SMALL FISH TO EVALUATE TOXIC CHEMICALS

该合同的目的是测试多达三种化学品， 作为NIEHS的一部分，对两种小鱼的职业兴趣， NTP正在努力开发亚哺乳动物的替代测试方法 物种 待研究的鱼类是青鳉（ORYZIAS LATIPES）和孔雀鱼（POECILIA RETICULATA）。 选择用于研究的化学品 要么是已被证实的致癌物，要么是初步数据表明致癌物 在大鼠和小鼠中的作用。 每一种化学品都是作为一个任务（任务1）提出的 - 2，2-二（溴甲基）-1，3-潘基文。 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。 任务5 - 邻硝基甲苯 每个任务包括三个阶段。 I期涉及散装 化学分析，预启动化学和健康的发展， 安全计划。 这些活动预计需要三个月的时间， 完成. 第二阶段的活动包括举行为期两天（48小时）的 静态研究，以确定28天剂量范围探索研究的剂量水平，以及 开展28天剂量范围探索研究。 这些活动 预计需要四个月完成。 第一阶段和第二阶段的结果 将由NTP进行评估，并确定是否 待测试的化学品适合于慢性长期暴露， 在这种情况下，可以进行可选的第三阶段。 第三阶段应 包括一项为期16个月的连续水暴露（慢性）研究， 还包括一项特殊的9个月连续暴露研究， 7-一个月的成长期 这些活动预计需要26个月。 基本合同的授予应针对任务1的执行 （2，2-双（溴甲基）-1，3-丙二醇），阶段I和II，以及任务2 （硝基甲烷），阶段I和II。 任务1和任务2均应进行 同时。 在基本合同授予将包括一个寿命 对这两种鱼的对照研究将在 任务1和任务2的第1阶段活动正在进行。 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途径研究过。 如果经过 任务1和任务2（I期和II期）研究完成后，发现 这两种化合物都不合适 也就是说，（溶解度或 稳定性问题）进行III期长期慢性水暴露 研究，将执行选项3-任务的I期和II期活动 3化学 如果任务3化学品（1，2，3-三氯丙烷）不 适合III期研究。 将采用备选方案5-第一阶段和 II.任务4化学品的活动。 如果任务4化学品 （2，3-二氯丙烯）不适用于III期研究。 备选方案7 - 任务5化学品的第一阶段和第二阶段活动 （邻硝基甲苯）。 可能有多达五种化学品， 开展了一、二项活动。 但是，不会有超过 三种化学品属于本合同下的第三阶段活动。

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.