Embryo embryotoxicity

Kankaanpaa J, Elovaara E, Hemminiki K, et al. 1979. Embryotoxicity of acrolein, acrylonitrile and acrylamide in developing chick embryos. Toxicol Lett 4 93-96. 

Octamethylcyclotetragermoxane reveals higher embryotoxicity for chicken embryos than acetone31,32. Oral toxicity of hexabutylcyclotrigermoxane and diethylpolygermoxane is low for chickens (2000-4000 mgkg-1)27. 

Korhonen, A., K. Hemminki, and H. Vainio. 1983. Embryotoxic effects of acrolein, methacrylates, guanidines and resorcinol on three day chicken embryos. Acta Pharmacol. Toxicol. 52 95-99. 

Slott, V.L. and B.F. Hales. 1987. Protection of rat embryos in culture against the embryotoxicity of acrolein using exogenous glutathione. Biochem. Pharmacol. 36 2187-2194. 

Korhonen A, Hemminki K, Vainio H. 1983a. Embryotoxic effects of phthalic acid derivatives, phosphates and aromatic oils used in the manufacturing of rubber on three day chicken embryos. Drug Chem Toxicol 6 191-207. 

Embryotoxic effects have occurred in rabbits exposed to hydroxylamine hydrochloride by intracoelomic injection. Subcutaneous or intravenous injection of pregnant rabbits with 50-650mg of hydroxylamine hydrochloride on gestational day 12 caused death or euthanasia of all rabbits within 30 hours. All maternally injected rabbits exhibited severe cyanosis, presumably due to methemoglobinemia. At 8 hours all embryos were dead from cardiovascular effects, which are considered to be secondary to the severe maternal toxicity. 

In Europe, the developmental toxicity testing (including teratogenicity) of new cosmetic ingredients is performed according to the Cosmetics Directive 76/768/EEC only alternatives leading to full replacement of animal experiments should be used. This chapter presents the three scientifically validated animal alternative methods for the assessment of embryotoxicity the embryonic stem cell test (EST), the micromass (MM) assay, and the whole embryo culture (WEC) assay. 

Piersma AH et al (2004) Validation of the postimplantation rat whole-embryo culture test in the international ECVAM validation study on three in vitro embryotoxicity tests. Altern Lab Anim 32 275-307... 

Key words DART, Teratology, Fertility, Preclinical methods. Embryo-fetal development, Embryotoxicity. 

A full embryotoxicity study in the rabbit is comprised of four groups (three treated plus one control) of 22 does each. The aim of this study is to evaluate maternal toxicity and embryo-fetal alterations from at least 16 litters per group. The dosing period, dosing frequency, and the maternal observations are the same as those described for the DRF study. 

Selderslaghs IW et al (2009) Development of a screening assay to identify teratogenic and embryotoxic chemicals using the zebrafish embryo. Reprod Toxicol 28 308-320... 

Yang L et al (2009) Zebrafish embryos as models for embryotoxic and teratological effects of chemicals. Reprod Toxicol 28 245-253... 

Frog embryo teratogenesis assay on Xenopus (FETAX) has been routinely used in oiu laboratory for the last 12 years as a routine developmental toxicity screening test for pharmaceutical candidate compoimds. To date, out of more than 400 candidates tested in FETAX, around 60 have also been evaluated in mammalian embryotoxicity studies according to standard ICH protocols. 

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

NA not available, NC not concluded, ND not determined, Mort. mortality (embryotoxicity), Dysm. dysmorphogenesis, TJteratogenic index Therapeutic axis/targets showed for each of the 58 compounds. FETAX and in ivo data summarized by three main endpoints compound foimd embryo-... 

In 2007, the DART committee held a workshop on alternative assays, which was followed up by a workshop held at the European Teratology Society Annual Meeting in 2009. These workshops focused on three alternative assays (1) whole embryo culture (WEC), (2) mouse embryonic stem cell tests (mESC), and (3) zebrafish. Each assay was presented and data from users were shared, and strengths and limitations were discussed. It should be noted that the WEC and mESC are validated by ECVAM as alternative embryotoxicity assays. Still, there are numerous research needs before even validated tests can achieve regulatory acceptance. The discussions, conclusions, and recommendations of the 2007 workshop were published by Chapin et al. (14). Bullet lists of next steps to move forward were defined for each assay (14) and are briefly summarized here ... 

Korhonen, A., Hemminki, K. Vainio, H. (1983a) Toxicity of rubber chemicals towards three-day chicken embryos. Scand. J. Work Environ. Health, 9, 115-119 Korhonen, A., Hemminki, K. Vainio, H. (1983b) Embryotoxic effects of phtalic acid derivatives, phosphates and aromatic oils used in the manufacturing of rubber on three day chicken embryos. Drug chem. Toxicol, 6, 191-207... 

Lindenau A Fischer (1996) Embryotoxicity of polychlorinated biphenyls (PCBs) for preimplantation embryos. Reprod Toxicol, 10 227-230. 

Piersma AH, Attenon P, Bechter R, Govers MJAP, Krafft N, Schmid BP, Stadler J, Verhoef A, Verseil C (1995) Interlaboratory evaluation of embryotoxicity in the postimplantation rat embryo culture. Reprod Toxicol, 9 275-280. 

---