Characterization of volatile organic compounds in smoke at municipal structural fires.

The objective of this study was to characterize volatile organic compounds (VOCs) found at municipal structural fires in order to identify sources of long-term health risks to firefighters, which may be contributing factors in heart disease and cancer. Firefighters collected air into evacuated Summa canisters inside burning buildings at nine municipal structural fires under conditions where they judged that at least some firefighters might remove their self-contained breathing apparatus masks. Volatile organic compounds were identified and quantified for 144 target compounds using cryogenic preconcentration and gas chromatography/mass spectral detection (GC/MSD) methodology operating in selected ion monitoring mode. Samples were also analyzed in SCAN mode and examined for the appearance of substances that were not present in the instrument standard calibration mixture. The spectra of municipal structural fires were surprisingly similar and remarkable for their simplicity, which was largely due to the dominating presence of benzene along with toluene and naphthalene. Propene and 1,3-butadiene were found in all of the fires, and styrene and other alkyl-substituted benzene compounds were frequently identified. Similar "fingerprints" of the same 14 substances (propene, benzene, xylenes, 1-butene/2-methylpropene, toluene, propane, 1,2-butadiene, 2-methylbutane, ethylbenzene, naphthalene, styrene, cyclopentene, 1-methylcyclopentene, isopropylbenzene) previously identified at experimental fires burning various solid combustible materials were also found at municipal structural fires, accounting for 76.8% of the total VOCs measured. Statistically significant positive correlations were found between increasing levels of benzene and levels of propene, the xylenes, toluene, 1-butene/2-methylpropene, 1,3-butadiene, and naphthalene. Given the toxicity/carcinogenicity of those VOCs that were found in the highest concentrations, particularly benzene, 1,3-butadiene, and styrene, further investigation of VOC exposures of firefighters is warranted. Benzene, or its metabolic product s-phenylmercapturic acid in urine, was identified as a suitable chemical marker for firefighter exposure to combustion products.

Characterization of volatile organic compounds in smoke at experimental fires.

Significant associations between firefighting and cancer have been reported; however, studies finding toxic products of combustion at municipal fires have been limited by (1) technical difficulties encountered at the scene of working fires, (2) the lack of a coherent sampling strategy, and (3) the absence of verified sampling methods. The objective of the present study was to characterize the presence of volatile organic compound (VOC) combustion products in fire smoke. Air samples from experimental fires burning various materials commonly found at structural fires were collected into evacuated Summa canisters and analyzed for 144 target VOCs using cryogenic preconcentration and gas chromatography/mass spectroscopy (GC/MSD) methodology. The resulting chromatograms were characterized by a small number of predominant peaks, with 14 substances (propene, benzene, xylenes, 1-butene/2-methylpropene, toluene, propane, 1,2-butadiene, 2-methylbutane, ethylbenzene, naphthalene, styrene, cyclopentene, 1-methylcyclopentene, isopropylbenzene) being found in proportionately higher concentrations in all experimental fires and accounting for 65% (SD = +/-12%) by mass of total measured VOCs. Benzene, toluene, 1,3-butadiene, naphthalene, and styrene were found at higher concentrations than most other VOCs and increased with the time of combustion together with increasing levels of carbon monoxide. Benzene was found in the highest concentrations, with peak levels ranging from 0.6 ppm to 65 ppm, while the levels of 1,3-butadiene, styrene, and naphthalene peaked at 0.1, 0.4, and 3 ppm, respectively. This study revealed that there were no new or novel, toxic nonpolar VOCs resulting from the burning of common building materials. This is important in view of the studies that have found associations between firefighting and various forms of cancer.

Pesticide use in developing countries.

Chemical pesticides have been a boon to equatorial, developing nations in their efforts to eradicate insect-borne, endemic diseases, to produce adequate food and to protect forests, plantations and fibre (wood, cotton, clothing, etc.). Controversy exists over the global dependence on such agents, given their excessive use/misuse, their volatility, long-distance transport and eventual environmental contamination in colder climates. Many developing countries are in transitional phases with migration of the agricultural workforce to urban centres in search of better-paying jobs, leaving fewer people responsible for raising traditional foods for themselves and for the new, industrialized workforce. Capable of growing two or three crops per year, these same countries are becoming "breadbaskets" for the world, exporting nontraditional agricultural produce to regions having colder climates and shorter growing seasons, thereby earning much needed international trade credits. To attain these goals, there has been increased reliance on chemical pesticides. Many older, nonpatented, more toxic, environmentally persistent and inexpensive chemicals are used extensively in developing nations, creating serious acute health problems and local and global environmental contamination. There is growing public concern in these countries that no one is aware of the extent of pesticide residue contamination on local, fresh produce purchased daily or of potential, long-term, adverse health effects on consumers. Few developing nations have a clearly expressed "philosophy" concerning pesticides. There is a lack of rigorous legislation and regulations to control pesticides as well as training programs for personnel to inspect and monitor use and to initiate training programs for pesticide consumers.

Municipal firefighter exposure groups, time spent at fires and use of self-contained-breathing-apparatus.

BACKGROUND: Previous studies have found significant associations between firefighting and cancer. METHODS: Fires, vehicle movement, and firefighter job assignment were determined, and storage and distribution of self-contained-breathing-apparatus (SCBAs) were tracked for 12 months. Time spent at fires and use of SCBAs were calculated. RESULTS: Only 66% of fire department personnel were 1st-line combat firefighters. Number of runs was an unreliable surrogate for time spent at fires. Eight firefighter exposure groups were identified (based on job title, firehall assignment, and time spent at fires), ranging from no exposures to 3,244 min/year/firefighter. SCBAs appear to have been used for approximately 50% of the time at structural fires but for only 6% of the time at all fires. CONCLUSIONS: Failure of previous studies to identify homogeneous exposure groups may have resulted in misclassification and underestimates of health risks. The approach used in this study may be used in epidemiological studies to identify exposure/response relationships.

Our changing perspectives on benefits and risks of pesticides: a historical overview.

The introduction of chemical pesticides following WW II ushered in the era of the "quick fix" for any aqricultural, forestry and human health problems. Scenarios of use, misuse, abuse and environmental contamination can be presented for any class of pesticide, culminating in dependence on these chemicals for increased production of food and fibre and improved health. With time, sophisticated agents having unique, target-specific mechanisms of action evolved but at increased cost(s) to crop production. Equatorial countries, rapidly becoming "breadbaskets" of the world, are particularly dependent on pesticides as they strive to increase production of nontraditional export products (NTEPS), valuable cash crops in demand in countries having more temperate climates. Developing nations have neither the legislation and regulations necessary to control pesticides nor trained personnel to inspect and monitor use, to analyze residues in produce or to initiate training programs. Their transition from agrarian to industrialized societies has meant that smaller, less well educated populations must shoulder the responsibility of increased traditional food production for consumption by urban populations as well as that of NTEPS. Unfortunately, to attain these goals, many older, more toxic, environmentally persistent and cheap pesticides, long banned in developed countries, are used extensively, creating serious local and global contamination and health problems.

Tentative explanatory variable of lung dust concentration in gold miners exposed to crystalline silica.

INTRODUCTION: The first objective of the study was to investigate the relationships between quantitative lung mineral dust burdens, dust exposure history, and pathological fibrosis grading in silicotic workers. The second objective was to evaluate the association between particle size parameters, concentration of retained silica particles and the severity of the silicosis. Sixty-seven paraffin-embedded lung tissue samples of silicotic patients were analyzed. The cases of silicosis included 39 non-lung cancer patients and 28 patients with lung cancer. All of the cases were gold miners in the Province of Ontario, Canada. MATERIAL AND METHODS: Particles, both angular and fibrous, were extracted from lung parenchyma by a bleach digestion method, mounted on copper microscopic grids by a carbon replica technique, and analyzed by transmission electron microscopy (TEM) and energy dispersive spectroscopy (EDS). Quartz concentration was also determined by X-ray diffraction (XRD) on a silver membrane filter after the extraction from the lung parenchyma. RESULTS: Total particles, silica, clay, and quartz also increase in concentration with increased age at death, although the trends are not statistically significant. Quartz concentration has a statistically significant correlation with the silicosis severity score (r = +0.45, p < 0.001), with the geometric mean concentration increasing from 2.24 micrograms/mg in the group having silicosis severity score less than 1 to 4.80 micrograms/mg in group with highest score. Quartz concentration is the only significant explanatory variable of the silicosis severity with a regression coefficient of +0.41 (p < 0.001). CONCLUSION: Among several dust exposure variables extracted from the work history of the miners, the calendar year of first exposure was the primary significant determinant of lung retained total particles, silica, and clay minerals, except for quartz. A statistically significant linear relationship between lung quartz concentration and silicosis severity in the gold miners was observed (p < 0.001). Among the several types of lung particles detected, quartz was the only significant determinant of the silicosis severity in the gold miners in this study and vice versa, although it explained only 20% of the variation in the severity. This study suggested no significant linear relationship between the duration of dust exposure and the lung burden of any particle types in the gold miners.

Carbon monoxide and water vapor contamination of compressed breathing air for firefighters and divers.

Compressed breathing air, used in self-contained breathing apparatus (SCBA) by firefighters and other categories of workers as well as by recreational and commercial divers, is prepared with the aid of high-pressure compressors operating in the range of 5000 psig. There have been reports of unexplained deaths of SCUBA divers and anecdotal accounts of decreased time to exhaustion in firefighters using SCBAs. Compressed breathing air has been found to contain elevated levels of carbon monoxide (CO) and water vapor that are consistent with carboxyhemoglobin (COHb) poisoning and freezing of the user's regulator on the breathing apparatus. The Coburn-Forster-Kane equation (CFK equation) was used to estimate COHb levels at rest and at maximum exercise when exposed to different levels of CO in contaminated breathing air. The results demonstrated that, at maximum exercise, the COHb ranged from 6.0 to 17% with the use of 1 to 4 SCBA cylinders contaminated by 250 ppm CO. Standard operating procedures have been developed at the Montreal Fire Department to minimize the risk of compressed breathing air contamination. Results of the quality analysis/quality control program indicate that implementation of these procedures has improved the quality of the compressed breathing air. Recommendations are made for improvement of the air testing procedures mandated by the Canadian CAN3 180.1-M85 Standard on Compressed Breathing Air and Systems.

Protective antioxidant mechanisms in rat and guinea pig tissues challenged by acute exposure to cigarette smoke.

Cellular damage from reactive intermediates formed during xenobiotic biotransformation is prevented by the presence of adequate levels of antioxidant chemicals in the tissues. Equally important for cell protection is the rate at which these chemicals are replaced if tissue stores are depleted. The present experiments, using adult male Sprague-Dawley rats and Hartley guinea pigs, were conducted to ascertain what effects mainstream (MS) and sidestream (SS) tobacco smoke would have on the water-soluble, cytoplasmic antioxidants, ascorbic acid (AA) and reduced glutathione (GSH). The animals were exposed by nose-only inhalation to varying doses (40, 120, 240 puffs) of a 1:5 dilution of a 35-ml volume of freshly generated MS from cigarettes made from different types of tobacco and delivered by a B.-A.T-Mason inhalation apparatus. The animals were euthanized either immediately following exposure or at 3 and 6 h. The blood, lungs, liver, kidneys, heart and bladder were removed for the quantitation of AA and GSH following homogenization and deproteinization. Immediately following exposure to MS, dose-dependent decreases in pulmonary and renal GSH were observed in rats whereas, in guinea pigs, reductions in pulmonary, hepatic and renal GSH were observed only at the highest level of exposure. No reductions in tissue AA were observed in either species at any exposure level. In both species, blood levels of GSH and AA remained unchanged following exposure. Mainstream smoke (240 puffs) from flue-cured or dark, air-cured tobaccos elicited a significant, immediate reduction in pulmonary and renal GSH, but MS from low tar, filter cigarettes was without effect. Within 3 h of exposure, GSH in all tissues has returned to pre-exposure levels. Whole-body, chamber exposure to concentrated SS, generated from smouldering cigarettes, caused a dose-dependent reduction in rat pulmonary, hepatic, renal, cardiac and bladder muscle GSH but only affected pulmonary GSH in the guinea pig. Lesser effects were observed in tissues of rats exposed to diluted SS. In the rat, a comparison of the results of diethylmaleate- and smoke-induced depletion of tissue GSH suggested that, even at exceptionally high levels of exposure, there was a significant store of GSH in tissues that did not interact with tobacco smoke.

Abiotic transformations and decomposition kinetics of 4-carbamoyl-2'-[(hydroxyimino)methyl]-1,1'-(oxydimethylene)-bis(pyridin ium chloride) in aqueous phosphate buffers.

The rate of disappearance of 4-carbamoyl-2'-[(hydroxyimino)methyl]-1,1'-(oxydimethylene) bis (pyridinium chloride) (HI-6) from aqueous phosphate buffers (pH 3.0-9.1) was both pH and temperature sensitive. In midrange buffers (pH 6.0-9.1, mu = 0.2 M) at 37, 25, or 4 degrees C the decomposition followed first-order kinetics consistent with hydroxide-promoted decomposition of the un-ionized drug or with hydrolysis of the ionized oxime anion to result in 4-carbamoyl-2'-hydroxy-1,1'-(oxydimethylene)bis(pyridinium) cation (intermediate 1). The subsequent conversion of intermediate 1 to 4-carboxy-2'-hydroxy-1,1'-(oxydimethylene)bis(pyridinium) cation (intermediate 2) followed higher order kinetics which were consistent with either acid- or base-promoted hydrolysis of the B-ring amide functionality. After approximately 138 days in the dark, the sum of the residual HI-6, intermediate 1, and intermediate 2 in the crude decomposition mixture accounted for 89.9 +/- 10.0% of the initial substrate. Minor byproducts included 4-carbamoyl-2'-carboxy-1,1'-(oxydimethylene)bis(pyridinium) cation, 2-pyridinealdoxime, 2-pyridinecarboxaldehyde, 2-hydroxypyridine, isonicotinamide, isonicotinic acid, and traces of cyanide. In addition, 2-cyanopyridine appeared to be a transient intermediate in more alkaline media. In total, this drug resembles other mono- and bis(pyridinium) aldoximes in terms of the decomposition routes in aqueous solutions at intermediate pHs.

Chemical management of forest pest epidemics: a case study.

The management of insect epidemics in large tracts of forest is difficult given the climatic conditions encountered, the topography of the forested land, the nature of the forest, the types of chemical and/or biological insecticides registered for use, and the technologies available for insecticide application. Since 1952, the province of New Brunswick, Canada, has been heavily involved in attempting to control an epidemic of the eastern spruce budworm (Choristoneura fumiferana. Clemens) that has ravaged the coniferous softwoods of eastern Canada and the United States. Of the available options, the provincial government chose to develop an aerial spraying program, eventually selecting two chemical insecticides (fenitrothion and aminocarb) and one biological control agent (Bacillus thuringiensis). Concerns about possible impacts on human health led to extensive studies of the toxicology of these insecticides, the technology of aerial spraying, the development of less hazardous formulations, and the quantitation of off-target drift of aerosolized insecticides. These studies culminated in improvements in pesticide application and the establishment of regulations on safety or buffer zones around human habitation for certain types of aircraft applying different formulations of the insecticides.

Kinetics, distribution, and biotransformation of the chemical HI-6 in the rat, dog, and rhesus monkey.

Disposition of the bis-pyridinium mono-oxime, HI-6, following intramuscular injection in rats (200 mg/kg bw), beagle dogs (10 and 50 mg/kg bw), and rhesus monkeys (50 mg/kg bw) revealed that the oxime was absorbed rapidly and completely from the site of injection, was distributed rapidly in the tissues, and that tissue concentrations decreased below the limits of detection by 4 h after treatment. No overt signs of toxicity were observed in any species at the concentrations given. Tissue analysis for HI-6 and degradation products was conducted by extraction followed by ion-pair, reverse phase, HPLC chromatography. The estimated plasma half-life values were 20, 40-55, and 25-30 min for rats, dogs, and monkeys, respectively. HI-6 and the degradation products were excreted via the urine. A marked species difference in disposition was observed in that HI-6 selectively accumulated in the diaphragmatic muscle of the rat to a level 10- to 20-fold higher than the level in blood plasma, whereas in the dog and monkey, diaphragmatic concentrations were comparable with those in the plasma. Three degradation products of HI-6 were detected in the plasma of the three species. One excreted product formed spontaneously since it was also detected in buffered solutions used for abiotic stability studies. The second product, the picolinic acid analog of HI-6, appeared to be metabolically formed in vivo. A third product remains unidentified.

Disposition and elimination of BIOLF-143, an antiviral agent, in the rabbit.

BIOLF-143, (N-(dimethylamino)methylene-9- [[2-hydroxy-1-(hydroxymethyl)ethoxy]methyl]guanine), an experimental, purine-based, acyclic nucleoside was administered by iv or ip injection to adult, male and female, albino New Zealand rabbits in order to determine: (1) the pharmacokinetic disposition, (2) the route and rate of excretion, (3) the biotransformation, and (4) the acute toxicity of the agent. HPLC analysis of blood plasma concentrations of BIOLF-143 was conducted following iv injections of 50 or 100 mg/kg and ip injections of 250 mg/kg. Tissue levels of BIOLF-143 were analyzed at 60 min following an ip injection of 100 mg/kg. Metabolism/excretion studies were conducted over a 48-hr period following ip injections of BIOLF-143 (100 mg/kg). The nucleoside was rapidly distributed in the body, with the dose-dependent, estimated plasma half-life being 21-44 min. The drug molecule was not extensively bound to proteins, being quantitatively recovered from plasma (94.4 +/- 3.2%) and a variety of tissues (85-100%). The bulk of the drug (80-87%) was recovered in the urine within 48 hr of treatment, with no metabolites or unique, unidentifiable peaks being detected in HPLC chromatograms. No drug residue was found in feces. No overt toxicity or untoward signs of latent toxicity were observed in animals receiving acute doses of BIOLF-143 up to 250 mg/kg ip. A potential target organ might be the kidney since high levels of drug residue were detected 60 min post-treatment and this appeared to be the route of elimination from the body.

Subacute inhalation of cigarette smoke by pregnant and lactating rodents: AHH changes in perinatal tissues.

To study the transplacental acquisition of tobacco smoke products and the effects on fetal tissue enzymes, pregnant rats, guinea pigs, and hamsters were exposed to freshly generated cigarette smoke via a nose-only inhalation system on a daily basis through the latter one-third (guinea pigs) or latter half (rats, hamsters) of the gestational period. Following euthanasia on the day of parturition, microsomal aryl hydrocarbon hydroxylase (AHH) activities were determined in the lungs, livers, and kidneys of both dams and fetuses. The possible acquisition of tobacco smoke products via the milk was studied by exposing lactating dams to cigarette smoke daily for either 4 or 14 days (rats), 4 or 7 days (guinea pigs), or 10 days (hamsters), with analysis of tissues from the euthanized pups for AHH. Pups were also exposed directly (nose only) to cigarette smoke. In the treated pregnant and lactating rat, maternal pulmonary, hepatic, and renal AHH was significantly increased but only fetal lung and the liver of 14-day-old pups showed a marked induction of AHH activity. In the pregnant and lactating guinea pig, only the pulmonary and renal AHH activities were increased following exposure, whereas in the fetuses and nursing pups, none of the tissue AHH activities was significantly altered by exposure. In the pregnant and lactating hamster, only the pulmonary AHH was increased following exposure to cigarette smoke, whereas the activity in fetal and pup tissues remained unchanged from the levels observed in control animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaminophen metabolism in vivo by pregnant, fetal, and neonatal guinea pigs.

Acetaminophen (50 mg/kg body weight) was administered by iv injection to pregnant guinea pigs (60-65 days of gestation) and by ip injection to cesarean-derived term (67 days of gestation) pups. At suitable time intervals after treatment, the concentrations of drug, glucuronide (GLU), and sulfate (SO4) in blood plasma, urine, and bile were measured by high-performance liquid chromatography (HPLC). At 60-65 days of gestation, guinea pig fetuses formed both GLU and SO4, an approximate ratio of 2:1 being observed with mean concentrations of the order of 43 and 27 micrograms/mL being measured for GLU and SO4, respectively at 180 min post-treatment. At the same time interval, the major detoxification product found in the blood plasma of the pregnant dams was GLU (104 micrograms/mL) with only minute amounts (4.2 micrograms/mL) of SO4 being detected. In cesarean-derived and acetaminophen-treated pups, euthanized at 2 or 4 hr post-treatment, plasma levels of GLU were approximately twofold higher relative to the concentration of SO4 at both time intervals. Significant differences were not observed in either bile or urine at 2 hr post-treatment but by 4 hr after treatment the levels of GLU found in the bile and urine were two- or threefold higher than those of SO4. In contrast to the adult guinea pig where GLU forms some 90% of the urinary excretory product and SO4 accounts for only 7%, the SO4 pathway of detoxification appears to be of significant importance to the fetal and neonatal animal.

Evaluation of exposure of health care personnel to ribavirin.

Reports that ribavirin was teratogenic in animals raised concerns of female health care personnel about possible occupational exposure during the care of infants having respiratory syncytial virus infections. Under simulated operational conditions, experiments were conducted to measure ribavirin residues in room air, in surface wipe samples, and in personal sampling devices worn by volunteers. There was exposure to a dispersible dust, presumably dried ribavirin, deposited inside the croupette or hood and on the bedding. Based on personal sampler data, it was estimated that, in a 12-h shift, the primary health care individual could inhale 2.4-9.1 micrograms ribavirin/kg bw.d. Recommendations to reduce the exposure of staff included the wearing of appropriate surgical gloves and a NIOSH-approved disposable respirator for dusts and mists while attending to the needs of the patients.

Drug disposition and biotransformation in the developing beagle dog.

The ability of developing male and female beagle pups to biotransform and eliminate drugs was studied by administering single intravenous doses of acetaminophen (50 mg/kg body wt), phenobarbital (15 mg/kg body wt), or phenytoin (15 mg/kg body wt) to the same groups of dogs (n = 6-8/drug) at 4, 10, 20, 40, and 60 days of age. At suitable intervals after treatment, small (1.0 ml) blood samples were obtained via the jugular vein and centrifuged and the plasma was recovered and stored at -20 degrees C to await analysis. Acetaminophen proved to be the most interesting "probe" of function with the plasma elimination half-life (beta t/2) in 40- to 60-day-old pups being 4.5-fold shorter than at 4 days of age. The synthesis of sulfate-conjugated drug decreased with age. In older pups, the synthesis of the glucuronide-conjugated drug was predominant. The elimination of sulfated acetaminophen from plasma was slow at all ages whereas the rate of glucuronide disappearance increased with age. Phenobarbital was slowly eliminated from the plasma at all ages and there was no indication of p-hydroxylated metabolite formation. The plasma beta t/2 of phenytoin decreased dramatically with age, a 10-fold difference occurring between 4- and 60-day-old pups. para-Hydroxylated phenytoin (pHPPH) was detected only in the plasma of 4- and 10-day-old pups, the plasma beta t/2 decreasing with age. With the appropriate chemical and using the technique of collecting small, serial blood samples, this animal model can be potentially useful in perinatal toxicity studies.

The acute toxicity of BIOLF-143 in the rat.

BIOLF-143, an experimental, purine-based acyclic nucleoside, was administered by iv or ip injection to young, adult, male and female Sprague-Dawley rats in order to determine the (1) pharmacokinetic disposition, (2) route and rate of excretion, and (3) acute toxicity. HPLC analysis of plasma, hepatic, and renal tissue levels was conducted following iv injections of 50 and 100 mg/kg and ip injections of 500 mg/kg. Metabolism/excretion studies were conducted following ip injections of BIOLF-143 (100 mg/kg). The assessment of acute toxicity was done following the ip injection of agent (250 mg/kg/hr for 8 consecutive hr). BIOLF-143 was rapidly distributed in the body, the estimated half-life in blood plasma being 18-23 min. The molecule was essentially unbound to plasma proteins (99% free) and was excreted unchanged in the urine. The recovery of the parent compound was 74.3 +/- 5.9% and 88.5 +/- 15.9% for male and female rats, respectively, with no metabolites or unidentifiable peaks being detected in HPLC chromatograms. No overt toxicity or untoward signs of latent toxicity were observed in the animals receiving doses up to 2000 mg/kg ip. No residues were detected in tissues at 24 hr post-treatment. A potential target organ in subchronic studies might be the kidney. High residue levels of BIOLF-143 were detected 1.0 hr post-treatment; however, the organ had cleared all residues by 24 hr after administration.

Hexahydrocarbon effects on intermediate filament organization in human fibroblasts.

We reported previously that 2,5-hexanedione (2,5-HD), the neurotoxic metabolite of methyl-n-butylketone (MnBK) and n-hexane, induced aggregation of intermediate filaments of the vimentin type in cultured fibroblasts. To determine if these findings have relevance to the mechanism by which these hexacarbons induce their filamentous axonopathy, it was necessary to show that only those hexacarbon analogues that induce focal accumulation of neurofilaments in nerve fibers do aggregate intermediate filaments in fibroblasts. We report here that the nonneurotoxic hexacarbons, 1,6-hexanediol and 2,4-hexanedione (2,4-HD), had no primary effect on intermediate filament distribution in fibroblasts, although the profound, nonspecific cytotoxicity of the latter controverted comparisons with equimolar, effective concentrations of 2,5-HD. Fibroblasts did not metabolize MnBK to 2,5-HD sufficiently to induce reproducible aggregation of intermediate filaments in these cells in culture.