ABSTRACT
With this effort, we continue our examination of data on selected pesticide chemicals and their related analogues that have been presented to the U.S. Environmental Protection Agency's (USEPA's) Office of Pesticide Programs (OPP). This report focuses on a group of selected chloroacetanilides and a few related compounds. As part of the registration process for pesticidal chemicals, interested parties (registrants) must submit toxicity information to support the registration including both mutagenicity and carcinogenicity data. Although this information is available to the public via Freedom of Information (FOI) requests to the OPP, publication in the scientific literature allows greater dissemination and examination of the data. For this Special Issue, graphic profiles have been prepared of the mutagenicity and carcinogenicity data available in the submissions to OPP. Also, a discussion is presented about how toxicity data are used to help establish tolerances (limits of pesticide residues in foods). The mutagenicity results submitted by registrants are supplemented by data on these chemicals from the open literature to provide a full perspective of their genetic toxicology. The group of chloroacetanilides reviewed here display a consistent pattern of mutagenic activity, probably mediated via metabolites. This mutagenic activity is a mechanistically plausible factor in the development of tumors seen in experimental animals exposed to this class of chemicals.
Subject(s)
Aniline Compounds/toxicity , Carcinogens/toxicity , Chlorine/toxicity , Mutagens/toxicity , Pesticides/toxicity , Acetamides/analysis , Acetamides/toxicity , Acetanilides/analysis , Acetanilides/toxicity , Alanine/analogs & derivatives , Alanine/analysis , Alanine/toxicity , Aniline Compounds/chemistry , Animals , Chlorine/chemistry , Female , Humans , Male , Mice , Mice, Inbred Strains , Rats , Rats, Sprague-Dawley , Tissue Distribution , Toluidines/analysis , Toluidines/toxicity , United States , United States Environmental Protection AgencyABSTRACT
Compiled results of the 1984 Genetic Toxicology Association's survey representing a total of 72 responses from governmental, contract, industrial, or academic institutions regarding the status of 32 recognized genetic toxicology assays, were as follows: Most frequently performed on a routine or occasional basis: Ames (76% of all respondents routinely or occasionally perform the assay); in vitro cytogenetics (59%); in vivo Bone Marrow Cytogenetics (56%); in vitro Sister Chromatid Exchange (56%); in vitro Unscheduled DNA Synthesis (43%); Mutation in CHO HGPRT (42%); Micronucleus test (41%); Mutation in L5178Y (36%). Assay associated with in vivo and in vitro chromosomal end points (aberrations, SCE, micronucleus) constituted the major area of increased use since the 1982 survey. Assays of developmental interest included DNAS binding both in vitro and in vivo and UDS in vivo. Quantitative analysis of the data indicated: Industrial and contract laboratories processed the largest volumes of chemicals over the broadest spectrum of assays. Industrial laboratories showed a marked increased since 1982 in testing compounds in-house. The number of assays sponsored by governmental laboratories, both in-house or subcontracted, increased from 1982. Academic institutions ranked lowest in number of compounds examined.
Subject(s)
Mutagenicity Tests , Animals , Cricetinae , DNA Repair , Drosophila , Hypoxanthine Phosphoribosyltransferase/analysis , Industry , Laboratories , Mice , Sister Chromatid Exchange/drug effects , Surveys and Questionnaires , Time Factors , Transformation, GeneticABSTRACT
Genetic Toxicology Association members from governmental, contract and industrial laboratories were surveyed to determine the status of 28 recognized genetic toxicology assays in their laboratories. Compiled results of the 1982 questionnaire indicate that the Ames test, in vitro cytogenetics, in vitro sister chromatid exchange, unscheduled DNA synthesis, mutation in Chinese hamster ovary cells at the HGPRT locus, and in vivo bone marrow assays were the most frequently performed routine tests by the majority of laboratory affiliations. Investigation of the number of transformation assays performed indicated a high routine use. However, their use was largely confined to contract laboratories. Volume analysis of chemicals tested for 1982 indicated: (i) contract laboratories studied the largest number of compounds over the broadest spectrum of assays; (ii) industrial laboratories processed more compounds in the Ames test than any other laboratory group; and (iii) governmental laboratories ranked lowest in numbers of compounds evaluated both in-house and/or subcontracted .
Subject(s)
Mutagenicity Tests/trends , Mutagens/toxicity , Animals , Contract Services , Cricetinae , Government , Humans , Industry , Laboratories , Mice , Societies, Scientific , United StatesABSTRACT
We have devised a microsuspension assay utilizing E coli indicator strains WP2, WP2 uvrA, WP67, CM611, WP100, W3110polA+, and p3478 pola- for the detection of chemically-induced preferential kill of repair-deficient strains. Data are presented from tests of 77 compounds representing a wide range of chemical classes which demonstrate the efficiency of the E coli microsuspension assay as both a qualitative and quantitative screen of DNA-modifying activity. Furthermore, the use of a battery of indicator strains lacking different repair systems offers the advantage of providing preliminary information concerning the mechanism of DNA damage induction by a test agent.
