摘要:

AbstractFormaldehyde (FA) has been commercially produced since the early 1900s. Its widespread use in a variety of applications is known to result in appreciable exposure of workers and of a section of the general population.Formaldehyde is a normal metabolite in mammalian systems. It occurs in air as a product of the natural photooxidation of automobile exhaust, combustion processes, incinerators; formaldehyde has been found in municipal and industrial effluents and is present in food either naturally (fruits and vegetables, in the order of parts per million), or as a result of its use as a food additive.The use of FA and its derivative, hexamethylenetetramine (HMT), which gradually decomposes to FA under acidic conditions as antimicrobial agents in food, raises questions about their potential chronic oral toxicity.Furthermore, since FA is a very reactive compound and reacts with different macromolecules such as proteins and nucleic acids, the safety evaluation of FA as a cheese additive must take into account the toxicity of the reaction products between FA and milk components.Biochemical aspects, acute and short-term toxicity studies including mutagenicity, multigeneration, and reproduction studies, long-term carcinogenicity studies after oral administration of FA and HMT are reviewed in this paper.The results of these studies indicate that repeated oral exposure of a relatively large amount of FA that could overwhelm the normal metabolic capacity of animals to convert FA into formiate, CO2, and water produces histopathological gastric changes.This paper correlates the hazard caused by the exposure to low levels of FA, as far as its carcinogenic potential by oral route is concerned per se or regarding its use as a food additive.Based on the evidence that FA is formed naturally in food and is a normal mammalian metabolite and that a threshold for carcinogenicity exists both after exposure by inhalation and oral administration, it may be deduced that FA is not carcinogenic at low levels of exposure.

ISSN:1040-8444    

DOI:10.3109/10408449109019569

出版商:Taylor&Francis    

年代:1991

数据来源: Taylor

摘要:

AbstractThe isolated perfused porcine skin flap (IPPSF) is a new perfused skin model which allowsin vitrocutaneous pharmacology and toxicology studies to be conducted in a viable skin preparation which has a normal anatomical structure and a functional microcirculation. the purpose of this review is to (1) outline the background of this field which indicated the need for this type of model; (2) outline the surgical procedures needed to create and harvest viable preparations; (3) overview the criteria (biochemical, physiological, and histological) used to assess viability during an experiment; (4) present results of percutaneous absorption, cutaneous metabolism, transdermal delivery (passive and active), and skin distribution experiments conducted to date; (5) present the strategy developed to quantitate percutaneous absorption and cutaneous drug distribution using compartmental and physiological-based pharmacokinetic models; (6) assess the correlation of IPPSF data toin vivoresults; (7) define the biochemical, physiological and histological (LM, TEM, enzyme histochemistry) response of the IPPSF to topically applied cutaneous vesicants; (8) overview where this type ofin vitromodel fits into the overall framework of cutaneous toxicology and pharmacology research; and (9) out-line possible paths for future development. This review should provide the reader with an appreciation of some unique problems in this field which require anin vitromodel that is closely integrated in structure and function to thein vivosetting.

ISSN:1040-8444    

DOI:10.3109/10408449109019570

出版商:Taylor&Francis    

年代:1991

数据来源: Taylor

摘要:

AbstractA decade ago, the ability of nasal tissues to metabolize inhalants was only dimly suspected. Since then, the metabolic capacities of nasal cavity tissues has been extensively investigated in mammals, including man. Aldehyde dehydrogenases, cytochrome P-450-dependent monooxygenases, rhodanese, glutathione transferases, epoxide hydrolases, flavincontaining monooxygenases, and carboxyl esterases have all been reported to occur in substantial amounts in the nasal cavity. the contributions of these enzyme activities to the induction of toxic effects from inhalants such as benzo-a-pyrene, acetaminophen, formaldehyde, cocaine, dimethylnitrosamine, ferrocene, and 3-trifluoromethylpyridine have been the subject of dozens of reports. In addition, the influence of these enzyme activities on olfaction and their contribution to vapor uptake is beginning to receive attention from the research community. Research in the next decade promises to provide answers to the many still unanswered questions posed by the presence of the substantial xenobiotic metabolizing capacity of the nasal cavity.

ISSN:1040-8444    

DOI:10.3109/10408449109019571

出版商:Taylor&Francis    

年代:1991

数据来源: Taylor

摘要:

AbstractDuring the last few decades, considerable progress has been made in the understanding of the pathophysiological mechanisms of proteinuria. A great variety of hemodynamic or bio-chemical mechanisms acting at different sites of the nephron have been shown to alter the renal handling and the urinary excretion of proteins. the finding which perhaps has had most practical implications is that the pattern of protein excretion quantitatively and qualitatively varies with the site and severity of renal damage. This has led to the development of a large array of methods for the identification and quantitation of specific urinary proteins. These methods have been most extensively used by toxicologists in experimental, epidemiological, or clinical studies on potentially nephrotoxic chemicals (e.g., drugs, heavy metals, solvents, etc.). the present review summarizes the current state of knowledge on the mechanisms of proteinuria and the use of urinary proteins as indicators of nephrotoxicity.

ISSN:1040-8444    

DOI:10.3109/10408449109019572

出版商:Taylor&Francis    

年代:1991

数据来源: Taylor