Placental toxicity

Gupta, R.C. (2007b). Placental toxicity. In Veterinary Toxicology Basic and Clinical Principles (R.C. Gupta, ed.), pp. 245-62. Elsevier Academic Press, New York. 

Another important source of information on the status of alternative test development, with particular emphasis on the requirements for cosmetics testing, is a review paper published in 2011 by Adler and coauthors [9], Table 1 summarizes those relevant for reproductive toxicity. Several assays refer to the detection of endocrine effects on steroidogenesis based on a variety of cell types, and, as already mentioned, they will be dealt with in another chapter of this book. The other tests can be subdivided in placental toxicity/transport, preimplantation toxicity, female and male toxicity, and developmental toxicity. The tests that are suitable for detecting developmental toxicity include the EST, the whole-embryo assay, the micromass test (all three already described above), the zebrafish embryo teratogenicity assay, and the frog embryo teratogenesis assay (FETAX). 

It has been recommended that the dosing interval of pentamidine be extended to 48 hours for patients with a GFR less than 10 ml/min [160]. The recent report of Conte [158], however, suggests that dose reduction of pentamidine for renal impairment is unnecessary. The author noted, however, that his patients had mild to moderate PCP, and that it remains unknown whether the pharmacokinetics of pentamidine might be altered in more severely ill patients. It has been shown that there is minimal transfer of pentamidine to the human fetus and significant concentration of the drug in placental tissue [161]. The last mentioned finding raises an important question about placental toxicity. 

In the assessment of placental toxicology of any foreign chemical substances, there are two major areas of concern what the placenta does to xenobiotics and what xenobiotics do to the placenta (Myllynen et ai, 2005). In the former area the major topics of concern are the entry and possible storage of substances in placental cells and through the placenta, aided perhaps by various transporters and efflux pumps the distribution and binding of compounds in placental cells and biotransformafion of substances by intracellular enzymes. Metabolic activation and production of reactive intermediates by placental enzymes link these areas with toxicodynamics of placental toxicants. In the latter area, effects of compounds on placental blood flow and vasculature and the presence of membrane and intracellular receptors, enzymes, and other potential targets for foreign substances are important areas of inquiry for placental toxicity. 

Depending on the duration, frequency, and level of exposure, anti-AChE pesticides and related compounds can adversely affect one or all three components of the matemal-placental-fetal unit, The outcome of placental toxicity to these pesticides can be Influenced by three major factors maternal toxicity, placental tran.sfer, and placentai-fetal metabolism. Evidence suggests that the pesticide residue is present not only in the exposed mother... 

Gupta, R. C. (1995). Rnvirooincnial agents and placental toxicity Anticholinesterases and other agents. In Placental Toxicology (B. V. R. Sastry. Ed.), pp. 257-278. CRC Press. Boca Raton, FL. 

Pelkonen, O., Vahakangas, K., Gupta, R.C., 2006. Placental toxicity of organophosphate and carbamate pesticides. In Gupta, R.C (Ed.), Toxicology of Organophosphate and Carbamate Compounds Elsevier Academic Press, New York, NY, pp. 463 79. 

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