SMALL FISH TO EVALUATE TOXIC CHEMICALS

本合同的目的是测试最多三种化学物质 作为NIEHS和NIEHS的一部分的两个小型鱼类的职业兴趣 NTP正在努力开发亚哺乳类动物的替代测试方法 物种。要研究的鱼类种类是Medaka(Oryzias Latips)和Guppy(Poecilia Reetata)。选定用于研究的化学物质 要么是已证实的致癌物质，要么是初步数据表明的致癌物质 对大鼠和小鼠均有影响。每一种化学品都是作为一项任务提出的(L任务 -2，2-二(溴甲基)L，3-正二醇。任务2--硝基甲烷。任务3。 1.2，3-三氯丙烷，任务4-2，3-二氯丙烯。和任务5- 邻硝基甲苯。每项任务由三个阶段组成。第一阶段涉及散装 化学分析、启动前化学和一种健康和 安全计划。这些活动预计将需要三个月的时间来 完成。第二阶段活动包括举办为期两天(48小时)的 静态研究，以确定28天测距研究的剂量水平，以及 这项为期28天的测距研究的进行。这些活动是 预计需要四个月的时间才能完成。第一阶段和第二阶段的结果 应由NTP进行评估，并将决定是否 被检测的化学品(S)适合长期慢性接触， 在这种情况下，可以行使可选的第三阶段。第三阶段应 包括一项持续16个月的水暴露(慢性)研究， 还包括一项特别的9个月连续暴露研究，随后是 7个月的成长期。这些活动预计需要26个月的时间。 基本合同授予应为执行任务的L (2，2-双(溴甲基)-L，3-丙二醇)，第一阶段和第二阶段，任务2 (硝基甲烷)，第一阶段和第二阶段。任务L和任务2都要进行 同时。基本合同授予中将包括生命周期 两种鱼的控制研究将于 正在进行L任务和任务2的第一阶段活动。 该合同包含八个选项。为任务1-5选择的化学品 NTP以前没有通过水溶液路线进行过研究。如果，之后 发现，L任务和任务2(第一阶段和第二阶段)研究已经完成 这两种化合物都不合适。即(溶解度或 稳定性问题)，用于第三阶段长期慢性水暴露 将进行研究，备选方案3--任务的第一阶段和第二阶段活动 3化学成分。如果任务3的化学品(L，2，3-三氯丙烷)不是 适用于第三阶段研究。将行使备选方案5--第一阶段和 活动任务为4个化学物质。如果任务4的化学物质 (2，3-二氯丙烯)不适合第三阶段研究。备选方案7 将进行练习-任务5的第一阶段和第二阶段的化学活动 (邻硝基甲苯)。对于每个阶段，可能有多达五种化学物质 进行了I和II活动。然而，将不会超过 根据本合同，三种化学品处于第三阶段活动。

The purpose of this contract is to test up to three chemicals of occupational interest in two small fish species as a part of the NIEHS and NTP's ongoing effort to develop alternative test methods in submammalian species. The species of fish to be studied are the Medaka (ORYZIAS LATIPES) and Guppy (POECILIA RETICULATA). The chemicals selected for study are either proven carcinogens or preliminary data indicate a carcinogenic effect in both rats and mice. Each chemical is set forth as a TASK (Task l - 2,2 bis(bromomethyl l,3panediol. TASK 2 - Nitromethane. TASK 3. 1.2,3-Trichloropropane, TASK 4 - 2,3-Dichloropropylene. and TASK 5 - o-Nitrotoluene. Each TASK consists of three phases. Phase I involves bulk chemical analysis, prestart chemistry and the development of a health and safety plan. These activities are expected to take three months to complete. Phase II activities include the conduct of a two-day (48hrs) static study to determine dose levels for a 28-day range-finding study, and the conduct of the 28-day range-finding study. These activities are expected to take four months to complete. The results of Phase I and II shall be evaluated by the NTP and a determination will be made on whether the chemical(s) to be tested are suitable for a chronic long-term exposure, in which case an optional Phase III may be exercised. Phase III shall consist of a 16-month continuous aqueous exposure (chronic) study which also includes a special 9-month continuous exposure study followed by a 7-month grow-out period. These activities are expected to take 26 months. The basic contract award shall be for the conduct of TASK l (2,2-bis(bromomethyl)-l,3-propanediol), Phases I and II, and Task 2 (nitromethane), Phases I and II. Both TASK l and TASK 2 shall be conducted concurrently. Included in the basic contract award will be a lifespan control study for both species of fish which will start at the time that the Phase 1 activities for TASK l and TASK 2 are being conducted. The contract contains eight options. The chemicals selected for TASKS 1-5 have not been previously studied by the NTP by an aqueous route. If, after the TASK l and TASK 2 (Phases I and II) studies are completed, it is found that either of these compounds are not appropriate. i.e., (solubility or stability problems) for Phase III longterm chronic aqueous exposure studies, OPTION 3 will be exercised-Phase I and II activities for the TASK 3 chemical. If the TASK 3 chemical (l,2,3-trichloropropane) is not suitable for the Phase III study. OPTION 5 will be exercised - Phase I and II activities for the TASK 4 chemical. If the TASK 4 chemical (2,3-dichloropropylene) is not suitable for the Phase III study. OPTION 7 will be exercised - Phase I and II activities for the TASK 5 chemical (o-nitrotoluene). There may be as many as five chemicals for which Phases I and II activities are conducted. However, there will be no more than three chemicals subjected to Phase III activities under this contract.