High-boiling petroleum distillates are quite different from crude coal liquids of similar boiling range and more likel hydrotreated coal liquids in their content of PAH dermal tumorigens, tumorigenicity, and mutagenicity. Refining levels our differences in the composition among the crude oils, and lesser compositional differences are observed for their refined naphthas. Differences (if any) in the toxicity of the vapors of the naphthas are likely to be small and subtle. More complex and comprehensive biological testing would be required to quantitate differences in potential health effects. However, the results suggest that the HFO/HD and VGO distillates of these petroleum crude oils are not substantially more mutagenic or tumorigenic than the undistilled petroleum crude oils, in comparison to crude coal liquids. Thus, there do not appear to be any substantial advantages to preparing and using distillate fractions (at least of these) petroleum crude oils as benchmarks for comparative mutagenicity and tumorigenicity testing. The original data in the literature on unfractionated petroleum crude oils appear suitable for comparison with coal liquids. The concentrations of selected four- to six-ring PAH dermal tumorigens in the high boiling distillate fractions of lighter petroleum crude oils were found to be only ca. 2.5 times more concentratedmore » than in the undistilled crude oils. Further, these PAH in the distillate fractions were at least one to two orders of magnitude lower than in crude coal liquids of comparable boiling range, and more similar to those of hydrotreated coal liquids. 26 refs., 2 figs., 12 tabs.« less

Toph's in Chemical Mutagenesis is a new series dedicated to studies in the areas of environmental chemical mutagenesis and genetic toxicology. In this series we will explore some of many topics that a

Polycyclic aromatic hydrocarbons and/or their pyrolle derivatives were found to be the primary contributors to the skin tumorigenicity of the neutral fractions of two coal oils. Mutagenicity of the neutral fraction in Salmonella test strains was found to be due primarily to polycyclic aromatics containing polar substituents. Thus, the chemical classes responsible for skin tumorigencity differ from those responsible for mutagenicity.

Studies by the Oak Ridge National Laboratory and at Pacific Northwest Laboratory on hydrogenated coal liquids have shown that hydrotreatment significantly reduces the toxicological properties of coal liquefaction products. However, the cost of hydrotreatment is significant. This report presents the initial results of studies designed to identify and evaluate promising non-hydrotreating processes for reducing the toxicological properties of coal liquids. In these studies to date, the biological evaluation has been limited to the Ames mutagenicity assay. Other bioassays including mouse dermal tumorigenicity and aquatic toxicity are in progress but have not yet been completed. Samples used in this study were two heavy fuel oils and one fuel oil blend obtained from the Catlettsburg, KY, H-Coal Pilot Plant. One of the heavy fuel oil samples was subjected to nine alternative processes which were designed to reduce or eliminate the microbial mutagenicity of the oil. Mutagenicity assays on the resulting products indicated that the first six treatments listed showed promise for removing mutagens. The fraction of the mass recovered after each of these treatments ranged from 70 to 85%. Five of the promising treatments identified in the exploratory study were applied to five H-coal liquid products. Each of the listed treatments (distillation,more » sulfuric acid treatment, deasphalting, pentane/furfural partition, and clay percolation) was found to significantly reduce the mutagenicity in the resulting product.« less

The mixed-function oxidases that metabolize dimethylnitrosamine, aminopyrine, benzphetamine, 7-ethoxycoumarin and benzo[alpha]pyrene were measured in adults of the Canton-S, Oregon-R and Hikone-R strains of Drosophila melanogaster. The expression of these activities is both genotype and age dependent.

The relationship between dimethylnitrosamine (DMN) demethylase activity and DMN-induced mutagenesis was investigated in Drosophila melanogaster. The activity of DMN-demethylase was at least 10-fold greater in the Hikone-R strain than in three other Drosophila strains. However, the sex-linked recessive lethal (SLRL) mutations induced by DMN in the four strains differed by less than 2-fold. Several possibilities to explain the lack of correlation between DMN-demethylase activity and DMN-induced mutations were tested and eliminated. They include: (i) the presence of inhibitors of DMN-demethylase in extracts of low-activity strains, (ii) a sex bias in the Hikone-R strain in which the enzyme activity is confined to the females, (iii) the possibility that DMN treatment induces DMN-demethylase activity in the low-activity strains and (iv) the possibility that Hikone-R has a much more efficient DNA repair system than the other strains. The results are discussed in terms of what is known about the role of DMN-demethylase in the metabolic activation of DMN in other systems.

Products from coal liquefaction facilities contain many compounds such as polycyclic aromatic hydrocarbons, aromatic amines, nitrogen-and-sulfur-containing heterocyclic compounds, phenols, and trace metal compounds that are known or suspected to be carcinogenic, mutagenic, teratogenic, or toxic. Biological activity has been identified in product materials derived from PDU and pilot plant operations, which are considered generically representative of raw materials that might be produced by demonstration or commercial-scale facilities. Exploratory research studies have indicated that hydrotreatment reduces significantly the biological response and ecological hazard of these generic liquid products. The Oak Ridge National Laboratory (ORNL) has been asked by the Office of Fossil Energy, the US Department of Energy to assist in a systematic study of coal-derived liquids which are upgraded. The approach to upgrading in this program was in part a result of research at ORNL and the Battelle Pacific Northwest Laboratory which showed hydrotreatment effective for reducing mutagenicity and other biological and ecological properties. Experience at these and other laboratories has shown it to be essential to generate data on the chemical properties of the samples to assist in interpretation of bioassay results. This report summarizes the current status of an interdivisional program evaluating the effectiveness of hydrotreatment in reducingmore » the biological response and ecological hazard of coal liquids derived from the SRC-II, Exxon Donor Solvent (EDS), and H-coal processes. Although the program is continuing and the full set of data are not yet available, the considerable set of results generated to date clearly demonstrate the beneficial effects of hydrotreatment.« less

Two oral contraceptive steroids, mestranol and norethynodrel, were evaluated for mutagenicity in the Salmonella histidine reversion assay. The pure forms of the hormones were not mutagenic when tested with either missense (TA1535, TA100) or frameshift (TA98, TA1538, TA1537) strains. In vitro activation of the hormones with liver homogenates from rats induced either with phenobarbital or Aroclor did not influence these results. However, mestranol was capable of enhancing the mutation yield obtained by an ineffective subthreshold dose of 2-acetylaminofluorene. Dimethyl sulfoxide extracts of two contraceptive pills, Ovulen-21 (containing mestranol) or Enovid-E (containing mestranol or norethynodrel), also were nonmutagenic. But again, both these extracts were capable of enhancing the mutation yield induced with an ineffective dosage of 2-acetylaminofluorene and N-nitrosopiperidine. These studies point to the possible promotional effect and subsequent potential hazard to the female consumers who use these hormones as a means of pregnancy control.

4 procedures used to prepare fossil-derived oils for bacterial mutagenicity testing have been examined. These are, (a) dewaxing by partitioning the oil between dimethyl sulfoxide (DMSO) and cyclohexane, (b) incorporating a surfactant to increase compatability of the oil with the bioassay media, (c) directly slurrying the oil in DMSO, and (d) computing the mutagenicity of the oil by summing the contributions of individual chemical class fractions. DMSO slurries generally exhibit higher mutagenicities than computed by summing the contributions of chemical class fractions. Results of testing DMSO-slurries correlate (r = 0.87) well, however, with those obtained by summation. Mutagenicity results agree within a factor of two for the samples tested by 4 sample preparation procedures.

Potential bacterial biodegradation products of polychlorobiphenyls (PCBs) were evaluated as environmental mutagens.p-Chlorophenylglyoxylic acid,p-chloromandelic acid and three monochlorinated benzoic acids were not mutagenic in either the sister chromatid exchange (SCE) orSalmonella typhimurium histidine reversion mutagenesis assays. Bacterial degradation may, therefore, tend to decrease the mutagenic potential of lesser chlorinated PCBs.

Mutagenic activities of a large number of nitrosamines were determined using Salmonella histidine reversion and Escherichia coli arginine reversion assays. The cyclic nitrosamines exhibited a close correlation between their mutagenic and carcinogenic properties, while no such relationship was evident with the aliphatic nitrosamines. Substitution of cyclic nitrosamines with methyl, hydroxy and oxy groups did not alter the mutagenic activities. However, when positions alpha to the N-nitroso groups were substituted with methyl groups, the biological activity was eliminated. Substitution with halogens enhanced, whereas carboxyl substitution eliminated the biological activity. The E. coli assay not only substantiated the observations made with Salmonella, but also demonstrated mutagenic activity in the case of certain carcinogenic nitrosamines which were not mutagenic in the Salmonella assay.

Raw and hydrotreated product liquids from process demonstration units of experimental “H-coal” and “solvent-refined coal” processes were examined for acute toxicity monitored as population growth impairment of Tetrahymena exposed to aqueous extracts and for mutagenic activity monitored as revertants of Salmonella exposed to metabolically activated chemical class fractions. With both systems, deleterious effects are generally reduced as the severity of hydrotreatment is increased. The major exception appears to be with the low severity hydrotreated H-coal distillate where mutagenicity in the polyaromatic fraction is slightly enhanced over that of the raw distillate. However, medium to high severity hydrotreatment appears to be an effective means of reducing biological activity monitored presumably by reducing aromaticity and heteroatom content.

4,4′-Methylenedianiline and its derivatives were assayed for mutagenicity in the Salmonella/microsomal mutagenicity assay developed by Ames. A specificity to revert strain TA98 suggests a mechanism of frameshift mutagenesis. Liver microsomal preparations (S-9) from rats induced with phenobarbital were most effective for metabolic activation. Alkyl substitution of 4,4′-methylenedianiline did not alter its mutagenic activity; however, substitution of both positions ortho to the amino group eliminated mutagenic activity. Substitution with alkoxy-carbonyl groups eliminated mutagenic activity, whereas halogen substitution (chlorine, fluorine) enhanced the mutagenic activity. The results presented here show the use of structure-activity studies as predictive tools for the assessment of genotoxic properties of industrial chemicals.