The Implications of Using a Physiologically Based Pharmacokinetic (PBPK) Model for Pesticide Risk Assessment

Background: A physiologically based pharmacokinetic (PBPK) model would make it possible to simulate the dynamics of chemical absorption, distribution, metabolism, and elimination (ADME) from different routes of exposures and, in theory, could be used to evaluate associations between exposures and biomarker measurements in blood or urine. Objective: We used a PBPK model to predict urinary excretion of 3,5,6-trichloro-2-pyridinol (TCPY), the specific metabolite of chlorpyrifos (CPF), in young children.Methods We developed a child-specific PBPK model for CPF using PBPK models previously developed for rats and adult humans. Data used in the model simulation were collected from 13 children 3–6 years of age who participated in a cross-sectional pesticide exposure assessment study with repeated environmental and biological sampling. Results: The model-predicted urinary TCPY excretion estimates were consistent with measured levels for 2 children with two 24-hr duplicate food samples that contained 350 and 12 ng/g of CPF, respectively. However, we found that the majority of model outputs underpredicted the measured urinary TCPY excretion. Conclusions: We concluded that the potential measurement errors associated with the aggregate exposure measurements will probably limit the applicability of PBPK model estimates for interpreting urinary TCPY excretion and absorbed CPF dose from multiple sources of exposure. However, recent changes in organophosphorus (OP) use have shifted exposures from multipathways to dietary ingestion only. Thus, we concluded that the PBPK model is still a valuable tool for converting dietary pesticide exposures to absorbed dose estimates when the model input data are accurate estimates of dietary pesticide exposures

Assessing Children’s Dietary Pesticide Exposure: Direct Measurement of Pesticide Residues in 24-Hr Duplicate Food Samples

Background: The data presented here are a response to calls for more direct measurements of pesticide residues in foods consumed by children and provide an opportunity to compare direct measures of pesticide residues in foods representing actual consumption with those reported by the U.S. Department of Agriculture Pesticide Data Program. Objective: We measured pesticide residues in 24-hr duplicate food samples collected from a group of 46 young children participating in the Children’s Pesticide Exposure Study (CPES). Methods: Parents were instructed to collect 24-hr duplicate food samples of all conventional fruits, vegetables, and fruit juices equal to the quantity consumed by their children, similarly prewashed/prepared, and from the same source or batch. Individual or composite food items were analyzed for organophosphate (OP) and pyrethroid insecticide residues. Results: We collected a total of 239 24-hr duplicate food samples collected from the 46 CPES children. We found 14% or 5% of those food samples contained at least one OP or pyrethroid insecticide, respectively. We measured a total of 11 OP insecticides, at levels ranging from 1 to 387 ng/g, and three pyrethroid insecticides, at levels ranging from 2 to 1,133 ng/g, in children’s food samples. We found that many of the food items consumed by the CPES children were also on the list of the most contaminated food commodities reported by the Environmental Working Group. Conclusions: The frequent consumption of food commodities with episodic presence of pesticide residues that are suspected to cause developmental and neurological effects in young children supports the need for further mitigation

First Observation of the Doubly Charmed Baryon Xi_cc^+

We observe a signal for the doubly charmed baryon Xi_cc^+ in the charged decay mode Xi_cc^+ --> Lambda_c^+ K- pi+ in data from SELEX, the charm hadro-production experiment at Fermilab. We observe an excess of 15.9 events over an expected background of 6.1 +/- 0.5 events, a statistical significance of 6.3sigma. The observed mass of this state is (3519 +/- 1) MeV/c^2. The Gaussian mass width of this state is 3MeV/c^2, consistent with resolution; its lifetime is less than 33fsec at 90% confidence.Comment: 5 pages, 3 figures, accepted for publication in Physical Review Letter

First Measurement of pi e -> pi e gamma Pion Virtual Compton Scattering

Pion Virtual Compton Scattering (VCS) via the reaction pi e --> pi e gamma was observed in the Fermilab E781 SELEX experiment. SELEX used a 600 GeV/c pi- beam incident on target atomic electrons, detecting the incident pi- and the final state pi-, electron and gamma. Theoretical predictions based on chiral perturbation theory are incorporated into a Monte Carlo simulation of the experiment and are compared to the data. The number of reconstructed events (9) and their distribution with respect to the kinematic variables (for the kinematic region studied) are in reasonable accord with the predictions. The corresponding pi- VCS experimental cross section is sigma=38.8+-13 nb, in agreement with the theoretical expectation sigma=34.7 nb.Comment: 10 pages, 12 figures, 4 tables, 25 references, SELEX home page is http://fn781a.fnal.gov/, revised July 21, 2002 in response to journal referee Comment

Confirmation of the Double Charm Baryon Xi_cc+ via its Decay to p D+ K-

We observes a signal for the double charm baryon Xi_cc+ in the charged decay mode Xi_cc+ -> p D+ K- to complement the previously reported decay Xi_cc+ -> Lambda_c K- pi+ in data from SELEX, the charm hadro-production experiment (E781) at Fermilab. In this new decay mode we observe an excess of 5.62 events over an expected background estimated by event mixing to be 1.38+/-0.13 events. The Poisson probability that a background fluctuation can produce the apparent signal is less than 6.4E-4. The observed mass of this state is (3518+/-3)MeV/c^2, consistent with the published result. Averaging the two results gives a mass of (3518.7+/-1.7)MeV/c^2. The observation of this new weak decay mode confirms the previous SELEX suggestion that this state is a double charm baryon. The relative branching ratio Gamma(Xi_cc+ -> pD+K-)/Gamma(Xi_cc+ -> Lambda_c K- pi+) = 0.36+/-0.21.Comment: 11 pages, 6 included eps figures. v2 includes improved statistical method to determine significance of observation. Submitted to PL

Polarization of Σ

We show that Sigma(+) hyperons produced by 800 GeV/c protons on targets of Be and Cu have significant polarizations (15-20%). These polarizations persist at values of p(t)approximate to2 GeV/c and a wide range of x(F). The polarizations from the Cu target are consistently less than from Be. The average ratio of the Sigma(+) polarization from Cu to that from Be is 0.68+/-0.08

Total Cross Section Measurements With π- , Σ- And Protons On Nuclei And Nucleons Around 600 Gev/c

Total cross sections for Σ- and π- on beryllium, carbon, polyethylene and copper as well as total cross sections for protons on beryllium and carbon have been measured in a broad momentum range around 600GeV/c . These measurements were performed with a transmission technique in the SELEX hyperon-beam experiment at Fermilab. We report on results obtained for hadron-nucleus cross sections and on results for σtot(Σ-N) and σtot(π-N) , which were deduced from nuclear cross sections. © 2000 Elsevier Science B.V.57901/02/15277312Langland, J.L., (1995) Ph.D. Thesis, , University of IowaKleinfelder, S.A., (1988) IEEE Trans. Nucl. Sci., 35 (1)Dersch, U., (1998) Ph.D. Thesis, HeidelbergBiagi, S.F., (1981) Nucl. Phys. B, 186, pp. 1-21Bellettini, G., (1966) Nucl. Phys., 79, pp. 609-624Schiz, A.M., (1980) Phys. Rev. D, 21, pp. 3010-3022Murthy, P.V.R., (1975) Nucl. Phys. B, 92, pp. 269-308Caso, C., (1998) Eur. Phys. J. C, 3. , http://pdg.lbl.gov/1998/contents_plots.html, and data on total cross sections from computer readable filesSchiz, A.M., (1979) Ph.D. Thesis, , Yale University(1973) Landolt Börnstein Tables, 7. , Springer editionEngler, J., (1970) Phys. Lett. B, 32, pp. 716-719Babaev, A., (1974) Phys. Lett. B, 51, pp. 501-504Glauber, R.J., (1959) Boulder Lectures, pp. 315-413Franco, V., (1972) Phys. Rev. C, 6, pp. 748-757Karmanov, V.A., Kondratyuk, L.A., (1973) JETP Lett., 18, pp. 266-268Burq, J.P., (1983) Nucl. Phys. B, 217, pp. 285-335Gross, D., (1978) Phys. Rev. Lett., 41, pp. 217-220Beznogikh, G.G., (1972) Phys. Lett. B, 39, pp. 411-413Vorobyov, A.A., (1972) Phys. Lett. B, 41, pp. 639-641Foley, K.J., (1967) Phys. Rev. Lett., 19, pp. 857-859Fajardo, L.A., (1981) Phys. Rev. D, 24, pp. 46-65Jenni, P., (1977) Nucl. Phys. B, 129, pp. 232-252Breedon, R.E., (1989) Phys. Rev. Lett. B, 216, pp. 459-465Amos, N., (1983) Phys. Rev. Lett. B, 128, pp. 343-348Amaldi, U., (1977) Phys. Rev. Lett. B, 66, pp. 390-394Amos, N., (1985) Nucl. Phys. B, 262, pp. 689-714Akopin, V.D., (1977) Sov. J. Nucl. Phys., 25, pp. 51-55Amirkhanov, I.V., (1973) Sov. J. Nucl. Phys., 17, pp. 636-637Foley, K.J., (1969) Phys. Rev., 181, pp. 1775-1793Apokin, V.D., (1976) Nucl. Phys. B, 106, pp. 413-429Burq, J.P., (1982) Phys. Lett. B, 109, pp. 124-127Dakhno, L.G., (1983) Sov. J. Nucl. Phys., 37, pp. 590-598Kazarinov, M., (1976) Sov. Phys. JETP, 43, pp. 598-606De Jager, C.W., (1974) At. Data Nucl. Data Tables, 14, pp. 479-508Donnachie, A., Landshoff, P.V., (1992) Phys. Lett. B, 296, pp. 227-232Lipkin, H., (1975) Phys. Rev. D, 11, pp. 1827-1831Barnett, R.M., (1996) Phys. Rev. D, 54, pp. 191-192Carroll, A.S., (1979) Phys. Lett. B, 80, pp. 423-427Badier, J., (1972) Phys. Lett. B, 41, pp. 387-39