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1.
J Mol Cell Cardiol ; 148: 15-24, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32882262

RESUMEN

BACKGROUND: The role of calcineurin (protein phosphatase 2B (PP2B)) in the pathogenesis of human dilated cardiomyopathy (DCM) has not been fully elucidated. We determined the potential involvement of calcineurin in the pathogenesis of DCM caused by mutations in CnB1, a subunit of calcineurin. METHODS: By whole-exome sequencing, we identified a new CnB1 variant in a Han Chinese proband with cardiomyopathy from a 3-generation family with 2 normal individuals and 3 individuals with familial dilated cardiomyopathy. The potential pathogenic variant was validated by Sanger sequencing. We performed functional and mechanistic experiments in a CnB1-knockin (KI) mouse model and at the cellular level. RESULTS: We detected a rare heterozygous CnB1 variant (p.D102A) in a proband with dilated cardiomyopathy. This variant was localized to the EF hand 3 region of CnB1, where no variants have been previously reported. KI mice harboring the p.D102A variant exhibited decreased cardiac function and cardiac dilatation. Immunoblotting, RT-PCR and immunofluorescence results showed decreased cardiomyocyte size and heart failure-related protein expression. A calcineurin activity assay demonstrated decreased calcineurin activity in the KI mice, accompanied by the decreased ability of CnB1 to bind CnA. CONCLUSIONS: CnB1 p.D102A is a disease-associated variant that confers susceptibility to cardiac dilatation. This variant is associated with impaired calcineurin activity and a subsequent decrease in the ability of CnB1 to bind CnA.


Asunto(s)
Calcineurina/genética , Cardiomiopatía Dilatada/genética , Mutación/genética , Subunidades de Proteína/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Calcineurina/química , Cardiomiopatía Dilatada/fisiopatología , Regulación de la Expresión Génica , Técnicas de Sustitución del Gen , Humanos , Ratones , Fenotipo , Unión Proteica
2.
Zhonghua Yi Xue Za Zhi ; 100(5): 382-386, 2020 Feb 11.
Artículo en Zh | MEDLINE | ID: mdl-32074784

RESUMEN

Objective: To analyze the relationship between tumors of the musculoskeletal system and adjacent nerves by reconstructing images of peripheral nerves, and explore its value in surgical treatment. Methods: From May 2016 to April 2019, a total of 27 patients were collected in Department of Imaging,Shougang Hospital, who were with skeletal muscle system tumors, including 15 primary soft tissue tumors, 9 primary bone tumors, 3 metastatic tumors, all of them were closely related to nerves. There were 17 males and 10 females, aged 13-67 years, with an average age of 34 years. Before the operation, CT volume scanning was performed, and curved planar reconstruction (CPR) was used to reconstruct the peripheral nerves. All patients were operated within 2 weeks after the examination. According to the image characteristics before the operation, the nerve invasion was judged. The sensitivity, characteristic, positive predictive value and negative predictive value of the tumor invasion (compression) nerve were calculated according to the intraoperative findings as the gold standard. Result: Of the 27 cases, 25 cases (25/27, 92.6%) could show the relationship between the tumors and the adjacent nerves at the same level, and 22 cases (22/25, 88.0%) had the same preoperative image judgments as the intraoperative findings. In the reconstructed images, the peripheral nerve was a continuous strip-like structure on the same level with the tumor. The invaded nerve became thicker and the edge was blurred. Enhanced scan showed enhancement. The sensitivity, specificity, positive predictive value and negative predictive value of neuroimaging reconstruction were 100.0%, 89.5%, 75.0% and 100.0% respectively. The sensitivity, specificity, positive predictive value and negative predictive value of the nerve compression were 92.3%, 100.0%, 100.0% and 80.0% respectively. Conclusions: Neurological reconstructed images can help clinicians evaluate the relationship between lesions and adjacent nerves quickly and intuitively. They can guide the selection of surgical methods, reduce the risk of intraoperative nerve injury, and have high sensitivity and specificity for nerves invasion.


Asunto(s)
Neoplasias de los Tejidos Blandos , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Músculo Esquelético , Neuroimagen , Tomografía Computarizada por Rayos X , Adulto Joven
3.
Wiad Lek ; 73(7): 1434-1437, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32759433

RESUMEN

OBJECTIVE: The aim:to study the content of trace elements (Fe, Cu, Zn, Co, Cr, Ni, Pb) in the placenta of pregnant healthy women and with signs of intrauterine infection of the fetus, features of transplacental transmission of infectious process from mother to fetus and to investigate the role of the placenta in trace element supply of the fetus. PATIENTS AND METHODS: Materials and methods. 43 pregnant women between the aged 16 to 40 years were monitored, including 12 with physiological pregnancy (group 1) and 31 with signs of STI (group 2). All pregnant women underwent standard comprehensive examination, evaluation of fetal cardiac output and non-stress testing using cardio-toсography (CTG) in the third trimester. The group of pregnant women with signs of fetal ulcers included women whose pregnancy was complicated by chronic fetoplacental dysfunction (FPD), infectious lesions of the fetoplacental complex, which were diagnosed on the basis of ultrasound signs of placenta, syndrome of infectious and surrounding infections. RESULTS: Results:The content of essential trace elements in the placenta of the main group was significantly lower than in the placenta of the control group. There was a decrease in the concentration of iron by 32%, zinc - by 46%, nickel - by 44%, copper more than tripled, chromium - 4 times. Deficiency of essential trace elements (iron, zinc, copper, chromium, nickel) and elevated lead content in the placenta leads to the formation of conditions for the development of placental dysfunction, the progression of which leads to fetal distress, developmental delay syndrome and antenatal fetal death. CONCLUSION: Conclusions:1. One of the links in the pathogenesis of intrauterine infection in the fetus is the imbalance of essential trace elements in the system «mother - placenta - fetus¼. 2. Pregnant women with signs of intrauterine infection are characterized by a deficiency of serum Fe, Cu, Zn, Ni and an increased content of Pb, Cr and Co compared with pregnant women with physiological pregnancy. 3. Umbilical cord blood of women with evidence of fetal fetal infection also has a reduced content of iron, copper, zinc and high levels of lead, cobalt and chromium. 4. Disruption of placental function in intrauterine infection of the fetus is caused by reduced content of iron, zinc, copper, nickel and lead accumulation.


Asunto(s)
Enfermedades Transmisibles , Adolescente , Adulto , Femenino , Feto , Humanos , Placenta , Embarazo , Oligoelementos , Adulto Joven , Zinc
4.
J Viral Hepat ; 25(3): 289-295, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29080231

RESUMEN

Persistent chronic infection with hepatitis B virus (HBV) is a major risk factor for the development of HBV-related diseases. The molecular mechanisms that underlie HBV infection and associated carcinogenesis are not fully understood. The aim of this study was to explore the role of ENO1 in HBV replication processes. Here, we examined ENO1 expression levels in HBV-infected and non-HBV-infected liver tissues and cells by Western blot analysis, real-time PCR and immunohistochemistry. In addition, HBsAg and HBeAg in the media of transfected HepG2.2.15 cells were detected using an electrochemical luminescence analyser within 48 hours after ENO1-specific siRNA transfection. The expression levels of HBV DNA, type I interferon and 5 downstream IFN-stimulated genes in HepG2.2.15 cells were examined using real-time PCR. We found ENO1 expression was upregulated in the HBV-infected liver tissues and cells. Silencing of ENO1 resulted in a significant reduction in HBV replication, and this siRNA-mediated reaction also caused the upregulation of expression of type I interferon and downstream IFN-stimulated genes. Therefore, we come to the conclusion ENO1 is involved in HBV replication. It is therefore likely that HBV replication is enhanced following suppression of the IFN signalling pathway. However, the mechanisms that underpin ENO1-mediated modulation of the IFN signalling pathway remain to be elucidated.


Asunto(s)
Virus de la Hepatitis B/fisiología , Interacciones Huésped-Patógeno , Evasión Inmune , Interferón Tipo I/antagonistas & inhibidores , Fosfopiruvato Hidratasa/metabolismo , Transducción de Señal , Replicación Viral , Adulto , Western Blotting , Femenino , Perfilación de la Expresión Génica , Células Hep G2 , Hepatocitos/enzimología , Hepatocitos/virología , Humanos , Inmunohistoquímica , Hígado/enzimología , Hígado/patología , Masculino , Persona de Mediana Edad , Reacción en Cadena en Tiempo Real de la Polimerasa
5.
Acta Paediatr ; 104(5): e200-5, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25649520

RESUMEN

AIM: This study explored neonatal morbidity and mortality in hospitalised patients in central Vietnam and risk factors associated with mortality. METHODS: We conducted a prospective cohort study of all newborn infants (<28 days) hospitalised in a neonatal unit over a 1-year period and followed until discharge. The main outcome measures were case fatality rate and the rate of different clinical diagnoses. RESULTS: There were 2555 admissions during the study period. The leading primary causes of admissions were infections (41%), haematological problems such as jaundice (23%) and prematurity and its complications (18%). The overall case fatality rate was 8.6%, and it was 59% among very low-birthweight (<1500 g) neonates. Mortality was inversely associated with birthweight and gestational age. Of the 220 deaths, 57% occurred within the first 7 days of life. Although the causes of death were often multifactorial, the leading primary causes were infections (32%), prematurity and its complications (25%), birth defects (24%) and birth asphyxia (6%). Risk factors associated with death were being outborn, early gestational age, small for gestational age, confirmed sepsis and birth defects. CONCLUSION: Mortality rates were high among hospitalised neonates in central Vietnam, and this paper suggests interventions that might improve outcomes.


Asunto(s)
Causas de Muerte , Mortalidad Infantil , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Admisión del Paciente/estadística & datos numéricos , Estudios Prospectivos , Vietnam/epidemiología
6.
J Prev Alzheimers Dis ; 9(1): 104-112, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35098980

RESUMEN

OBJECTIVE: To assess the effectiveness of a mindfulness-based Tai Chi Chuan on physical performance and cognitive function among cognitive frailty older adults. DESIGN: A single-blind,three-arm randomized controlled trial. SETTING: Three communities in Daqing, China. PARTICIPANTS: The study sample comprised 93 men and women aged 65 years or older who were able to walk more than 10 m without helping tools, scored 0.5 on Clinical Dementia Rating (CDR) and absence of concurrent dementia, identified pre-frailty (scored 1-2 on Fried Frailty Criteria) and frailty older adults (scored 3-5 on Fried Frailty Criteria). INTERVENTION: Subjects were randomly allocated to three groups: Group1, which received mindfulness intervention (formal and informal mindfulness practices); Group 2, which received Tai-Chi Chuan intervention; Group 3, which received MTCC intervention. MEASUREMENTS: The primary outcomes was cognitive frailty rate(measured by Fried Frailty Criteria and Clinical Dementia Rating-CDR) , the secondary outcome were cognitive function (measured by Min-Mental State Examination-MMES) and physical level (measured by Short physical performance battery- SPPB, Timed up and Go test-TUG and the 30-second Chair test). They were all assessed at Time 1-baseline, Time 2-after the end of 6-month intervention and the follow up (Time 3-half year after the end of 6-month intervention). RESULTS: The baseline characteristics did not differ among the groups.Improvements in the cognitive function (MMES), physical performance (SPPB, TUG, 30-second Chair test) were significantly difference between time-group interaction (p<.05). The rate of CF was significantly different among groups at 6-month follow-up period (χ2=6.37, p<.05). A lower prevalence of frailty and better cognitive function and physical performance were found in the Group 3 compared with other two groups at the follow-up period (p<.05). CONCLUSIONS: MTCC seems to be effectively reverse CF, improving the cognitive and physical function among older adults, suggesting that MTCC is a preferably intervention option in community older adults with cognitive frailty.


Asunto(s)
Fragilidad , Atención Plena , Taichi Chuan , Anciano , Cognición , Femenino , Estudios de Seguimiento , Fragilidad/terapia , Humanos , Masculino , Rendimiento Físico Funcional , Equilibrio Postural , Método Simple Ciego , Estudios de Tiempo y Movimiento
7.
Nat Commun ; 13(1): 3096, 2022 Jun 02.
Artículo en Inglés | MEDLINE | ID: mdl-35654938

RESUMEN

In spintronics, the two main approaches to actively control the electrons' spin involve static magnetic or electric fields. An alternative avenue relies on the use of optical fields to generate spin currents, which can bolster spin-device performance, allowing for faster and more efficient logic. To date, research has mainly focused on the optical injection of spin currents through the photogalvanic effect, and little is known about the direct optical control of the intrinsic spin-splitting. To explore the optical manipulation of a material's spin properties, we consider the Rashba effect. Using time- and angle-resolved photoemission spectroscopy (TR-ARPES), we demonstrate that an optical excitation can tune the Rashba-induced spin splitting of a two-dimensional electron gas at the surface of Bi2Se3. We establish that light-induced photovoltage and charge carrier redistribution - which in concert modulate the Rashba spin-orbit coupling strength on a sub-picosecond timescale - can offer an unprecedented platform for achieving optically-driven spin logic devices.

9.
Food Chem Toxicol ; 163 Suppl 1: 113055, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35460830

RESUMEN

Therefore, the phenethyl formate MOE for the fertility endpoint can be calculated by dividing the phenethyl alcohol NOAEL in mg/kg/day by the total systemic exposure to phenethyl formate, 1000/0.00062 or 1612903.


Asunto(s)
Odorantes , Perfumes , Seguridad de Productos para el Consumidor , Formiatos , Perfumes/toxicidad , Fenilacetatos , Sistema de Registros , Medición de Riesgo , Pruebas de Toxicidad
10.
Food Chem Toxicol ; 161 Suppl 1: 112912, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35278499

RESUMEN

Therefore, the (-)-(R)-α-phellandrene MOE for the repeated dose toxicity endpoint can be calculated by dividing the (-)-(R)-α-phellandrene NOAEL in mg/kg/day by the total systemic exposure to (-)-(R)-α-phellandrene, 8.33/0.00040, or 20825.


Asunto(s)
Monoterpenos Ciclohexánicos/toxicidad , Odorantes , Humanos , Pruebas de Mutagenicidad , Pruebas de Toxicidad
11.
Science ; 376(6595): 860-864, 2022 05 20.
Artículo en Inglés | MEDLINE | ID: mdl-35587968

RESUMEN

Superconductivity and charge density waves (CDWs) are competitive, yet coexisting, orders in cuprate superconductors. To understand their microscopic interdependence, a probe capable of discerning their interaction on its natural length and time scale is necessary. We use ultrafast resonant soft x-ray scattering to track the transient evolution of CDW correlations in YBa2Cu3O6+x after the quench of superconductivity by an infrared laser pulse. We observe a nonthermal response of the CDW order characterized by a near doubling of the correlation length within ≈1 picosecond of the superconducting quench. Our results are consistent with a model in which the interaction between superconductivity and CDWs manifests inhomogeneously through disruption of spatial coherence, with superconductivity playing the dominant role in stabilizing CDW topological defects, such as discommensurations.

12.
Food Chem Toxicol ; 161 Suppl 1: 112853, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35150761

RESUMEN

The existing information supports the use of this material as described in this safety assessment. 5-Hydroxy-7-decenoic acid δ-lactone was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data from read-across material tetrahydro-6-(3-pentenyl)-2H-pyran-2-one (CAS # 32764-98-0) show that 5-hydroxy-7-decenoic acid δ-lactone is not expected to be genotoxic. The repeated dose, reproductive, and local respiratory toxicity endpoints were evaluated using the Threshold of Toxicological Concern (TTC) for a Cramer Class I material, and the exposure to 5-hydroxy-7-decenoic acid δ-lactone is below the TTC (0.03 mg/kg/day, 0.03 mg/kg/day, and 1.4 mg/day, respectively). Data show that there are no safety concerns for 5-hydroxy-7-decenoic acid δ-lactone for skin sensitization under the current declared levels of use. The phototoxicity/photoallergenicity endpoints were evaluated based on ultraviolet/visible (UV/Vis) spectra; 5-hydroxy-7-decenoic acid δ-lactone is not expected to be phototoxic/photoallergenic. The environmental endpoints were evaluated; 5-Hydroxy-7-decenoic acid δ-lactone was found not to be Persistent, Bioaccumulative, and Toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards, and its risk quotients, based on its current volume of use in Europe and North America (i.e., Predicted Environmental Concentration/Predicted No Effect Concentration [PEC/PNEC]), are <1.


Asunto(s)
Lactonas/toxicidad , Odorantes , Humanos , Pruebas de Mutagenicidad , Pruebas de Toxicidad
13.
Food Chem Toxicol ; 161 Suppl 1: 112870, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35183650

RESUMEN

The existing information supports the use of this material as described in this safety assessment. Octyl isobutyrate was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data from read-across analog hexyl isobutyrate (CAS # 2349-07-7) show that octyl isobutyrate is not expected to be genotoxic. Data on analog propyl (2S)-2-(1,1-dimethylpropoxy)-propanoate (CAS # 319002-92-1) provide a calculated Margin of Exposure (MOE) > 100 for the repeated dose and reproductive toxicity endpoints. Data from analog hexyl 2-methylbutyrate (CAS # 10032-15-2) provided octyl isobutyrate a No Expected Sensitization Induction Level (NESIL) of 7000 µg/cm2 for the skin sensitization endpoint. Octyl isobutyrate is not expected to be phototoxic/photoallergenic based on ultraviolet/visible (UV/Vis) spectra. The local respiratory toxicity endpoint was evaluated using the Threshold of Toxicological Concern (TTC) for a Cramer Class I material; exposure to is below the TTC (1.4 mg/day). The environmental endpoints were evaluated; octyl isobutyrate was found not to be Persistent, Bioaccumulative, and Toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards, and its risk quotients, based on its current volume of use in Europe and North America (i.e., Predicted Environmental Concentration/Predicted No Effect Concentration [PEC/PNEC]), are <1.


Asunto(s)
Isobutiratos/toxicidad , Odorantes , Humanos , Pruebas de Mutagenicidad , Pruebas de Toxicidad
14.
Food Chem Toxicol ; 161 Suppl 1: 112876, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35189309

RESUMEN

The existing information supports the use of this material as described in this safety assessment. 2,6-Nonadienenitrile was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data show that 2,6-nonadienenitrile is not genotoxic. Data on read-across analog E- and Z-2(+3),12-tridecadiennitrile (CAS # 124071-40-5) provided 2,6-nonadienenitrile a calculated Margin of Exposure (MOE) > 100 for the repeated dose toxicity endpoint. The reproductive and local respiratory toxicity endpoints were evaluated using the Threshold of Toxicological Concern (TTC) for a Cramer Class III material, and the exposure to 2,6-nonadienenitrile is below the TTC (0.0015 mg/kg/day and 0.47 mg/day, respectively). Data show that there are no safety concerns for 2,6-nonadienenitrile for skin sensitization under the current declared levels of use. The phototoxicity/photoallergenicity endpoints were evaluated based on ultraviolet/visible (UV/Vis) spectra; 2,6-nonadienenitrile is not expected to be phototoxic/photoallergenic. The environmental endpoints were evaluated; 2,6-nonadienenitrile was found not to be Persistent, Bioaccumulative, and Toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards, and its risk quotients, based on its current volume of use in Europe and North America (i.e., Predicted Environmental Concentration/Predicted No Effect Concentration [PEC/PNEC]), are <1.


Asunto(s)
Nitrilos/toxicidad , Odorantes , Humanos , Pruebas de Mutagenicidad , Pruebas de Toxicidad
15.
Food Chem Toxicol ; 161 Suppl 1: 112865, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35176436

RESUMEN

The existing information supports the use of this material as described in this safety assessment. 4-(2,6,6-Trimethyl-2-cyclohexen)-2-methylbutanal was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data show that 4-(2,6,6-trimethyl-2-cyclohexen)-2-methylbutanal is not genotoxic. The repeated dose, reproductive, and local respiratory toxicity endpoints were evaluated using the Threshold of Toxicological Concern (TTC) for a Cramer Class I material, and the exposure to 4-(2,6,6-trimethyl-2-cyclohexen)-2-methylbutanal is below the TTC (0.03 mg/kg/day, 0.03 mg/kg/day, and 1.4 mg/day, respectively). Data provided 4-(2,6,6-trimethyl-2-cyclohexen)-2-methylbutanal a No Expected Sensitization Induction Level (NESIL) of 1100 µg/cm2 for the skin sensitization endpoint. The phototoxicity/photoallergenicity endpoints were evaluated based on data and ultraviolet/visible (UV/Vis) spectra; 4-(2,6,6-trimethyl-2-cyclohexen)-2-methylbutanal is not expected to be phototoxic/photoallergenic. The environmental endpoints were evaluated; 4-(2,6,6-trimethyl-2-cyclohexen)-2-methylbutanal was found not to be Persistent, Bioaccumulative, and Toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards, and its risk quotients, based on its current volume of use in Europe and North America (i.e., Predicted Environmental Concentration/Predicted No Effect Concentration [PEC/PNEC]), are <1.


Asunto(s)
Aldehídos/toxicidad , Odorantes , Humanos , Pruebas de Mutagenicidad , Pruebas de Toxicidad
16.
Food Chem Toxicol ; 163 Suppl 1: 112959, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35341829

RESUMEN

In addition, the total systemic exposure to α-irone (1.1 µg/kg/day) is below the TTC (30 µg/kg/day; Kroes et al., 2007) for the repeated dose toxicity endpoint of a Cramer Class I material at the current level of use.


Asunto(s)
Odorantes , Perfumes , Pruebas de Mutagenicidad , Norisoprenoides , Perfumes/toxicidad , Sistema de Registros , Medición de Riesgo , Pruebas de Toxicidad
17.
Food Chem Toxicol ; 163 Suppl 1: 112975, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35364130

RESUMEN

l-Carvone was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data show that l-carvone is not genotoxic and provided a No Expected Sensitization Induction Level (NESIL) of 2600 µg/cm2 for the skin sensitization endpoint. Data on l-carvone provided a calculated Margin of Exposure (MOE) >100 for the repeated dose toxicity and reproductive toxicity endpoints. The phototoxicity/photoallergenicity endpoint was completed based on data and ultraviolet/visible (UV/Vis) spectra; l-carvone is not phototoxic/photoallergenic. The local respiratory toxicity endpoint was evaluated using the Threshold of Toxicological Concern (TTC) for a Cramer Class II material (0.47 mg/day); the exposure to l-carvone is below the TTC. The environmental endpoints were evaluated; l-carvone was found not to be persistent, bioaccumulative, and toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards, and its risk quotients, based on its current volume of use in Europe and North America (i.e., Predicted Environmental Concentration/Predicted No Effect Concentration [PEC/PNEC]), are <1.


Asunto(s)
Dermatitis Fototóxica , Perfumes , Monoterpenos Ciclohexánicos , Humanos , Pruebas de Mutagenicidad , Odorantes , Perfumes/toxicidad , Sistema de Registros , Medición de Riesgo , Pruebas de Toxicidad
18.
Food Chem Toxicol ; 159 Suppl 1: 112707, 2022 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-34848252

RESUMEN

The existing information supports the use of this material as described in this safety assessment. ß-Caryophyllene was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data show that ß-caryophyllene is not genotoxic. Data on ß-caryophyllene provided a calculated Margin of Exposure (MOE) > 100 for the repeated dose toxicity and fertility endpoints. The developmental and local respiratory toxicity endpoints were evaluated using the Threshold of Toxicological Concern (TTC) for a Cramer Class I material, and the exposure to ß-caryophyllene is below the TTC (0.03 mg/kg/day and 1.4 mg/day, respectively. Data show that there are no safety concerns for ß-caryophyllene for skin sensitization under the current declared levels of use. The phototoxicity/photoallergenicity endpoints were evaluated based on data and ultraviolet/visible (UV/Vis) spectra; ß-caryophyllene is not expected to be phototoxic/photoallergenic. The environmental endpoints were evaluated; ß-caryophyllene was found not to be Persistent, Bioaccumulative, and Toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards, and its risk quotients, based on its current volume of use in Europe and North America (i.e., Predicted Environmental Concentration/Predicted No Effect Concentration [PEC/PNEC]), are <1.


Asunto(s)
Exposición a Riesgos Ambientales/efectos adversos , Odorantes/análisis , Perfumes/toxicidad , Plantas Comestibles/química , Sesquiterpenos Policíclicos/toxicidad , Seguridad , Academias e Institutos/normas , Animales , Dermatitis Fotoalérgica , Dermatitis Fototóxica , Determinación de Punto Final , Europa (Continente) , Fertilidad/efectos de los fármacos , Humanos , Pruebas de Mutagenicidad , América del Norte , Perfumes/química , Sesquiterpenos Policíclicos/análisis , Relación Estructura-Actividad Cuantitativa , Sistema de Registros , Reproducción/efectos de los fármacos , Sistema Respiratorio/efectos de los fármacos , Medición de Riesgo , Piel/efectos de los fármacos , Pruebas de Toxicidad
19.
Food Chem Toxicol ; 159 Suppl 1: 112715, 2022 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-34848254

RESUMEN

The Research Institute for Fragrance Materials, Inc. (RIFM) has evaluated safety data for fragrance materials for 55 years. The safety assessment of Natural Complex Substances (NCS) is similar to that of discrete fragrance materials; all of the same endpoints are evaluated. A series of decision trees, reflecting advances in risk assessment approaches of mixtures and toxicological methodologies, follows a tiered approach for each endpoint using a 4-step process with testing only as a last resort: 1) evaluate available data on NCS; 2) verify whether the Threshold of Toxicological Concern (TTC) can be applied; 3) verify whether the NCS risk assessment can be achieved on a component basis; and 4) determine whether data must be generated. Using in silico tools, RIFM examined NCS similarities based on the plant part, processing, and composition of materials across 81 plant families to address data gaps. Data generated from the Creme RIFM Aggregate Exposure Model for over 900 fragrance NCS demonstrate that dermal exposure is the primary route of human exposure for NCS fragrance uses. Over a third of materials are below the most conservative TTC limits. This process aims to provide a comprehensive Safety Assessment of NCS used as a fragrance ingredient.


Asunto(s)
Exposición a Riesgos Ambientales/efectos adversos , Odorantes/análisis , Perfumes/toxicidad , Extractos Vegetales/efectos adversos , Plantas/química , Seguridad , Piel , Academias e Institutos , Administración Cutánea , Animales , Mezclas Complejas , Árboles de Decisión , Dermatitis Fototóxica , Determinación de Punto Final , Humanos , Pruebas de Mutagenicidad , Perfumes/análisis , Extractos Vegetales/química , Sistema de Registros , Medición de Riesgo , Piel/efectos de los fármacos
20.
Food Chem Toxicol ; 159 Suppl 1: 112711, 2022 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-34843869

RESUMEN

The existing information supports the use of this material as described in this safety assessment. Phenethyl phenylacetate was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data show that phenethyl phenylacetate is not genotoxic. Data provide a calculated MOE >100 for the repeated dose toxicity endpoint. Data on read-across analog benzyl benzoate (CAS # 120-51-4) provide an MOE >100 for the developmental toxicity endpoint. The fertility and local respiratory toxicity endpoints were evaluated using the TTC for a Cramer Class I material, and the exposure to phenethyl phenylacetate is below the TTC (0.03 mg/kg/day, and 1.4 mg/day, respectively). Data from analog benzyl phenylacetate (CAS # 102-16-9) show that there are no safety concerns for phenethyl phenylacetate for skin sensitization under the current declared levels of use. The phototoxicity/photoallergenicity endpoints were evaluated based on UV/Vis spectra; phenethyl phenylacetate is not expected to be phototoxic/photoallergenic. The environmental endpoints were evaluated; phenethyl phenylacetate was found not to be PBT as per the IFRA Environmental Standards and its risk quotients, based on its current volume of use in Europe and North America (i.e., PEC/PNEC), are <1.


Asunto(s)
Acetatos/toxicidad , Exposición a Riesgos Ambientales/efectos adversos , Odorantes/análisis , Perfumes/toxicidad , Fenoles/toxicidad , Fenilacetatos/toxicidad , Seguridad , Academias e Institutos/normas , Acetatos/análisis , Animales , Dermatitis Fotoalérgica , Dermatitis Fototóxica , Determinación de Punto Final , Europa (Continente) , Fertilidad/efectos de los fármacos , Humanos , Pruebas de Mutagenicidad , América del Norte , Perfumes/química , Fenoles/análisis , Fenilacetatos/análisis , Sistema de Registros , Reproducción/efectos de los fármacos , Sistema Respiratorio/efectos de los fármacos , Medición de Riesgo , Piel/efectos de los fármacos , Pruebas de Toxicidad
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