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Biomedical subjects

R I Krieger

Publications and source records attributed to R I Krieger.

At least 37 records · Page 2Linked to original sources
PubMed1995

Long vs. short monitoring intervals for peach harvesters exposed to foliar azinphos-methyl residues.

A dermal monitoring study of peach harvesters exposed to azinphos-methyl (AM) residues was conducted in Sutter County, California. Harvesters were paid by piecework, which allowed characterization of the relationship between dermal exposure (DE) and time or production. Workers wore 2 long-sleeved knit T-shirts for each monitoring interval and also provided a hand residue sample. Dislodgeable foliar residue (DFR) samples were also collected. The highest correlations were found for inner shirts vs. production and DE vs. time worked (r2 = 0.67, P < 0.01). DE was greatest after 2-h exposures and reached equilibrium after 3 h, indicating that exposure estimates from shorter intervals would overestimate exposure.

Agriculture↗
PubMed1995

Pesticide exposure assessment.

Unintended, accidental, or unavoidable human exposures may result from pesticide use. Risk Characterization provides registrants, regulators, and the public a means to assess relative risks of pesticide use. Exposure Assessments are less standardized. Potential Dermal Exposure (PDE; mg/kg) is the amount of contact with the potential for dermal absorption (DA). Mixer/loader/applicator data developed using passive dosimetry and skin washing forms a Tier 1 Generic Database. If disqualifying estimates are obtained a more accurate estimate (Tier 2) may be developed from measurements of DA, clothing protection, and PDE under use conditions. Direct estimates of absorbed dose (Tier 3) require metabolic and kinetic data and biological monitoring. Harvesters and other persons who contact treated surfaces need reentry intervals to minimize acute and chronic exposure. Work tasks, dislodgeable foliar residue, and duration of exposure are the foundations for exposure-based, generic estimates of harvester PDE.

Environmental Exposure↗
PubMed1993

Metabolism and excretion of dimethoate following ingestion of overtolerance peas and a bolus dose.

Data to guide an exposure assessment were obtained by giving sugar peas containing overtolerance dimethoate residues (17 ppm; 8% oxon) and a bolus dose of dimethoate to a healthy adult male. The dimethoate tolerance on peas was and remains 2 ppm. Serial total urine samples were collected and analysed for dimethoate and its oxon, dimethylphosphate, dimethylphosphorothioate (DMTP) and dimethylphosphorodithioate. The dose of dimethoate administered was approx. 0.1 mg/kg body weight and produced no symptoms of toxicity. Dimethylphosphates appeared in the urine within 2 hr. The major metabolite (about 60%) was DMTP. Only traces (< 0.5%) of dimethoate and oxon were recovered from urine. Acetylcholinesterase inhibition was not observed although urinary metabolites were prominent, indicating that they are better indicators of acute exposure than cholinesterase inhibition. The results obtained using a bolus dose were virtually identical to those from the trial with overtolerance peas, and indicated that dimethoate is readily absorbed and its urinary metabolites are readily eliminated following exposures to low doses (0.1 mg/kg body weight).

Administration, Oral↗
PubMed1993

Risk assessments in the pesticide regulatory process.

The risk assessment process offers regulators, registrants, public interest groups and users a means of weighing apparent health effects of pesticides and other chemicals, and measuring their safety for use. This report contains the method for developing relative measures of safety for acute toxicity and expressions of risk for chronic toxicity and assesses-human exposure under a variety of extreme scenarios. Since workplace exposures usually exceed environmental exposures by two or more orders of magnitude, occupational experience with pesticides is critical to the regulatory process. Default assumptions, the adoption of conventional numbers in the absence of empirical data, for factors such as dermal absorption, metabolism, clearance and worker protective measures that seem conservative may weaken the reliability of the risk characterization process and may reduce the likelihood of recognizing significant risk. An exposure-based regulatory policy should feature measurements of absorbed dose validated using biomonitoring and margins of safety and estimates of risk that reflect human experience. This paper lists basic characteristics of unit processes of risk assessment and presents some strategies and pitfalls of the process as practiced in California in recent years.

Animals↗
PubMed1993

Captan metabolism in humans yields two biomarkers, tetrahydrophthalimide (THPI) and thiazolidine-2-thione-4-carboxylic acid (TTCA) in urine.

Captan fungicide (N-(trichloromethylthio)-4-cyclohexene-1,2-dicarboximide) metabolism in two human volunteers rapidly yields THPI (tetrahydrophthalimide) and TTCA (thiazolidine-2-thione-4-carboxylic acid). The work was done to evaluate usefulness of TTCA and THPI as biomarkers of occupational exposure and to compare human and rat dermal absorption and metabolism. THPI in 12h urine ranged from MDL (5 ppb) to 640 ppb and was stable for at least one year. TTCA was also a stable metabolite, but the MDL was 50 ppb. THPI was detectable in urine for 72 hours following oral dosages of 1 mg/kg, but most was eliminated 0-24 h. No THPI was detectable in urine following application of a chloroform solution to hands, forearms, or inguinal region. Dermal absorption and metabolism of captan are substantially different in humans and rats.

Administration, Cutaneous↗
PubMed1992

Assessing human exposures to pesticides.

Pesticide use is inevitably associated with chemical exposures that range from inferred nondetectable levels to easily measurable ones using sensitive, readily available analytical tools. Whether these exposures are of any biological significance is determined by duration, dose, and biological reactivity. The overwhelming majority of human exposures occur in a diverse chemical milieu of a nutritive substances and are of no known significance. Technologies that minimize human chemical exposures and maximize pesticide effectiveness are favored. The risk characterization process is ideally suited to assist decision makers concerning the protection of human health and evaluation of agricultural tools. It is the best means available to balance the review of pesticide impacts on health and agriculture. Regulators must be cautious to acknowledge the relative rather than absolute nature of the risk characterization process. Workplace biological monitoring must become more commonplace as a means to evaluate the chemical exposure potential of various work tasks and greater attention must be given to the biological validation of methods. Earlier needs for data to develop workplace hygiene strategies have been replaced in recent years by demands of the risk assessment process, which utilizes direct estimates of exposure and absorbed dose. Animal models, no matter how attractive, are not presently a substitute for human experience. Opportunities to gather more information on human experience associated with pesticide exposures must be more aggressively identified and pursued. Only a very small time lag should exist between identification of pesticide metabolites in rats and evaluation of metabolic similarities in humans. At the present levels of analytical sensitivity, most of our current uncertainty about the extent of worker exposure and patterns of metabolism between species can be at least clarified with the cooperation of persons who are exposed during normal day-to-day activities in the workplace. Only with better human data will the risk assessment process warrant greater reliance in decision making concerning our chemical exposures and human experience.

Environmental Exposure↗
PubMed1992

Acute pesticide morbidity and mortality: California.

The California Pesticide Illness Surveillance Program collects, investigates, abstracts, and records reports received from physicians. A minority of the reports are received through the county health officers who are notified by physicians under a state requirement for reporting pesticide-caused conditions. Most of the cases are identified by review of workers' compensation records. All the cases identified are investigated by the agricultural commissioners of the counties where exposure occurred. The investigation reports are reviewed and abstracted by staff of the Worker Health and Safety Branch of the California Department of Pesticide Regulation, California Environmental Protection Agency (Cal/EPA). The crucial determination is assessment of the degree of relationship between the exposure and subsequent disease: definite, probable, possible, unlikely, or unrelated. In most years, the number of cases investigated has been between 2,500 and 3,000. Excluding antimicrobials, the number of cases found after investigation to have a definite, probable, or possible relationship with pesticide exposure has ranged from 970 (in 1989) to 1,372 (in 1988). Cases involving antimicrobials rarely were reported prior to 1987. In that year, surveillance staff began reviewing workers' compensation records personally, with the specific goal of identifying antimicrobial cases. Since then, antimicrobials have been found to account for 746-813 cases annually, primarily involving splashes and squirts to the eye and inhalation of fumes or vapors. Numbers of case reports from agricultural situations have varied irregularly, driven by small numbers of episodes concerning multiple individuals. Variability in numbers of cases involving the skin has depended almost entirely on variation in numbers of field worker dermatitis. The most common situation for field worker dermatitis has been summer work in table grapes grown in the southern San Joaquin valley. In the two years since reentry intervals for the acaricide propargite were lengthened, there have been no more major clusters of field worker dermatitis. Although the cases collected by the surveillance program are predominantly occupational, because of dependence on workers' compensation for case identification, most recorded deaths are nonoccupational. Nonoccupational fatalities include suicides, mistaken ingestion of pesticides (especially if stored in food containers), and entry into structures being fumigated. Occupational deaths are less common and more varied. The circumstances of each reported occupational death are summarized above.

California↗
PubMed1992

Exposure to pesticide mixer/loaders and applicators in California.

Pesticide exposure occurs both when preparing (mixing/loading) the pesticide for application and when actually applying the pesticide. Equipment cleanup and repair may also contribute to exposure. These separate tasks may be done by different people or a single individual may combine them. Different formulations, handling methods, and application methods may affect levels of exposure. Good workplace hygiene dictates that the first priority in workplace safety is to put in place engineering and administrative controls to make the workplace safer rather than rely on the use of PPE to prevent exposure. Providing a physical barrier, such as closed systems for the mixer/loader and an enclosed cab or cockpit for applicators, is associated with reduced exposures of workers. The Worker Health and Safety Branch in the DPR of Cal/EPA has been monitoring various work task exposures. The results of these studies are summarized in Figures 1-4, where exposure is shown based on both time worked and amount of material handled. The studies were done using dosimeters, skin washes/wipes, and air pumps. Water-soluble packets, which are very popular with users, surpassed closed systems in reducing exposure to mixer/loaders in these studies. Hand spraying proved to present the greatest risk of exposure of the methods of application studied. It was found that the dermal route of exposure is most important, comprising 87-95% of a handler's exposure. Although this survey cannot be considered conclusive, since it leaves many formulations, systems, and methods incompletely studied or unstudied, it is clear that exposure is affected by different handling strategies. Manufacturers, regulators and users should work more closely to refine or develop new systems for safely handling pesticides.

California↗
PubMed1991

Effect of route of exposure and repeated doses on the acute toxicity in mice of the cyanobacterial nicotinic alkaloid anatoxin-a.

Anatoxin-a (ANTX-a) is a potent nicotinic cholinergic alkaloid produced by some toxigenic strains of cyanobacteria. We have examined i.p. and oral LD50 values of two ANTX-a producing Anabaena sp. and synthetic (+)-ANTX-a in outbred Swiss Webster mice. All three appeared equivalent by i.p. injection, but Anabaena flos-aquae NRC-44-1 was approximately twice as potent orally as the other two. Additionally, we were unable to demonstrate development of any biologically significant tolerance to acute ANTX-a exposure using two different repeated dose regimens.

Administration, Oral↗
PubMed1991

Stability studies on the cyanobacterial nicotinic alkaloid anatoxin-A.

Anatoxin-a (ANTX-a) is a potent nicotinic cholinergic bicyclic secondary amine produced by some toxigenic strains of Anabaena spp. cyanobacteria (LD50 = 0.20-0.25 mg/kg i.p., mouse). Studies were undertaken to examine the effects of sunlight, pH, oxygen, and copper and iron, known catalysts of nitrogen oxidation, on the stability of ANTX-a. Photolysis of this extremely potent toxin was demonstrated under conditions resembling those which occur naturally. First-order decay kinetics of ANTX-a in sunlight was both pH and light intensity dependent. In the solutions examined, which represented expected biological conditions, the half-life of ANTX-a was on the order of 1-2 hr. This compares to half-lives on the order of several days in the absence of sunlight, even in the presence of metal ions. Mouse bioassays indicate that the breakdown products of ANTX-a, by both mechanisms, are inactive. Sunlight photolysis is concluded to be a possible important detoxification route of ANTX-a.

Animals↗
PubMed1991

Chlorothalonil exposure of workers on mechanical tomato harvesters.

Worker exposure to chlorothalonil (tetrachloroisophthalonitrile, Bravo during mechanical tomato harvester operations of fruit for processing was estimated from passive dermal dosimetry monitoring (gauze pad and undershirt dosimetry), air concentration measurements and hand washes. Gauze pad dosimeters placed outside of workers' clothing gave an average potential dermal exposure of 499.6 micrograms/h. Dermal exposure based on undershirt dosimetry averaged 43.4 micrograms/h. Air concentrations ranged from 0.002-0.02 microgram/l. Dislodgeable fruit residues were measured and used to develop transfer factors (cm2 h) for both the pad dosimetry (450) and shirt dosimetry (40). Study results indicate that normal work clothing provides a 90% reduction in dermal exposure to chlorothalonil and that contribution of inhalation to total exposure ranges from 8.1-28%.

Agriculture↗
PubMed1990

Paraquat pharmacokinetics using a subcutaneous toxic low dose in the rat.

The pharmacokinetics of paraquat were examined at a dose which produced lung disease but avoided renal damage. Following single sc injections of 14CH3-paraquat (72 mumols/kg) in male Sprague-Dawley rats, blood was sampled via indwelling jugular cannulas. Noncannulated rats were exsanguinated by cardiac puncture during a 7-day test period. Blood, liver, kidney, lung, brain, heart, spleen, gi tract, injection site, adrenals, body, urine, and feces were analyzed for total radioactivity. Histology of lung after 7 days revealed (+1) paraquat lung disease. No evidence of renal damage was observed. Paraquat was rapidly absorbed. Peak blood concentrations of 58 nmol/ml were measured at 20 min. Peak lung and kidney paraquat concentrations at 40 min were 65 and 359 nmol/g, respectively. Paraquat pharmacokinetics (NONLIN) were best described by a two-compartment open model; the mean biological half-life was 40.9 hr. Eighty-five percent of the dose was eliminated in urine by 7 days. The body contained 79% of the remaining radioactivity. The residual radioactivity is associated with prolonged paraquat excretion and, perhaps, progressive lung disease.

Animals↗
PubMed1987

Paraquat-induced, dose-dependent conditioned taste aversions and weight loss mediated by the area postrema.

Paraquat's (PQ) effect on feeding behavior in the rat was examined using a conditioned taste aversion (CTA) paradigm. CTA is a learned avoidance of tastes closely associated with prior illness. Male Sprague-Dawley rats trained to drink an instant breakfast solution were subsequently offered a novel-flavored solution and consumption was measured over 30 min. Following consumption of the novel solution, PQ (0.48-48.0 mumol/kg) was injected subcutaneously. Peak blood PQ concentrations were measured by serially sampling blood (0.15 ml) from an indwelling jugular cannula between 10 and 35 min after injection. Two days later, the rats were offered the same novel-flavored solution. Paraquat produced dose-dependent avoidance of the novel solution when injected subcutaneously. A PQ dosage of 2.7 mumol/kg or less did not alter consumption. The ED50 for CTA production of 13.0 mumol/kg was determined by log-probit analysis. The minimum effective dosage was 4.2 micron/kg. The doses examined did not produce overt clinical or histological signs of toxicity. Peak blood paraquat concentration was linearly related (r = 0.995) to dosage. Additionally when administered by gavage CTAs occurred only with a much larger PQ dosage (480 mumol/kg). Thermal lesions of a hindbrain circumventricular organ, the area postrema (AP), prevented PQ-induced CTAs despite repeated PQ injections. Additionally, weight loss following PQ exposure was also attenuated by AP lesions. CTAs were induced in these same AP-lesioned rats by oral administration of copper sulfate. This substance conditions taste aversions by activating vagal afferent neurons. The fact that copper sulfate-induced aversions were not blocked by lesions of the area posterema indicates that the lesioned rats are capable of forming CTAs when treated with a toxicant which does not act via the AP. These data indicate that PQ produces CTAs in a dose-dependent manner. Furthermore, PQ-induced CTAs and weight loss are mediated by the AP. The AP may contain receptors which detect xenobiotics, enabling animals to avoid future contact with these compounds.

Animals↗