Pub Date : 2018-09-03DOI: 10.1787/9789264304741-34-en
{"title":"Extended One-Generation Reproductive Toxicity Study (EOGRTS) (OECD TG 443)","authors":"","doi":"10.1787/9789264304741-34-en","DOIUrl":"https://doi.org/10.1787/9789264304741-34-en","url":null,"abstract":"","PeriodicalId":19458,"journal":{"name":"OECD Series on Testing and Assessment","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85914251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-09-03DOI: 10.1787/9789264304741-20-en
650. This assay is a short-term in vivo screening assay in female rodents for chemicals that interact with the estrogen receptor (ER). It is based on the increase in uterine weight (or uterotrophic response) that is elicited by ER agonists in animal models where endogenous estrogen levels are minimal. There are two variants of the assay; one uses immature animals, the other uses ovariectomised animals. The immature rodent assay may detect modalities acting via mechanisms other than ER, as the animals have an intact hypothalamic/pituitary/gonadal (HPG) axis, but the ability to detect these is limited. The assay may be conducted using rats or mice, but the there is more experience with the rat assay and this species was used in the OECD validation of this assay (OECD, 2006). Route of administration of test substance is via oral gavage or subcutaneous injection. This assay has been considered to be the “gold standard” bioassay screen for identifying ER agonists. A recently curated database of bioactivity with results from over 2 500 Uterotrophic Bioassays in rats and mice provides comprehensive information on this assay (Kleinstreuer et al., 2016).
{"title":"Uterotrophic Bioassay in Rodents (UT assay) (OECD TG 440) (including OECD GD 71 on the procedure to test for anti-estrogenicity)","authors":"","doi":"10.1787/9789264304741-20-en","DOIUrl":"https://doi.org/10.1787/9789264304741-20-en","url":null,"abstract":"650. This assay is a short-term in vivo screening assay in female rodents for chemicals that interact with the estrogen receptor (ER). It is based on the increase in uterine weight (or uterotrophic response) that is elicited by ER agonists in animal models where endogenous estrogen levels are minimal. There are two variants of the assay; one uses immature animals, the other uses ovariectomised animals. The immature rodent assay may detect modalities acting via mechanisms other than ER, as the animals have an intact hypothalamic/pituitary/gonadal (HPG) axis, but the ability to detect these is limited. The assay may be conducted using rats or mice, but the there is more experience with the rat assay and this species was used in the OECD validation of this assay (OECD, 2006). Route of administration of test substance is via oral gavage or subcutaneous injection. This assay has been considered to be the “gold standard” bioassay screen for identifying ER agonists. A recently curated database of bioactivity with results from over 2 500 Uterotrophic Bioassays in rats and mice provides comprehensive information on this assay (Kleinstreuer et al., 2016).","PeriodicalId":19458,"journal":{"name":"OECD Series on Testing and Assessment","volume":"50 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85126411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-09-03DOI: 10.1787/9789264304741-13-en
Tg
391. This test is widely used as a sub-chronic assay for non-endocrine disrupting (ED) chemicals, and can be used to predict concentrations causing chronic effects on growth and reproduction in fish. It was developed before concerns about endocrine disrupting chemicals (EDCs) arose and cannot be used to identify these chemicals. It exposes fish from immediately post-fertilisation to the larval free-feeding stage (28-60 days post-hatch [dph], depending on species). Permitted species include rainbow trout (Oncorhynchus mykiss), fathead minnow (Pimephales promelas), zebrafish (Danio rerio), medaka (Oryzias latipes), sheepshead minnow (Cyprinodon variegatus) and silverside (Menidia sp.). The main endpoints include mortality, time to hatching, hatching success, growth, morphological abnormalities and abnormal behaviour.
{"title":"Fish, Early-Life Stage (FELS) Toxicity Test (OECD TG 210)","authors":"Tg","doi":"10.1787/9789264304741-13-en","DOIUrl":"https://doi.org/10.1787/9789264304741-13-en","url":null,"abstract":"391. This test is widely used as a sub-chronic assay for non-endocrine disrupting (ED) chemicals, and can be used to predict concentrations causing chronic effects on growth and reproduction in fish. It was developed before concerns about endocrine disrupting chemicals (EDCs) arose and cannot be used to identify these chemicals. It exposes fish from immediately post-fertilisation to the larval free-feeding stage (28-60 days post-hatch [dph], depending on species). Permitted species include rainbow trout (Oncorhynchus mykiss), fathead minnow (Pimephales promelas), zebrafish (Danio rerio), medaka (Oryzias latipes), sheepshead minnow (Cyprinodon variegatus) and silverside (Menidia sp.). The main endpoints include mortality, time to hatching, hatching success, growth, morphological abnormalities and abnormal behaviour.","PeriodicalId":19458,"journal":{"name":"OECD Series on Testing and Assessment","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91089433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-09-03DOI: 10.1787/9789264304741-33-en
Tg
942. The OECD Two-Generation Reproduction Toxicity Study is an apical assay designed to provide general information concerning the effects of a chemical on the male and female reproductive systems including gonadal function, the estrus cycle, mating, conception, gestation, parturition, lactation, weaning, and growth and development of the offspring. The rat is the preferred species. The recommended route of administration is oral, via the diet, by gavage or in drinking water. The study is not specifically designed to detect endocrine active substances (EASs), but has many endpoints relevant for the assessment of possible endocrine disruption and provides data on adverse effects related to reproduction and development. OECD TG 416 was revised in January 2001 to include a more comprehensive range of endpoints. These endpoints include sexual maturation (VO and PPS) which are particularly sensitive to EASs. One-generation studies and two-generation studies conducted prior to the adoption of the revised OECD TG 416 are therefore unlikely to provide as much data as studies conducted to the revised OECD TG 416, particularly with respect to endocrine disruption. They do, however, provide a great deal of useful data, particularly on adverse effects on reproduction, that may be sufficient for hazard assessment purposes even if the etiology of the effect(s) is not fully characterised.
{"title":"Two-Generation Reproduction Toxicity Study (OECD TG 416)","authors":"Tg","doi":"10.1787/9789264304741-33-en","DOIUrl":"https://doi.org/10.1787/9789264304741-33-en","url":null,"abstract":"942. The OECD Two-Generation Reproduction Toxicity Study is an apical assay designed to provide general information concerning the effects of a chemical on the male and female reproductive systems including gonadal function, the estrus cycle, mating, conception, gestation, parturition, lactation, weaning, and growth and development of the offspring. The rat is the preferred species. The recommended route of administration is oral, via the diet, by gavage or in drinking water. The study is not specifically designed to detect endocrine active substances (EASs), but has many endpoints relevant for the assessment of possible endocrine disruption and provides data on adverse effects related to reproduction and development. OECD TG 416 was revised in January 2001 to include a more comprehensive range of endpoints. These endpoints include sexual maturation (VO and PPS) which are particularly sensitive to EASs. One-generation studies and two-generation studies conducted prior to the adoption of the revised OECD TG 416 are therefore unlikely to provide as much data as studies conducted to the revised OECD TG 416, particularly with respect to endocrine disruption. They do, however, provide a great deal of useful data, particularly on adverse effects on reproduction, that may be sufficient for hazard assessment purposes even if the etiology of the effect(s) is not fully characterised.","PeriodicalId":19458,"journal":{"name":"OECD Series on Testing and Assessment","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82344701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-09-03DOI: 10.1787/9789264304741-22-en
{"title":"Repeated Dose 28-Day Oral Toxicity Study in Rodents (OECD TG 407)","authors":"","doi":"10.1787/9789264304741-22-en","DOIUrl":"https://doi.org/10.1787/9789264304741-22-en","url":null,"abstract":"","PeriodicalId":19458,"journal":{"name":"OECD Series on Testing and Assessment","volume":"109 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78103148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-09-03DOI: 10.1787/9789264304741-2-en
33. The purpose of this section is to provide background information on the relevance of various types of data for supporting decisions about the endocrine disrupting properties of chemicals and other test materials (e.g. effluents, natural waters, contaminated foods, etc.) in humans and non-mammalian vertebrates. Interpretation of results from some invertebrate test guidelines is also included, but due to the rather poor current understanding of endocrinology in most invertebrates, and the lack of diagnostic screening endpoints with these taxonomic groups (e.g. OECD [2010c]), guidance cannot yet be given for many of these assays. Nevertheless, non-OECD test assays, including those utilising invertebrate species, may provide information that can be used in a weight of evidence (WOE) approach. Furthermore, the document only deals with estrogen-, androgenand thyroidmediated endocrine disruption, and with interference with steroidogenesis (although some guidance is also provided for evaluation of juvenile hormone, ecdysteroid and retinoid activity). It does not cover other possible types of endocrine disruption, such as effects on the hypothalamus-pituitary-adrenal axis or other receptor pathways. Some advice on the endocrine control of neural development is provided, but this is only rudimentary. The section is organised according to the OECD Conceptual Framework (CF) (see Section A.2), as updated in 2017 with tests which were unavailable or not included when it was first proposed.
{"title":"General Guidance on Endocrine Assessment: Assays and Endpoints","authors":"","doi":"10.1787/9789264304741-2-en","DOIUrl":"https://doi.org/10.1787/9789264304741-2-en","url":null,"abstract":"33. The purpose of this section is to provide background information on the relevance of various types of data for supporting decisions about the endocrine disrupting properties of chemicals and other test materials (e.g. effluents, natural waters, contaminated foods, etc.) in humans and non-mammalian vertebrates. Interpretation of results from some invertebrate test guidelines is also included, but due to the rather poor current understanding of endocrinology in most invertebrates, and the lack of diagnostic screening endpoints with these taxonomic groups (e.g. OECD [2010c]), guidance cannot yet be given for many of these assays. Nevertheless, non-OECD test assays, including those utilising invertebrate species, may provide information that can be used in a weight of evidence (WOE) approach. Furthermore, the document only deals with estrogen-, androgenand thyroidmediated endocrine disruption, and with interference with steroidogenesis (although some guidance is also provided for evaluation of juvenile hormone, ecdysteroid and retinoid activity). It does not cover other possible types of endocrine disruption, such as effects on the hypothalamus-pituitary-adrenal axis or other receptor pathways. Some advice on the endocrine control of neural development is provided, but this is only rudimentary. The section is organised according to the OECD Conceptual Framework (CF) (see Section A.2), as updated in 2017 with tests which were unavailable or not included when it was first proposed.","PeriodicalId":19458,"journal":{"name":"OECD Series on Testing and Assessment","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89986163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-09-03DOI: 10.1787/9789264304741-16-en
{"title":"Avian Reproduction Test (OECD TG 206)","authors":"","doi":"10.1787/9789264304741-16-en","DOIUrl":"https://doi.org/10.1787/9789264304741-16-en","url":null,"abstract":"","PeriodicalId":19458,"journal":{"name":"OECD Series on Testing and Assessment","volume":"271 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83512459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-09-03DOI: 10.1787/9789264304741-8-en
Tg
311. Modality detected/endpoints: thyroid activity (advanced development; asynchronous development; delayed development in absence of non-specific systemic toxicity; thyroid histopathology), but note that this covers several different modes of action (MOA), including thyroid agonists and antagonists, as well as substances interfering with thyroid hormone synthesis and transport. According to OECD TG 231, there is disagreement about the implications of the different endpoints in this larval development screen. Some experts accept that changes in one of the thyroid-relevant apical endpoints (advanced development; asynchronous development; delayed development in absence of non-specific systemic toxicity) may on their own provide information on thyroid activity, while others will only reach this conclusion if one of the apical endpoints is accompanied by significant thyroid histopathology, such as moderate or severe follicular hypertrophy and/or hyperplasia (OECD, 2007). Note that the AMA is subject to indirect thyroid effects such as those that result from cytochrome P450 induction (e.g. phenobarbital, the model compound for the latter effect, tests positive in the AMA). Therefore, interpretation of the AMA may be complicated.
{"title":"Amphibian Metamorphosis Assay (AMA) (OECD TG 231)","authors":"Tg","doi":"10.1787/9789264304741-8-en","DOIUrl":"https://doi.org/10.1787/9789264304741-8-en","url":null,"abstract":"311. Modality detected/endpoints: thyroid activity (advanced development; asynchronous development; delayed development in absence of non-specific systemic toxicity; thyroid histopathology), but note that this covers several different modes of action (MOA), including thyroid agonists and antagonists, as well as substances interfering with thyroid hormone synthesis and transport. According to OECD TG 231, there is disagreement about the implications of the different endpoints in this larval development screen. Some experts accept that changes in one of the thyroid-relevant apical endpoints (advanced development; asynchronous development; delayed development in absence of non-specific systemic toxicity) may on their own provide information on thyroid activity, while others will only reach this conclusion if one of the apical endpoints is accompanied by significant thyroid histopathology, such as moderate or severe follicular hypertrophy and/or hyperplasia (OECD, 2007). Note that the AMA is subject to indirect thyroid effects such as those that result from cytochrome P450 induction (e.g. phenobarbital, the model compound for the latter effect, tests positive in the AMA). Therefore, interpretation of the AMA may be complicated.","PeriodicalId":19458,"journal":{"name":"OECD Series on Testing and Assessment","volume":"157 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77634380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-09-03DOI: 10.1787/9789264304741-14-en
Tg
406. Modality detected/endpoints: estrogens (♀ and ♂ VTG ↑; phenotypic sex ratio ♀↑); anti-estrogens (♀ VTG ↓; phenotypic sex ratio ♂↑; sexually undifferentiated fish ↑); androgens (phenotypic sex ratio ♂↑; ♀ VTG ↓); anti-androgens (intersex fish ↑; ♀ VTG ↑; phenotypic sex ratio ♀↑); aromatase inhibitors (♀ VTG ↓; phenotypic sex ratio ♂↑); (optional endpoints – gonadal histopathology; genetic sex in medaka and stickleback). OECD TG 234 (FSDT) has been fully validated for Japanese medaka, zebrafish and stickleback. The test may also be responsive to certain thyroid-disrupting chemicals. It is known that thyroid hormone receptors TRα and TRβ are both present in fish early embryos and larvae (Power et al., 2001), and that maternally derived thyroxine (T4) is important for thyroiddependent processes in fish early life stages (Nelson et al., 2014). One of these processes is swimbladder inflation, an endpoint which could be recorded in the FSDT test, and which is vital for the survival of fish fry. It has been shown, for example, that fathead minnow embryos exposed to a thyroid peroxidase (TPO) inhibitor (2-mercaptobenzothiazole) do not develop inflated swimbladders, probably because inhibition of TPO leads to decreased thyroid hormone synthesis (Villeneuve et al., 2013; Nelson et al., 2014). Also, Liu and Chan (2002) have shown that metamorphosis from embryo to larva in zebrafish is arrested by exposure to amiodarone (a TR antagonist) and by the goitrogen methimazole. Furthermore, Shi et al. (2008) demonstrated that the thyroid disrupter perfluorooctanesulfonic acid (PFOS) is able to delay hatching and cause developmental malformations in zebrafish embryos while upregulating two thyroid-related developmental genes, hhex and pax8. However, it is important to note that many non-ED chemicals will also cause these types of apical response, but by different mechanisms.
406. 检测形态/终点:雌激素(♀和♂VTG↑;表型性比♀↑);抗雌激素(♀VTG↓;表现型性比♂↑;性未分化的鱼^);雄性激素(表型性比♂↑;♀VTG↓);抗雄激素(双性鱼)↑;♀VTG↑;表型性比♀↑);芳香酶抑制剂(♀VTG↓;表型性比♂↑);(可选终点-性腺组织病理学;medaka和棘鱼的基因性别)。OECD TG 234 (FSDT)已对日本medaka、斑马鱼和棘鱼进行了全面验证。该测试也可能对某些干扰甲状腺的化学物质有反应。众所周知，甲状腺激素受体TRα和TRβ都存在于鱼类早期胚胎和幼虫中(Power et al.， 2001)，母体衍生的甲状腺素(T4)对鱼类早期生命阶段的甲状腺依赖过程很重要(Nelson et al.， 2014)。其中一个过程是鱼鳔膨胀，这是一个可以在FSDT测试中记录的终点，对鱼苗的生存至关重要。例如，研究表明，暴露于甲状腺过氧化物酶(TPO)抑制剂(2-巯基苯并噻唑)的鱼头鱼胚胎不会发育出膨胀的鳔，这可能是因为TPO的抑制导致甲状腺激素合成减少(Villeneuve等人，2013;Nelson et al.， 2014)。此外，Liu和Chan(2002)已经证明斑马鱼从胚胎到幼虫的蜕变可以通过暴露于胺碘酮(一种TR拮抗剂)和甲状腺素甲巯咪唑来阻止。此外，Shi等人(2008)证明，甲状腺干扰物全氟辛烷磺酸(PFOS)能够延迟斑马鱼胚胎的孵化并导致发育畸形，同时上调两种与甲状腺相关的发育基因hhex和pax8。然而，重要的是要注意，许多非ed化学品也会引起这些类型的顶点反应，但通过不同的机制。
{"title":"Fish Sexual Development Test (FSDT) (OECD TG 234)","authors":"Tg","doi":"10.1787/9789264304741-14-en","DOIUrl":"https://doi.org/10.1787/9789264304741-14-en","url":null,"abstract":"406. Modality detected/endpoints: estrogens (♀ and ♂ VTG ↑; phenotypic sex ratio ♀↑); anti-estrogens (♀ VTG ↓; phenotypic sex ratio ♂↑; sexually undifferentiated fish ↑); androgens (phenotypic sex ratio ♂↑; ♀ VTG ↓); anti-androgens (intersex fish ↑; ♀ VTG ↑; phenotypic sex ratio ♀↑); aromatase inhibitors (♀ VTG ↓; phenotypic sex ratio ♂↑); (optional endpoints – gonadal histopathology; genetic sex in medaka and stickleback). OECD TG 234 (FSDT) has been fully validated for Japanese medaka, zebrafish and stickleback. The test may also be responsive to certain thyroid-disrupting chemicals. It is known that thyroid hormone receptors TRα and TRβ are both present in fish early embryos and larvae (Power et al., 2001), and that maternally derived thyroxine (T4) is important for thyroiddependent processes in fish early life stages (Nelson et al., 2014). One of these processes is swimbladder inflation, an endpoint which could be recorded in the FSDT test, and which is vital for the survival of fish fry. It has been shown, for example, that fathead minnow embryos exposed to a thyroid peroxidase (TPO) inhibitor (2-mercaptobenzothiazole) do not develop inflated swimbladders, probably because inhibition of TPO leads to decreased thyroid hormone synthesis (Villeneuve et al., 2013; Nelson et al., 2014). Also, Liu and Chan (2002) have shown that metamorphosis from embryo to larva in zebrafish is arrested by exposure to amiodarone (a TR antagonist) and by the goitrogen methimazole. Furthermore, Shi et al. (2008) demonstrated that the thyroid disrupter perfluorooctanesulfonic acid (PFOS) is able to delay hatching and cause developmental malformations in zebrafish embryos while upregulating two thyroid-related developmental genes, hhex and pax8. However, it is important to note that many non-ED chemicals will also cause these types of apical response, but by different mechanisms.","PeriodicalId":19458,"journal":{"name":"OECD Series on Testing and Assessment","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76370060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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