Pattern of Response of Intact Drosophila to Known Teratogens

Abstract

Drosophila, as the test organism, was used to assess 17 chemicals. The teratogenic potential of 15 of these chemicals is well established from animal studies or human epidemiology. The test involves examination of adult flies following treatment during larval stages of development. Flies are examined for abnormal external morphology. The incidence of abnormalities in treated and control populations is compared using the Chi-square test. All 17 chemicals were active to varying degrees in the test system. Most chemicals produced a unique response yielding individual patterns of abnormalities. These results suggest that Drosophila may have the potential to become a valuable teratogen screen, but further, more rigorous examinationparticularly with nonteratogensis required.

Evaluation of Drosophila for screening developmental toxicants: Test results with eighteen chemicals and presentation of a new Drosophila bioassay

“…Results of testing 17 chemicals which included 15 known mammalian developmental toxicants, 1 negative compound, and 1 weak developmental toxicant were presented. All 17 chemicals showed some activity, and 15/15 of the known developmentally active chemicals induced a statistically elevated incidence of one or more morphological abnormalities in the emergent flies [6].…”

“…In addition, information on the potential developmental toxicity of many chemicals is lacking. Desirable screening tests should be simple, rapid, inexpensive and reliable [6]. Wilson [I] noted that Drosophila had many desirable characteristics as an organism for screening chemicals.…”

“…Encouraging results were obtained which indicated that treatment of Drosophila from the egg through the three larval stages with selected test chemicals produced specific defects in the emerging flies. This work was followed by a preliminary, primarily descriptive, evaluation of Drosophilu's use as a screening organism [6]. Results of testing 17 chemicals which included 15 known mammalian developmental toxicants, 1 negative compound, and 1 weak developmental toxicant were presented.…”

13th Meeting of the Scientific Group on Methodologies for the Safety Evaluation of Chemicals (SGOMSEC): alternative testing methodologies for ecotoxicity.

“…Acute toxicity to fish is required in the (21). Various experiments have shown that this assay can be used as a teratogen screen; in mechanistic studies of abnormal development, it can be used to investigate gene involvement in teratogenic resistance, and the possible role of heat-shock proteins in preventing birth defects (21)(22)(23)(24).…”

The Validation and Use of In Vitro Teratogenicity Tests

“…A new drug (exception life saving indications) will not be administered to women of childbearing potential with the appropriate safety margins or the appropriate safety precautions if it has not proven to be non-toxic to intrauterine development in animal models. A developmentally toxic compound with a (false) negative in vitro result will be identified during further in vivo Renault et al 1989 Brain cell aggregate Differentiation Honegger et al 1979;Honegger and Proliferation Werffeli 1988;Schilter Toxicity 1992, 1993;Kucera et al 1993;Schmid et al 1993 Sleet and Brendel 1983, 1985Lethality Sleet 1992 Cricket embryo Differentiation Walton 1983 Lethality Drosophila embryo Differentiation Schuler et al 1982Schuler et al , 1985Lethality Ranganathan et al 1987 Bumand 1987Bumand , 1988Kucera et al 1993;Schmid et al 1993Birge et al 1983Herrmann 1933Dumont et al 1983Dawson and Bantle 1987;Fort et al 1988New 1978Fantel 1982;Schmid 1985;Sadler et al 1982;Klug et al 1985;Schmid 1987 Naya et al 1991;Ninomiya et al 1993 testing in animal studies (Williams 1994). However, loosing a novel and efficient therapy principle due to false positive in vitro data cannot be accepted.…”