Reproductive toxicity teratogenesis

Tests of neonicotinoids for neurotoxicity, reproductive toxicity, teratogenesis and mutagenesis in a... 

Key words FETAX, Frog, Embryo, Teratogenesis, Xenopus, Developmental and reproductive toxicity, Predictivity, Embryotoxicity... 

REPRODUCTION, MUTAGENESIS, TERATOGENESIS, FERTILITY AND FETAL TOXICITY... 

The topic of teratogenesis as a disruption of the control of embryological development is covered later in this chapter. Safety screening requires evaluation of developmental and reproductive toxicity of the compounds of interest [5],... 

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). 

A review of reproductive and developmental toxicity studies of methyl salicylate indicated that, under conditions of sufficient exposure, there is a pattern of embryotoxicity and teratogenesis that is similar to that caused by comparable doses of salicylic acid. The abnormalities included neural tube defects and malformations of the skeleton and viscera. Studies of orally administered methyl salicylate indicated that the no-observed-adverse-effect level (NOAEL) for reproductive toxicity is 75-100 mg/kg daily, which is a level consistent with data from subchronic and chronic toxicity studies and is also consistent with the reproductive NOAEL for salicylic acid, which has been reported as 80 mg/kg daily (Belsito et al. 2007). 

It is possible to perform a one-generation reproduction test (Table XVI) which would assess the impact of all ST and LT toxic effects on mating, fertility, fetal toxicity, dominant lethal mutagenesis, teratogenesis, gestational and post-natal effects on survival, growth, lactation, etc., in a period of four to five months. 

Much of the evidence for the adverse reproductive effects of selected toxicants will be based on cases involving wildlife exposures to environmental contaminants or on the experimental results of research exposing laboratory animals to large, pharmacological doses of potential toxicants. When available, data will be presented from accidental or intentional human and domestic animal exposures to toxicants associated with riot control and chemical warfare or with environmental catastrophes where incidences of infertility, abortion, and teratogenesis have been traced over the course of a number of years. 

Trosko JE, Chang CC, and Upham B (2002) Modulation of gap junctional communication by epigenetic toxicants A shared mechanism in teratogenesis, carcinogenesis, at-herogenesis, immunomodulation, reproductive- and ne-uro-toxicities. In Wilson SH and Suk WA (eds.) Biomarkers of Environmentally Associated Diseases, pp. 445—454. Boca Raton, FL Lewis Publishers. 

Recent additions to the toxicity test protocols may now require formulized examinations for genetic effects (i.e., teratogenesis, mutagenesis, reproduction) as well as determination of the metabolic alterations of the additive and their disposition. Each of these activities has become an important sub-branch of toxicity testing. 

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