Relative induction potencies

In vivo studies in animals suggest that endosulfan may disrupt normal reproductive hormone levels in male animals, but that it is not an endocrine disrupter in females. Persistent depressed testicular testosterone was seen in male rats after intermediate duration oral exposures to endosulfan. In ovariectomized female rats, orally administered endosulfan did not induce normal development of female reproductive tissues, and in female mice and immature female rats, acute parenteral exposure to endosulfan did not affect several endocrine-related end points. In vitro studies have evaluated endosulfan for estrogen receptor (ER) and cytosolic protein binding affinity, ER-mediated reporter gene expression, estrogenic induction of cell proliferation, and alteration of relative abundance of active estradiol metabolites. Overall, in vitro evidence in favor of endosulfan estrogenicity indicates relatively weak potency compared to 17[3-estradiol. Apparently contradictory results were reported in different... 

PCMP was equipotent with (+)PCMP in induction of ataxia (figure 2), Furthermore, TCM, which was one-fifth as potent as PCP in the induction of stereotyped behavior, was as potent as PCP in induction of ataxia. The ability of PCP-like drugs to bind to PCP receptors, as measured by their ability to inhibit the binding of 3H- PC P, was determined as described by Contreras et al. (in preparation). The order of relative potencies of drugs as compared to PCP was TCP > PCE > PCP = NIPCA > dexoxadrol > (+) PCMP > TCM =... 

Horii Y, Khim JS, Higley EB, Giesy JP, Ohura T, Kannan K (2009) Relative potencies of individual chlorinated and brominated polycyclic aromatic hydrocarbons for induction of aryl hydrocarbon receptor-mediated responses. Environ Sci Technol 43(6) 2159-2165. doi 10.102 l/es8030402... 

Induction ofmRNA for pS2 and secretion of cell-type-specific proteins. pS2 was measured in the culture medium of MCF7 cells with the ELSA-pS2 immunoradiometric assay (CIS Bio International, Gif-sur-Yvette, France). Cells were subcultured in 24-well plates for 144 h in 10% CDHuS. The culture medium was centrifuged at 1200g for 10 min to eliminate floating and detached cells. Results are expressed as ng of secreted protein per million cells. The relative-induced protein potency (RIPP) was calculated as 100 X the ratio between the dose of E2 and that of the chemical needed to produce maximal expression of cell-type-specific proteins (pS2). 

Similar to the relative potencies for toxicity, relative potencies for receptor binding, vitellogenin induction and several other ER mediated responses, such as those from the in vitro tests presented in Table 7.3.2... 

The guinea pig intratracheal test has been used to establish the relative potency of different detergent enzymes and establish safe occupational exposure levels. As the name implies, guinea pigs are sensitized by intratracheal exposure and induction of cytophilic antibodies are assessed. Dose responses obtained for new enzymes are compared to a reference enzyme for which safe exposure levels have been established. The relative potency of the new enzyme to this reference is used to establish a safe exposure level for the new enzyme. 

Induction of peroxisome proliferation following treatment with DEHP is not due to the parent compound, but to DEHP metabolites. Studies with MEHP in vitro have demonstrated that the proximate peroxisome proliferators are mono(2-ethyl-5-oxohexyl) phthalate (metabolite VI) and mono(2-ethyl-5-hydroxyhexyl) phthalate, (metabolite IX) and that for 2-ethylhexanol, the proximate proliferator is 2-ethylhexanoic acid (Elcombe and Mitchell 1986 Mitchell et al. 1985a). Similar findings were observed by Maloney and Waxman (1999), who showed that MEHP (but not DEHP) activated mouse and human PPARa and PPARy, while 2-ethylhexanoic acid activated mouse and human PPARa only, and at much higher concentrations. Based on its potency to induce enzyme activities, such as the peroxisomal fatty acid (3-oxidation cycle and carnitine acetyltransferase, DEHP might be considered a relatively weak proliferator. 

Walker JS, Levy G (1989) Induction of experimental thyroid dysfunction in rats with implantable pellets of thyroxine or propylthiouracil. J Pharmacol Meth 21 223-229 Wiberg GS, Carter JR, Stephenson NR (1964) The effects of various goitrogens on the determination of the relative potency of thyroid by the goiter prevention assay. Acta Endocrin 45 370-380... 

Zabel, E.W., R.S. Pollenz and R.E. Peterson. Relative potencies of individual dibenzofuran, and biphenyl congeners and congener mixtures based on induction of cytochrome P4501A mRNA in a rainbow trout gonadal cell line (RTG-2). Environ. Toxicol. Chem. 15 2310-2318, 1996. 

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