Abstract:
:Recently, considerable attention has been focused on certain environmental contaminants--"endocrine disruptors"--of industrial origin that may mimic the action of sex hormones. Natural compounds and their effects on other types of hormonal activity (eg, on adrenal or thyroid function) have for some reason not provoked similar attention. As exemplified by tributyltin and certain bioaccumulating chlorinated compounds, available evidence indicates that "endocrine disruption" caused by xenobiotics is primarily an ecotoxicologic problem. In mammals, certain phenylmethyl-substituted siloxanes have been found to be by far the most potent endocrine disrupters among various synthetic xenobiotics. On the other hand, it has not been possible to scientifically substantiate either certain alarming reports of powerful synergistic effects between chlorinated pesticides or the alleged adverse effects on the male reproductive tract in rodents (induced by alkylphenols and plasticizers at extremely low exposures). Whereas there is compelling evidence that estrogens in certain foods and herbal medicines can induce hormonal changes in women as well as overt toxicity in men, existing data are insufficient to support a causal relationship between exposure of the general human population to nonpharmaceutical industrial chemicals and adverse effects operating via the endocrine system. Moreover, in terms of magnitude and extent, all such exposures to so-called endocrine disruptors are dwarfed by the extensive use of oral contraceptives and estrogens for treatment of menopausal and postmenopausal disorders. Also, the exposure to hormonally active xenobiotics is virtually insignificant when compared with the intake of the phytoestrogens that are present in food and beverages, and it is even more insignificant when compared with certain herbal potions used in "alternative medicine." Furthermore, while there has been much concern about negligible exposures to xenobiotics with weak hormonelike activities, the potent endocrine disruptor licorice is freely given to children. Long-term exposure to this substance induces severe toxic symptoms of mineral corticoid hormone imbalance. Although exposures to xenobiotics and many natural compounds occur by identical routes of administration and may contribute to the same toxicological end point, they are, regrettably, judged by completely different standards. As is the case with all other chemicals, rational risk assessment and risk management of man-made and natural endocrine modulators must be based on the mode of action and dose-response relationships. Such end points as the induction of reproductive developmental effects, cancer, etc, relating to actual exposures must also be taken into consideration.
journal_name
Toxicol Patholjournal_title
Toxicologic pathologyauthors
Nilsson Rdoi
10.1177/019262330002800311subject
Has Abstractpub_date
2000-05-01 00:00:00pages
420-31issue
3eissn
0192-6233issn
1533-1601journal_volume
28pub_type
杂志文章,评审abstract::In preclinical safety studies, drug-induced vascular injury can negatively impact candidate-drug selection because there are no obvious diagnostic markers for monitoring this pathology preclinically or clinically. Furthermore, our current understanding of the pathogenesis of this lesion is limited. While vasodilatatio...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1080/01926230500512076
更新日期:2006-01-01 00:00:00
abstract::A significant correlation exists between average daily food consumption and 2-yr survival in control ad libitum (AL)-fed Sprague-Dawley (SD) rats. SD rats were fed Purina Rodent Chow 5002 or a modified chow, 5002-9, with lower protein, fat, metabolizable energy and increased fiber AL or by dietary restriction (DR) to ...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339402200308
更新日期:1994-05-01 00:00:00
abstract::There is increased interest to use minipigs in ocular toxicology studies due to their anatomical similarities with human eyes and as a substitute for nonhuman primates. This requires adaptation of enhanced optical coherence tomography (OCT) techniques and of ocular relevant immunohistochemistry (IHC) or in situ hybrid...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623315615553
更新日期:2016-04-01 00:00:00
abstract::Swine, especially the miniature swine or minipigs, are increasingly being used in preclinical safety assessment of small molecules, biopharmaceutical agents, and medical devices as an alternate nonrodent species. Although swine have been used extensively in biomedical research, there is a paucity of information in the...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623315611762
更新日期:2016-04-01 00:00:00
abstract::Epidemiological associations have been made between the new onset of childhood rhinitis/asthma and exposures to elevated ambient levels of ozone, a commonly encountered gaseous air pollutant. Our laboratory was the first to find that mice repeatedly exposed to ozone develop nasal type 2 immunity and eosinophilic rhini...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/0192623319873872
更新日期:2019-12-01 00:00:00
abstract::Cancer affects approximately 1 in 3 individuals. An individual's susceptibility to cancer is partly determined by environmental exposures and by the combination of inherited cancer susceptibility and resistance genes. Initial mapping of these low penetrance cancer susceptibility genes has been done in the mouse becaus...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1080/01926230490424716
更新日期:2004-03-01 00:00:00
abstract::Interrelationships among induction of cytochrome P-450 (CYP) 1A1/2, decrease in connexin 32 (Cx32), and liver tumor-promoting activity by beta-naphthoflavone (BNF) in the promotion stage were examined in a 2-stage liver carcinogenesis model. A total of 20 male Fischer 344 rats were initiated with a single intraperiton...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262330002800406
更新日期:2000-07-01 00:00:00
abstract::Over the past decade, laser capture microdissection (LCM) has grown as a tool for gene expression profiling of small numbers of cells from tumor samples and of specific cell populations in complex tissues. LCM can be used to study toxicant effects on selected cell populations within the testis at different stages of s...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623314526319
更新日期:2014-12-01 00:00:00
abstract::A comparative study of histochemical detection of eosinophils in fixed murine tissue is lacking. Five histochemical methods previously reported for eosinophil detection were quantitatively and qualitatively compared in an established murine RSV vaccine-enhanced inflammation model. Nonspecific neutrophil staining was e...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623308329342
更新日期:2009-02-01 00:00:00
abstract::Histopathology of the reproductive system of 76 young adult Dutch Belted and 22 young adult or adult male New Zealand White rabbits was conducted as part of fertility studies. Thirty-five (46%) of the Dutch Belted and 11 (50%) of the New Zealand White males had multifocal vesicular gland basal epithelial cell atypia a...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262338501300309
更新日期:1985-01-01 00:00:00
abstract::Cardiac troponin (cTn) is a sensitive and specific biomarker for assessing cardiac damage and should be utilized in drug safety assessment. Lactate dehydrogenase and creatine kinase isoenzyme analyses have historically been used in pre-clinical toxicity testing to assess cardiac injury, but since these assays are less...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623310382438
更新日期:2010-12-01 00:00:00
abstract::Recent advances in immunocytochemical techniques allow the localization of specific antigens in tissue sections. The work reported here attempts to evaluate the application of antibody-labeled, disease-related protein, followed by microscopy and computerized image analysis. Using an experimental anti-tumor, polyclonal...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262338701500308
更新日期:1987-01-01 00:00:00
abstract::Many common inflammatory disorders are characterized by the infiltration of neutrophils across epithelial lined (mucosal) surfaces resulting in disruption of critical barrier function that protects from microbes and noxious agents. In such conditions, disease symptoms are complex but directly related to leukocyte effe...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/0192623313511336
更新日期:2014-01-01 00:00:00
abstract::Cells have to double their protein mass in order to divide. Whether this is achieved through increased synthesis (PS), decreased degradation (PD), or a combination of both is still debated. Likewise open are other basic questions: whether, beyond differences relating to growth phase (GP) or rate, reduced PD rates are ...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262338401200312
更新日期:1984-01-01 00:00:00
abstract::Mixed-function oxidase (MFO) induction in the mouse liver results in a rapid and sustained centrilobular hypertrophy associated with a hyperplastic response. In many studies, the long-term sequela of prolonged exposure is an increased incidence of lesions considered to be adenomas. Studies have shown in aged control m...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/019262339602400411
更新日期:1996-07-01 00:00:00
abstract::Histopathology is a widely used approach to evaluate effects of endocrine-active chemicals in the thyroid. However, effects at an ultrastructural level have hardly been examined in fish thyroids. In the present study, zebrafish was exposed to sublethal concentrations of propylthiouracil (PTU; 0-50 mg/L) and perchlorat...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623317721748
更新日期:2017-07-01 00:00:00
abstract::Oxymetholone has been identified as a suspected nongenotoxic carcinogen and has recently completed testing in a conventional National Toxicology Program (NTP) 2-yr rodent bioassay program. As a synthetic androgen with a limited historical database in toxicology, oxymetholone is an ideal candidate for prospective exami...
journal_title:Toxicologic pathology
pub_type: 评论,杂志文章
doi:10.1177/019262339902700503
更新日期:1999-09-01 00:00:00
abstract::Perfluorooctanoic acid (PFOA) is a chemical used in the production of fluoropolymers. Its persistence in the environment and presence in humans and wildlife has raised health concerns. Liver tumor induction by PFOA is thought to be mediated in rodents by PPAR-alpha. A recent US EPA scientific advisory board questioned...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623308318216
更新日期:2008-06-01 00:00:00
abstract::Spontaneous neoplasm rates were determined for control Fischer 344 (F344) rats and B6C3F1 mice from 2-yr rodent carcinogenicity studies carried out by the National Toxicology Program (NTP). The most frequently occurring neoplasms in untreated male F344 rats were testicular adenoma (89.1%), mononuclear cell leukemia (5...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339802600318
更新日期:1998-05-01 00:00:00
abstract::Alternate transgenic mouse models are accepted as replacements for the standard carcinogenicity mouse bioassay by regulatory agencies with a companion 2-year rat bioassay. The slower rate of industry acceptance of these shorter transgenic mouse cancer bioassays has been due to lack of historical data and diagnostic cr...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623311436181
更新日期:2012-06-01 00:00:00
abstract::This is a survey of the results of recent investigations on gastrointestinal (GI) peptide hormones. In addition to the classical GI hormones (secretin, gastrin, and cholecystokinin-pancreozymin (CCK-PZ], there are at least nine other peptides whose structures and GI effects are known. These include vasoactive intestin...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/019262338801600203
更新日期:1988-01-01 00:00:00
abstract::The histologic effect of 400 mg/M2/day of hydrocortisone, given alternatively from day 7 to day 19 after birth, was studied on the spleen of the immunologically immature rat. Two days after the cessation of treatment, the periarteriolar lymphatic sheaths were found to be largely depleted of small lymphocytes. Immunope...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339302100406
更新日期:1993-01-01 00:00:00
abstract::Hyaline droplet formation in the proximal tubular cells of the kidney commonly occurs under different pathological conditions in experimental animals. In rats, intracytoplasmic hyaline droplet formation is predominantly associated with accumulation of the male rat-specific alpha(2u)-globulin, whereas under other (path...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230390213775
更新日期:2003-07-01 00:00:00
abstract::Pentostatin, an adenosine deaminase inhibitor, has been approved for the treatment of refractory hairy cell leukemia. In a preclinical toxicity study, Wistar rats were administered 0, 1, 10, 25, and 50 mg/kg (0, 6, 60, 150, and 300 mg/m2, respectively) pentostatin intravenously once a week for 26 wk (1.5-75-fold above...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339402200506
更新日期:1994-09-01 00:00:00
abstract::The spleen is the largest secondary lymphoid organ, is considered the draining site for compounds that are administered intravenously, and is therefore considered an important organ to evaluate for treatment-related lesions. Due to the presence of B and T lymphocytes, the immunotoxic effects of xenobiotics or their me...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1080/01926230600865523
更新日期:2006-01-01 00:00:00
abstract::Phentolamine is a reversible competitive alpha-adrenergic antagonist with similar affinities for alphal and alpha2 receptors. It has a long history of safe clinical use, and was developed as a potential therapy for male erectile dysfunction because of its capacity to increase the arteriolar blood flow to the corpora c...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230490505086
更新日期:2004-09-01 00:00:00
abstract::The spleen contains hematopoietic and lymphoid elements, is a primary site of extramedullary hematopoiesis, and removes degenerate and aged red blood cells as well as particulate materials and circulating bacteria from the blood supply. Lesions of this important component of the immune system may center on the red pul...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1080/01926230600867750
更新日期:2006-01-01 00:00:00
abstract::We describe 2 cases of a relatively rare tumor diagnosed as pituicytoma in the pars nervosa of rat pituitary. This tumor was spontaneously noted in one 110-week-old female and one 109-week-old male Fischer 344 (F344)/DuCrj rats during 2-year carcinogenicity studies. Although no gross abnormality of the pituitary was d...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262330002800612
更新日期:2000-11-01 00:00:00
abstract::In tissue slice models, interactions between the heterogeneous cell types comprising the lung parenchyma are maintained thus providing a controlled system for the study of pulmonary toxicology in vitro. However, validation of the model in vitro system must be affirmed. Previous reports, in in vivo systems, have demons...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230390183689
更新日期:2003-03-01 00:00:00
abstract::Developmental exposure to estrogenic chemicals is an established risk factor for cancer of the female reproductive tract. This increase in risk has been associated with disruption of normal patterns of cellular differentiation during critical stages of morphogenesis. The goal of this study was to document uterine epit...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623318779326
更新日期:2018-07-01 00:00:00