A physiologically-based pharmacokinetic/pharmacodynamic (PBPK/PD) model for the insecticide dimethoate.

1. Dimethoate is an organophosphate insecticide that is converted in vivo to omethoate, the active toxic moiety. Omethoate inhibits acetylcholinesterase (AChE) in the brain and red blood cells (RBCs). This paper describes the development of rat and human physiologically-based pharmacokinetic/pharmacodynamic (PBPK/PD) models for dimethoate.2. The model simulates the absorption and distribution of dimethoate and omethoate, the conversion of dimethoate to omethoate and to other metabolites, the metabolism and excretion of omethoate, and the inhibition of RBC and brain AChE. An extensive data collection program to estimate metabolism and inhibition parameters is described.3. The suite of models includes an adult rat, post-natal rat, and human model. The rat models were evaluated by comparing model predictions of dimethoate and omethoate to measured blood time course data, and with RBC and brain AChE inhibition estimates from an extensive database of in vivo AChE measurements.4. After the demonstration of adequately fitted rat models that were robust to sensitivity analysis, the human model was applied for estimation of points-of-departure (PODs) for risk assessment using the human-specific parameters in the human PBPK/PD model. Thus, the standard interspecies uncertainty factor can be reduced from 10X to 1X.

Atrazine and its degradates have little effect on the corticosteroid stress response in the zebrafish.

The present study examined the effects of atrazine on basal and forced swimming induced changes in whole body cortisol content in adult zebrafish. Zebrafish were exposed to graded concentrations of atrazine or the atrazine degradates deisopropylatrazine (DIA), deethylatrazine (DEA) and diamino-s-chlorotriazine (DACT) for up to 10 days. Some fish were sampled for the measurement of whole body cortisol levels under basal conditions while others were sampled after being subjected to a 20 min swimming challenge in order to quantify stress induced cortisol levels. In one experiment, zebrafish were subjected to two bouts of forced swimming 3h apart to test whether prior atrazine exposure affects the ability of the fish to respond appropriately to a repeated stressor. The results demonstrated that controls not exposed to atrazine and zebrafish exposed to atrazine or the atrazine degradates at nominal concentrations of up to 100 µg/L consistently exhibited increased whole body cortisol content in response to the swimming challenge. Separate analyses revealed few changes in basal or stress induced cortisol levels following atrazine exposure. Overall, these data suggest that atrazine and some of its degradates at the concentrations tested have minimal effects on the cortisol mediated stress response in the zebrafish.

Risk assessment considerations with regard to the potential impacts of pesticides on endangered species.

Simple, deterministic screening-level assessments that are highly conservative by design facilitate a rapid initial screening to determine whether a pesticide active ingredient has the potential to adversely affect threatened or endangered species. If a worst-case estimate of pesticide exposure is below a very conservative effects metric (e.g., the no observed effects concentration of the most sensitive tested surrogate species) then the potential risks are considered de minimis and unlikely to jeopardize the existence of a threatened or endangered species. Thus by design, such compounded layers of conservatism are intended to minimize potential Type II errors (failure to reject a false null hypothesis of de minimus risk), but correspondingly increase Type I errors (falsely reject a null hypothesis of de minimus risk). Because of the conservatism inherent in screening-level risk assessments, higher-tier scientific information and analyses that provide additional environmental realism can be applied in cases where a potential risk has been identified. This information includes community-level effects data, environmental fate and exposure data, monitoring data, geospatial location and proximity data, species biology data, and probabilistic exposure and population models. Given that the definition of "risk" includes likelihood and magnitude of effect, higher-tier risk assessments should use probabilistic techniques that more accurately and realistically characterize risk. Moreover, where possible and appropriate, risk assessments should focus on effects at the population and community levels of organization rather than the more traditional focus on the organism level. This document provides a review of some types of higher-tier data and assessment refinements available to more accurately and realistically evaluate potential risks of pesticide use to threatened and endangered species.

Characterization of fine particulate matter in Ohio: indoor, outdoor, and personal exposures.

Ambient, indoor, and personal PM2.5 concentrations were assessed based on an exhaustive study of PM2.5 performed in Ohio from 1999 to 2000. Locations in Columbus, one in an urban corridor and the other in a suburban area were involved. A third rural location in Athens, Ohio, was also established. At all three locations, elementary schools were utilized to determine outdoor, indoor, and personal PM2.5 concentrations for fourth and fifth grade students using filter-based measurements. Three groups of 30 students each were used for personal sampling at each school. Continuous ambient PM2.5 mass concentrations were also measured with tapered element oscillating microbalances (TEOMs). At all three sites, personal and indoor PM2.5 concentrations exceeded outdoor levels. This trend is consistent on all week days and most evident in the spring as compared to fall and winter. The ambient PM2.5 concentrations were similar among the three sites, suggesting the existence of a common regional source influence. At all the three sites, larger variations were found in personal and indoor PM2.5 than ambient levels. The strongest correlations were found between indoor and personal concentrations, indicating that personal PM2.5 exposures were significantly affected by indoor PM2.5 than by ambient PM2.5. This was further confirmed by the indoor to outdoor (I/O) ratios of PM2.5 concentrations, which were greater when school was in session than non-school days when the students were absent.

Analysis of trace elements and ions in ambient fine particulate matter at three elementary schools in Ohio.

The results from a chemical characterization study of fine particulate matter (PM2.5) measured at three elementary schools in Central and Southeast Ohio is presented here. PM2.5 aerosol samples were collected from outdoor monitors and indoor samplers at each monitoring location during the period of February 1, 1999, through August 31, 2000. The locations included a rural elementary school in Athens, OH, and two urban schools within Columbus, OH. The trace metal and ionic concentrations in the collected samples were analyzed using an X-ray fluorescence spectrophotometer and ion chromatography unit, respectively. Sulfate ion was found to be the largest component present in the samples at all three of the sites. Other abundant components included nitrate, chloride, ammonium, and sodium ions, as well as calcium, silicon, and iron. The average PM2.5 concentrations showed similar temporal variations among the three sites within the study region. PM2.5 and its major component, sulfate ion, showed strong seasonal variations with maximum concentrations observed during the summer at all three of the sites. The indoor environment was found to be more contaminated during the spring months (March through May) at New Albany (a suburb of Columbus, OH) and East Athens (rural Ohio area). Potential source contribution function analysis showed that particulate matter levels at the monitoring sites were affected by transport from adjoining urban areas and industrial complexes located along the Ohio River Valley. A preliminary outdoor source apportionment using the principal component analysis (PCA) technique was performed. The results from the PCA suggest that the study region was primarily impacted by industrial, fossil fuel combustion, and geological sources. The 2002 emissions inventory data for PM2.5 compiled by Ohio Environmental Protection Agency also showed impacts of similar source types, and this was used to validate the PCA analysis.

The Steubenville Comprehensive Air Monitoring Program (SCAMP): concentrations and solubilities of PM(2.5) trace elements and their implications for source apportionment and health research.

The elemental compositions of the water-soluble and acid-digestible fractions of 24-hr integrated fine particulate matter (PM(2.5)) samples collected in Steubenville, OH, from 2000 to 2002 were determined using dynamic reaction cell inductively coupled plasma-mass spectrometry. The water-soluble elemental compositions of PM(2.5) samples collected at four satellite monitoring sites in the surrounding region were also determined. Fe was the most abundant but least water soluble of the elements determined at the Steubenville site, having a mean ambient concentration of 272 ng/m3 and a median fractional solubility of 6%. Fe solubility and its correlations with SO4(2-) and temperature varied significantly by season, consistent with the hypothesis that secondary sulfates may help to mobilize soluble Fe under suitable summertime photochemical conditions. Significantly higher ambient concentrations were observed at Steubenville than at each of the four satellite sites for 10 of the 18 elements (Al, As, Ca, Cd, Fe, Mg, Mn, Na, Pb, and Zn) determined in the water-soluble PM(2.5) fraction. Concentrations of Fe, Mn, and Zn at Steubenville were substantially higher than concentrations reported recently for larger U.S. cities. Receptor modeling identified seven sources affecting the Steubenville site. An (NH4)2SO4-dominated source, likely representing secondary PM(2.5) from coal-fired plants to the west and southwest of Steubenville, accounted for 42% of the PM(2.5) mass, and two sources likely dominated by emissions from motor vehicles and from iron and steel facilities in the immediate Steubenville vicinity accounted for 20% and 10%, respectively. Other sources included an NH4NO3 source (15%), a crustal source (6%), a mixed nonferrous metals and industrial source (3%), and a primary coal combustion source (3%). Results suggest the importance of very different regional and local source mechanisms in contributing to PM(2.5) mass at Steubenville and reinforce the need for further research to elucidate whether metals such as Fe, Mn, and Zn play a role in the PM(2.5) health effects observed previously there.