RESUMEN
Consumers are confronted with conflicting information regarding the safety of specific foods. For example, the Environmental Working Group (EWG) publishes an annual consumer guide in which they rank the pesticide contamination of 46 popular fruits and vegetables, which includes designating the 12 with the greatest pesticide contamination as the "Dirty Dozen," to help consumers reduce exposures to toxic pesticides. However, consumer guides like EWG's only incorporate some hazard assessment principles and do not reflect a dietary risk assessment. Therefore, the purpose of this study is to apply risk assessment techniques to EWG's Dirty Dozen list using a uniform screening-level approach to estimate pesticide exposures for U.S. consumers and to characterize the associated chronic human health risks. The most commonly detected pesticide and its representative residue concentrations were identified for each produce type on the 2022 Dirty Dozen list using the USDA Pesticide Data Program database. Estimates of mean dietary consumption in the U.S. were used to calculate dietary exposure to each pesticide-produce combination for adults and children. Pesticide-specific U.S. EPA dietary health-based guidance values (HBGVs) were then used as benchmarks to evaluate the chronic human health risk of consuming each produce type. Overall, the estimated daily exposure for each pesticide-produce combination was below the corresponding HBGV for all exposure scenarios. The current analysis demonstrates that excessive produce-specific pesticide exposure is unexpected as the amount of produce that would need to be consumed on a chronic basis, even among children, far exceeds typical dietary intake. Future research is necessary to assess acute dietary exposure scenarios and to consider cumulative risk.
Asunto(s)
Exposición Dietética , Contaminación de Alimentos , Frutas , Residuos de Plaguicidas , Humanos , Medición de Riesgo , Residuos de Plaguicidas/toxicidad , Residuos de Plaguicidas/análisis , Contaminación de Alimentos/análisis , Verduras , Estados Unidos , DietaRESUMEN
Cobalt (Co) alloys have been used for over seven decades in a wide range of medical devices, including, but not limited to, hip and knee implants, surgical tools, and vascular stents, due to their favorable biocompatibility, durability, and mechanical properties. A recent regulatory hazard classification review by the European Chemicals Agency (ECHA) resulted in the classification of metallic Co as a Class 1B Carcinogen (presumed to have carcinogenic potential for humans), primarily based on inhalation rodent carcinogenicity studies with pure metallic Co. The ECHA review did not specifically consider the carcinogenicity hazard potential of forms or routes of Co that are relevant for medical devices. The purpose of this review is to present a comprehensive assessment of the available in vivo preclinical data on the carcinogenic hazard potential of exposure to Co-containing alloys (CoCA) in medical devices by relevant routes. In vivo data were reviewed from 33 preclinical studies that examined the impact of Co exposure on local and systemic tumor incidence in rats, mice, guinea pigs, and hamsters. Across these studies, there was no significant increase of local or systemic tumors in studies relevant for medical devices. Taken together, the relevant in vivo data led to the conclusion that CoCA in medical devices are not a carcinogenic hazard in available in vivo models. While specific patient and implant factors cannot be fully replicated using in vivo models, the available in vivo preclinical data support that CoCA in medical devices are unlikely a carcinogenic hazard to patients.
Asunto(s)
Aleaciones/análisis , Cobalto/análisis , Equipos y Suministros , Aleaciones/administración & dosificación , Animales , Carcinogénesis , Cobalto/administración & dosificación , HumanosRESUMEN
Black Americans make up 13% of the U.S. population, yet account for 54% of HIV deaths and 44% of new HIV diagnoses. Why do Black Americans die from HIV at such a disproportionate rate? In the current study, we asked whether the presence and behavior of in-group peers in public health settings may influence Black Americans' attention to HIV information, given the racialized nature of HIV-stigma in Black American communities. In a quasi-experimental field study conducted in a public health clinic (N = 260), we found that Black patients were less likely to pay attention to HIV-prevention information in the presence of other Black patients, unless those patients were also paying attention to the information. In contrast, Black patients' attention was unaffected by the presence of White patients. We end by discussing the implications of these findings for health communication theories and health practice geared toward reducing racial-health disparities in the United States.
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Síndrome de Inmunodeficiencia Adquirida , Infecciones por VIH , Negro o Afroamericano , Comunicación , Infecciones por VIH/prevención & control , Humanos , Salud Pública , Estados UnidosRESUMEN
Due to the widespread application of glyphosate, a nonselective herbicide, to a variety of resistant food crops, the general population is exposed to glyphosate through dietary intake. Despite this, dietary exposures to glyphosate are considered low in comparison to application-related exposures. Although previous studies have evaluated exposure to horticultural and agricultural workers, to date only one study, which we recently conducted, has characterized exposure to glyphosate in consumers following heavy residential application of a glyphosate-containing herbicide in a residential yard and garden setting. In this previous study, we demonstrated that urinary glyphosate concentrations in these applicators were similar to or in some circumstances greater than those in occupational applicators, likely due to the nature of the simulation study, which ensured a heavy application protocol. However, it is unknown whether these urinary glyphosate concentrations in consumer applicators correspond to internal doses that may be of concern. Therefore, the purpose of this study is to provide a comprehensive risk assessment of glyphosate exposure in consumer applicators using a margin of safety approach. Here, we incorporated data collected from multiple spot urine samples across time from our previous study that assessed consumer exposure to glyphosate from Roundup® application. Estimated internal doses, even with the use of conservative assumptions across unique approaches, were below internal doses estimated from established health-based guidance values. Overall, this study demonstrates that glyphosate exposure from even heavy consumer application of a commercially available glyphosate-containing herbicide does not appear to be a health concern.
Asunto(s)
Exposición a Riesgos Ambientales , Glicina/análogos & derivados , Herbicidas/toxicidad , Medición de Riesgo , Animales , Peso Corporal , Exposición Dietética , Conducta de Ingestión de Líquido , Femenino , Glicina/toxicidad , Humanos , Masculino , Proyectos Piloto , GlifosatoRESUMEN
OBJECTIVES: The purpose of this study was to evaluate the individual contributions of inhalation and dermal exposures to urinary glyphosate levels following the heavy residential consumer application of a glyphosate-containing herbicide. METHODS: A pilot study was conducted in which each participant mixed and continuously spray-applied 16.3 gallons of a 0.96% glyphosate-containing solution for 100 min using a backpack sprayer. Twelve participants were divided evenly into two exposure groups, one equipped to assess dermal exposure and the other, inhalation exposure. Personal air samples (n = 12) and dermal patch samples (n = 24) were collected on the inhalation group participants and analyzed for glyphosate using HPLC-UV. Serial urine samples collected 30-min prior to application and 3-, 6-, 12-, 24-hr (inhalation and dermal groups) and 36-hr (dermal group only) post-application were analyzed for glyphosate and glyphosate's primary metabolite (AMPA) using HPLC-MS/MS. RESULTS: The mean airborne glyphosate concentration was 0.0047 mg/m3, and the mean concentrations of glyphosate for each applicator's four patch samples ranged from 0.04 µg/mm2 to 0.25 µg/mm2. In general, urinary glyphosate, AMPA, and total effective glyphosate levels were higher in the dermal exposure group than the inhalation exposure group, peaked within 6-hr following application, and were statistically indistinguishable from background at 24-hr post-application. CONCLUSIONS: This is the first study to characterize the absorption and biological fate of glyphosate in residential consumer applicators following heavy application. The results of this pilot study are consistent with previous studies that have shown that glyphosate is rapidly eliminated from the body, typically within 24 hr following application.
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Exposición a Riesgos Ambientales/análisis , Glicina/análogos & derivados , Herbicidas/análisis , Pulmón/metabolismo , Absorción Cutánea , Piel/metabolismo , Aerosoles/análisis , Seguridad de Productos para el Consumidor , Femenino , Glicina/análisis , Glicina/orina , Herbicidas/orina , Humanos , Masculino , Proyectos Piloto , GlifosatoRESUMEN
Hormones influence neurodevelopment which can result in vulnerability to endocrine disruptors such as phthalates during both the perinatal period and adolescence. Using a rat model, we have previously shown that perinatal exposure to an environmentally relevant phthalate mixture at low doses results in cognitive flexibility deficits in adults and a reduction in neuron and synapse number within the medial prefrontal cortex. Here, we further examined the behavioral effects of exposure to an environmentally relevant mixture of phthalates at low doses during either perinatal development or adolescence. Using the elevated plus maze, adult females, not males, exposed to phthalates during adolescence showed indications of reduced anxiety-like behavior while perinatal exposed animals were unaffected. There was no effect of adolescent phthalate exposure on cognitive flexibility using the attentional set shift paradigm in either sex, unlike the impairments we have previously reported following perinatal exposure (Kougias et al., 2018b). Finally, there was no effect of phthalate exposure during either time frame on sensorimotor gating measured using prepulse inhibition. Environmentally relevant phthalate exposure during the perinatal period or during adolescence did not induce widespread changes in the adult behaviors measured here.
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Conducta Animal/efectos de los fármacos , Disruptores Endocrinos/toxicidad , Ácidos Ftálicos/toxicidad , Factores de Edad , Animales , Ansiedad/inducido químicamente , Atención/efectos de los fármacos , Femenino , Masculino , Inhibición Prepulso/efectos de los fármacos , Ratas Long-Evans , Maduración Sexual/efectos de los fármacosRESUMEN
Perinatal exposure to endocrine disrupting chemicals negatively impacts health, but the mechanism by which such toxicants damage long-term reproductive and metabolic function is unknown. Lipid metabolism plays a pivotal role in steroid hormone synthesis as well as energy utilization and storage; thus, aberrant lipid regulation may contribute to phthalate-driven health impairments. In order to test this hypothesis, we specifically examined epigenetic disruptions in lipid metabolism pathways after perinatal phthalate exposure. During gestation and lactation, pregnant Long-Evans rat dams were fed environmentally relevant doses of phthalate mixture: 0 (CON), 200 (LO), or 1000 (HI) µg/kg body weight/day. On PND90, male offspring in the LO and HI groups had higher body weights than CON rats. Gene expression of lipid metabolism pathways was altered in testis and adipose tissue of males exposed to the HI phthalate dosage. Specifically, Srebf1 was downregulated in testis and Srebf2 was upregulated in adipose tissue. In testis of HI rats, DNA methylation was increased at two loci and reduced at one other site surrounding Srebf1 transcription start site. In adipose tissue of HI rats, we observed increased DNA methylation at one region within the first intron of Srebf2. Computational analysis revealed several potential transcriptional regulator binding sites, suggesting functional relevance of the identified differentially methylated CpGs. Overall, we show that perinatal phthalate exposure affects lipid metabolism gene expression in a tissue-specific manner possibly through altering DNA methylation of Srebf1 and Srebf2.
RESUMEN
Environmental factors such as diet and endocrine-disrupting chemicals have individually been shown to mediate metabolic function. However, the underlying mechanism by which the combination disrupts adipocyte morphology and fat storage remains unknown. The current study evaluated early-life programming by diet and phthalate exposure. During gestation and lactation, pregnant Long-Evans hooded rat dams were fed either a control (C) or high-fat (HF) diet and were orally administered one of three phthalate dosages (0, 200 or 1000 µg/kg/day), yielding six groups of offspring: C-0, C-200, C-1000, HF-0, HF-200 and HF-1000. On postnatal day (PND) 90, gonadal fat pads were collected and analyzed for histology, gene expression and DNA methylation. Differences in body weight were observed only in males. Hematoxylin and eosin staining revealed larger adipocyte size in HF-0 vs. C-0 females. Exposure to 200 or 1000 µg/kg/day phthalates modulated diet-induced changes in adipose morphology. Compared to C-0 females, HF-0 females also had higher expression of the adipogenesis gene Wnt receptor, frizzled 1 (Fzd1) and the triglyceride cleaving enzyme lipoprotein lipase (Lpl). These increases in gene expression were accompanied by lower DNA methylation surrounding the transcription start sites of the two genes. Diet-driven effects were observed in unexposed females but not in phthalate-treated rats. Results suggest a sex-specific association between perinatal HF diet and body weight, adipocyte size and DNA methylation. Perinatal phthalate exposure appears to produce a phenotype that more closely resembles HF-fed animals.
Asunto(s)
Adipocitos/efectos de los fármacos , Metilación de ADN/efectos de los fármacos , Dieta Alta en Grasa/efectos adversos , Ácidos Ftálicos/toxicidad , Adipogénesis/efectos de los fármacos , Adipogénesis/genética , Animales , Animales Recién Nacidos , Composición Corporal/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Tamaño de la Célula/efectos de los fármacos , Femenino , Receptores Frizzled/genética , Regulación de la Expresión Génica/efectos de los fármacos , Lactancia , Lipoproteína Lipasa/genética , Masculino , Embarazo , Efectos Tardíos de la Exposición Prenatal , Ratas Long-Evans , Receptores de Neurotransmisores/genética , Factores SexualesRESUMEN
The growth and organization of the developing brain are known to be influenced by hormones, but little is known about whether disruption of hormones affects cortical regions, such as mPFC. This region is particularly important given its involvement in executive functions and implication in the pathology of many neuropsychiatric disorders. Here, we examine the long-term effects of perinatal exposure to endocrine-disrupting compounds, the phthalates, on the mPFC and associated behavior. This investigation is pertinent as humans are ubiquitously exposed to phthalates through a variety of consumer products and phthalates can readily cross the placenta and be delivered to offspring via lactation. Pregnant dams orally consumed an environmentally relevant mixture of phthalates at 0, 200, or 1000 µg/kg/d through pregnancy and for 10 d while lactating. As adults, offspring were tested in an attentional set-shifting task, which assesses cognitive flexibility. Brains were also examined in adulthood for stereological quantification of the number of neurons, glia, and synapses within the mPFC. We found that, independent of sex, perinatal phthalate exposure at either dose resulted in a reduction in neuron number, synapse number, and size of the mPFC and a deficit in cognitive flexibility. Interestingly, the number of synapses was correlated with cognitive flexibility, such that rats with fewer synapses were less cognitively flexible than those with more synapses. These results demonstrate that perinatal phthalate exposure can have long-term effects on the cortex and behavior of both male and female rats.SIGNIFICANCE STATEMENT Humans globally are exposed on a daily basis to a variety of phthalates, which are endocrine-disrupting chemicals. The effects of phthalate exposure on the developing brain, especially on cognitively relevant regions, such as the mPFC, are not known. Here, we use a rat model of human prenatal exposure to an environmentally relevant mixture of phthalates and find that there is an appreciable reduction in neuron number, synapse number, and size of the mPFC and a deficit in cognitive flexibility. These results may have serious implications for humans given that the mPFC is involved in executive functions and is implicated in the pathology of many neuropsychiatric disorders.
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Trastornos del Conocimiento/inducido químicamente , Disruptores Endocrinos/toxicidad , Contaminantes Ambientales/toxicidad , Neuronas/patología , Ácidos Ftálicos/toxicidad , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Adulto , Animales , Recuento de Células , Trastornos del Conocimiento/patología , Femenino , Humanos , Masculino , Neuronas/efectos de los fármacos , Corteza Prefrontal/efectos de los fármacos , Embarazo , Efectos Tardíos de la Exposición Prenatal/patología , Ratas , Ratas Long-Evans , Disposición en Psicología , Sinapsis/efectos de los fármacosRESUMEN
The purpose of this review is to discuss the structural and physiological changes that underlie age-related neuromuscular dysfunction and to summarize current evidence on the potential role of nutritional interventions on neuromuscular dysfunction-associated pathways. Age-related neuromuscular deficits are known to coincide with distinct changes in the central and peripheral nervous system, in the neuromuscular system, and systemically. Although many features contribute to the age-related decline in neuromuscular function, a comprehensive understanding of their integration and temporal relationship is needed. Nonetheless, many nutrients and ingredients show promise in modulating neuromuscular output by counteracting the age-related changes that coincide with neuromuscular dysfunction. In particular, dietary supplements, such as vitamin D, omega-3 fatty acids, ß-hydroxy-ß-methylbutyrate, creatine, and dietary phospholipids, demonstrate potential in ameliorating age-related neuromuscular dysfunction. However, current evidence seldom directly assesses neuromuscular outcomes and is not always in the context of aging. Additional clinical research studies are needed to confirm the benefits of dietary supplements on neuromuscular function, as well as to define the appropriate population, dosage, and duration for intervention.
Asunto(s)
Envejecimiento , Dieta , Suplementos Dietéticos , Músculo Esquelético/efectos de los fármacos , Unión Neuromuscular/efectos de los fármacos , Sarcopenia/fisiopatología , Creatina/farmacología , Creatina/uso terapéutico , Proteínas en la Dieta/farmacología , Proteínas en la Dieta/uso terapéutico , Ácidos Grasos Omega-3/farmacología , Ácidos Grasos Omega-3/uso terapéutico , Humanos , Músculo Esquelético/fisiopatología , Unión Neuromuscular/fisiopatología , Fosfolípidos/farmacología , Fosfolípidos/uso terapéutico , Sarcopenia/prevención & control , Valeratos/farmacología , Valeratos/uso terapéutico , Vitamina D/farmacología , Vitamina D/uso terapéuticoRESUMEN
Humans are ubiquitously exposed to many phthalates, a class of endocrine-disrupting chemicals commonly used in many consumer goods, and diet, especially fatty food, is presumed to be a major source of exposure. Here, we use a rat model of human prenatal exposure to investigate the potential interactive effects of an environmentally relevant mixture of phthalates and a maternal high-fat diet (HFD). From gestation through postnatal day (P)10, dams consumed the mixture of phthalates (0, 200, or 1000 µg/kg/d) and were fed a control diet or HFD. In males, perinatal exposure to the mixture of phthalates decreased prepubertal body weight and, in a dose-specific manner, periadolescent social play behavior. A dose-specific effect from phthalates with HFD was also seen in increased time alone in females during social play. HFD resulted in dams consuming more calories, having greater gestational weight gain, and licking and nursing their pups more, such that an early postnatal HFD generally increased pup body weight. There also was a tendency for increased oxidative stress markers at P10 within the medial prefrontal cortex of males exposed to the relatively high dose of phthalates and HFD. Effects on gene expression were inconsistent at P10 and P90 in both the medial prefrontal cortex and hypothalamus. Overall, this study demonstrates that phthalates and a maternal HFD only rarely interacted, except in oxidative stress markers in males. Additionally, perinatal exposure to an environmentally relevant mixture of phthalates can have a modest, but lasting, impact on social behaviors in both males and females.
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Dieta Alta en Grasa , Crecimiento/efectos de los fármacos , Conducta Materna/efectos de los fármacos , Ácidos Ftálicos/toxicidad , Juego e Implementos de Juego , Efectos Tardíos de la Exposición Prenatal , Conducta Social , Animales , Animales Recién Nacidos , Dieta Alta en Grasa/efectos adversos , Femenino , Masculino , Fenómenos Fisiologicos Nutricionales Maternos , Juego e Implementos de Juego/psicología , Embarazo , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Efectos Tardíos de la Exposición Prenatal/psicología , Ratas , Ratas Long-Evans , Maduración Sexual/efectos de los fármacosRESUMEN
Beta-hydroxy-beta-methylbutyrate (HMB) is commonly supplemented to maintain muscle in elderly and clinical populations and has potential as a nootropic. Previously, we have shown that in both male and female rats, long-term HMB supplementation prevents age-related dendritic shrinkage within the medial prefrontal cortex (mPFC) and improves cognitive flexibility and working memory performance that are both age- and sex-specific. In this study, we further explore the cognitive effects by assessing visuospatial learning and memory with the Morris water maze. Female rats were ovariectomized at 11months of age to model human menopause. At 12months of age, male and female rats received relatively short- or long-term (1- or 7-month) dietary HMB (450mg/kg/dose) supplementation twice a day prior to testing. Spatial reference learning and memory was assessed across four days in the water maze with four trials daily and a probe trial on the last day. Consistent with previous work, there were age-related deficits in water maze performance in both sexes. However, these deficits were ameliorated in HMB-treated males during training and in both sexes during probe trial performance. Thus, HMB supplementation prevented the age-related decrement in water maze performance, especially in male rats.
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Envejecimiento/efectos de los fármacos , Discapacidades para el Aprendizaje/tratamiento farmacológico , Aprendizaje por Laberinto/efectos de los fármacos , Trastornos de la Memoria/tratamiento farmacológico , Nootrópicos/farmacología , Valeratos/farmacología , Envejecimiento/fisiología , Envejecimiento/psicología , Animales , Femenino , Discapacidades para el Aprendizaje/fisiopatología , Masculino , Aprendizaje por Laberinto/fisiología , Trastornos de la Memoria/fisiopatología , Pruebas Neuropsicológicas , Ovariectomía , Ratas Long-Evans , Caracteres Sexuales , Aprendizaje Espacial/efectos de los fármacos , Aprendizaje Espacial/fisiologíaRESUMEN
OBJECTIVES: Normal aging results in cognitive decline and nutritional interventions have been suggested as potential approaches for mitigating these deficits. Here, we used rats to investigate the effects of short- and long-term dietary supplementation with the leucine metabolite ß-hydroxy-ß-methyl butyrate (HMB) on working memory and cognitive flexibility. METHODS: Beginning â¼12 months of age, male and female Long-Evans rats were given twice daily access to sipper tubes containing calcium HMB (450â mg/kg) or vehicle (285â mg/kg calcium lactate) in a sucrose solution (20% w/v). Supplementation continued for 1 or 7 months (middle- and old-age (OA) groups, respectively) before testing began. Working memory was assessed by requiring rats to respond on a previously sampled lever following various delays. Cognitive flexibility was assessed by training rats to earn food according to a visual strategy and then, once acquired, shifting to an egocentric response strategy. RESULTS: Treatment with HMB improved working memory performance in middle-age (MA) males and OA rats of both sexes. In the cognitive flexibility task, there was a significant age-dependent deficit in acquisition of the visual strategy that was not apparent in OA males treated with HMB. Furthermore, HMB ameliorated an apparent deficit in visual strategy acquisition in MA females. DISCUSSION: Together, these findings suggest that daily nutritional supplementation with HMB facilitates learning and improves working memory performance. As such, HMB supplementation may mitigate age-related cognitive deficits and may therefore be an effective tool to combat this undesirable feature of the aging process.
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Envejecimiento/efectos de los fármacos , Cognición/efectos de los fármacos , Memoria a Corto Plazo/efectos de los fármacos , Valeratos/farmacología , Animales , Suplementos Dietéticos , Modelos Animales de Enfermedad , Femenino , Masculino , Ratas , Ratas Long-EvansRESUMEN
Beta-hydroxy-beta-methylbutyrate (HMB), a supplement commonly used to maintain muscle in elderly and clinical populations, has been unexplored in the aging brain. In both healthy aging humans and rat models, there are cognitive deficits associated with age-related dendritic shrinkage within the prefrontal cortex. The present study explores the effects of relatively short- and long-term (7 and 31 weeks) oral HMB supplementation starting at 12 months of age in male and female rats on the dendritic tree of layer 5 pyramidal neurons in the medial prefrontal cortex. Since female rats continue to secrete ovarian hormones after reaching reproductive senescence, middle-aged female rats were ovariectomized to model humans. As expected, there were fewer spines and a retraction of dendritic material in the apical and basilar trees in old age controls of both sexes compared with their middle-aged counterparts. However, these losses did not occur in the HMB-treated rats in either dendrites or the total number of dendritic spines. Thus, HMB forestalled the effects of aging on the dendritic tree of this population of neurons.