Design strategy for assessing multi-pathway exposure for children: the Minnesota Children's Pesticide Exposure Study (MNCPES).

Although children are exposed to a variety of environmental hazards, including pesticides, there is a scarcity of information available to estimate exposures realistically. This article reports on one of the first attempts to measure multi-pathway pesticide exposures in a population-based sample of urban and non-urban children. A design strategy was developed to assess multi-pathway pesticide exposures in children using personal exposure measurements in combination with complimentary measurements of biological markers of exposure, concentrations in relevant environmental media, and time spent in important microenvironments and participating in exposure-related activities. Sample collection and analysis emphasized measurement of three insecticides (i.e., chlorpyrifos, diazinon, and malathion) and one herbicide (i.e., atrazine). These compounds were selected because of their frequent use, presence in multiple environmental media, expected population exposures, and related hazard/toxicity. The study was conducted during the summer of 1997 in Minnesota and involved a stratified sample of households with children ages 3-12 years. Participants resided in either (a) the cities of Minneapolis and St. Paul (urban households), or (b) Rice and Goodhue Counties just south of the metropolitan area (non-urban households). Results from a residential inventory documenting storage and use of products containing the target pesticides were used to preferentially select households where children were likely to have higher exposures. The study successfully obtained pesticide exposure data for 102 children, including measurements of personal exposures (air, hand rinse, duplicate diet), environmental concentrations (residential indoor/outdoor air, drinking water, residential surfaces, soil), activity patterns (obtained by questionnaire, diary, videotaping), and internal dose (metabolites in urine).

Pesticide storage and use patterns in Minnesota households with children.

As part of the National Human Exposure Assessment Survey (NHEXAS), residential pesticide storage and use patterns were evaluated in a population-based sample of Minnesota households with children aged 3-13. In-home interviews and inventories were conducted to identify pesticide products stored and used in and around 308 households. This statistically based sample represents more than 49,000 urban and rural households in the census tracts sampled. More than 850 unique products were identified using Environmental Protection Agency (EPA) registration numbers. Pesticide products were found in 97% and reported used in 88% of study households. Population-weighted mean values for pesticide storage and use were 6.0 and 3.1 products per household, respectively. The most common active ingredients found were diethyl toluamide (DEET) and related compounds, piperonyl butoxide, pyrethrins, dimethylamine 2-[2-methyl-4-chlorophenoxyl propionate (MCPA) and chlorpyrifos. Household socio-demographic characteristics explained little of the variability in pesticide storage and use patterns, and there were no significant differences in residential storage and use patterns between households located in urban versus non-urban census tracts. Although the prevalence of households with pesticide products was similar to recent national surveys, observed storage and use rates were almost twice those obtained in recent national studies, reflecting improved inventory techniques used by this study and/or increased rates of pesticide presence and use in study households.

Measurement of multi-pollutant and multi-pathway exposures in a probability-based sample of children: practical strategies for effective field studies.

The purpose of this manuscript is to describe the practical strategies developed for the implementation of the Minnesota Children's Pesticide Exposure Study (MNCPES), which is one of the first probability-based samples of multi-pathway and multi-pesticide exposures in children. The primary objective of MNCPES was to characterize children's exposure to selected pesticides through a combination of questionnaires, personal exposure measurements (i.e., air, duplicate diet, hand rinse), and complementary monitoring of biological samples (i.e., pesticide metabolites in urine), environmental samples (i.e., residential indoor/outdoor air, drinking water, dust on residential surfaces, soil), and children's activity patterns. A cross-sectional design employing a stratified random sample was used to identify homes with age-eligible children and screen residences to facilitate oversampling of households with higher potential exposures. Numerous techniques were employed in the study, including in-person contact by locally based interviewers, brief and highly focused home visits, graduated subject incentives, and training of parents and children to assist in sample collection. It is not feasible to quantify increases in rates of subject recruitment, retention, or compliance that resulted from the techniques employed in this study. Nevertheless, results indicate that the total package of implemented procedures was instrumental in obtaining a high percentage of valid samples for targeted households and environmental media.

Fish consumption advisories and outreach programs for Southeast Asian immigrants.

Southeast Asian immigrants and refugees, in particular the Hmong people of Laos, have settled in large numbers in metropolitan areas of Minnesota. These communities, accustomed to hunting and fishing for food in Laos, now fish in some of the most contaminated waters of Minnesota. Fishing and fish-preparation customs of their homeland emphasize using all fish caught and discarding very little waste. These practices result in a potentially high exposure to PCBs and mercury. Educational outreach efforts to inform this population of the potential health hazards from consuming the fish are hindered by language and cultural barriers. While most Hmong anglers welcome information about contaminants and fishing, the typical press releases and mailings that convey fish advisory information to the public do not reach this community. The Minnesota Department of Health and the Minnesota Department of Natural Resources collaborated to determine the health messages and communication methods that would best meet the needs of these communities. Using the results of interviews and a behavioral survey, the Minnesota Department of Health has tailored fish consumption advisories to meet the unique needs of Southeast Asian anglers. Over the past four years, educational programs involving specialized advisories, translations, signs, a Hmong language video, and workshops have been used to inform Hmong anglers and other Southeast Asians about fish contaminants.

Na+/K(+)-adenosine triphosphatase activity of pulmonary arteries after intoxication with the pyrrolizidine alkaloid, monocrotaline.

Na+/K(+)-Adenosine triphosphatase-dependent activities of K(+)- return relaxation and 86Rb uptake were studied in pulmonary arteries taken from rats with pulmonary hypertension induced by monocrotaline. Rats were given monocrotaline in drinking water, 20 mg/l, for 4 or more days. Isolated arteries were placed in tissue baths and contracted with norepinephrine or 5-hydroxy-tryptamine under K(+)-free conditions. The arteries relaxed when K+ was "returned" to the bath. Compared to arteries from untreated rats, arteries taken from rats pretreated with monocrotaline developed less force in response to contracting agents and did not relax to the same extent. After 4 days treatment with monocrotaline, the rate of relaxation of the arteries in response to K(+)-return was slower than that of arteries taken from untreated rats. Endothelial trauma or in vitro treatment with ouabain produced a similar decrease in the rate of relaxation. Uptake of radiolabeled Rb by perfused arteries was not altered by 4 days of monocrotaline pretreatment. Isolated lungs taken from monocrotaline-pretreated rats (5 days of ingestion of 20 mg/l of monocrotaline drinking water) accumulated similar quantities of 86Rb+ during 40-sec perfusions. Shorter perfusion times, 10 and 20 sec, resulted in greater rates of uptake of 86Rb- by lungs taken from monocrotaline-treated rats. Monocrotaline produced changes in both the mechanical and biochemical properties of pulmonary arteries after only 4 to 5 days. These changes were associated with ouabain-sensitive processes. It appears, therefore, that one of the early targets in monocrotaline intoxication is the Na+/K+ pump of the pulmonary arteries.

Effect of suckling and diurnal influences on the concentrations of taurine and other free amino acids in milk.

Factors affecting the taurine and free amino acid content of human milk from a single donor have been examined. Taurine concentration was highest during the transition from colostrum to milk, attaining 400 microM. Concentrations fell thereafter, reaching 150 microM at 115 d post partum. Other free amino acids showed an opposite developmental pattern. Samples collected immediately after infant feeding were systematically lower in taurine than those collected immediately before feeding, but the differences were relatively small. Concentrations of other amino acids were unaffected by suckling on day 4. On day 6, however, decreases ranged from 16 per cent for glutamate to 46 per cent for threonine. Samples collected every 2 h over a 72-h period on days 113 to 115 post partum showed no diurnal variation in taurine content, neither did samples collected over a 24-h period on days 4, 6, 11, and 12. Serine and glycine showed a similar lack of periodicity. Aspartate, alanine, glutamine, threonine and glutamate levels, on the other hand, were lowest in the early morning, and highest in the early afternoon. High to low ratios ranged from 1.7 for glutamate to 4.1 for aspartate. Sample collection for taurine, serine and glycine analysis can probably be made without concern as to time of day or relationship to infant feeding. For the other amino acids, however, these factors need to be considered.

Dose-response relationship in intoxication by the pyrrolizidine alkaloid monocrotaline.

Rats develop pulmonary hypertension over a 2-wk period of continuous ingestion of monocrotaline dissolved in drinking water (20 mg/l). The relationship between monocrotaline concentration and duration of exposure was investigated by giving male rats (initial body weight 100 g) monocrotaline in drinking water (5, 10, 20, 40, or 60 mg/l) for 0, 1, 2, 4, 6, 10, or 20 d. Rats were killed 20 d after initiating treatment, and increased lung and right ventricular to body weight ratios were measured as indices of pulmonary hypertension. The accumulative dose of monocrotaline delivered over a 10-d period using a drinking water concentration of 10 mg/l (18 mg/kg) produced the same degree of right ventricular hypertrophy and lung weight increases as the doses ingested over a 4-d period by rats consuming 20 or 40 mg/l monocrotaline water (14 and 29 mg/kg). Phenobarbital pretreatment did not substantially alter the time course of toxicity induced with 20 mg/l monocrotaline water. Ingestion of 60 mg/l monocrotaline water for 1 d (11 mg/kg) resulted in right ventricular hypertrophy at 20 d. Since accumulative doses of less than 11 mg/kg did not produce toxicity and all doses greater than 14 mg/kg did, this range may be considered a threshold for inducing toxicity. However, organ weight increases following threshold exposures reversed over a 4-wk period. Increases in the wall thickness of pulmonary arteries correlated with the development of right ventricular hypertrophy. Pulmonary inflammation was not an early response to monocrotaline administration, since there was no change in the proportion of cell types recovered in lung lavage fluid during the first 6 d of monocrotaline treatment.

In vitro cytotoxicity of allyl alcohol and bromobenzene in a novel organ culture system.

Two well-known hepatotoxicants, allyl alcohol (AA) and bromobenzene (BB), were studied using an in vitro system of cultured liver slices from control and phenobarbital-treated rats, respectively. Dose- and time-dependent increases in media lactate dehydrogenase (LDH), and decreases in slice K+ content and in protein synthesis were observed in rat liver slices incubated with either compound at concentrations between 0.1 and 1 mM over a period of 6 hr. The histopathological changes which occurred in the intoxicated slices appeared to parallel these biochemical changes. Additionally, the toxicity of either BB or AA, evaluated at 4 hr, was inhibited when slices were preincubated for 30 min with beta-ethyl-2,2-diphenylvalerate hydrochloride (SKF 525-A) (0.1 mM) or pyrazole (1.0 mM), respectively. In this in vitro incubation system the cytotoxicity of xenobiotics can be studied under conditions where the multicellular hepatic lobular architecture is partially maintained, and alterations in biochemical and functional processes may be correlated to pathological changes.

Pulmonary vascular responses induced by the pyrrolizidine alkaloid, monocrotaline, in rats.

Studies were conducted with isolated segments of pulmonary artery to characterize vessel contractility in monocrotaline-induced pulmonary hypertension. Contractions of pulmonary artery segments from rats given monocrotaline in drinking water (20 mg/l) for up to 20 days were measured in tissue baths. Dose response curves were produced with norepinephrine or serotonin and the response to 120 mM potassium chloride (KCl) was measured. Monocrotaline treatment significantly reduced the KCl-induced maximum contractile responses of pulmonary artery. Norepinephrine-induced maximal contractions (both in terms of mg developed force and as percentage of KCl-induced contractions) decreased with increasing length of monocrotaline treatment. Serotonin-induced maximal contractions were not altered by monocrotaline treatment. A minimum of 4 days treatment with monocrotaline drinking water reduced the contractile responses of pulmonary artery removed 16 days later. In separate experiments using continuous exposure to monocrotaline, a minimum of 15 days treatment was required before contractile activity was significantly altered. Results indicate monocrotaline treatment reduces the contractile activity of muscular pulmonary artery. Alterations in vessel responsiveness were produced after a minimum of 4 days treatment with monocrotaline in drinking water (an estimated exposure of 14-20 mg/kg) but required 15-20 days to develop.