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Abstract:

Due to extensive use, human exposure to multiple pyrethroid insecticides occurs frequently. Studies of pyrethroid neurotoxicity suggest a common mode of toxicity and that pyrethroids should be considered cumulatively to model risk. The objective of this work was to use a pyrethroid mixture that reflects human exposure to common pyrethroids to develop comparative toxicokinetic profiles in rats, and then model the relationship between brain concentration and motor activity. Data from a national survey of child care centers were used to make a mixture reflecting proportions of the most prevalent pyrethroids: permethrin, cypermethrin, β-cyfluthrin, deltamethrin, and esfenvalerate. The mixture was administered orally at one of two concentrations (11.2 and 27.4 mg/kg) to adult male rats. At intervals from 1 to 24h, motor activity was assessed and the animals were sacrificed. Pyrethroid concentrations were measured in the blood, liver, fat, and brain. After controlling for dose, there were no differences in any tissue concentrations, except blood at the initial time point. Elimination half-lives for all pyrethroids in all tissues were < 7h. Brain concentrations of all pyrethroids (when cis- and trans-permethrin were pooled) at the initial time point were proportional to their relative doses. Decreases in motor activity indicated dose additivity, and the relationship between pyrethroid brain concentration and motor activity was described by a four-parameter sigmoidal Emax model. This study links environmental data with toxicokinetic and neurobehavioral assays to support cumulative risk assessments of pyrethroid pesticides. The results support the additive model of pyrethroid effect on motor activity and suggest that variation in the neurotoxicity of individual pyrethroids is related to toxicodynamic rather than toxicokinetic differences. Published by Oxford University Press 2012.

Registro:

Documento: Artículo
Título:Environmentally relevant mixtures in cumulative assessments: An acute study of toxicokinetics and effects on motor activity in rats exposed to a mixture of pyrethroids
Autor:Starr, J.M.; Scollon, E.J.; Hughes, M.F.; Ross, D.G.; Graham, S.E.; Crofton, K.M.; Wolansky, M.J.; DeVito, M.J.; Tornero-Velez, R.
Filiación:U.S. Environmental Protection Agency, Office of Research and Development, National Exposure Research Laboratory, Research Triangle Park, NC 27711, United States
U.S. Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Research Triangle Park, NC 27711, United States
U.S. Environmental Protection Agency, Office of Air Quality Planning and Standards, Health and Environmental Impacts Division, Research Triangle Park, NC 27711, United States
U.S. Environmental Protection Agency, Office of Pesticide Programs, Health Effects Division, Arlington, VA 22202, United States
Laboratorio de Toxicología de Mezclas Químicas (LATOMEQ), Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria UBA, Ciudad Autónoma, Buenos Aires (1428), Argentina
National Institute of Environmental Health Sciences, National Toxicology Program, Toxicology Branch, Research Triangle Park, NC 27711, United States
Palabras clave:Cumulative risk; Motor activity; Pyrethroids; Toxicokinetics; beta cyfluthrin; cipermethrin; deltamethrin; fat; fenvalerate; permethrin; pyrethroid; unclassified drug; animal experiment; animal tissue; article; blood sampling; brain; concentration (parameters); exposure; liver; male; motor activity; neurotoxicity; nonhuman; rat; toxicokinetics; Adipose Tissue; Animals; Behavior, Animal; Body Burden; Brain; Dose-Response Relationship, Drug; Environmental Monitoring; Environmental Pollutants; Half-Life; Insecticides; Limit of Detection; Liver; Male; Models, Animal; Models, Biological; Motor Activity; Neurotoxicity Syndromes; Pyrethrins; Rats; Rats, Long-Evans; Reproducibility of Results; Risk Assessment; Tissue Distribution; Animalia; Rattus
Año:2012
Volumen:130
Número:2
Página de inicio:309
Página de fin:318
DOI: http://dx.doi.org/10.1093/toxsci/kfs245
Título revista:Toxicological Sciences
Título revista abreviado:Toxicol. Sci.
ISSN:10966080
CODEN:TOSCF
CAS:cipermethrin, 52315-07-8; deltamethrin, 52918-63-5; fenvalerate, 51630-58-1; permethrin, 51877-74-8, 52645-53-1; Environmental Pollutants; Insecticides; Pyrethrins
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_10966080_v130_n2_p309_Starr

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Citas:

---------- APA ----------
Starr, J.M., Scollon, E.J., Hughes, M.F., Ross, D.G., Graham, S.E., Crofton, K.M., Wolansky, M.J.,..., Tornero-Velez, R. (2012) . Environmentally relevant mixtures in cumulative assessments: An acute study of toxicokinetics and effects on motor activity in rats exposed to a mixture of pyrethroids. Toxicological Sciences, 130(2), 309-318.
http://dx.doi.org/10.1093/toxsci/kfs245
---------- CHICAGO ----------
Starr, J.M., Scollon, E.J., Hughes, M.F., Ross, D.G., Graham, S.E., Crofton, K.M., et al. "Environmentally relevant mixtures in cumulative assessments: An acute study of toxicokinetics and effects on motor activity in rats exposed to a mixture of pyrethroids" . Toxicological Sciences 130, no. 2 (2012) : 309-318.
http://dx.doi.org/10.1093/toxsci/kfs245
---------- MLA ----------
Starr, J.M., Scollon, E.J., Hughes, M.F., Ross, D.G., Graham, S.E., Crofton, K.M., et al. "Environmentally relevant mixtures in cumulative assessments: An acute study of toxicokinetics and effects on motor activity in rats exposed to a mixture of pyrethroids" . Toxicological Sciences, vol. 130, no. 2, 2012, pp. 309-318.
http://dx.doi.org/10.1093/toxsci/kfs245
---------- VANCOUVER ----------
Starr, J.M., Scollon, E.J., Hughes, M.F., Ross, D.G., Graham, S.E., Crofton, K.M., et al. Environmentally relevant mixtures in cumulative assessments: An acute study of toxicokinetics and effects on motor activity in rats exposed to a mixture of pyrethroids. Toxicol. Sci. 2012;130(2):309-318.
http://dx.doi.org/10.1093/toxsci/kfs245