To assess the effect of interim clean-up measures on the current health of a community, we conducted a follow-up survey of 193 residents living near the McColl waste disposal site and a comparison area located approximately 5 miles from the site. Results from this survey were compared with results from a similar survey conducted 7 years earlier. Odors were detected at least once per week by 32.7% of "high-exposed" respondents in 1988 compared with 68.5% in 1981, but prevalence odds ratios (PORs) comparing symptom reporting between "high-exposed" and comparison-area respondents were greater than that of the 1981 survey for 89% of symptoms. PORs comparing symptom reporting between these two areas were greater than 2.0 for 64% of symptoms assessed in the current survey. Symptoms reported in excess did not represent a single organ system or suggest a mechanism of response. PORs comparing respondents who were very worried about the environment and those reporting no worry were greater than 2.0 for 86% of symptoms. These finding, along with environmental data from the area, suggest that living near the waste disposal site and being very worried about the environment, rather than a toxicologic effect of chemical from the site, explain excess symptom reporting found in this follow-up study.

Seventeen structurally homologous nitroaromatics were tested for direct-acting mutagenic potency in nine strains of Salmonella typhimurium. The following four structural features were determined to have a strong influence on mutagenic activity: physical dimensions of the aromatic rings, isomeric position of the nitro group, conformation of the nitro group with respect to the plane of the aromatic rings, and ability to resonance-stabilize the ultimate electrophile. Progressive addition of five- and six-membered rings to a nitrobenzene nucleus demonstrated that mutagenic activity was a direct function of size. Fluoranthene was of optimal size (four rings) for mutagenicity; an additional benzene ring, giving benzo[k]fluoranthene, reduced mutagenic activity. Nitroaromatics with a nitro group oriented along the long axis of symmetry of the molecule were more potent mutagens than those with the nitro group oriented along the short axis. These results are discussed in light of the insertion-denaturation model for intercalation of certain DNA adducts. Nitroaromatics with nitro groups sterically forced out of the plane of the aromatic rings were weakly mutagenic or nonmutagenic. Nitro groups located between two peri hydrogens or in a bay-region are examples of this conformation. Finally, structural features that contribute to resonance stabilization of the reactive nitrenium ion enhance mutagenic potency. Thus, 6-nitroindene was at least tenfold more mutagenic than 5-nitroindene. These positional isomers are structurally identical with the exception of the position of an olefinic bond in the adjacent five-membered ring which can contribute to resonance stabilization of a carbonium ion formed after bioactivation of 6-nitroindene but not of 5-nitroindene. The predictive value of these structure-activity relationships should permit a first approximation in the assessment of mutagenic potency of nitroaromatics.

Twenty-nine derivatives of fluorene were tested for mutagenic potency in four strains of Salmonella typhimurium with and/or without S9 microsomal activation. The effects of a second functional group on the mutagenic activity of an amino-, nitroso-, and nitrofluorene were correlated with its physical and chemical properties. When the functional group is conjugated by resonance, both inductive and resonance effects are determinants of mutagenic potency. Electron-withdrawing groups such as the halogens (F, C1, Br, and I), nitro, nitroso, and cyano at C-7 increased the mutagenic potency of 2-nitrofluorene. Electron-donating substituents such as hydroxy and amino groups at C-7 decreased the mutagenic potency of 2-amino, 2-nitroso-, and 2-nitrofluorene. Acetylation of a hydroxy or an amino group at C-7 increased the mutagenic potency of 2-nitrofluorene, presumably by decreasing the electron-donating properties of these groups. In contrast, acetylation of a nonresonance-conjugated amino group decreased mutagenic activity. The physical properties of a second functional group are expected to exert their effect(s) at three points in the metabolic activation of 2,7-disubstituted fluorene derivatives: initial reduction of the nitro group (redox effect), stabilization of the hydroxylamine (inductive effect), and stabilization/destabilization of the nitrenium ion (resonance and inductive effects). The relationships between the physical properties of a second functional group and their effects on biological activities of nitro- and aminofluorenes in the Ames Salmonella assay may be of predictive value in a first approximation of both the mutagenic and carcinogenic potency of chemicals with comparable structures such as fluoranthene and biphenyl.