RESUMEN
Vegetable oils are frequently used as a vehicle in the administration of lipophilic drugs in animal tests. However, the composition of these oils may interfere with the results. One alternative to reduce this potential bias is the use of mineral oil, which is not supposed to interfere in the physiology of experimental models, since this oil is considered to be innocous. The present study shows for the first time the effects of the oral administration of corn and mineral on the prostate, demonstrating their interference in homeostasis and revealing their potential to act as endocrine disruptors. Mineral oil treatment increased the expression of AR and ERα and serum estradiol concentrations, while corn oil increased the expression of positive cells for both types of estrogen receptors. The variation in the expression of these hormone receptors resulted in morphological changes in the prostate.
Asunto(s)
Aceite de Maíz/toxicidad , Disruptores Endocrinos/toxicidad , Aceite Mineral/toxicidad , Vehículos Farmacéuticos/toxicidad , Próstata/efectos de los fármacos , Administración Oral , Animales , Estradiol/sangre , Receptor alfa de Estrógeno/metabolismo , Receptor beta de Estrógeno/metabolismo , Gerbillinae , Homeostasis/efectos de los fármacos , Masculino , Próstata/metabolismo , Próstata/patología , Receptores Androgénicos/metabolismo , Testosterona/sangreRESUMEN
We prepared mineral oil-based emulsion adjuvants by employing simple self-emulsifying drug delivery system (SEDDS). Mineral oil emulsions (3%, 5%, and 7%) were prepared using deionized water and C-971P NF and C-940 grade carbomer solutions with concentrations 0.01% (w/v) and 0.02% (w/v). In total, 15 emulsions were prepared and mixed with a solution containing inactivated Mycoplasma hyopneumoniae (J101 strain) antigen and porcine circovirus type 2 antigen to prepare vaccines. Droplet sizes in the submicron range and zeta potential values between - 40 and 0 mV were maintained by most emulsion adjuvants for a period of 6 months. Emulsion adjuvants were regarded safe, and their M. hyopneumoniae-specific IgG, IgG1, and IgG2a titers were either better or comparable to those of aluminum gel.
Asunto(s)
Sistemas de Liberación de Medicamentos/métodos , Emulsionantes/toxicidad , Inmunoglobulina G/inmunología , Aceite Mineral/toxicidad , Mycoplasma hyopneumoniae/inmunología , Agua , Adyuvantes Inmunológicos/administración & dosificación , Adyuvantes Inmunológicos/toxicidad , Animales , Emulsionantes/administración & dosificación , Emulsiones/administración & dosificación , Emulsiones/toxicidad , Ratones , Ratones Endogámicos BALB C , Aceite Mineral/administración & dosificación , Mycoplasma hyopneumoniae/efectos de los fármacos , Porcinos , Agua/administración & dosificaciónRESUMEN
Leakage of transformer dielectric fluids is a concern because it may pose a risk of environmental contamination. In this study, the deleterious effects of vegetable and mineral dielectric fluids in water bodies were investigated using biodegradability and acute toxicity tests with Danio rerio and Artemia salina. Regarding biodegradability, all four tested vegetable oils (soy, canola, sunflower and crambe) were considered as easily biodegradable, presenting degradation rates significantly higher than the Lubrax-type mineral fluid. Acute toxicity tests were performed in two separate experiments without solution renewal. In the first experiment, the organisms were exposed in direct contact to different concentrations of vegetable (soy) and mineral (Lubrax) oils. Total soy-type vegetable oil has a higher toxic effect than Lubrax-type mineral oil. In the second experiment, the organisms were exposed to increasing percentages of the water-soluble fraction (WSF) of both types of tested oils. The LC50 values for the water-soluble fraction of the Lubrax-type mineral oil were about 5 and 8% for the Danio rerio and Artemia salina bioindicators, respectively, whereas the vegetable oil did not present toxic effect, regardless of its WSF. These results have shown that a strict selection of dielectric fluids and monitoring the leakage from power transformers is a serious duty of environmental protection agencies.
Asunto(s)
Suministros de Energía Eléctrica , Monitoreo del Ambiente/métodos , Aceite Mineral/toxicidad , Aceites de Plantas/toxicidad , Animales , Artemia/efectos de los fármacos , Biodegradación Ambiental , Brasil , Dosificación Letal Mediana , Aceite Mineral/análisis , Aceites de Plantas/análisis , Pruebas de Toxicidad Aguda , Aguas Residuales/microbiología , Pez Cebra/crecimiento & desarrolloRESUMEN
PURPOSE: Successful in vitro fertilization (IVF) relies on sound laboratory methods and culture conditions which depend on sensitive quality control (QC) testing. This study aimed to improve the sensitivity of mouse embryo assays (MEA) for detection of mineral oil toxicity. METHODS: Five experiments were conducted to study modifications of the standard mouse embryo assay (MEA) in order to improve sensitivity using clinical grade mineral oil with known peroxide concentrations. Assessment of blastocyst development at either 96 h or in an extended MEA (eMEA) to 144 h was tested in each experiment. In experiment 1, ability to detect peroxides in oil was compared in the MEA, eMEA, and cell number at 96 h. In experiment 2, serial dilutions of peroxide in oil were used along with time-lapse imaging to compare sensitivity of the morphokinetic MEA to the eMEA. Culture conditions that may affect assay sensitivity were assessed in experiments 3-5, which examined the effect of group versus individual culture, oxygen concentration, and protein supplementation. RESULTS: Extended MEA and cell counts identified toxicity not detected by the routine endpoint of blastocyst rate at 96 h. The eMEA was fourfold more sensitive than the standard MEA, and this sensitivity was similar to the morphokinetic MEA. Group culture had a protective effect against toxicity, while oxygen concentration did not affect blastocyst development. Protein supplementation with HSA had a protective effect on blastocyst development in eMEA. CONCLUSIONS: The standard MEA used by manufacturers does not detect potentially lethal toxicity of peroxides in mineral oil. While group culture may mask toxicity, protein supplementation and oxygen concentration have minimal effect on assay sensitivity. The eMEA and time-lapse morphokinetic assessment are equally effective in detection of peroxide toxicity and thus provide manufacturers and end-users a simple process modification that can be readily adopted into an existing QC program.
Asunto(s)
Blastocisto/metabolismo , Técnicas de Cultivo de Embriones , Desarrollo Embrionario/efectos de los fármacos , Aceite Mineral/toxicidad , Animales , Blastocisto/efectos de los fármacos , Embrión de Mamíferos/efectos de los fármacos , Desarrollo Embrionario/genética , Fertilización In Vitro/métodos , Humanos , Ratones , Peróxidos/metabolismoRESUMEN
CONTEXT: The non-invasive ophthalmic therapy has a drawback: low residence time in the eye socket. Nanoparticles and contact lenses have been studied as promising ocular drug delivery systems. OBJECTIVE: To develop a nanoemulsion and evaluate its compatibility with a soft contact lens as a potential strategy for ocular delivery. MATERIALS AND METHODS: The formulations were developed by spontaneous emulsification and fully characterized. Two drops of nanoemulsion were instilled on the surface of a commercial contact lens and its transparency was measured using a UV-Vis spectrophotometer. Before and after the instillation of the drops, the morphology (scanning electron microscopy - SEM) and ion permeability of the lenses were analyzed. RESULTS: The formulations had a mean particle size of 234 nm, polydispersity below 0.16, zeta potential of -8.56 ± 3.49 mV, slightly acid pH, viscosity ≈1.2 mPa s(-1) and spherical-shaped particles. Nanoemulsion was non-irritant (hen's egg test-chorioallantoic membrane), which was confirmed by the cytotoxicity studies in the SIRC cell cultures. After instillation, SEM analysis showed nanodroplets inside and on the surface of the lenses, although their transparency remained near 100%. No significant differences were found between lens ion permeability coefficients before and after instillation. CONCLUSIONS: Formulations presented appropriate physicochemical characteristics and suitability for ocular application. The contact lens remained transparent and ion-permeable after association with the formulation.
Asunto(s)
Aceite de Ricino/química , Lentes de Contacto Hidrofílicos , Emulsiones/química , Aceite Mineral/química , Soluciones Oftálmicas/química , Animales , Aceite de Ricino/toxicidad , Línea Celular , Supervivencia Celular/efectos de los fármacos , Pollos , Emulsiones/toxicidad , Humanos , Microscopía Electrónica de Rastreo , Aceite Mineral/toxicidad , Soluciones Oftálmicas/toxicidad , Tamaño de la Partícula , Permeabilidad/efectos de los fármacos , ConejosRESUMEN
A paving asphalt and a vacuum residuum (derived from crude oil by atmospheric and subsequent vacuum distillation and used as a blend stock for asphalt) were tested in skin carcinogenesis assays in mice and in optimized Ames assays for mutagenic activity. In the skin cancer tests, each substance was applied twice weekly for 104 weeks to the clipped backs of groups of 50 male C3H mice. Neither the paving asphalt nor the vacuum residuum (30% weight/volume and 75% weight/weight in US Pharmacopeia mineral oil, respectively) produced any tumors. The positive control benzo[a]pyrene (0.05% w/v in toluene) induced tumors in 46 of 50 mice, demonstrating the effectiveness of the test method. Salmonella typhimurium tester strain TA98 was used in the optimized Ames assay to evaluate mutagenic potential. Dimethylsulfoxide (DMSO) extractions of the substances were not mutagenic when tested up to toxic limits. Thus, under the conditions of these studies, neither the paving asphalt nor the vacuum residuum was carcinogenic or mutagenic.
Asunto(s)
Carcinógenos/toxicidad , Hidrocarburos/toxicidad , Mutágenos/toxicidad , Petróleo/toxicidad , Neoplasias Cutáneas/inducido químicamente , Animales , Benzo(a)pireno/toxicidad , Dimetilsulfóxido/toxicidad , Masculino , Ratones , Ratones Endogámicos C3H , Aceite Mineral/toxicidad , Salmonella typhimurium/efectos de los fármacos , Salmonella typhimurium/crecimiento & desarrollo , Pruebas de Toxicidad CrónicaAsunto(s)
Carcinógenos Ambientales/envenenamiento , Aceite Mineral/envenenamiento , Animales , Pruebas de Carcinogenicidad , Carcinógenos Ambientales/toxicidad , Exposición a Riesgos Ambientales/efectos adversos , Exposición a Riesgos Ambientales/legislación & jurisprudencia , Exposición a Riesgos Ambientales/normas , Regulación Gubernamental , Guías como Asunto , Haplorrinos , Humanos , Ratones , Aceite Mineral/toxicidad , Exposición Profesional/efectos adversos , Exposición Profesional/legislación & jurisprudencia , Exposición Profesional/normas , Petróleo/envenenamiento , Petróleo/toxicidad , ConejosRESUMEN
OBJECTIVES: To identify and describe the exposure to selected known and suspected carcinogenic agents, mixtures and exposure circumstances for defined job categories in Norway's offshore petroleum industry from 1970 to 2005, in order to provide exposure information for a planned cohort study on cancer. METHODS: Background information on possible exposure was obtained through company visits, including interviewing key personnel (n = 83) and collecting monitoring reports (n = 118) and other relevant documents (n = 329). On the basis of a previous questionnaire administered to present and former offshore employees in 1998, 27 job categories were defined. RESULTS: This study indicated possible exposure to 18 known and suspected carcinogenic agents, mixtures or exposure circumstances. Monitoring reports were obtained on seven agents (benzene, mineral oil mist and vapour, respirable and total dust, asbestos fibres, refractory ceramic fibres, formaldehyde and tetrachloroethylene). The mean exposure level of 367 personal samples of benzene was 0.037 ppm (range: less than the limit of detection to 2.6 ppm). Asbestos fibres were detected (0.03 fibres/cm3) when asbestos-containing brake bands were used in drilling draw work in 1988. Personal samples of formaldehyde in the process area ranged from 0.06 to 0.29 mg/m3. Descriptions of products containing known and suspected carcinogens, exposure sources and processes were extracted from the collected documentation and the interviews of key personnel. CONCLUSIONS: This study described exposure to 18 known and suspected carcinogenic agents, mixtures and exposure circumstances for 27 job categories in Norway's offshore petroleum industry. For a planned cohort study on cancer, quantitative estimates of exposure to benzene, and mineral oil mist and vapour might be developed. For the other agents, information in the present study can be used for further assessment of exposure, for instance, by expert judgement. More systematic exposure surveillance is needed in this industry. For future studies, new monitoring programmes need to be implemented.
Asunto(s)
Carcinógenos/toxicidad , Exposición Profesional/efectos adversos , Petróleo , Amianto/toxicidad , Benceno/toxicidad , Cerámica/toxicidad , Formaldehído/toxicidad , Humanos , Hidrocarburos Clorados/toxicidad , Aceite Mineral/toxicidad , Noruega/epidemiología , Dióxido de Silicio/toxicidadRESUMEN
Vegetable-derived lubricants (VDL) might be more biodegradable than mineral-derived lubricants (MDL) due to the absence of high molecular weight aromatics, but this remains largely untested in tropical conditions. In this laboratory study, the degradation rates of 2-stroke, 4-stroke and hydraulic VDLs were compared with their MDL counterparts in the presence of mangrove and coral reef microbial communities. While MDLs were comprised largely of unresolved saturated and some aromatic hydrocarbons, their VDL counterparts contained, potentially more degradable, fatty acid methyl esters. Degradation of some VDL was observed by day 7, with the 2-stroke VDL markedly consumed by mangrove microorganisms and the hydraulic VDL degraded by both microorganism communities after this short period. All of the VDL groups were significantly more degraded than the comparable MDLs mineral oil lubricants over 14 days in the presence of either mangrove or coral reef microbial communities. In general the mangrove-sourced microorganisms more efficiently degraded the lubricants than reef-sourced microorganisms.
Asunto(s)
Ecosistema , Aceites de Plantas/toxicidad , Clima Tropical , Contaminación del Agua , Animales , Antozoos , Avicennia , Biodegradación Ambiental , Lubrificación , Aceite Mineral/toxicidad , Microbiología del AguaRESUMEN
An increasing number of vegetable-based oils are being developed as environmentally friendly alternatives to petroleum products. However, toxicity towards key tropical marine species has not been investigated. In this study we used laboratory-based biomarker induction experiments to compare the relative stress of a vegetable-based lubricating oil for marine 2-stroke engines with its mineral oil-based counterpart on tropical fish. The sub-lethal stress of 2-stoke outboard lubricating oils towards the fish Lates calcarifer (barramundi) was examined using liver microsomal mixed function oxidase (MFO) induction assays. This study is the first investigation into the use of this key commercial species in tropical North Queensland, Australia in stress assessment of potential hydrocarbon pollution using ethoxyresorufin O-deethylase (EROD) induction. Our results indicated that barramundi provide a wide range of inducible rates of EROD activity in response to relevant organic stressors. The vegetable- and mineral-based lubricants induced significant EROD activity at 1.0 mg kg(-1) and there was no significant difference between the two oil treatments at that concentration. At increasing concentrations of 2 and 3 mg kg(-1), the mineral-based lubricant resulted in slightly higher EROD activity than the vegetable-based lubricant. The EROD activity of control and treated barramundi are found to be within ranges for other species from temperate and tropical environments. These results indicate that vegetable-based lubricants may be less stressful to barramundi than their mineral counterparts at concentrations of lubricant > or =2 mg kg(-1). There is great potential for this species to be used in the biomonitoring of waterways around tropical North Queensland and SE Asia.
Asunto(s)
Peces/metabolismo , Aceite Mineral/toxicidad , Aceites de Plantas/toxicidad , Clima Tropical , Contaminación del Agua , Animales , Monitoreo del Ambiente/métodos , Inducción Enzimática , Lubrificación , Masculino , Mitocondrias Hepáticas/efectos de los fármacos , Mitocondrias Hepáticas/enzimología , Oxigenasas de Función Mixta/metabolismoRESUMEN
Biodegradable vegetable-derived lubricants (VDL) might be less toxic to marine organisms than mineral-derived oils (MDL) due to the absence of high molecular weight aromatics, but this remains largely untested. In this laboratory study, adult corals and coral gametes were exposed to various concentrations of a two-stroke VDL-1A and a corresponding MDL to determine which lubricant type was more toxic to each life stage. In the fertilization experiment, gametes from the scleractinian coral Acropora microphthalma were exposed to water-accommodated fractions (WAF) of VDL-1A and MDL for four hours. The MDL and VDL-1A WAFs inhibited normal fertilization of the corals at 200 microg l(-1) total hydrocarbon content (THC) and 150 microg l(-1) THC respectively. Disturbance of a stable coral-dinoflagellate symbiosis is regarded as a valid measure of sub-lethal stress in adult corals. The state of the symbiosis in branchlets of adult colonies of Acropora formosa was monitored using indicators such as dinoflagellate expulsion and dark-adapted photosystem II yields of dinoflagellate (using pulse amplitude modulation fluorescence). An effect on symbiosis was measurable following 48 h exposure to the lubricants at concentrations of 190 microg l(-1) and 37 microg l(-1) THC for the MDL and VDL-1A respectively. GC/MS revealed that the main constituent of the VDL-1A WAF was the compound coumarin, added by the manufacturer to improve odour. The fragrance containing coumarin was removed from the lubricant formulation and the toxicity towards adult corals re-examined. The coumarin-free VDL-2 exhibited significantly less toxicity towards the adult corals than all of the other oil types tested, with the only measurable effect being a slight but significant drop in photosynthetic efficiency at 280 microg l(-1).
Asunto(s)
Antozoos/efectos de los fármacos , Ecosistema , Aceite Mineral/toxicidad , Aceites de Plantas/toxicidad , Clima Tropical , Contaminación del Agua , Animales , Antozoos/fisiología , Estadios del Ciclo de Vida , Fotosíntesis/efectos de los fármacos , Reproducción/efectos de los fármacos , SimbiosisRESUMEN
Although mineral oils are generally considered nontoxic and have a long history of use in humans, the mineral oil Bayol F (incomplete Freund's adjuvant, IFA) and certain mineral oil components (squalene and n-hexadecane) induce lupus-related anti-nRNP/Sm or -Su autoantibodies in nonautoimmune mice. In the present study, we investigated whether medicinal mineral oils can induce other types of autoantibodies and whether structural features of hydrocarbons influence autoantibody specificity. Female 3-month-old BALB/c (16-45/group) mice each received an i.p. injection of pristane (C19), squalene (C30), IFA, three medicinal mineral oils (MO-F, MO-HT, MO-S), or PBS. Sera were tested for autoantibodies and immunoglobulin levels. Hydrocarbons were analyzed by gas chromatography/mass spectrometry. IFA contained mainly C15-C25 hydrocarbons, whereas MO-HT and MO-S contained C20-C40, and MO-F contained C15-C40. Pristane and n-hexadecane were found in IFA (0.17% and 0.10% w/v, respectively) and MOs (0.0026-0.027%). At 3 months, pristane and IFA induced mainly IgG2a, squalene IgG1, and MOs IgG3 and IgM in sera. Anti-cytoplasmic antibodies were common in mice treated with MO-F, as well as those treated with pristane, squalene, and IFA. Anti-ssDNA and -chromatin antibodies were higher in MO-F and MO-S than in untreated/PBS, squalene-, or IFA-treated mice, suggesting that there is variability in the induction of anti-nRNP/Sm versus -chromatin/DNA antibodies. The preferential induction of anti-chromatin/ssDNA antibodies without anti-nRNP/Sm/Su by MO-S and MO-F is consistent with the idea that different types of autoantibodies are regulated differently. Induction of autoantibodies by mineral oils considered nontoxic also may have pathogenetic implications in human autoimmune diseases.
Asunto(s)
Autoanticuerpos/biosíntesis , Hipergammaglobulinemia/inducido químicamente , Aceite Mineral/toxicidad , Alcanos/análisis , Animales , Anticuerpos Antinucleares/biosíntesis , Anticuerpos Antinucleares/sangre , Autoanticuerpos/sangre , Autoinmunidad , Cromatina/inmunología , ADN de Cadena Simple/inmunología , Femenino , Adyuvante de Freund/química , Adyuvante de Freund/toxicidad , Cromatografía de Gases y Espectrometría de Masas , Humanos , Hipergammaglobulinemia/sangre , Inmunoglobulinas/biosíntesis , Inmunoglobulinas/sangre , Ratones , Ratones Endogámicos BALB C , Aceite Mineral/química , Escualeno/análisis , Escualeno/toxicidad , Terpenos/análisis , Terpenos/toxicidadRESUMEN
The notice of intended change for the threshold limit value (TLV) for mineral oil mist contains a notation for human carcinogenicity. A description is provided of the current European regulatory approach used to distinguish between carcinogenic and non-carcinogenic mineral base oils on the basis of oil refining process and chemical marker information. This approach has proven effective in creating a market situation in the countries of the European Union where many customers require severely refined, non-carcinogenic oils. It is recommended that ACGIH consolidate the distinction between poorly and severely refined base oils in the recommended TLV for mineral oil mist and use different toxicological considerations to derive exposure control guidelines.
Asunto(s)
Contaminantes Ocupacionales del Aire/clasificación , Aceite Mineral/clasificación , Petróleo/clasificación , Administración de la Seguridad/legislación & jurisprudencia , Contaminantes Ocupacionales del Aire/normas , Carcinógenos/clasificación , Europa (Continente) , Regulación Gubernamental , Humanos , Lubrificación , Aceite Mineral/toxicidad , Petróleo/toxicidad , Administración de la Seguridad/métodos , Valores Limites del UmbralRESUMEN
The purpose of this study was to provide data to be used in The Netherlands for development of ecotoxicologically based quality criteria for oil-contaminated sediments and dredged material. In addition, the relation of toxicity to specific oil boiling-point fraction ranges was explored. Natural marine sediment, with a moisture, organic carbon, and silt content of approximately 80, 1.8, and 33% of the dry weight, respectively, was artificially spiked using a spiking method developed in this project. Aliquots of one part of the sediment were spiked to several concentrations of Gulf distillate marine grade A (DMA) gasoil (containing 64% C10-19) and aliquots of the other part to several concentrations of Gulf high viscosity grade 46 (HV46) hydraulic oil (containing 99.2% C19-40). Thus, for each individual oil type, a concentration series was created. Vibrio fischeri (endpoint: bioluminescence inhibition), Corophium volutator (endpoint:mortality), and Echinocardium cordatum (endpoint:mortality) were exposed to these spiked sediments for 10 min, 10 d and 14 d, respectively. Based on the test results, the effective concentration on 50% of the test animals was statistically estimated. For DMA gasoil and HV46 hydraulic oil, respectively, the effective concentrations were 43.7 and 2,682 mg/kg dry weight for V. fischeri, 100 and 9,138 mg/kg dry weight for C. volutator, 190, and 1064 mg/kg dry weight for E. cordatum. This study shows that the toxicity is strongly correlated with the lower boiling-point fractions and especially to those within the C10-C19 range.
Asunto(s)
Crustáceos/efectos de los fármacos , Sedimentos Geológicos/química , Petróleo/toxicidad , Erizos de Mar/efectos de los fármacos , Vibrio/efectos de los fármacos , Contaminantes Químicos del Agua/toxicidad , Animales , Gasolina/toxicidad , Aceite Mineral/toxicidad , Pruebas de ToxicidadAsunto(s)
Disulfuros/farmacología , Inflamación/tratamiento farmacológico , Aceite Mineral , Aceite Mineral/farmacología , Piel/efectos de los fármacos , Uracilo/análogos & derivados , Cicatrización de Heridas/efectos de los fármacos , Adyuvantes Inmunológicos/administración & dosificación , Adyuvantes Inmunológicos/farmacología , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/farmacología , Quemaduras/tratamiento farmacológico , Sistema Nervioso Central/efectos de los fármacos , Diclofenaco/administración & dosificación , Diclofenaco/farmacología , Disulfuros/administración & dosificación , Disulfuros/toxicidad , Ecología , Industria Procesadora y de Extracción , Femenino , Dosificación Letal Mediana , Masculino , Ratones , Aceite Mineral/administración & dosificación , Aceite Mineral/toxicidad , Modelos Teóricos , Ratas , Piel/lesiones , Factores de Tiempo , Uracilo/administración & dosificación , Uracilo/farmacologíaRESUMEN
A Panel of medical and veterinary pathologists reviewed published and unpublished reports dealing with studies of various white mineral oils and waxes in F344 and Sprague-Dawley rats. They also had available and studied histologic slides from both subchronic and chronic studies of certain mineral hydrocarbons (90-day oral study of low melting point wax (LMPW) in female Fischer 344 and Sprague-Dawley rats; 90-day studies of P15H* and P70H white oil and high melting point wax (HMPW) in male and female F344 rats and 24 month study of P70H white oil in male and female F344 rats. The Panel also reviewed mineral oil-induced alterations in tissues of human patients (liver, hepatic lymph node and spleen). The Panel agreed that certain of the mineral hydrocarbons produced lesions in the mesenteric lymph nodes and liver of the F344 rat and these lesions were best described as microgranulomas/granulomas. The lesions were fundamentally similar in both organs, although varying in severity with dose and type of mineral hydrocarbons. The Panel agreed that hepatic lesions with inflammatory cell infiltration, necrosis, and fibrosis were produced only by feeding of LMPW and the lesions were confined to F344 rats and not found in Sprague-Dawley rats. The most severe granulomatous lesions in the mesenteric lymph nodes were found in high dose LMPW-fed F344 rats. The microgranulomas were similar in subchronic and chronic studies. Also, little difference existed between controls and treated F344 rats in the incidence and severity of the lesions after 2 years of feeding P70H white oil. The Panel agreed that some slight reversibility existed for these lesions, but also agreed that complete resolution was unlikely as regression of the lesions in the rat would likely be slow. The Panel agreed that a minimal severity infiltrate of mononuclear inflammatory cells occurred in the base of the mitral valve in a slightly increased incidence in F344 rats fed LMPW. The Panel concluded that these mitral valve alterations had little if any toxicologic significance as the focal infiltrate was minimal in severity, occurred in controls, occurred in association with murine cardiomyopathy, and were unlike the responses in the liver and mesenteric lymph nodes. The Panel agreed that the lesions observed in the liver and mesenteric lymph nodes of F344 rats exposed to MHCs, especially the LMPW, were different morphologically from changes observed in lymph node, liver, and spleen of humans that were mineral oil-users. These changes in humans are usually found incidentally in tissues taken at biopsy or autopsy. The MHC-induced lesions can be considered incidental and inconsequential in humans.
Asunto(s)
Hígado/efectos de los fármacos , Ganglios Linfáticos/efectos de los fármacos , Aceite Mineral/toxicidad , Ceras/toxicidad , Animales , Dieta , Femenino , Granuloma/inducido químicamente , Granuloma/patología , Humanos , Hígado/patología , Ganglios Linfáticos/patología , Masculino , Mesenterio/efectos de los fármacos , Mesenterio/patología , Aceite Mineral/administración & dosificación , Ratas , Ratas Endogámicas F344 , Ratas Sprague-Dawley , Especificidad de la Especie , Bazo/efectos de los fármacos , Bazo/patologíaRESUMEN
The acute phase response to inflammation induces changes in the secretion of hepatic proteins. To examine the time course of an acute phase protein response in broiler chickens, the plasma levels of hemopexin (HX) and alpha1-acid glycoprotein (AGP) and liver HX mRNA were measured at various time points from 3 hr to 336 hr after an intraabdominal injection of either lipopolysaccharide (LPS), complete Freund's adjuvant, incomplete Freund's adjuvant, phytohemagglutin, or mineral oil. Uninjected chicks served as controls. The accumulation of liver HX mRNA began within 3 hr of stimulation and peaked at 12 hr. Relative to control levels, plasma HX and AGP levels increased by 6-12 hr postchallenge and peaked at 24 hr. Complete Freund's adjuvant and LPS treatments induced the greatest increase in plasma HX (threefold; P < 0.05). Plasma levels of HX and AGP returned to control levels at 336 and 168 hr postinjection, respectively. A second experiment demonstrated that turpentine induced a similar AGP response as LPS and that albumin is a negative acute phase protein. The results suggest that plasma levels of HX or AGP could be used as an indicator of the systemic component of a local inflammatory response in chickens.
Asunto(s)
Pollos/metabolismo , Hemopexina/metabolismo , Inflamación/veterinaria , Orosomucoide/metabolismo , Enfermedades de las Aves de Corral/inmunología , Animales , Estudios de Casos y Controles , Pollos/inmunología , Adyuvante de Freund/toxicidad , Hemopexina/análisis , Inflamación/inducido químicamente , Inflamación/inmunología , Inflamación/metabolismo , Irritantes/toxicidad , Cinética , Lipopolisacáridos/toxicidad , Hígado/metabolismo , Masculino , Aceite Mineral/toxicidad , Orosomucoide/análisis , Fitohemaglutininas/toxicidad , Enfermedades de las Aves de Corral/inducido químicamente , Enfermedades de las Aves de Corral/metabolismo , ARN Mensajero/metabolismo , Conejos , Ratas , Trementina/toxicidadRESUMEN
The objective was to study the risk of cytogenetic damage among high voltage laboratory workers exposed to electromagnetic fields and mineral oil. This is a cross sectional study of 24 exposed and 24 matched controls in a Norwegian transformer factory. The exposure group included employees in the high voltage laboratory and in the generator soldering department. Electric and magnetic fields and oil mist and vapor were measured. Blood samples were analyzed for chromosomal aberrations in cultured lymphocytes. In addition to conventional cultures, the lymphocytes were also treated with hydroxyurea and caffeine. This procedure inhibits DNA synthesis and repair in vitro, revealing in vivo genotoxic lesions that are repaired during conventional culturing. In conventional cultures, the exposure group and the controls showed similar values for all cytogenetic parameters. In the DNA synthesis- and repair-inhibited cultures, generator welders showed no differences compared to controls. Among high voltage laboratory testers, compared to the controls, the median number of chromatid breaks was doubled (5 vs. 2.5 per 50 cells; P<0.05) the median number of chromosome breaks was 2 vs. 0.5 (P>0.05) and the median number of aberrant cells was 5 vs. 3.5 (P<0.05). Further analysis of the inhibited culture data from this and a previous study indicated that years of exposure and smoking increase the risk of aberrations. We conclude that there was no increase in cytogenetic damage among exposed workers compared to controls in the conventional lymphocyte assay. In inhibited cultures, however, there were indications that electromagnetic fields in combination with mineral oil exposure may produce chromosomal aberrations.
Asunto(s)
Aberraciones Cromosómicas , Campos Electromagnéticos , Linfocitos/efectos de la radiación , Aceite Mineral/toxicidad , Exposición Profesional , Adulto , Consumo de Bebidas Alcohólicas , Cromátides/efectos de los fármacos , Cromátides/efectos de la radiación , Café , Estudios Transversales , Reparación del ADN/efectos de los fármacos , Reparación del ADN/efectos de la radiación , Replicación del ADN/efectos de los fármacos , Replicación del ADN/efectos de la radiación , Exposición a Riesgos Ambientales , Humanos , Linfocitos/citología , Linfocitos/efectos de los fármacos , Persona de Mediana Edad , Noruega , Valores de Referencia , Estudios Retrospectivos , Fumar , Encuestas y CuestionariosRESUMEN
In this study, five different oil based adjuvants were compared to assess efficacy and side effects. Mice were injected subcutaneously (s.c.) or intraperitoneally (i.p.) with a weak immunogen (synthetic peptide) emulsified in Freund's adjuvant (FA), Specol, RIBI, TiterMax or Montanide ISA50. Efficacy of adjuvants was evaluated based on their properties to induce peptide specific IgG1, IgG2a and total IgG antibodies, native protein cross-reactive antibodies and cytokine production. Side effects were evaluated based on clinical and behavioural abnormalities, and (histo)pathological changes. Although marked differences in isotype profile and height of titre are observed among the different adjuvants used, we found that FA, Montanide ISA50 and Specol worked equally well in the s.c. and i.p. route, TiterMax functioned only when given i.p. and RIBI also did not perform up to par. The number of cytokine (interferon-gamma and interleukin-4) producing spleen cells was significantly higher after injection of RIBI compared with other adjuvants. Injection of FA or TiterMax resulted in severe pathological changes while after RIBI injection minimal changes were observed. In conclusion, high peptide specific antibody levels with limited side effects can be obtained by s.c. injection of peptide combined with Montanide ISA50 or Specol as alternatives to FA.
Asunto(s)
Adyuvantes Inmunológicos/farmacología , Adyuvantes Inmunológicos/toxicidad , Adyuvantes Inmunológicos/administración & dosificación , Animales , Especificidad de Anticuerpos , Esqueleto de la Pared Celular/administración & dosificación , Esqueleto de la Pared Celular/farmacología , Esqueleto de la Pared Celular/toxicidad , Factores Cordón/administración & dosificación , Factores Cordón/farmacología , Factores Cordón/toxicidad , Reacciones Cruzadas , Citocinas/biosíntesis , Emulsiones , Femenino , Adyuvante de Freund/administración & dosificación , Adyuvante de Freund/farmacología , Adyuvante de Freund/toxicidad , Hidrocarburos/administración & dosificación , Hidrocarburos/farmacología , Hidrocarburos/toxicidad , Inmunoglobulina G/biosíntesis , Inyecciones Intraperitoneales , Inyecciones Subcutáneas , Lípido A/administración & dosificación , Lípido A/análogos & derivados , Lípido A/farmacología , Lípido A/toxicidad , Manitol/administración & dosificación , Manitol/análogos & derivados , Manitol/farmacología , Manitol/toxicidad , Ratones , Ratones Endogámicos BALB C , Aceite Mineral/administración & dosificación , Aceite Mineral/farmacología , Aceite Mineral/toxicidad , Aceites , Ácidos Oléicos/administración & dosificación , Ácidos Oléicos/farmacología , Ácidos Oléicos/toxicidad , Péptidos/inmunología , Poloxaleno/administración & dosificación , Poloxaleno/farmacología , Poloxaleno/toxicidad , Polisorbatos/administración & dosificación , Polisorbatos/farmacología , Polisorbatos/toxicidad , Bazo/citología , Bazo/inmunologíaRESUMEN
Many different agents, including mineral oil and silicone, have the capacity to act as immunological adjuvants, i.e., they can contribute to the activation of the immune system. Some adjuvants, including mineral oil, are known to induce arthritis in certain strains of rats after intradermal injection or percutaneous application. The aim of this study was to determine if common commercial cosmetic products containing mineral oil could induce arthritis in the highly susceptible DA (Dark Agouti) rat. Intradermal injection of five out of eight assayed cosmetic products without further additives resulted in arthritis with synovitis. One of the products induced a very aggressive arthritis, which had declined after 5-9 weeks. When this product was also assayed for arthritogenicity upon percutaneous administration, it induced a mild and transient arthritis in 5 out of 10 DA rats, whereas control animals showed no clinical signs of joint involvement. No arthritic reaction was seen in rats after peroral feeding with the most arthritogenic product or by intravaginal application of Freund's adjuvants. Silicone gel implants in DA rats did not cause arthritis. We conclude that mineral oils included in common commercially available products retain their adjuvant properties and are arthritogenic in the presently investigated arthritis-prone rat strain. There is yet no evidence that mineral oils present in cosmetics may contribute to arthritis in humans, but we suggest that this question should be subject to further investigation.