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.
| Kissling, Grace E; Bernheim, Naomi J; Hawkins, William E et al. (2006) The utility of the guppy (Poecilia reticulata) and medaka (Oryzias latipes) in evaluation of chemicals for carcinogenicity. Toxicol Sci 92:143-56 |
