New Jersey. Results show that 16% of the conventionally produced samples and 32% of the organically produced samples had quantifiable levels of perchlorate using ion chromatography. Estimated perchlorate exposure from organically produced leafy vegetables was approximately 2 times that of conventional produce, but generally less than 10% of the reference dose recommended by the National Academy of Sciences. Furthermore, the iodide uptake inhibition potential of perchlorate was less than 1% of that of the nitrate present. These data are consistent with those of other reported perchlorate survey work with lettuce, bottled water, breast milk, dairy milk, and human urine, and suggest a wide national presence of perchlorate.

Environmental Monitoring↗

Accumulation and perchlorate exposure potential of lettuce produced in the Lower Colorado River region.

The Colorado River is contaminated with perchlorate concentrations of 1.5-8 microg/L, an anion linked to thyroid dysfunction. Over 90% of the lettuce (Lactuca sativa L.) consumed during the winter months in the United States is produced in the Lower Colorado River region. Studies were conducted in this region to survey the potential for lettuce perchlorate accumulation and estimate potential human exposure to perchlorate from lettuce. Total uptake of perchlorate in the above-ground plant of iceberg lettuce was approximately 5 g/ha. Exposure estimates ranged from 0.45 to 1.8 microg/day depending on lettuce types and trimming. For all lettuce types, hypothetical exposures were less than 4% of the reference dose recommended by the National Academy of Sciences. Results show the relative iodide uptake inhibition potential because of lettuce nitrate was 2 orders of magnitude greater than that associated with the corresponding trace levels of perchlorate. These data support the conclusion that potential perchlorate exposures from lettuce irrigated with Colorado River water are negligible relative to acute or long-term harmful amounts.

Arizona↗

Environmental residues and biomonitoring estimates of human insecticide exposure from treated residential turf.

Intentional and unavoidable human exposure is a consequence of using pesticides to nurture and protect residential turf. Limited exposure studies have been conducted for assessing potential human exposure of turf residues. Exposure was measured in persons who performed a 20-minute structured activity (Jazzercise) on chlorpyrifos (CP)-treated Kentucky bluegrass (12 +/- 4 microg CP/cm(2)). CP exposure was measured by determining urine clearance of the 3,5,6-trichloro-2-pyridinol (TCP). Study participants wore either 100% cotton whole body dosimeters (union suit, gloves, and socks) or exercise suits (shorts and a sports top or one-piece suit with similar amounts of exposed skin). An average of 1.6 mg CP/person was extracted from whole body dosimeters worn by study participants. The measured residue transfer was well below the 35 mg CP/person estimated using the US EPA standard operating procedures. Biomonitoring based on urine clearance of TCP indicated that an average of 1.3 microg CP/kg was absorbed. Absorbed dosages (0.5 to 2 microg CP/kg) derived from transferable residue on cotton cloths pressed to the turf with a weighted roller were similar to estimates from biomonitoring. A very limited amount of CP applied to turf is available for transfer and absorption during intensive human contact.

Absorption↗

Could pesticide toxicology studies be more relevant to occupational risk assessment?

Pesticide toxicology study design has evolved from concern for oral exposure via food residues. The emphasis on the oral route does not generally apply to workers that are exposed primarily via the dermal route either handling pesticides or re-entering treated fields. As a result numerous assumptions about how oral toxicology results relate to dermal exposure must be made when conducting worker risk assessments. These assumptions introduce a high degree of uncertainty. Alternative toxicology study designs are suggested to reduce uncertainty when assessing risk. Because the dermal route is so important to characterizing occupational risk, methods to improve the accuracy of dermal absorption estimates are suggested, including the use of human subjects to study dermal absorption. Additional suggestions include tailoring dermal, oral and inhalation kinetic study designs to reflect worker exposure dosages. Suggestions are made to routinely conduct a single dose toxicity study patterned after the neurotoxicity study design to distinguish single dose effects and NOAELs from those resulting from multiple doses. Finally, interspecies pharmacokinetics studies are proposed to determine which toxicology study regimen of dosing best reflects intermittent worker exposure.

Administration, Inhalation↗

Biomonitoring of persons exposed to insecticides used in residences.

Pesticides used indoors inevitably result in some unintentional and unavoidable exposures of residents. Measured dosages of residents are well below toxic levels. Exposures (microg/kg-day) are substantially less and occur over a longer time than suggested by unvalidated estimates derived from previous extreme, conservative default assumptions based solely on environmental residues. Human chlorpyrifos exposures were monitored following three different types of applications: fogger, broadcast, and crack-and-crevice. Persistence of total residue on carpet was substantially greater than the persistence of transferable residue (microg/cm(2)). Low-level (microg/kg) exposures of family members persisted for periods of weeks to a month after pesticide use. Although few children who resided with their parents in pest-protected homes have been monitored, they eliminated more biomarker than their parents on a kg body weight-day basis when absorbed dosages (microg/kg-day) were derived from spot urine specimens corrected for volume by an age-specific creatinine correction. Ultimately environmental residues may become useful elements of predictive residential exposure models, but their potential contribution to indirect exposure assessments must include careful determination of residue availability for contact transfer to clothing or skin and biological validation. When environmental data from monitoring studies reported here were used to estimate residential exposure according to Residential Exposure Assessment Standard Operating Procedures (SAP meeting, 1997), measured exposures were substantially less than assessments. Experimental and situational monitoring of exposed persons is essential for meaningful and responsible predictive resident exposure model building.

Administration, Cutaneous↗

Improved HPLC method for analysis of 1-hydroxypyrene in human urine specimens of cigarette smokers.

A method for the rapid and sensitive analysis of 1-hydroxypyrene in human urine was improved by high performance liquid chromatography (HPLC) with fluorescence detection. The limit of detection decreased approximately threefold when triethylamine was added to the extracts prior to the chromatographic determination. The sensitivity was increased mainly due to triethylamine blockage of the secondary-retention effects. The analysis time was approximately 20 min per run. This method was applied to the analysis of 1-hydroxypyrene in 125 urine specimens collected from cigarette smokers who had non-occupational exposure to polycyclic aromatic hydrocarbons. The average concentrations of urinary 1-hydroxypyrene were 0.04 micromol/mol creatinine in non-smokers, 0.20 micromol/mol creatinine in light smokers, 0.46 micromol/mol creatinine in medium smokers, and 1.16 micromol/mol creatinine in heavy cigarette smokers. The levels of urinary 1-hydroxypyrene correlated strongly with cigarette intake (r2 = 0.93, P < 0.001).

Adolescent↗

Conservatism in pesticide exposure assessment.

Three important factors are commonly encountered in exposure assessment that when combined could overestimate the exposure to pesticides by as much as two orders of magnitude. The three factors discussed are dermal absorption from laboratory animal studies, daily dose extrapolated from partial day monitoring, and nonbolus dose from dermal or inhalation exposure. Conservatism built into the process by each of these three factors is substantiated with available empirical data. The dose overestimation from these factors varies discriminatively by exposure scenarios and peculiarities of a given chemical. It is for this reason that a generic overestimation factor cannot be ascribed. Following the empirical illustrations, the authors conclude that the most effective approach for dealing with the problem is to generate the most appropriate data possible. This means producing human rather than laboratory animal dermal absorption data, conducting full-day exposure monitoring studies, and whenever feasible generating dermal rather than oral toxicology data (or alternatively data on both oral and dermal pharmacokinetics) in those cases where the dermal route predominates.

Animals↗

Captan fungicide exposures of strawberry harvesters using THPI as a urinary biomarker.

Clothing affords harvesters considerable protection against the elements and can retain substantial amounts of pesticide residue from treated crops. Normal work clothing of female harvesters was supplemented with rubber latex gloves and facial scarves to determine whether those measures reduced exposure. Captan fungicide exposures in female strawberry harvesters were assessed by determining urine clearance rates of tetrahydrophalimide (THPI). Clean rubber gloves were supplied to the 41 harvesters for the 3 days of the study period in October 1995. The workers were divided into two groups consisting of either bare-handed or gloved workers, and 24-h urine specimens were collected each day. Female harvesters who worked bare-handed cleared 5.3 microg captan equivalents as THPI with a range of 0.4 to 13.8 microg/person/day. Harvesters who worked wearing rubber latex gloves cleared only 2.0 microg captan equivalents with a range of 0.9 to 4.3 microg/person/day. In this case clean rubber latex gloves reduced absorbed dose by 38%, compared to the dose absorbed by bare-handed workers. These results additionally indicate that when a pesticide is avidly retained by rubber latex gloves and not readily absorbed dermally as captan, estimates of absorbed dose based on passive dosimetry data may be less reliable than exposure estimates derived from urine biomonitoring.

Administration, Cutaneous↗

Malathion deposition, metabolite clearance, and cholinesterase status of date dusters and harvesters in California.

Date gardens in the Coachella Valley in California typically receive multiple treatments of malathion to control major insect pests. Variable amounts of malathion dust retention by skin and clothing and individual work behaviors limit the usefulness of clothing as an exposure dosimeter in date dusters and harvesters. To determine malathion absorption in workers, urine clearance of dimethyl phosphates (alkyl phosphates; AP) and malathion mono- (MCA) and di- (DCA) acids were estimated from date dusters (loaders/applicators) and harvesters (both on ground and high in trees). A series of self-administered doses of malathion were either ingested in gelatin capsules or applied to the volar surface of the forearm to guide biomonitoring. Each of the dimethyl phosphates (dimethylthio> dimethyldithio > dimethyl-) and both malathion mono- and diacids were present in urine as soon as 2-3 h of work. On a micromole basis dimethylthiophosphate and the malathion acids (MCA > DCA) were the most prominent metabolites in urine. Applicator exposures ranged from 95-210 mg equivalents per day (1-3 mg/kg-day). Harvester exposures ranged from 1-270 microg/kg-day. Mid-season Monday morning urine specimens before work contained low or unmeasurable levels of malathion acids, indicating that malathion is rapidly metabolized and cleared from the body in the urine. Saliva was not useful for biomonitoring. No inhibition of cholinesterase activity was measured in any members of two separate crews of harvesters who had previous prolonged dust exposure (1 and 2 months).

Agriculture↗

Estimation of dermal absorption using the exponential saturation model.

Estimates of dermal absorption are used in exposure assessment to calculate the internal dose of persons contacting pesticides and are a critical part of risk assessments. An exponential saturation model with lag time was validated against a classic dermal absorption study of 12 pesticides administered to human volunteers. The model gave dermal absorption estimates consistent with reported values in the literature. Moreover, this model gave more realistic estimates of the percentage of dermal absorption for some pesticides, which have special properties. In most submitted dermal absorption studies in animals, especially rats, "bound" skin residues (BSR) at treated skin sites were generally high when animals were sacrificed more than 24 h after the dose was administered. The direct addition of the total BSR as an absorbed dose would likely overestimate actual dermal absorption. From a well-conducted dermal absorption study, this model can be utilized to estimate maximum excretion of the administered dermal dose as a result of further absorption of bioavailable BSR. Resulting dermal absorption estimates are appropriate for regulatory purposes in the risk assessment of pesticides because they take into account the bioavailability of BSR while at the same time the estimates are not overly conservative.

Animals↗

Toxicity of methomyl following intravenous administration in the horse.

Methomyl (S-methyl-N-((methylcarbamoyl)oxy) thioacetimidate) toxicity was studied in horses using i.v. dosages from 0.01 to 3.0 mg/kg. Doses of 1-3 mg methomyl/kg produced increased GI motility and respirations, facial fasiculations, salivation, lacrimation and convulsions. The only effect at 0.5 mg/kg was increased GI sounds in 1/4 horses. This extensively used crop insecticide had been associated with episodes of morbidity and mortality and led to speculation that it was extremely potent to the horse. This was not supported by these clinical studies.

Animals↗