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1.
Regul Toxicol Pharmacol ; 92: 55-66, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29158042

RESUMO

An inhalation reference concentration (RfC) was developed for diethanolamine (DEA), based principally on evaluation of three animal studies (Gamer et al., 1993, 1996, 2008). The RfC (25 µg/m3) was based on statistically significantly increased relative liver weight in female rats in Gamer et al. (2008) as the critical effect. The lower confidence limit on the benchmark dose (BMDL10 of 5.5 mg/m3) was adjusted to a human equivalent concentration and to continuous exposure before dividing the final point of departure (2.3 mg/m3) by a total factor of 90 that considered standard key areas of uncertainty (intrahuman variability, potential interspecies toxicodynamic differences, database limitations). While laryngeal effects observed in Gamer et al. (2008) were also considered as candidate critical effects, evaluation of the adversity and human relevance of rat laryngeal squamous metaplasia and concomitant effects at the various exposure levels resulted in identifying a LOAEL for laryngeal squamous hyperplasia and chronic inflammation that was much higher than the liver weight LOAEL identified. The RfC of 25 µg/m3 is considered health protective for the general population and can be used to evaluate the potential health effects of long-term environmental exposure of the general public (i.e., long-term, ambient air dispersion modelling or monitoring data).


Assuntos
Etanolaminas/administração & dosagem , Etanolaminas/química , Animais , Etanolaminas/efeitos adversos , Feminino , Humanos , Hiperplasia/induzido quimicamente , Inflamação/induzido quimicamente , Inalação/efeitos dos fármacos , Doenças da Laringe/induzido quimicamente , Masculino , Metaplasia/induzido quimicamente , Ratos
2.
J Toxicol Environ Health B Crit Rev ; 13(6): 460-75, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20711928

RESUMO

A chronic noncancer toxicity assessment for 1,3-butadiene (BD) has been conducted by the Texas Commission on Environmental Quality (TCEQ) using information not available to the U.S. Environmental Protection Agency (U.S. EPA) in 2002. The TCEQ developed a chronic reference value (ReV) of 33 microg/m3 (15 ppb). The chronic ReV is based on the same animal study and critical endpoint used by U.S. EPA for ovarian atrophy in B6C3F1 mice, but uses mode of action (MOA) information that indicates the diepoxide metabolite is responsible for ovarian atrophy. In addition, diepoxide-specific hemoglobin adduct data in mice, rats, and humans and other experimental data that became available after 2002 were used to support a conservative data-derived toxicokinetic animal-to-human uncertainty factor (UFA) of 0.3. The default toxicodynamic UFA of 3 was used, together with the data-derived toxicokinetic UFA of 0.3, resulting in a total UFA of 1. The necessary experimental data were not available to calculate a chemical-specific adjustment factor, although supporting data suggest the toxicokinetic UFA may range from 0.01 to 0.2. The chronic ReV value, along with a unit risk factor developed by the TCEQ, will be used to evaluate ambient air monitoring data so that the general public is protected against adverse health effects from chronic exposure to BD.


Assuntos
Butadienos/efeitos adversos , Animais , Atrofia/induzido quimicamente , Butadienos/metabolismo , Relação Dose-Resposta a Droga , Exposição Ambiental/normas , Feminino , Humanos , Macaca fascicularis , Masculino , Camundongos , Ovário/efeitos dos fármacos , Ovário/patologia , Gravidez , Ratos , Valores de Referência
3.
Risk Anal ; 29(12): 1726-42, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19878488

RESUMO

The Texas Commission on Environmental Quality (TCEQ) has developed an inhalation unit risk factor (URF) for 1,3-butadiene based on leukemia mortality in an updated epidemiological study on styrene-butadiene rubber production workers conducted by researchers at the University of Alabama at Birmingham. Exposure estimates were updated and an exposure estimate validation study as well as dose-response modeling were conducted by these researchers. This information was not available to the U.S. Environmental Protection Agency when it prepared its health assessment of 1,3-butadiene in 2002. An extensive analysis conducted by TCEQ discusses dose-response modeling, estimating risk for the general population from occupational workers, estimating risk for potentially sensitive subpopulations, effect of occupational exposure estimation error, and use of mortality rates to predict incidence. The URF is 5.0 x 10(-7) per microg/m(3) or 1.1 x 10(-6) per ppb and is based on a Cox regression dose-response model using restricted continuous data with age as a covariate, and a linear low-dose extrapolation default approach using the 95% lower confidence limit as the point of departure. Age-dependent adjustment factors were applied to account for possible increased susceptibility for early life exposure. The air concentration at 1 in 100,000 excess leukemia mortality, the no-significant-risk level, is 20 microg/m(3) (9.1 ppb), which is slightly lower than the TCEQ chronic reference value of 33 microg/m(3) (15 ppb) protective of ovarian atrophy. These values will be used to evaluate ambient air monitoring data so the general public is protected against adverse health effects from chronic exposure to 1,3-butadiene.


Assuntos
Poluentes Ocupacionais do Ar/toxicidade , Butadienos/toxicidade , Carcinógenos/toxicidade , Exposição Ocupacional , Butadienos/administração & dosagem , Carcinógenos/administração & dosagem , Indústria Química , Relação Dose-Resposta a Droga , Humanos , Leucemia/induzido quimicamente , Leucemia/mortalidade , Análise Multivariada , Modelos de Riscos Proporcionais , Medição de Risco , Fatores de Risco , Texas/epidemiologia , Estados Unidos , United States Environmental Protection Agency
4.
Chem Biol Interact ; 166(1-3): 44-51, 2007 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-17011534

RESUMO

This paper provides information on 1,3-butadiene (BD) and chloroprene as atmospheric pollutants in Texas and reviews available emission estimates and monitoring data. Ambient BD concentrations in most areas of Texas are predominantly influenced by on-road and off-road vehicular emissions or biomass burning, since BD is a product of combustion. However, large industrial point sources of BD emissions in Texas locally influence ambient concentrations. Total industrial BD emissions to the atmosphere in Texas for 2003 were estimated at 695 tonnes per year (TPY), approximately 70% of the total reported national industrial BD air emissions. Since 1998, there have not been any large industrial sources of chloroprene emissions in Texas, and total industrial chloroprene emissions for 2003 was estimated at only 0.09 TPY. Chloroprene was never detected at air monitoring sites. In 2003, the Texas Commission on Environmental Quality (TCEQ) monitored BD ambient air concentrations at 57 sites, some of which have been operational since 1992. These air monitors provide information on ambient BD concentrations in Texas and allow spatial and temporal trend evaluation. In 2003, annual average concentrations at monitoring sites in Texas ranged from less than the reporting limit of 0.01 to 3.2 parts per billion by volume (ppbv) with an overall average of 0.2 ppbv. This overall average is reduced to 0.1 ppbv if BD data from monitoring sites in Port Neches and Milby Park in Houston, which are located downwind of significant point sources of BD, are excluded. Ambient air monitoring has been conducted in Port Neches and in Milby Park in Houston since 1996 and 1999, respectively. At the Port Neches monitor, trend evaluation indicates that ambient concentrations of BD have declined since 1996 due to cooperative agreements with industries emitting BD. Annual average BD concentrations at the Port Neches monitor decreased from 8.3ppbv in 1996 to 1.3 ppbv in 2003, giving an 8-year average of 3.8 ppbv. Annual average BD concentrations at the Milby Park monitor varied between 2.1 and 4.4 ppbv from 1999 through 2003, giving a 5-year average of 3.1 ppbv. The results of cancer cluster studies based on Cancer Registry 1995-2001 incidence data and 1993-2002 mortality data conducted by the Texas Department of State Health Services for zip codes 77017/77012 (Houston) and 77651 (Port Neches) will be presented.


Assuntos
Poluentes Atmosféricos/análise , Butadienos/análise , Cloropreno/análise , Poluentes Atmosféricos/toxicidade , Atmosfera/química , Butadienos/toxicidade , Carcinógenos/análise , Carcinógenos/toxicidade , Cloropreno/toxicidade , Análise por Conglomerados , Humanos , Neoplasias/epidemiologia , Texas/epidemiologia , Fatores de Tempo , Estados Unidos , United States Environmental Protection Agency , Emissões de Veículos/análise , Emissões de Veículos/toxicidade
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