Screening Chemicals for Reproductive Toxicity: The Current Alternatives

Anon. (1994). ECVAM News & Views. ATLA 22, 7–11.

Anon. (1993). A Strategy for the Assessment of the Reproductive Toxicity of New Substances: Risk Assessment of Notified New Substances (Directive 93/67/EEC). Technical Guidance Document, Chapter 8, 14 pp. Brussels: European Commission (DGXI).

Anon. (1993). OECD Guidelines for the Testing of Chemicals, Draft Guideline 421: Reproduction/Developmental Toxicity Screening Test, 8 pp. Paris: OECD.

Anon. (1993). OECD Guidelines for the Testing of Chemicals, Draft Guideline 422: Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test, 8 pp. Paris: OECD.

Villeneuve D.C. , & Koëter H.B.W.M. eds (1993). Proceedings of the International Workshop on In Vitro Methods in Reproductive Toxicology. Reproductive Toxicology 7, Suppl. 1. 1–175.

Anon. (1983). OECD Guidelines for Testing of Chemicals, No. 415 (One-Generation Reproduction Toxicity Study, 8 pp.) and No. 416 (Two-Generation Reproduction Toxicity Study, 8 pp.). Paris: OECD.

Mattison D.R. (1993). Sites of female reproductive vulnerability: implications for testing and risk assessment. Reproductive Toxicology 7, Suppl. 1, 53–62.

Holloway A.J. , Moore H.D.M. , and Foster P.M.D. (1990). The use of in vitro fertilisation to detect reductions in fertility of male rats exposed to 1,3–dinitrobenzene. Fundamental and Applied Toxicology 14, 113–122.

Spielmann H. , and Vogel R. (1989). Unique role of studies on preimplantation embryos to understand mechanisms of embryotoxicity in early pregnancy. Critical Reviews in Toxicology 20, 51–64.

Morrissey R.E. , Schwetz B.A. , Lamb J.C. , Ross M.D. , Teague J.L. , and Morris R.W. (1988). Evaluation of rodent sperm, vaginal cytology and reproductive organ weight from NTP 13-week studies. Fundamental and Applied Toxicology 11, 343–358.

Evenson D.P. , Baer R.K. , and Jost L.K. (1989). Long-term effects of triethylene-melamine exposure on mouse testis cells and sperm chromatin structure assayed by flow cytometry. Environmental and Molecular Mutagenesis 14, 79–89.

Ulbrich B. , and Palmer A.K. (1995). Detection of effects on male reproduction: a literature survey. Journal of the American College of Toxicology 14, 293–327.

Evenson D.P. (1986). Flow cytometry of acridine orange stained sperm is a rapid and practical method for monitoring occupational exposure to genotoxicants. In Monitoring of Occupational Genotoxicants (ed. Sorsa M. , Norppa H. ), pp. 121–132. New York: Alan R. Liss.

Evenson D.P. , Higgins P.H. , Grueneberg D. , and Ballachey D.E. (1985). Flow cytometric analysis of mouse spermatogenic function following exposure to ethylnitrosourea. Cytometry 6, 238–253.

Balls M. , Blaauboer B.J. , Fentem J.H. , Bruner L. , Combes R.D. , Ekwall B. , Fielder R.J. , Guillouzo A. , Lewis R.W. , Lovell D.P. , Reinhardt C.A. , Repetto G. , Sladowski D. , Spielmann H. , and Zucco F. (1995). Practical aspects of the validation of toxicity test procedures. The report and recommendations of ECVAM workshop 5. ATLA 23, 129–147.

Pratt R.M. , Grove R.I. , and Willis W.D. (1982). Prescreening for environmental teratogens using cultured mesenchymal cells from the human embryonic palate. Teratogenesis, Carcinogenesis and Mutagenesis 2, 313–318.

Braun A.G. , Nichinson B.B. , and Horowicz P.B. (1982). Inhibition of tumour cell attachment to concanavalin A-coated surfaces as an assay for teratogenic agents: approaches to validation. Teratogenesis, Carcinogenesis and Mutagenesis 2, 343–354.

Mummery C.L. , van der Brink C.E. , van der Saag P.T. , & De Laat S.W. (1984). A short-term screening test for teratogens using differentiating neuroblastoma cells in vitro. Teratology 29, 271–279.

Steele V.E. , Morrissey R.E. , Elmore E.L. , Gurganus-Rocha D. , Wilkinson B.P. , Curren R.D. , Schmetter B.S. , Louie A.T. , Lamb J.C. , and Yang L.I.L. (1988). Evaluation of two in vitro assays to screen for potential development toxicants. Fundamental and Applied Toxicology 11, 673–684.

Rohwedel J. , Maltsev V. , Bober E. , Arnold H.H. , Hescheler J. , and Wobus A.M. (1994). Muscle cell differentiation of embryonic stem cells reflects myogenesis in vivo: developmental^ regulated expression of myogenic determination genes and functional expression of ionic currents. Developmental Biology 164, 87–101.

Heuer J. , Graeber I.M. , Pohl I. , and Spielmann H. (1994). An in vitro embryotoxicity assay using the differentiation of embryonic mouse stem cells into haematopoietic cells. Toxicology in Vitro 8, 585–587.

Laschinski G. , Vogel R. , and Spielmann H. (1991). Cytotoxicity test using blastocyst-derived euploid embryonal stem cells: a new approach to in vitro teratogenesis screening. Reproductive Toxicology 5, 57–64.

Newall D.R. , and Beedles K.E. (1994). The stem-cell test: a novel in vitro assay for teratogenic potential. Toxicology in Vitro 8, 697–701.

Hooghe R.J. , and Ooms D. (1995). Use of the fluorescence-activated cell sorter (FACS) for in vitro assays of developmental toxicity. Toxicology in Vitro 9, 349–354.

Umansky R. (1966). The effect of cell population density on the developmental fate of reaggregating mouse limb bud mesenchyme. Developmental Biology 13, 31–56.

Flint O.P. (1983). A micromass culture method for rat embryonic neural cells. Journal of Cell Science 61, 247–262.

Flint O.P. , and Orton T.C. (1984). An in vitro assay for teratogens with cultures of rat embryo midbrain and limb cells. Toxicology and Applied Pharmacology 76, 383–395.

Flint O.P. (1993). In vitro tests for teratogens: desirable endpoints, test batteries and current status of the micromass teratogen test. Reproductive Toxicology 7, Suppl. 1, 103–111.

Brown N.A. , and Wiger R. (1992). A comparison of rat and chick limb bud micromass cultures for developmental toxicity screening. Toxicology in Vitro 6, 101–108.

Renault J-Y. , Melcion C. , and Cordier A. (1989). Limb bud cell culture for in vitro teratogen screening: validation of an improved assessment method using 51 compounds. Teratogenicity, Carcinogenicity and Mutagenicity 9, 83–96.

Flint O.P. , Orton T.C. , and Ferguson R.A. (1984). Differentiation of rat embryo cells in culture: response following acute maternal exposure to teratogens and non-teratogens. Journal of Applied Toxicology 4, 109–116.

Kistler A. , Tsuchiya T. , Tsuchiya M. , and Klaus M. (1990). Teratogenicity of arotinoids (retinoids) in vivo and in vitro. Archives of Toxicology 64, 616–622.

Flint O.P. , and Boyle F.T. (1986). Structure-teratogenicity relationships among antifungal triazoles. In Handbook of Experimental Pharmacology, Volume 96, Chemotherapy of Fungal Disease (ed. Ryley J.F. ), pp. 231–249. Berlin: Springer-Verlag.

Tsuchiya T. , Takahashi A. , Asada S. , Takakubo F. , Ohsumi-Yamashita N. , and Eto K. (1991). Comparative study of embryotoxic action of ethylenethiourea in rat whole-embryo and embryonic cell culture. Teratology 43, 319–324.

Tsuchiya T. , Nakamura A. , Iio T. , and Takahashi A. (1991). Species differences between rats and mice in the teratogenic action of ethylenethiourea: in vivo/in vitro tests and teratogenic activity of sera using an embryonic cell differentiation system. Toxicology and Applied Pharmacology 109, 1–6.

Newall D.R. (1990). Strain differences in the response of embryonic cells to teratogens as determined in vitro using the micromass test. Teratology 42, 28A.

Brown L.P. , Foster J.R. , Orton T.C. , Flint O.P. , and Gibson G.G. (1989). Localization and identification of cytochrome P450 in differentiating rat embryo cells in vitro and in foetal tissue in vivo by immunocytochemistry. Toxicology in Vitro 3, 245–252.

Brown L.P. , Foster J.R. , Orton T.C. , Flint O.P. , and Gibson G.G. (1989). Inducibility and functionality of rat embryonic/foetal cytochrome P450: a study of differentiating limb bud and mid-brain cells in vitro. Toxicology in Vitro 3, 253–260.

Wise L.D. , Clark R.L. , Rundell J.O. , and Robertson R.T. (1990). Examination of a rodent limb bud micromass assay as a pre-screen for developmental toxicity. Teratology 41, 341–351.

Koelman H.J.S. , Jongeling A.J. , van Erp Y.H.M. , Weterings P.J.M. , Koopmans M.E. , Joosten H.F. , van der Dobbelsteen D.J. , van der Aa E.M. , and Yih T.D. (1991). International ring validation of the in vitro micromass teratogenicity test: preliminary results of three Dutch laboratories. Teratology 44, 30A.

Sabourin T.D. , and Faulk R.T. (1987). Comparative evaluation of a short-term test for developmental effects using frog embryos. In Banbury Report 26: Developmental Toxicology: Mechanisms and Risk (ed. McLachlan J.A. , Pratt R.M. , Markert C.L. ), pp. 203–223. New York: Cold Spring Harbor Laboratory.

Dawson D.A. , Fort D.J. , Newell D.L. , and Bantle J.A. (1989). Developmental toxicity testing with FETAX: evaluation of five compounds. Drug and Chemical Toxicology 12, 67–75.

Bantle J.A. , Fort D.J. , Rayburn J.R. , DeYoung D.J. , and Bush S.J. (1990). Further validation of FETAX: evaluation of the developmental toxicity of five known mammalian teratogens and non-teratogens. Drug and Chemical Toxicology 13, 267–282.

Anon. (1967). Principles for the testing of drugs for teratogenicity. Report of a WHO scientific group. WHO Technical Report Series 364, 1–18.

Jelínek R. (1977). The chick embryotoxicity screening test (CHEST). In Methods in Prenatal Toxicology (ed. Neubert D. , Merker H.J. , Kwasigroch T.E. ), pp. 381–386. Stuttgart: G. Thieme.

Jelínek R. , Rychter Z. , and Peterka M. (1979). Embryotoxicity assay on morphogenetic systems. In Evaluation of Embryotoxicity, Mutagenicity and Carcinogenicity Risks in New Drugs (ed. Benesova O. , Rychter Z. , & Jelínek R. ), pp. 195–205. Prague: Univerzita Karlova.

Jelínek R. , and Peterka M. (1981). Morphogenetic systems and in vitro techniques in teratology. In Culture Techniques, Applicability for Studies on Prenatal Differentiation and Toxicity (ed. Neubert D. , Merker H.J. ), pp. 553–557. Berlin: Walter de Gruyter.

Marhan O. , & Jelínek R. (1979). Efficiency of the embryotoxicity testing procedures. II. Comparison between the official, MEST and CHEST methods. Toxicology Letters 4, 389–392.

Vesely D. , & Jelínek R. (1982). Nineteen mycotoxins tested on chicken embryos. Toxicology Letters 13, 239–245.

Jelínek R. , Peterka M. , and Rychter Z. (1985). Chick embryotoxicity screening test: 130 substances tested. Indian Journal of Experimental Biology 23, 588–595.

Peterka M. , Jelínek R. , and Pavllik A. (1992). Embryotoxicity of 25 psychotropic drugs: a study using CHEST. Reproductive Toxicology 6, 367–374.

Kucera P. , Cano E. , Honegger P. , Schilter B. , Zulstra A. , and Schmid B. (1993). Validation of whole chick embryo cultures, whole rat embryo cultures and aggregating embryonic brain cell cultures using six pairs of coded compounds. Toxicology in Vitro 7, 785–798.

Sadler T.W. , Horton W.E. , and Warner C.W. (1982). Whole-embryo culture: a screening technique for teratogens? Teratogenesis, Carcinogenesis and Mutagenesis 2, 243–253.

Schmid B.P. (1985). Teratogenicity testing of new drugs with the postimplantation embryo culture system. In Concepts in Toxicology, Volume 3 (ed. Homburger F. ), pp. 46–57. Basle: Karger.

Ninomiya H. , Kishida K. , Ohno Y. , Tsurumi K. , & Eto K. (1993). Effects of trypan blue on rat and rabbit embryos cultured in vitro. Toxicology in Vitro 7, 707–717.

Bechter R. , Terlouw G.D.C. , Lee Q.P. , and Juchau M.R. (1991). Effects of QA 208–199 and its metabolite 209–668 on embryonic development in vitro after microinjection into the exocoelomic space or into the amniotic cavity of cultured rat conceptuses. Teratogenesis, Carcinogenesis and Mutagenesis 11, 185–194.

Sadler T.W. (1979). Culture of early somite mouse embryos during organogenesis. Journal of Embryology and Experimental Morphology 49, 17–25.

Klug S. , Lewandowski C. , and Neubert D. (1985). Modification and standardization of the culture of early postimplantation embryos for toxicological studies. Archives of Toxicology 58, 84–88.

Klein N.W. , Plenefisch J.D. , Carey S.W. , Fredrickson W.T. , Sackett G.P. , Burbacher T.M. , and Parker R.M. (1982). Serum from monkeys with histories of fetal wastage causes abnormalities in cultures of whole rat embryos. Science 215, 66–69.

Chatot C.L. , Klein N.W. , Piatek J. , and Pierro L.J. (1980). Successful culture of rat embryos in human serum: use in the detection of teratogens. Science 207, 1471–1473.

Fantel A.G. , Greenaway J.C. , Juchau M.R. , and Shepard T.H. (1979). Teratogenic bioactivation of cyclophosphamide in vitro. Life Sciences 25, 67–72.

Kitchin K.T. , Schmid B.P. , and Sanyai M.K. (1981). Teratogenicity of cyclophosphamide in a coupled microsomal activating/embryo culture system. Biochemical Pharmacology 30, 59–64.

Zhao J. , Krafft N. , Terlouw G.D.C. , & Bechter R. (1993). A model combining the whole-embryo culture with human liver S9 fraction for human teratogenic prediction. Toxicology in Vitro 7, 827–831.

Oglesby L.A. , Ebron-McCoy M.T. , Logsdon T.R. , Copeland F. , Beyer P.E. , and Kavlock R.J. (1992). In vitro embryotoxicity of a series of para-substituted phenols: structure, activity, and correlation with in vivo data. Teratology 45, 11–33.

Bechter R. , Bouis P. , and Fischer V. (1989). Primary hepatocyte culture as an activating system for xenobiotics tested in the rat whole embryo in vitro. In Alternative Methods in Toxicology, Volume 7, In Vitro Toxicology — New Directions (ed. Goldberg A.M. , Principe M.L. ), pp. 313–326. New York: Mary Ann Liebert.

Schmid B.P. , Trippmacher A. , and Bianchi A. (1982). Teratogenicity induced in cultured rat embryos by the serum of procarbazine treated rats. Toxicology 25, 53–60.

van Maele-Fabry G. , Delhaise F. , Gofflot F. , and Picard J.J. (1993). Developmental table of the early mouse postimplantation embryo. Toxicology in Vitro 7, 719–725.

Brown N.A. , and Fabro S. (1981). Quantitation of rat embryonic development in vitro: a morphological scoring system. Teratology 24, 65–78.

Bechter R. , and Brouillard J.F. (1988). The effects of different chemical forms of a test compound on embryotoxicity, distribution and metabolism in vitro. Toxicology in Vitro 2, 181–188.

Schmid B.P. , Trippmacher A. , and Bianchi A. (1983). Validation of whole-embryo culture method for in vitro teratogenicity testing. In Developments in the Science and Practice of Toxicology (ed. Hayes A.W. , Schnell R.C. , Miya T.S. ), pp. 563–566. Amsterdam: Elsevier.

Cicurel L. , and Schmid B.P. (1988). Postimplantation embryo culture: validation with selected compounds for teratogenicity testing. Xenobiotica 18, 617–624.

Cicurel L. , and Schmid B.P. (1988). Postimplantation embryo culture for the assessment of the teratogenic potential and potency of compounds. Experientia 44, 833–840.

van Maele-Fabry G. , Picard J.J. , Attenon P. , Berthet P. , Delhaise F. , Govers M.J.A.P. , Peters P.W.J. , Piersma A.H. , Schmid B.P. , Stadler J. , Verhoef A. , and Verseil C. (1991). Interlaboratory evaluation of three culture media for postimplantation rodent embryos. Reproductive Toxicology 5, 417–426.

Govers M.J. , van Maele-Fabry G. , Peters P.W. , Picard J. , Piersma A.H. , Schmid B.P. , Verhoef A. , and Verseil C. (1989). Interlaboratory validation of rodent postimplantation embryo culture as a screening test for teratogenic compounds. Teratology 39, 456.

Piersma A.H. , Attenon P. , Bechter R. , Govers M.J.A.P. , Krafft N. , Schmid B.P. , Stadler J. , Verhoef A. , and Verseil C. (1995). Interlaboratory evaluation of embryotoxicity in the postimplantation rat embryo culture. Reproductive Toxicology 9, 275–280.

Bechter R. , Terlouw G.D.C. , Tsuchiya M. , Tsuchiya T. , and Kistler A. (1992). Teratogenicity of arotinoids (retinoids) in the rat whole-embryo culture. Archives of Toxicology 66, 193–197.

Nau H. (1990). Pharmacokinetic aspects of ire vitro teratogenicity studies: comparison to in vivo. In In Vitro Methods in Developmental Toxicology: Use in Defining Mechanisms and Risk Parameters (ed. Kimmel G.L. , Kochhar D.M. ), pp. 29–43. Boca Raton, FL, USA: CRC Press.

Nau H. (1990). Correlation of transplacental and maternal pharmacokinetics of retinoids during organogenesis with teratogenicity. Methods in Enzymology 190, 437–448.

Nau H. , Lewandowski C. , Klug S. , and Neubert D. (1988). Pharmacokinetic aspects of drug effects in vitro. II. Placental transfer to the embryo and activity of some carboxylic acids structurally related to valproic acid in whole embryos in culture. Toxicology in Vitro 2, 169–174.

Nau H. , Hauck R.S. , and Ehlers K. (1991). Valproic acid-induced neural tube defects in mouse and human: aspects of chirality, alternative drug development, pharmacokinetics and possible mechanisms. Pharmacology and Toxicology 69, 310–321.

Klug S. , Creech Kraft J. , Wildi E. , Merker H-J. , Persaud T.V.N. , Nau H. , and Neubert D. (1989). Influence of 13-cis and all-trans retinoic acid on rat embryonic development in vitro: correlation with isomerisation and drug transfer to the embryo. Archives of Toxicology 63, 185–192.

Nau H. (1993). Retinoid teratogenesis: toxi-cokinetics and structure-specificity. Archives of Toxicology, Suppl. 16, 118–127.

Hauck R-S. , & Nau H. (1992). The enantiomers of the valproic acid analogue 2-n-propyl-penti-noic acid (4-yn-VPA): asymmetric synthesis and highly stereoselective teratogenicity in mice. Pharmaceutical Research 9, 850–855.

Hauck R-S. , Elmazar M.M.A. , Plum C. , and Nau H. (1992). The enantioselective teratogenicity of 2-n-propyl-4 pentinoic acid (4-yn-VPA) is due to stereoselective intrinsic activity and not differences in pharmacokinetics. Toxicology Letters 60, 145–153.

Andrews J.E. , Ebron-McCoy M. , Bojic U. , Nau H. , and Kavlock R.J. (1995). Validation of an in vitro teratology system using chiral substances: stereoselective teratogenicity of 4-yn-valproic acid in cultured mouse embryos. Toxicology and Applied Pharmacology 132, 310–316.