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991.
992.
993.
Two hundred and three human volunteers were tested for evidence of sensitization to several plasticizers following 3 weeks of dermal application three times a week. Tris(2-ethylhexyl)mellitate (TOTM; 1%, v/v), 2,2,4-trimethyl-1,3-pentanediol-diisobutyrate (TXIB; 1%, v/v), di(2-ethylhexyl)terephthalate (DEHT; 0.5%, v/v) and diethylphthalate (DEP; 2%, v/v) were applied to the skin of volunteers under semi-occlusive patch for 3 consecutive weeks and the reactions to a challenge application noted following a 2-week rest period. Slight erythema was observed in four individuals exposed to TOTM, two of which resolved within 96 h and one that occurred only after 96 h. Slight erythema was noted in three subjects exposed to TXIB, one of which resolved by 96 h and one that occurred only after 96 h. Two subjects had slight erythema to DEHT, one that resolved by 96 h and one that occurred only after 96 h. One reaction occurred with DEP at 96 h after challenge. Of the positive responses, one subject reacted to all test substances. No subject had a response grade of 1.0 or greater. Because of the low response, the overall conclusion is that none of the plasticizers demonstrated evidence of sensitization or irritation. 相似文献
994.
995.
Van Buskirk Glenn A. González Mario A. Shah Vinod P. Barnhardt Scott Barrett Colin Berge Stephen Cleary Gary Chan Keith Flynn Gordon Foster Thomas Gale Robert Garrison Raymond Gochnour Scott Gotto Amanda Govil Sharad Gray Vivian A. Hammar James Harder Samuel Hoiberg Charles Hussain Ajaz Karp Carol Llanos Hector Mantelle Juan Noonan Patrick Swanson David Zerbe Horst 《Pharmaceutical research》1997,14(7):848-852
Pharmaceutical Research - 相似文献
996.
997.
Summary The effectiveness of a surveillance program for breast cancer recurrence in extending survival is predicated on two assumptions: 1) most recurrences are detected at an early stage at surveillance visits; and 2) the early treatment of recurrence offers a better chance of cure or longer survival. However, the data suggest that neither of these two assumptions is correct, and that postoperative follow-up of patients with breast cancer is expensive and does not significantly extend survival.This minisymposium was presented December 8, 1992, at the annual San Antonio Breast Cancer Symposium, and was sponsored by educational grants from Amgen and from Bristol-Myers Oncology Division. 相似文献
998.
Vanessa Vu J. Carl Barrett Joseph Roycroft Loretta Schuman David Dankovic Paul BBaro Ted Martonen William Pepelko David Lai 《Regulatory toxicology and pharmacology : RTP》1996,24(3):202-212
On May 8–10, 1995, a workshop on chronic inhalation toxicity and carcinogenicity testing of respirable fibrous particles was held in Chapel Hill, North Carolina. The workshop was sponsored by the Office of Pollution Prevention and Toxics, U.S. Environmental Protection Agency (EPA), in collaboration with the National Institute of Environmental Health Sciences (NIEHS), the National Institute for Occupational Safety and Health (NIOSH), and the Occupational Safety and Health Administration (OSHA). The goal of the workshop was to obtain input from the scientific community on a number of issues related to fiber testing. Major issues for discussion were: (i) the optimal design and conduct of studies of the health effects of chronic inhalation exposure of animals to fibers; (ii) preliminary studies which would be useful guides in designing the chronic exposure study; (iii) mechanistic studies which would be important adjuncts to the chronic exposure study to enable better interpretation of study results and extrapolation of potential effects in exposed humans; and (iv) available screening tests which can be used to develop a minimum data set for (a) making decisions about the potential health hazard of the fibers and (b) prioritizing the need for further testing in a chronic inhalation study. After extensive discussion and debate of the workshop issues, the general consensus of the expert panel is that chronic inhalation studies of fibers in the rat are the most appropriate tests for predicting inhalation hazard and risk of fibers to humans. A number of guidances specific for the design and conduct of prechronic and chronic inhalation studies of fibers in rodents were recommended. For instance, it was recommended that along with other information (decrease in body weight, systemic toxicity, etc.), data should be obtained on lung burdens and bronchoalveolar lavage fluid analysis to assist in establishing the chronic exposure levels. Lung burden data are also important for quantifying aspects of risk assessment related to dosimetric adjustments before extrapolation. Although mechanistic studies are not recommended as part of the standard chronic inhalation studies, the expert panel stressed the need for obtaining mechanistic information as far as possible during the course of subchronic or chronic inhalation studies. At present, no single assay and battery of short-term assays can predict the outcome of a chronic inhalation bioassay with respect to carcinogenic effects. Meanwhile, several short-termin vitroandin vivostudies that may be useful to assess the relative potential of fibrous substances to cause lung toxicity/carcinogenicity have been identified. 相似文献
999.
1000.
Surber Christian Wilhelm Klaus-P. Bermann David Maibach Howard I. 《Pharmaceutical research》1993,10(9):1291-1294
Etretinate and acitretin are given orally to treat psoriasis and various keratinization disorders. Acitretin, the main active metabolite of etretinate, has the pharmacokinetic advantage of being rapidly eliminated, but it shares etretinate's toxicologic profile. Thus a topical delivery of acitretin with no or reduced systemic adverse effects is desirable. To characterize the therapeutic potential of topically delivered acitretin, we quantitatively assessed its percutaneous penetration in healthy human volunteers. Additionally, three skin sampling techniques, the punch biopsy, the shave biopsy, and the suction blister technique, were validated to quantitate acitretin in the skin. The results suggest that topical delivery of acitretin renders skin concentrations which exceed those reported after oral administration of etretinate or acitretin. However, because of possible interlaminate drug contamination, drug localization within a particular skin compartment cannot be determined. 相似文献