RESUMO
Hydrofluoropolyethers (HFPE) are a family of linear oligomeric fluorinated fluids comprising a chain of difluoromethoxy and tetrafluoroethoxy repeating units with terminal OCF2H end groups, each of which contains an isolated hydrogen atom. These fluids have been designed as low environmental impact substitutes for perfluorinated organic substances in a number of applications including heat transfer and fire suppression agents, and as a solvent. The toxicological profile of these new fluids has been evaluated and is presented in this paper. Acute toxicity tests have been performed on Sprague-Dawley Crl: CD (SD) BR rats using oral, dermal, and inhalation routes. No deaths were recorded even at the highest tested concentrations, and the resultant LD50/LC50 values were >5000 mg/kg (oral), >2000 mg/kg (dermal), and >26,411 ppm (inhalation: reversible anaesthetic effects, e.g., lethargy, seen at this exposure concentration). Other short-term tests (skin and eye irritation, skin sensitisation, genotoxicity tests in vitro and in vivo, cardiac sensitisation) were also performed, and no hazardous properties were identified. Effects of repeated exposure by inhalation were examined in rats over test periods of 5, 14, 28, and 90 days. Effects on embryo-foetal development in the rat have also been studied. The 28-day, 90-day and developmental studies were performed using nominal HFPE concentrations of 1000, 3300, and 10,000 ppm (6h/day: actual exposures confirmed by test atmosphere analysis), and the highest tested concentration proved to be an NOAEL in each study. Major observed effects were elevated urinary (inorganic) fluoride levels and increased liver weights with centrilobular hepatocyte hypertrophy (considered an adaptive response, linked to hepatic metabolism of absorbed material).
Assuntos
Compostos de Flúor/toxicidade , Fígado/patologia , Polímeros/toxicidade , Animais , Desenvolvimento Embrionário , Éteres , Feminino , Fluoretos/urina , Exposição por Inalação , Dose Letal Mediana , Masculino , Nível de Efeito Adverso não Observado , Ratos , Ratos Sprague-Dawley , Medição de RiscoRESUMO
A GLP OECD guideline study was conducted to evaluate the subchronic toxicity of hydrogen peroxide (HP) when administered continuously in the drinking water of catalase-deficient (C57BL/6N) mice and reversibility of toxic effects. Groups of mice (15/sex/group) received solutions of 0, 100, 300, 1000 or 3000 ppm HP in distilled water for 13 weeks; five/sex/group continued on untreated distilled water for an additional 6 weeks. Animals drinking 3000 ppm HP exhibited depressed water and food consumption and body weight. Females drinking 1000 ppm HP had reduced water consumption with intermittent effects on food consumption, but no body weight effects. HP administration did not produce any mortality, clinical signs, hematological effects or organ weight effects on brain, liver, kidneys, adrenals, testes, heart or spleen. Total protein and globulin were depressed among high dose males. Mild to minimal duodenal mucosal hyperplasia was noted in animals receiving 1000 and 3000 ppm HP and one male receiving 300 ppm for 13 weeks. There were no other histopathological findings. All effects noted during the treatment period, including the duodenal hyperplasia, were reversible during the 6-week recovery period. Females dosed with 300-3000 ppm HP during the treatment period showed increased water consumption during the recovery period. The no-observed-effect level (NOEL), based on duodenal mucosal hyperplasia, is 100 ppm in drinking water or 26 and 37 mg/kg/day HP, respectively, for males and females.
Assuntos
Acatalasia , Peróxido de Hidrogênio/toxicidade , Animais , Peso Corporal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ingestão de Líquidos/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Feminino , Peróxido de Hidrogênio/análise , Hiperplasia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Masculino , Camundongos , Nível de Efeito Adverso não Observado , Fatores Sexuais , Água/análiseRESUMO
HCFC 123 is one of the chemicals being developed as a replacement for CFC 11 in refrigerant and solvent applications. Supplementing earlier rat teratology studies, a rabbit inhalation teratology study was conducted. In addition, one-generation and two-generation inhalation reproduction studies were conducted. In the teratology study, the pregnant rabbits were exposed to levels of 0 (control), 500, 1500, and 5000 ppm, 6 hr per day from Days 6 through 18 of gestation. Slight body weight losses and reduced food consumption were seen in does in all three exposure level groups. This response followed an exposure-related pattern. There were no other signs of maternal toxicity. There was also no evidence of treatment-related effects on the kits. A probe one-generation reproduction study was conducted. In this study four groups of 12 male and 12 female rats were exposed to vapors of HCFC 123 6 hr per day, 7 days per week from 4 weeks prior to mating through weaning of their offspring. The exposure levels for this study were 0 (control), 300, 1000, and 5000 ppm. There were no effects on mating and fertility, or on pup survival or birth weight. A two-generation study was subsequently conducted. In this study, five groups of 32 male and female rats were exposed to HCFC 123 from 6 weeks of age through weaning. From the offspring of these animals, groups of 28 males and females were selected for the F1 generation. These animals were exposed to HCFC 123 from weaning (4 weeks of age) through weaning of the F1 generation. All exposures were 6 hr per day, 7 days per week. The exposure levels for this study were 0 (control), 30, 100, 300, and 1000 ppm. There were no effects on any of the fertility or reproductive indices measured. As with prior studies, decreases in serum triglyceride levels were seen. Pup survival and birth weight were unaffected by treatment. Pup body weight gain was lower in all treatment groups during nursing, following an exposure-related pattern. Since weight gain for the F1 animals was normal following weaning, this depression of body weight gain may be related to the depression of serum triglycerides. In addition, liver weights of the adult rats exposed to levels of 100 ppm and higher of HCFC 123 were higher than controls, histological examination revealed only hepatic enlargement and vacuolation. It was concluded that exposure to HCFC 123 did not cause reproductive effects although it did effect the body weight gain of the offspring during lactation.
Assuntos
Anormalidades Induzidas por Medicamentos/patologia , Clorofluorcarbonetos/toxicidade , Reprodução/efeitos dos fármacos , Administração por Inalação , Animais , Peso Corporal/efeitos dos fármacos , Clorofluorcarbonetos/administração & dosagem , Etano Clorofluorcarbonos , Feminino , Hormônios/sangue , Tumor de Células de Leydig/induzido quimicamente , Tumor de Células de Leydig/patologia , Tamanho da Ninhada de Vivíparos/efeitos dos fármacos , Masculino , Exposição Materna , Exposição Paterna , Gravidez , Coelhos , Ratos , Ratos Sprague-Dawley , Maturidade Sexual/efeitos dos fármacos , Especificidade da EspécieRESUMO
Fomblin HC products are a 'family' of high-purity perfluoropolyethers manufactured for barrier cream and other personal care applications which involve direct application to the skin. To confirm the safety of such use, representative Fomblin HC products were tested in experimental animals for acute toxicity, primary and repeated insult irritancy, sensitization and photosensitization, subacute oral toxicity and comedogenicity; mutagenicity was examined in vitro, and irritancy or sensitization was also investigated on human skin (in patch tests with volunteers). A high molecular weight Fomblin HC only was tested in rats for subacute oral toxicity and in man for dermal effects. Single oral doses of 15 g/kg body weight were without evident toxicity to rats, as were single dermal applications or an ip injection at 5 g/kg. No primary irritant action was seen in rabbits or man, and similarly there was no evidence of skin sensitization or photosensitization in guinea pigs, or sensitization in man. No mutagenic action on Salmonella strains of tester bacteria was seen. In repeat dose irritancy or oral toxicity tests in rabbits or rats, no adverse effects of Fomblin HC products were noted; in particular, daily oral administration (1000 mg/kg/day) to rats over 28 days produced no significant reaction. No comedogenic action was found. From the known chemistry of the perfluoropolyethers, the test programme reported here and the limited published data, it is concluded that the intended use of Fomblin HC products in formulations applied to human skin has a high margin of safety.
Assuntos
Éteres/toxicidade , Fluorocarbonos/toxicidade , Polímeros/toxicidade , Adulto , Idoso , Animais , Bile/química , Fármacos Dermatológicos/toxicidade , Emolientes/toxicidade , Éteres/química , Feminino , Fluoretos/análise , Fluoretos/sangue , Fluoretos/urina , Fluorocarbonos/química , Cobaias , Humanos , Irritantes/toxicidade , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/efeitos dos fármacos , Testes do Emplastro , Transtornos de Fotossensibilidade/induzido quimicamente , Coelhos , Ratos , Pele/efeitos dos fármacos , Testes de ToxicidadeRESUMO
Acute, subacute, and subchronic inhalation toxicity studies, developmental toxicity studies, a cardiac sensitization evaluation, and mutagenicity assays were conducted with pentafluoroethane (HFC-125). In the acute study, rats were exposed to a single concentration of 800,000 ppm for 4 hr. Ataxic gait and abnormal respiration were observed during exposure but not after exposure. There was no mortality or other signs of toxicity. Repeated exposures of rats to 50,000 ppm, 6 hr/day, 5 days/week for either 4 or 13 weeks elicited no effects on body weight, food consumption, clinical signs, hematology, biochemistry, urinalysis, organ weight, or tissue morphology. Positive evidence of cardiac sensitization in response to an intravenous epinephrine challenge in dogs was seen at 100,000 ppm and above, but not at 75,000 ppm. HFC-125 was not mutagenic in Salmonella typhimurium and Escherichia coli strains at concentrations of 20 to 100% (v/v) with and without activation. No evidence of clastogenic activity was observed in cultured Chinese hamster ovary (CHO) cells or human lymphocytes at < or = 70% HFC-125 when treatments were conducted for 3-4 hr with activation or for 24 and 48 hr (human lymphocytes only) without activation. However, a statistically significant increase in chromosomally aberrant cells was observed in CHO cells at 60% HFC-125 when treatment without activation was extended to 48 hr. The biological significance of this effect is questionable since signs of severe toxicity were also present. In vivo, no micronuclei were induced in mouse bone marrow at concentrations as high as 600,000 ppm HFC-125 for a 6-hr exposure. In addition, HFC-125 did not induce embryotoxic or teratogenic effects in either the rat or the rabbit at exposure concentrations as high as 50,000 ppm.
Assuntos
Fluorocarbonos/toxicidade , Testes de Toxicidade , Anormalidades Induzidas por Medicamentos , Administração por Inalação , Animais , Peso Corporal/efeitos dos fármacos , Medula Óssea , Células CHO/efeitos dos fármacos , Cricetinae , Cães , Desenvolvimento Embrionário e Fetal/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Feminino , Fluorocarbonos/administração & dosagem , Coração/efeitos dos fármacos , Humanos , Linfócitos/efeitos dos fármacos , Masculino , Testes para Micronúcleos , Testes de Mutagenicidade , Gravidez , Coelhos , Ratos , Ratos Sprague-Dawley , Salmonella typhimurium/efeitos dos fármacosRESUMO
Polyester and acrylic fibers often have prolonged contact with human skin: the sucking of childrens' toys may lead to ingestion. During manufacture, occupational exposure to fiber components may occur. An evaluation of these possible hazards was undertaken by data appraisal, chemical analyses, and animal plus human testing. Occupational exposure limits have already been set for the chemicals used in polymer manufacture. Finishing agents (applied to the fibers) were examined in bacterial mutation and rat acute oral toxicity tests. Finished fibers were tested for acute toxicity and then for sensitizing potential (on guinea pig skin). Human volunteer trials for skin irritance and sensitization followed. No adverse reactions were seen. Only when fibers were burnt was toxicity seen: smoke from acrylic fiber proved more toxic than that from polyester fiber (due principally to hydrogen cyanide release). Migration tests showed that little material leached out from the fibers: < 1 mg/dm2 surface area in saline, 0.4 mg/dm2 from acrylic fibers in methanol, 3.6 mg/dm2 from polyester fibers in chloroform. Analysis showed only fiber polymer components and finish in saline and methanol leachates. Whilst further testing may be required for areas of special concern, since only a limited range of biological endpoints have been addressed, it is concluded that current and foreseeable future uses of these chemical fibers pose little or no toxicological hazard.
Assuntos
Acrilonitrila/toxicidade , Qualidade de Produtos para o Consumidor , Poliésteres/toxicidade , Têxteis/toxicidade , Compostos de Vinila/toxicidade , Acrilonitrila/química , Animais , Feminino , Tecnologia de Alimentos , Cobaias , Humanos , Masculino , Poliésteres/química , Ratos , Salmonella typhimurium/efeitos dos fármacos , Fumaça , Têxteis/normas , Compostos de Vinila/químicaRESUMO
Animal studies were carried out using an oral solution of a low osmolality non ionic contrast medium iopamidol, developed for gastrointestinal examinations. The new formulation was evaluated for image quality in studies of the upper and lower gastrointestinal tract. Margins of safety were defined by subjecting the compound to a number of toxicological and pharmacological experiments. The experiments were designed to reveal qualitative and quantitative differences between the formulation of iopamidol and Gastrografin, a conventional ionic contrast medium. The results indicate that the formulation of iopamidol is safer than a conventional hypertonic water soluble contrast medium and diagnostically superior in the gastrointestinal tract examinations.