Haloethylene-related compounds of industrial, environmental, and medical significance.

A broad-based literature survey was made for chemicals that contain either a haloethylene or a related substructure. Two hundred and sixty-two compounds, including synthetic intermediates, pesticides, solvents, drugs, food components, natural products, and metabolites, are grouped by their structures. Some are in current use or are bioavailable while little exposure is expected from others. As more biologic-response information is reported for small compounds of these types, it should become possible to select others for research on additional questions of structure–activity relationships. Some of the compounds are widespread while others are not. Some are used or found in large amounts while others may be trace contaminants, minor or more major by-products of synthesis or isolation. The pesticides and solvents, for example, are knowingly and often deliberately released to the environment, sometimes in very large quantities. Inadvertent release also occurs, sometimes referred to as fugitive emission. Food contaminants and drugs are directly accessible to humans. Sparsely distributed natural products could be accessible to humans, for example, via the food chain. Some of the compounds in food may be formed during preparation, storage or metabolically. Last, the haloethylene function has often been synthesized into compounds in order to achieve desired biologic activities. There are many types and degrees of relatedness of structure, depending upon atomic dimensions and stereochemical, polar, resonance, and other factors. Furthermore, for some chemical series, biologic responses are continuously variable while, in other cases, it is not uncommon that qualitatively different types of response occur with apparently very close homologs. Genetic, metabolic, and behavioral factors affecting response must also be considered. Thus, safety or hazard cannot yet be predicted conclusively by apparent relatedness of structure alone. Also, since the tables are noncomprehensive, some relevant compounds have likely been omitted. The haloalkanes, for example, are not here because of their large number, despite the knowledge that some are either metabolized or nonbiologically converted to haloalkenes.


Introduction
Vinyl chloride and some lower homologs have drawn attention in the past few years because of demonstrated or potential health hazards. A sufficient number of these have come into question so that a broad survey for this functional group in larger molecules was undertaken in order to permit an extended consideration of structure-activity relationships.
There are many subtleties of closeness of structure. Also, initially related or unrelated compounds *Office of Health Hazard Assessment, National Institute of Environmental Health Sciences, National Institutes of Health, P. 0. Box 12233, Research Triangle Park, North Carolina 27709. may become, respectively, unrelated or related by either metabolic or nonbiologic reactions. While Tables 1-6 are broad in scope, they are not comprehensive. There are at least three types of omissions: inadvertent; purposeful, because of the large number of compounds within a series (for example, the many alkanes that may be converted to alkenes); and those omitted because of an inability to be comprehensive without diluting the list with compounds for which there is scant reported use or human exposure.
The physicochemical factors of both the chemicals and exposed biologic species can be of immense importance in the control of biologic uptake, distribution, metabolism, storage, and subsequent excretion, secretion, or exhalation of the com- Cc--H c-0i. Environmental Health Perspectives a) co co      pounds. Also, the forms in which the chemicals are naturally present or are made commercially available may increase or decrease biologic availability and response.

Sources and Methods
The primary documents searched were The Condensed Chemical Dictionary (1), a portion of which was screened because in most cases the structural formula is omitted, The Merck Index (2) and the Pesticide Index (3). Each reports uses for the compounds. Because an immediately preceding (1,2) or earlier edition (3) was first used, newly listed compounds could have been omitted. However, all compounds chosen were verified for their current listing and their updated uses. Compounds were also found in other collections, in reviews, and in research reports.
The principle used in deciding on which names to use of the many alternate names listed was, first, the Chemical Abstracts name and, second, perhaps more general recognition by alternate names. Other names can be determined by looking at the names of closely related compounds and by referral to the cross indexes in the literature (1)(2)(3)(4)(5)(6)(7)(8)11). Repeatable variations are not routinely shown. The first name is uninverted, as given in the Ninth Collective Index (9CI) of Chemical Abstracts. These names are sometimes quite different from those appearing in the Eighth Collective Index (8CI) because of fairly extensive modification of the nomenclature rules in 1972. Generally, in our tables a common name is the first within parentheses. This is an "approved," "official," "generic," "abbreviated chemical," "source" or "trivial name" as defined in Pharmacological and Chemical Synonyms (4). Then another chemical name or research code number is indicated. The Registry of Toxic Effects of Chemical Substances (5) and Abstracts on Health Effects ofEnvironmental Pollutants: Chemical Index Guide (6) assisted in identifying additional names. # The first name used in the above collections has been called the "prime," "index" or "title name" and it varies considerably from one collection to another. The following guide should assist in determining a first name used elsewhere. Equivalent nomenclature forms are: -ene and -ylene; ethenyl and vinyl; chloro-, chlorand clor-; di4and bi-; a, ,3 ... and 1,2 . . .; inverted forms such as bromochloroand chlorobromo-; abbreviated names as in dibromodiiodoethene (which is ambiguous) and 1 ,2-dibromo-1 ,2-diiodoethene, and both CFE and CTFE for chlorotrifluoroethene; and other examples of earlier Chemical Abstracts and other nomenclature systems. Frankly misleading names remain popular. Some have been based upon a route of synthesis, for example, acetylene dichloride for 1,2-dichloroethene, and abbreviation, for example, both ethylene chloride and ethylene dichloride (which suggest an alkene) for 1,2dichloroethane. The stereochemical isomers or mixtures of isomers of the compounds are not uniformly noted in our tables and these are not standardized to the latest systems because of the complexity of the subject. However, the existence of multiple isomers should be kept in mind and it is, in fact quite common. Some compounds have two or even three stereochemical sites, for example, compounds 1-68 and 1-69 have three such sites. A compound may no longer actually be used as indicated, and probably not all uses have been identified. It is essentially impossible to sort these and be completely up to date. Vinyl chloride, for example, should no longer be used as a propellant or refrigerant since it has been banned in these uses. In the case of pesticides, those currently registered, even for very limited uses, are indicated as such. Some of these might be under reconsideration. Drugs included in APhA Druig Names (7) and Physician's Desk Reference (8) are indicated'. A few of the compounds are included here because of their close structural relationship to other listed compounds despite absence of an indicated use or source.
We are pleased to acknowledge the help of Mr. Ralph Hester in assembling some of the information in this report.