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Thirteen-Week, Repeated Inhalation Exposure of F344/N Rats and B6C3F1 Mice to Ferrocene. Nikula, K. J., Sun, J. D., Barr, E. B., Bechtold, W. E., Haley, P. J., Benson, J. M., Eidson, A. F., Burt, D. G., Dahl, A. R., Henderson, R. F., Chang, I. Y., Mauderly, J. L., Dieter, M.P., and Hobbs, C. H. (1993). Fundam. Appl. Toxicol. 21, 127-139. Ferrocene (dicyclopentadienyl iron; CAS No. 102-54-5) is a relatively volatile compound used as a chemical intermediate, a catalyst, and an antiknock additive in gasoline. This organometallic chemical is of particular interest because of its structural similarities to other metallocenes, some of which are carcinogenic. F344/N rats and B6C3F1 mice were exposed to 0, 3.0, 10, and 30 mg ferrocene vapor/m³, 6 hr/day, 5 days/week, for 13 weeks. During these exposures, no rats or mice died, nor were any clinical signs of ferrocene-related toxicity observed. At the end of the exposures, male rats exposed to the lowest and highest level of ferrocene had decreased body weight gains compared to filtered-air-exposed control male rats, while body weight gains for all groups of both ferrocene- and filtered-air-exposed female rats were similar. Male mice exposed to ferrocene had no differences in body weight gains, compared to controls, but female mice had decreases in body weight gains at the 10 and 30 mg/m³ exposure levels. There were exposure concentration- and exposure-time-related increases in lung burdens of iron. The mean iron lung burden in rats exposed to 30 mg ferrocene vapor/m³ for 90 days was four times greater than the burden in control rats. No exposure-related changes in respiratory function, lung biochemistry, bronchoalveolar lavage cytology, total lung collagen, clinical chemistry, and hematology parameters were observed. This suggests that the accumulations of iron in lung did not cause an inflammatory response nor any functional impairment of the lung. There were no indications of developing pulmonary fibrosis nor of any hematologic toxicity. No exposure-related gross lesions were seen in any of the rats or mice at necropsy. Exposure-related histopathologic alterations, primarily pigment accumulations, were observed in the nose, larynx, trachea, lung, and liver of both species, and in the kidneys of mice. Lesions were most severe in the nasal olfactory epithelium where pigment accumulation, necrotizing inflammation, metaplasia, and epithelial regeneration occurred. Nasal lesions were observed in all ferrocene-exposed animals and differed only in severity, which was dependent on the exposure concentration. Histochemical stains of these target tissues showed the presence of iron ions. The results suggest that the mechanism of ferrocene toxicity may be the intracellular release of ferrous ion through ferrocene metabolism, followed by either iron-catalyzed lipid peroxidation of cellular membranes or the iron-catalyzed Fenton reaction to form hydroxyl radicals that directly react with other key cellular components, such as protein or DNA. Copyright 1993, 1999 Academic Press

While 1,3-butadiene is carcinogenic in rodents, cancer causation in humans is less certain. We examined a spectrum of genotoxic outcomes in 41 butadiene polymer production workers and 38 non-exposed controls, in China, to explore the role of butadiene in human carcinogenesis. Because in vitro studies suggest that genetic polymorphisms in glutathione S-transferase enzymes influence genotoxic effects of butadiene, we also related genotoxicity to genetic polymorphisms in GSTT1 and GSTM1. Among butadiene-exposed workers, median air exposure was 2 p.p.m. (6 h time-weighted average), due largely to intermittent high level exposures. Compared with unexposed subjects, butadiene-exposed workers had greater levels of hemoglobin N-(2,3,4-trihydroxybutyl)valine (THBVal) adducts (P < 0.0001) and adduct levels tended to correlate, among butadiene-exposed workers, with air measures (P = 0.03). Butadiene-exposed workers did not differ, however, from unexposed workers with respect to frequency of uninduced or diepoxybutane-induced sister chromatid exchanges, aneuploidy as measured by fluorescence in situ hybridization of chromosomes 1, 7, 8 and 12, glycophorin A variants or lymphocyte hprt somatic mutation. Also among the exposed, greater THBVal levels were not associated with increases in uninduced sister chromatid exchanges, aneuploidy, glycophorin A or hprt mutations. Butadiene-exposed workers had greater lymphocyte (P = 0.002) and platelet counts (P = 0.07) and lymphocytes as a percentage of white blood cells were moderately correlated with greater THBVal levels (Spearman's phi = 0.32, P = 0.07). Among butadiene-exposed workers, neither GSTM1 nor GSTT1 genotype status predicted urinary mercapturic acid butanediol formation, THBVal adducts, uninduced sister chromatid exchanges, aneuploidy or mutations in the glycophorin A or hprt genes. Overall, the study demonstrated exposure to butadiene in these workers, by a variety of short-term and long-term measures, but did not show specific genotoxic effects, at the chromosomal or gene levels, related to that exposure.

Mainstream cigarette smoke generated using different puffing profiles and delivered under different exposure modes was characterized for particle size distribution, vaporlgas concentration, and chemical composition. Three exposure modes were compared: (1) nose-only, intermittent (NO-I), which simulated a periodic exposure; (2) nose-only, continuous (NO-C), in which a constant smoke concentration was maintained for several hours; and (3) whole-body, continuous (WB-C), which was similar to the NO-C mode except that the smoke was routed to a whole-body instead of to a nose-only exposure chamber. Three different puffing profiles were compared: (1) a standard (SP), 2-s, 35-ml puff once per minute; (2) a puff of double the standard volume (70 ml) once per minute (OP); and (3) a double puff twice per minute (2-DP). Results from multijet Mercer impactor samples indicated that the mass median aerodynamic diameter of smoke particles increased with mass concentration and decreased with puff volume. Gas samples showed no substantive differences between exposure modes with or without rats in the exposure chambers, except for CO2 concentrations in the WE-C chambers, NO2 concentrations in the NO-I chambers, and NO concentrations in the NO-C chambers. Linear relationships were observed between the concentration of total particulate matter and that of CO, NO, and volatile organic hydrocarbons under all exposure and puffing modes. Concentrations of six different organic vapors (acetone, 2-methylfuran, benzene, meta- and para-xylene, ortho-xylene, and limonene) were measured using Tenax trapping technique. The results showed no substantive differences among the three exposure modes or three puffing profiles, except that the concentrations of toluene, orthoxylene, and limonene were higher in smoke from the WE-C than from the NO-C (or NO-I) modes. The amounts of four particulate-phase constituents (nicotine, glycerol, hydroquinone, and palmitic acid) were analyzed chemically; good agreement was found in the amounts resulting from all of the puffing profiles and most of the exposure modes, except that nicotine was found to be slightly lower in the WE-C mode than in the other exposure modes.Sampling results indicated that there were few substantive differences in smoke composition among the different exposure and puffing modes used in this study We concluded that WB-C exposures to the cigarette smoke generated under 2-DP profiles might produce biological effects similar to those produced under SP profiles by nose-only exposures, and might be useful for chronic animal exposures.

Urinary phenol determinations have traditionally been used to monitor high levels of occupational benzene exposure, but the same technique cannot be used to monitor low-level exposures because of the high background of phenol resulting from its Presence in many foods and from metabolism of aromatic amino acids. Thus, new biological indexes for exposure to low levels of benzene are needed. Animal studies indicate that muconic acid is a metabolite of benzene that is excreted in the urine as an increasing fraction of the total benzene metabolites with decreasing dose of benzene. Thus, urinary muconic acid is potentially useful as a monitor for low levels of exposure to benzene. It is also of interest to determine the level of muconic acid in the urine of humans exposed to benzene for comparison with animal data as an aid for use of the animal studies in risk assessments for humans. This report describes the development of a gas chromatographylmass spectrometry assay to detect and quantitate the benzene metabolise, muconic acid, in urine. The internal standard used in the assay, muconic acid-d4, was biosynthesized bY F344/N rats administered benzene-d6 by gavage; the muconic acid was isolated from the rat's urine. Muconic acid was measured in experimental urine samples by adding the internal stalldard, followed by extraction and derivatization. Phenol was also measured in urine after extraction and derivatization. The assays were applied to the urine samples from 14 workers occupationally exposed to benzene and 8 workers with no known benlene exposure. Muconic acid could be detected in all of the urine samples at levels greater than 100 ng/mL. A linear correlation could be fitted to the time-weighted average (TWA) benzene concentrations, as measured by room air monitoring, and muconic acid in urine (R=0.9). Workers exposed to benzene concentrations of as little as 4.4 ppm over an 8-hr day possessed higher urinary muconic acid concentrations than did any control individual (p<0.005). In contrast, no significant difference could be detected for urinary phenol between exposed and control workers at these levels. The ratio between muconic acid and phenol in the urine of the workers exposed to benzene (0.38) was similar to that observed in rats (0.31), but not mice (0.62), exposed to similar amounts of benzene. The assay for muconic acid may potentially be useful as a biological exposure index for benzene at levels approaching the current American Conference of Governmental Industrial Hygienists' threshold limit value (TLY) of 1 ppm; however, improved knowledge of the excretion of muconic acid as a function of both dose and time after exposure will need to be made.

Burning incense in houses and temples for religious functions is especially common in Asia. Smoke from burning incense is a source of indoor aerosols, and extracts from this smoke are mutagenic in the Ames Salmonella test. This paper describes characterization of the smoke in terms of particle size, shape, concentration, density, and chemical composition. Our data showed that aerosols from incense smoke were spherical droplets with a count median diameter of about 0.13 μm and mass median aerodynamic diameter of 0.28 μm. The particle density was 1.06 ± 0.08 g cm-3. Aerosols produced from incense are therefore similar to other aerosols formed by condensation, such as environmental tobacco smoke found indoors. The aerosol concentration profiles and size distributions within a room during typical burning cycles were monitored. The air ventilation rate in the room was also measured by the SF6 tracer gas method. Respirable aerosol concentrations up to several hundred μg m-3 were produced by burning one to three joss sticks. By modeling the concentration change in the room with time using mathematical equations, we estimated the incense aerosol generation rate as a function of time and the aerosol removal rate constant. This source term information can be used to estimate incense smoke concentration in indoor environments.

A seven-cell, screen-type, parallel-flow diffusion battery (PFDB) was calibrated with monodisperse, yellow-green fluorescent, polystyrene latex particles. The particles were aerosolized and introduced into the PFDB with a flow that was uniformly distributed among the seven cells. The particles penetrating the screens in each cell were then collected on backup filters. To determine the mass of particles able to penetrate each cell, the particles were removed from the filters by dissolving them in ethyl acetate, and the fluorescence intensity of the solubilized material was determined using a fluorescence spectrophotometer. The results showed that the median sizes of the latex spheres could be estimated accurately from the mass penetration curves of the cells, even though the geometric standard deviations of the size distributions were overestimated. Particles in diluted main-stream cigarette smoke were sized using both diffusion battery and multijet Mercer impactor techniques. For smoke particles generated from a 2-see, 70-mL puff/min having a mean concentration of 161 mg/m3, the mass median diameter was estimated to be 0.35 µm by both techniques. However, for cigarette smoke containing >18% (by mass) of particles larger than 0.656 µm (the upper operable size of the PFDB at a flow rate of 1.58 L/min Per cell), the diffusion battery cannot provide accurate size measurements and only the impactor technique should be used.

Benzene is a ubiquitous environmental pollutant that is known to cause hematotoxicity and leukemia in humans. The initial oxidative metabolite of benzene has long been suspected to be benzene oxide (3,5-cyclohexadiene-1,2-oxide). During in vitro experiments designed to characterize the oxidative metabolism of [14C]benzene, a metabolite was detected by HPLC-radioactivity analysis that did not elute with other known oxidative metabolites. The purpose of our investigation was to prove the hypothesis that this metabolite was benzene oxide. Benzene (1 mM) was incubated with liver microsomes from human donors, male B6C3F1 mice, or male Fischer-344 rats, NADH (1 mM), and NADPH (1 mM) in 0.1 M sodium phosphate buffer (pH 7.4) and then extracted with methylene chloride. Gas chromatography-mass spectrometry analysis of incubation extracts for mice, rats, and humans detected a metabolite whose elution time and mass spectrum matched that of synthetic benzene oxide. The elution time of the benzene oxide peak was approximately 4.1 min, while phenol eluted at approximately 8 min. Benzene oxide also coeluted with the HPLC peak of the previously unidentified metabolite. Based on the 14C activity of this peak, the concentration of benzene oxide was determined to be approximately 18 microM, or 7% of total benzene metabolites, after 18 min of incubation of mouse microsomes with 1 mM benzene. The metabolite was not observed in incubations using heat-inactivated microsomes. This is the first demonstration that benzene oxide is a product of hepatic benzene metabolism in vitro. The level of benzene oxide detected suggests that benzene oxide is sufficiently stable to reach significant levels in the blood of mice, rats, and humans and may be translocated to the bone marrow. Therefore benzene oxide should not be excluded as a possible metabolite involved in benzene-induced leukemogenesis.

The acid catalyzed rate for hydrolysis of methylphosponfluoridic acid has been determined at several hydrogen ion concentrations and temperatures. The acid hydrolysis is second order (in acid and substrate). Assumed rate expressions, observed rate constants, and hydrogen ion concentrations were used to calculate the thermodynamic equilibrium constant (Ka=0.56) and rate constants for acid catalysis. The activation energy Ea has been determined as 18.3 Kcal/mole. Finally, the acid catalyzed deuterolysis was determined to be about 1.47 times the rate of hydrolysis. The data suggest a two-step mechanism consisting of a rapid proton transfer, followed by slow hydration of the protonated complex.

Two-Week, Repeated Inhalation Exposure of F344/N Rats and B6C3F1 Mice to Ferrocene. SUN, J. D., DAHL, A. R., GILLETT, N. A., BARR, E. B., CREWS, M. L., EIDSON, A. F., BECHTOLD, W. E., BURT, D. G., DIETER, M. P., AND HOBBS, C. H. (1991). Fundam. Appl Toxicol. 17, 150-158. Ferrocene (dicyclopentadienyl iron; CAS No. 102-54-5) is a relatively volatile, organometallic compound used as a chemical intermediate, a catalyst, and as an antiknock additive in gasoline. It is of particular interest because of its structural similarities to other metallocenes that have been shown to be carcinogenic. F344/N rats and B6C3F, mice were exposed to 0, 2.5, 5.0, 10, 20, and 40 mg ferrocene vapor/m3, 6 hr/day for 2 weeks. During these exposures, there were no mortality and no observable clinical signs of ferrocene-related toxicity in any of the animals. At the end of the exposures, male rats exposed to the highest level of ferrocene had decreased body-weight gains relative to the weight gained by filtered air-exposed control rats, while body-weight gains for all groups of both ferrocene- and filtered air-exposed female rats were similar. Male mice exposed to the highest level of ferrocene also had decreased body-weight gains, relative to controls, while female mice had relative decreases in body-weight gains at the three highest exposure levels. Male rats had a slight decrease in relative liver weight at the highest level of exposure, whereas no relative differences in organ weights were seen in female rats. Male mice had exposure-relative decreases in liver and spleen weights, and an increase in thymus weights, relative to controls. For female mice, relative decreases in organ weights were seen for brain, liver, and spleen. No exposure-related gross lesions were seen in any of the rats or mice at necropsy. Histopathological examination was done only on the nasal turbinates, lungs, liver, and spleen. The only exposure-related finding was histopathologic lesions in the nasal turbinates of both species. These lesions were primarily centered in the olfactory epithelium and were morphologically diagnosed as subacute, necrotizing inflammation. Nasal lesions were observed in all ferrocene-exposed animals and differed only in severity, which was dependent on the exposure concentration. In vitro metabolism studies of ferrocene showed that nasal tissue, particularly the olfactory epithelium, had 10 times higher “ferrocene hydroxylating” activity than did liver tissue from the same animals. These results suggest that the mechanism of ferrocene toxicity may be the intracellular release of ferrous ion through ferrocene metabolism, followed by iron-catalyzed lipid peroxidalion of cellular membranes.

Effect of Inhaled Azodicarbonamide on F344/N Rats and B6C3F, Mice with 2-Week and 13-Week Inhalation Exposures. MEDINSKY, M. A., BECHTOLD, W. E., BIRNBAUM, L. S., BOND, J. A., BURT, D. G., CHENG, Y. S., GILLFTT, N. A., GULATI, D. K., HOBBS, C. H., AND PICK-RELL, J. A. (1990). Fundam. Appl. Toxicol 15, 308/319. Azodicarbonamide (ADA), a compound used in the baking and plastics industries, has been reported to cause pulmonary sensiti-zation and dermatitis in people. Two-week repeated and 13-week subchronic inhalation exposures of F344/N rats and B6C3F, mice to ADA were conducted to determine the toxicity of inhaled ADA. The mean air concentrations of ADA in the 2-week studies were 207, 102, 52, 9.4, or 2.0 mg/m3. No exposure-related mortality nor abnormal clinical signs were observed in rats or mice during or after exposure. The terminal body weights were slightly depressed in the highest exposure group. Liver weights were lower in male rats exposed to 200 mg ADA/m3. No significant lesions were noted on either gross or histologic evaluation of rats or mice. In the 13-week subchronic study, the mean air concentrations of ADA were 204, 100, or 50 mg/m3. No mortality or clinical signs related to exposure were observed. The terminal body weights of exposed rats were not significantly different from those of control rats but were significantly depressed in mice exposed to 100 or 200 mg ADA/m3. No histopathological lesions were noted in mice. Lung weights were increased and enlarged mediastinal and/or tracheobronchial lymph nodes were noted in rats exposed to 50 mg ADA/m3. No exposure-related lesions were observed microscopically in rats exposed to 100 or 200 mg ADA/m3. All rats in the 50 mg ADA/m3 exposure group only had lung lesions that consisted of perivascular cuffing with lymphocytes and a multifocal type II cell hyperplasia, suggesting a possible immune reaction to an antigen in the lung. Viral titers for rats exposed to 50 mg ADA/m3 were negative for Sendai virus and pneumonia virus of mice, which produce similar lesions. The possibility of an unknown viral antigen causing this lesion cannot be eliminated. Lung tissue from male rats was analyzed for ADA and biurea, the major metabolite of ADA. No ADA was detected. The amount of biurea in the lungs increased nonlinearly with increasing exposure concentration, suggesting that clearance was somewhat impaired with repeated exposures. However, even at the highest exposure concentration, this amount of biurea was less than 1 % of the estimated total ADA deposited over the exposure period. In summary, ADA is rapidly cleared from the lungs, even when inhaled at concentrations up to 200 mg/m3. Exposure to ADA for up to 13 weeks did not appear to be toxic to rodents

The Fate of Inhaled Azodicarbonamide in Rats. Mewhinney, J. A., AYRES, P. H., BECHTOLD, W. E., DUTCHER, J. S., CHENG, Y. S., BOND, J. A., MEDINSKY, M. A., HENDERSON, R. F., AND BIRNBAUM, L. S. (1987). Fundam. Appl. Toxicol. 8, 372–381. Azodicarbonamide (ADA) is widely used as a blowing agent in the manufacture of expanded foam plastics, as an aging and bleaching agent in flour, and as a bread dough conditioner. Human exposures have been reported during manufacture as well as during use. Groups of male F344/N rats were administered ADA by gavage, by intratracheal instillation, and by inhalation exposure to determine the disposition and modes of excretion of ADA and its metabolites. At 72 hr following gavage, 30% of the administered ADA was absorbed whereas following intratracheal instillation, absorption was 90%. Comparison between groups of rats exposed by inhalation to ADA to achieve body burdens of 24 or 1230 μg showed no significant differences in modes or rates of excretion of [14C]ADA equivalents. ADA was readily converted to biurea under physiological conditions and biurea was the only 14C-labeled compound present in excreta. [14C]ADA equivalents were present in all examined tissues immediately after inhalation exposure, and clearance half-times on the order of 1 day were evident for all tissues investigated. Storage depots for [14C]ADA equivalents were not observed. The rate of buildup of [14C]ADA equivalents in blood was linearly related to the lung content as measured from rats withdrawn at selected times during a 6-hr inhalation exposure at an aerosol concentration of 25 μg, ADA/liter. In a study extending 102 days after exposure, retention of [14C]ADA equivalents in tissues was described by a two-component negative exponential function. The results from this study indicate that upon inhalation, ADA is rapidly converted to biurea and that biurea is then eliminated rapidly from all tissues with the majority of the elimination via the urine.

Effect of Dose on the Disposition of 2-Ethoxyethanol after Inhalation by F344/N Rats. Kennedy, C. H., Bechtold, W. E., Chang, I-Y., and Henderson, R. F. (1993). Fundam. Appl. Toxicol.21, 486-491.

Uptake of Vinylidene Fluoride in Rats Simulated by a Physiological Model. Medinsky, M. A., Bechtold, W. E., Birnbaum, L. S., Chico, D. M., Gerlach, R. F., and Henderson, R. F. (1988). Fundam. Appl. Toxicol 11, 250–260. The purpose of this study was to develop a physiological model to simulate the uptake of vinylidene fluoride (VDF), an important plastics monomer, in laboratory animals. Male Fischer 344/N rats were exposed nose-only for 6 hr to concentrations of VDF ranging from 27 to 16,000 ppm. Tidal volume (mean, 1.51 ml/breath) and respiratory frequency (mean, 132 breaths/min) were not influenced by exposure concentration. Experimentally determined, steady-state blood levels of VDF, obtained by gas chromatog-raphy-head space analysis of samples from rats with indwelling jugular cannulas, increased linearly with increasing exposure concentration up to 16,000 ppm. VDF tissue/air partition coefficients were determined experimentally to be 0.07,0.18,0.8, 1.0, and 0.29 for water, blood, liver, fat, and muscle, respectively. These values and calculated constants for total body elimination of VDF, Km and Vmax were incorporated into the physiological model. Model predictions agreed with the experimentally determined data. Time to reach steady-state blood levels of VDF was less than 15 min for all concentrations. After cessation of exposure, blood levels of VDF decreased to 10% of steady-state levels by 1 hr. Simulation of the metabolism of VDF indicated that although blood levels of VDF increased linearly with increasing concentration the amount of VDF metabolized per 6-hr exposure period approached a maximum at about 2000 ppm VDF.

Excretion and Metabolism of 1-Nitropyrene in Rats after Oral or Intraperitoneal Administration. DUTCHER, J. S., SUN, J. D., BECHTOLD, W. E., and UKEFER, C. J. (1985). Fundam. Appl. Toxicol. 5, 287–296. Many nitro-substituted polycyclic aromatic hydrocarbons (NPAHs) have been identified as environmental pollutants and have been found to be mutagens and carcinogens in bacteria and mammalian systems. They require metabolism to express their biological activity. The metabolism and excretion of 1-nitropyrene (NP), a prevalent NPAH, by Fischer-344 rats after intraperitoneal (ip) or oral administration was studied. Radiolabeled NP was administered to rats (10 mg NP/kg body wt), and urine and feces were collected for 7 days. After ip administration of [14C]NP, 60% of the radioactivity was found in the urine and 20% in the feces. Likewise, 55 and 35% of the orally administered 14C was found in urine and feces, respectively. Both urine and feces were analyzed by high-pressure liquid chromatography for metabolites. The majority of the radioactivity in both urine and feces was associated with very polar metabolites, none accounting for more than 10% of the dose. Small amounts (less than 1% of the dose) of aminopyrene (AP), acetylaminopyrene, and NP were detected. A urinary metabolite (3–8% of the dose) was found that converted to acetylaminopyrene phenol (two isomers) when urine was heated overnight at 37°C at pH 4.5. More of this metabolite (2.2 times) as well as AP (1.8 times), was excreted after oral than after ip administration of NP. The NP metabolites found in this study demonstrate that reduction of the nitro group is a significant route of NP metabolism in rats. Since nitroreduction appears to be necessary in the activation of NPAHs to bacterial mutagens, this indicates that similar metabolic pathways are present in rats (catalyzed by mammalian and/or gut bacterial enzymes) and that activation of NPAHs to carcinogens or toxins by nitroreduction is possible.

Chemical and Biological Properties of Diesel Exhaust Particles Collected during Selected Segments of a Simulated Driving Cycle. BECHTOLD, W. E., DUTCHER, J. S., MOKLER, B. V., LOPEZ, J. A., WOLF, I., LI, A. P., HENDERSON, T. R., AND MCCLELLAN, R. O. (1984). Fundam. Appl. Toxicol. 4, 370–377. Particle emissions, percentage of organic extractable materials, and mutagenicities of extracts from a diesel engine operating on a test stand have been determined for the full Federal Test Procedure driving cycle and several individual segments thereof. Particle samples were collected using a computer controlled high volume sampler. Extracts of the exhaust particles were screened for the potent mutagens nitropyrene/nitrofluoranthenes by mass spectrometry/mass spectrometry (MS/MS). Results indicate that a long acceleration from 0-55 mph produced approximately seven times more particles per second than the full cycle. Also, the 0-to 55-mph acceleration and a subsequent 55-mph cruise produced significantly higher amounts of mutagens than other segments or the full FTP cycle. A direct correlation of both NOx levels and temperature with mutagenicity was noted (r = 0.89 and r = 0.89). The specific activities of the extracts showed decreases or remained unchanged when assayed in TA-98 NR or TA-98 1,8 DNP6, nitroreductase deficient strains of TA-98. Three extracts were found to have high levels of nitropyrenes/nitrofluoranthenes, and two of the three had high specific activities in TA-98.

Gender differences in haematotoxicity and weight changes associated with exposure to gasoline vapours (6hrs/day for 20 weeks) in rats was assessed in this study. The results showed that the levels of Hb, PCV and RBC counts in both male and female rats reduced significantly, while the WBC count increased significantly (P0.05) in male rats, exposed to gasoline vapours. The comparative percentage decrease in Hb, PCV, RBC were significantly higher (P Keywords: gasoline-vapours, haematotoxicity, weight-loss, growth-depression, gender-differences, Table of Contents Abstract Introduction Materials And Methods Results And Discussion References Introduction Liquid gasoline is composed of approximately 150 different hydrocarbons including 60-70% alkanes, 25-35% aromatics, and 5-10% alkenes [...]