Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Inhalation Exposure”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,531 records · Page 85Linked to original sources
PubMed1999

Inhaled uranium ore dust and lung cancer risk in rats.

Using a nose-only inhalation system, male Sprague-Dawley rats were exposed 4.2 h d(-1), 5 days per week for 65 weeks to one of two concentrations of natural uranium ore dust aerosol (44% U, 50 mg m(-3) and 19 mg m(-3)) without significant radon content. After inhalation exposure ceased, the rats were allowed to live for their natural lifetime. Lung uranium burdens, measured at the time of death of each animal, declined exponentially after dust inhalation ceased, and the rate of decline was independent of the initial lung burden. Lymph node specific burdens ranged from 1 to 60 fold greater than the specific lung burden in the same animal. No lymph node tumors were observed. The frequency of primary malignant lung tumors was 0.016, 0.175 and 0.328 and primary non-malignant lung tumors 0.016, 0.135 and 0.131 in the control, low and high aerosol exposed groups, respectively. There was no difference in tumor latency between the groups. Absorbed dose to the lung was calculated for each animal in the study. The average doses for all the animals exposed to the low and high dust aerosol concentrations were 0.87 Gy and 1.64 Gy respectively, resulting in an average risk of malignant lung tumors of about 0.20 tumors per animal per Gy in both groups. The frequency of primary lung tumors was also calculated as a function of dose increment for both exposed groups individually and combined. The data indicate that, in spite of the above result, lung tumor frequency was not directly proportional to dose. However, when malignant lung tumor frequency was calculated as a function of dose rate (as measured by the lung burden at the end of dust inhalation) a direct linear relationship was seen (p < 0.01) suggesting dose rate may be a more important determinant of lung cancer risk than dose. Conversely, non-malignant lung tumors were significantly correlated with low lung burdens (p = 0.01). We conclude that chronic inhalation of natural uranium ore dust alone in rats creates a risk of primary malignant and non-malignant lung tumor formation and that malignant tumor risk was not directly proportional to dose, but was directly proportional to dose rate.

Adenocarcinoma↗
PubMed1985

Normal serum activities of liver enzymes in Swedish paint industry workers with heavy exposure to organic solvents.

The serum activities of the liver enzymes alanine aminotransferase, aspartate aminotransferase, ornithine carbamyl transferase, and gamma-glutamyl transferase were examined in 47 paint industry workers and unexposed age matched referents. The workers were exposed to a mixture of industrial solvents, of which xylene was the main component in most cases. The median total exposure was about 50% of Swedish 1981 threshold limit values according to measurements of individual solvent exposure performed at the same time. No differences in enzyme activities were shown either when the whole exposed and referent groups were compared or when the five workers with outstanding solvent exposures of five times the TLV or more were compared with their referents. It is concluded that in most workers the liver seems to remain largely undamaged from inhalation exposure to a commonly used mixture of non-chlorinated solvents. In many workers this seems to hold true even for high exposures for limited periods.

Adult↗
PubMed1983

Comparing epidemiologic studies of ingested asbestos for use in risk assessment.

Epidemiologic data can be used in risk assessment in various ways: to calculate the dose-response relationship between exposure levels and adverse effects; to establish ranges of exposure known to be safe or unsafe; to verify an endpoint in humans derived from a route or species extrapolation; to support assumptions necessary for performing extrapolation procedures. These points are illustrated in the risk assessment for exposure to asbestos in drinking water. A previous risk assessment for asbestos, the EPA's Ambient Water Quality Criteria (AWQC) for Asbestos, was derived from cohort studies of inhalation exposure. Epidemiologic studies of ingested asbestos, all of geographical correlation design, were compared on the basis of their ability to add information in support of both the route extrapolation and low-dose extrapolation used in this risk assessment. Results of these ingestion studies were inconsistent due to variable ability to detect a risk from chronic low-level exposure. After preliminary comparisons of factors that determine scientific validity and statistical power, two ingestion studies were selected to determine if they had the potential to detect the risk predicted by the AWQC. This evaluation has shown that these studies do not offer quantitative data for estimating levels associated with a defined risk. Due to short exposure duration and limited power, clearly safe and clearly unsafe ranges could not be definitely identified. The most appropriate ingestion studies suggest, but do not prove, the endpoint derived from the route extrapolation in the AWQC.

Asbestos↗
PubMed1982

Efficacy of orally-administered chelating agents for nickel carbonyl toxicity in rats.

The oral efficacy of several chelating drugs, disulfiram, sodium diethyldithiocarbamate (dithiocarb), and D-penicillamine, was studied in relation to their ability to prevent lethality due to acute inhalation exposure to nickel carbonyl. Dithiocarb and, to a lesser degree, D-penicillamine were found to be especially effective as therapeutic agents. Since dithiocarb is chemically unstable (although it is an active metabolite of disulfiram), its practical usefulness outside the laboratory is limited. Therefore, further investigation was conducted to elucidate the pharmacokinetic differences between dithiocarb and disulfiram in order to explain their relative efficacies. Kinetic analysis indicated that oral dithiocarb provided moderately high but prolonged plasma levels of active chelating agent, while disulfiram resulted in a very high but transient level. These results suggested that small, repeated oral doses of disulfiram would be just as effective in nickel carbonyl poisoning as a single large dithiocarb dose. This was not borne out in subsequent experiments. Investigation into the tissue distribution of inhaled 63Ni-labeled nickel carbonyl 24 hours after exposure showed that all three chelating agents significantly reduced the amounts of nickel in heart and lung, and D-penicillamine further reduced the amounts in blood and kidney. Only disulfiram increased on average the nickel retained in brain tissue, possibly accounting for its limited efficacy. Our results suggest caution in the use of oral disulfiram in human nickel carbonyl intoxication.

Animals↗
PubMedDate not supplied

A rat model of neurobehavioral sensitization to toluene.

Some individuals report that, following either a single high-level or repeated lower-level exposures to chemicals (initiation), subsequent exposure to very low concentrations of chemicals (triggering) produces a variety of adverse effects, including disruption of cognitive processes. Our objective was to model this two-step process in a laboratory animal. Two groups of 16 rats, eight male and eight female, received whole-body inhalation exposure to toluene, either at 80 ppm for 6 h/day for 4 weeks (Repeat group) or to 1600 ppm for 6 h/day on one day only (Acute group). Two other groups (Trigger group and Clean group) of 16 were sham-exposed. After 17 days without toluene exposure, the Acute, Repeat and Trigger groups began a series of daily toluene 'trigger' exposures (10 ppm for 1 h) followed immediately by testing on an operant repeated-acquisitions task requiring learning within and across sessions. The Clean group was sham-exposed prior to operant testing. Trigger or sham exposures and operant testing continued 5 days/week for 17 sessions. Analysis of variance revealed a variety of statistically significant (P < 0.05) differences between treatment groups. Furthermore, the patterns of differences between groups differed (P < 0.05) for female and male rats. For example, male rats of the Trigger group made the most responses, and female rats of the Repeat group responded most slowly. The observation of important changes in the operant behavior of female and male rats previously exposed to toluene, at relatively low concentrations (80 or 1600 ppm) and then later re-exposed at very low concentrations (10 ppm), is consistent with the experiences of humans reporting cognitive difficulties following acute or chronic exposures to chemicals.

Administration, Inhalation↗
PubMed1990

Dose-dependent kinetics of inhaled methylethylketone in man.

Physiologically based stimulation of earlier human inhalation exposure to methylethylketone (MEK) at a concentration of 200 ppm for 4 h suggested that the kinetics were dose-dependent. Two male volunteers were therefore exposed to MEK for 4 h at 3 exposure concentrations: 25, 200 and 400 ppm. Blood MEK concentrations were monitored during and after exposure. The results showed clearly that the kinetics of MEK were dose-dependent at higher exposure concentrations. Simulated exposure to MEK for 8 h suggests that saturation kinetics are reached at an exposure concentration of 50-100 ppm, depending on the physical work load.

Administration, Inhalation↗
PubMed1987

Hyalin droplet nephrosis in male Fischer-344 rats following inhalation of diisobutyl ketone.

Four groups, each consisting of 10 male and 10 female Fischer-344 rats, were exposed 6 h/day, 5 days/week, for 9 days to diisobutyl ketone (DIBK) vapor at concentrations of 905, 300, 98, or 0 (control) ppm. An additional 10 rats/sex were assigned to the 905 and 0 ppm groups and allowed two weeks recovery prior to sacrifice. Rats exposed to 905 ppm had mild ocular irritation (lacrimation) and evidence of kidney toxicity, manifested as: 1) an increase in absolute and relative (as a percentage of body weight) kidney weights, 2) an increase in urine volume (and water intake) with a concomitant decrease in urine osmolality (males only), and 3) an increase in severity of hyalin droplet nephrosis in the proximal tubules (males only). Absolute and relative liver weights were also increased in both male and female rats of the 905 and 300 ppm groups. These effects either disappeared or lessened in severity following the 2-week recovery period. Male rats exposed to 300 ppm had similar renal alterations to the males of the 905 ppm group, although the alterations were fewer in number and smaller in magnitude. Kidney weights and renal histology of the males of the 98 ppm group were similar to the control male rats, although an increase in urine volume with a decrease in urine osmolality was observed. The kidney findings in this study were not surprising because of the chemical relationship of DIBK with other aliphatic ketones (e.g., methyl isobutyl ketone, methyl isoamyl ketone) which, after repeated inhalation exposure, cause hyalin droplet nephropathy in male rats. The significance of this male rat nephrosis with regard to human exposure is unknown.

Administration, Inhalation↗
PubMed1991

Particle-associated polycyclic aromatic hydrocarbons--a reappraisal of their possible role in pulmonary carcinogenesis.

According to the model presented here, large aggregates of inert dust forming in the lung can drastically increase retention of polycyclic aromatic hydrocarbons (PAHs) that are either adsorbed or precipitated onto the dust particles. Experiments designed to demonstrate the carcinogenicity of PAHs in animals require that large amounts of PAHs be administered to induce lung cancer. If the PAHs are attached to an inert carrier dust before instillation, aggregation of particles is a very significant factor in the retention of PAHs in the lung. A slow release of particle-associated PAHs would result in a prolonged exposure to surrounding tissues from a limited number of administrations. Because an increased incidence of tumors has been observed following these types of exposures, it has been concluded that the increased retention of PAHs due to their association with inert particles is an important factor in PAH-induced pulmonary carcinogenesis. However, large aggregates of inert dust containing crystalline PAHs are unlikely to form with the much lower doses typical of human exposures. Inhaled particles are more likely to deposit and react with the surrounding lung medium without interference from other particles. Our model demonstrates that, under more typical, low-dose exposure conditions, particle-associated PAHs will be released rapidly from the particles. Sustained exposure of target tissues to PAHs will result from repeated exposures, not from increased retention due to association of PAHs with their carrier particles. This distinction is very important, because in high-dose, instillation experiments in animals, critical doses to cells, and thus tumors, should occur at the sites at which particles are retained; whereas, the much lower, but more frequent exposures common for humans should instead lead to tumors at the sites at which particles are initially deposited, but not necessarily retained.

Animals↗
PubMed2004

Acute inhalant-induced neurotoxicity with delayed recovery.

OBJECTIVE: To report a case of neurotoxicity and subsequent hospitalization due to abuse of an ethyl chloride inhalant. CASE SUMMARY: A 41-year-old African American male presented to the emergency department due to mental status changes and an inability to walk. After the blood alcohol and urine drug screen returned negative, a family member revealed that the patient frequently abused an inhalant containing the volatile solvent ethyl chloride. DISCUSSION: Inhalant abuse is common and is facilitated by the widespread availability of volatile solvents that have legitimate commercial or household uses. Most inhalants are central nervous system depressants and are highly lipophilic. Maximum Impact, which contains ethyl chloride, is sold in stores and is readily available over the Internet. While the product has a legitimate use as a VCR head cleaner, it is often illicitly marketed over the Internet as a means of getting a "rush" or "high" and for enhancing sexual pleasure. Neurologic symptoms have been reported after deliberate inhalational exposure to ethyl chloride, and 2 deaths have been associated with its use. An objective causality assessment using the Naranjo probability scale revealed a probable adverse drug event. CONCLUSIONS: Inhalants should be included in the differential diagnosis of patients presenting with acute mental status changes and neurologic impairment that resolve over less than one week.

Adult↗
PubMedDate not supplied

Pharmacokinetics of gentamicin administered intratracheally or as an inhalation aerosol to guinea pigs.

The pharmacokinetics of gentamicin were studied after intratracheal, inhalation, and iv administration to guinea pigs. Gentamicin injected intratracheally was almost completely systemically available. The comparison of the gentamicin plasma AUCs after inhalation and iv administration showed that an inhalation exposure lasting 10 min resulted in an absorption of 1.13 mg gentamicin/kg body weight into systemic circulation. This absorbed dose was 40.4 or 67.3% of the amount of gentamicin inhaled, depending on tidal volume assumed, and 1.4% of the amount of gentamicin aerosolized. The postinhalation gentamicin concentration in the lungs decreased with a half-life of 67.3 min. The data differentiate topical pulmonary gentamicin from systemic gentamicin and give a rational basis for study of the mechanism of the therapeutic effect of gentamicin inhalation aerosol in bronchopulmonary infections.

Aerosols↗
PubMed1981

Evaluation of an occupational respiratory exposure to a zirconium-containing dust.

A group of handfinishers of zirconium metal reactor components questioned whether the dust to which they were exposed would cause chronic lung disease or cancer, or both. To investigate this possibility, the work environment was surveyed, and 32 male employees who had worked as handfinishers from one to seventeen years, were compared to a group of controls in reference to a respiratory questionnaire, chest x-ray findings, and expiratory lung function tests. The controls were matched to the handfinishers for age, sex, payroll status and smoking history. No significant differences were found between the exposed and the control groups. Results of earlier animal respiratory studies vary from no effect to definite pathology. Previous employee exposure studies are short-term and have methodological shortcomings. It would appear that lifetime animal respiratory studies and systematic epidemiological studies of employee populations with long-term inhalation exposure are needed to demonstrate unequivocally whether zirconium and zirconium compounds are harmful.

Cross-Sectional Studies↗
PubMed2002

Urinary naphthalene mercapturates as biomarkers of exposure and stereoselectivity of naphthalene epoxidation.

Previous work has shown that the rate and stereochemistry of naphthalene epoxidation correlates with differences in susceptibility to cytotoxicity. The development of methods for measuring epoxide formation in vivo could provide a marker for assessing events critical to naphthalene cytotoxicity that are applicable to humans. Here, urinary diastereomeric mercapturates have been measured in mice (susceptible) and rats (nonsusceptible) after intraperitoneal administration (1.56-200 mg/kg) or inhalation exposures (0.8-110 ppm, 4 h) to naphthalene. No significant differences were observed in the percentage of the dose eliminated as mercapturate in urine between mice (25-34%) and rats (24-35%) or at varying doses after i.p. administration. The amounts of urinary mercapturate after 4-h exposures were considerably greater in mice than rats. In mice, the ratio of diastereomeric mercapturates derived from the 1R,2S- to 1S,2R-epoxide was 1:1 at low doses (1-3 mg/kg), increased to 3:1 at intermediate doses (50 mg/kg), and decreased to 2:1 at high doses (100 and 200 mg/kg). In rats, these ratios remained less than 1:1 at all doses. After inhalation, ratios were 5 to 6:1 at low concentrations (less than 15 ppm) and decreased to 3:1 at higher concentrations (15-100 ppm) in mice, whereas in rats, the ratios were 1:1 or less for all concentrations. These studies show that mercapturates provide good assessments of internal dose, that there are not significant differences between mice and rats in the percentage eliminated as mercapturate but that the ratios of mercapturates derived from the 1R,2S- versus 1S,2R-epoxide differ markedly and are consistent with previous in vitro metabolism studies.

Acetylcysteine↗
PubMed2005

Ethylene glycol exposure: an evidence-based consensus guideline for out-of-hospital management.

In 2002, poison centers in the US reported 5816 human exposures to ethylene glycol. A guideline that effectively determines the threshold dose for emergency department referral and need for pre-hospital decontamination could potentially avoid unnecessary emergency department visits, reduce health care costs, optimize patient outcome, and reduce life disruption for patients and caregivers. An evidence-based expert consensus process was used to create this guideline. Relevant articles were abstracted by a trained physician researcher. The first draft of the guideline was created by the primary author. The entire panel discussed and refined the guideline before distribution to secondary reviewers for comment. The panel then made changes based on the secondary review comments. The objective of this guideline is to assist poison center personnel in the out-of-hospital triage and initial management of patients with a suspected exposure to ethylene glycol by (1) describing the process by which the exposure might be evaluated, (2) identifying the key decision elements in managing the case, (3) providing clear and practical recommendations that reflect the current state of knowledge, and (4) identifying needs for research. This guideline is based on an assessment of current scientific and clinical information. The panel recognizes that specific patient care decisions may be at variance with this guideline and are the prerogative of the patient and health professionals providing care, considering all of the circumstances involved. Recommendations are in chronological order of likely clinical use. The grade of recommendation is in parentheses. (1) A patient with exposure due to suspected self-harm, misuse, or potentially malicious administration should be referred to an emergency department immediately regardless of the dose reported (Grade D). (2) Patients with inhalation exposures will not develop systemic toxicity and can be managed out-of-hospital if asymptomatic (Grade B). Patients with clinically significant mucous membrane irritation should be referred for evaluation (Grade D). (3) Decontamination of dermal exposures should include routine cleansing with mild soap and water. Removal of contact lenses and immediate irrigation with room temperature tap water is recommended for ocular exposures. All patients with symptoms of eye injury should be referred for an ophthalmologic exam (Grade D). (4) Patients with symptoms of ethylene glycol poisoning should be referred immediately for evaluation regardless of the reported dose (Grade C). (5) The absence of symptoms shortly after ingestion does not exclude a potentially toxic dose and should not be used as a triage criterion (Grade C). (6) Adults who ingest a "swallow" (10-30 mL), children who ingest more than a witnessed taste or lick, or if the amount is unknown of most ethylene glycol products should be referred immediately for evaluation. The potential toxic volume of dilute solutions (e.g., concentration <20%) is larger and can be estimated by a formula in the text (Grade C). (7) A witnessed taste or lick only by a child, or an adult who unintentionally drinks and then expectorates the product without swallowing, does not need referral (Grade C). (8) Referral is not needed if it has been >24 hours since a potentially toxic unintentional exposure, the patient has been asymptomatic, and no alcohol was co-ingested (Grade D). (9) Gastrointestinal decontamination with ipecac syrup, gastric lavage or activated charcoal is not recommended. Transportation to an emergency department should not be delayed for any decontamination procedures (Grade D). (10) Patients meeting referral criteria should be evaluated at a hospital emergency department rather than a clinic. A facility that can quickly obtain an ethylene glycol serum concentration and has alcohol or fomepizole therapy available is preferred. This referral should be guided by local poison center procedures and community resources (Grade D). (11) The administration of alcohol, fomepizole, thiamine, or pyridoxine is not recommended in the out-of-hospital setting (Grade D).

Adult↗
PubMed2001

Differential effects of airway anesthesia on ozone-induced pulmonary responses in human subjects.

We examined the effect of tetracaine aerosol inhalation, a local anesthetic, on lung volume decrements, rapid shallow breathing, and subjective symptoms of breathing discomfort induced by the acute inhalation of 0.30 ppm ozone for 65 min in 22 ozone-sensitive healthy human subjects. After 50 min of ozone inhalation FEV(1) was reduced 24%, breathing frequency was increased 40%, tidal volume was decreased 31%, and total subjective symptom score was increased (71.2, compared with 3.8 for filtered air exposure). Inhalation of tetracaine aerosol resulted in marked reductions in ozone-induced subjective symptoms of throat tickle and/or irritation (92.1%), cough (78.5%), shortness of breath (72.5%), and pain on deep inspiration (69.4%). In contrast, inhalation of tetracaine aerosol (mass median aerodynamic diameter of 3.52 microm with a geometric standard deviation of 1.92) resulted in only minor and inconsistent rectification of FEV(1) decrements (5.0%) and breathing frequency (-3.8%) that was not significantly different from that produced by saline aerosol alone (FEV(1), 5.1% and breathing frequency, -2.7%). Our data are consistent with afferent endings located within the large conducting airways of the tracheobronchial tree being primarily responsible for ozone-induced subjective symptoms and provides strong evidence that ozone-induced inhibition of maximal inspiratory effort is not dependent on conscious sensations of inspiratory discomfort.

Administration, Inhalation↗
PubMed2005

Health effects from breathing air near CAFOs for feeder cattle or hogs.

There is concern that livestock operations for fattening cattle and raising hogs known as concentrated animal feeding operations (CAFOs) release substances into the air that have negative effects on the health of persons living nearby. These substances include dust containing endotoxin and other microbial products as well as ammonia, hydrogen sulfide and a variety of volatile organic compounds. Odors from these farms are considered offensive by some neighbors. A variety of medical complaints are reported to be more common in those people who live near CAFOs for raising hogs than in people without this exposure. Respiratory health effects, including symptoms of pulmonary disease and lung function test result abnormalities, have been described in workers employed in CAFOs where hogs are raised. Health effects after inhalation exposure of neighbors to substances released into the ambient air from these farms is less well characterized. It must be noted that CAFO workers may differ from neighbors in terms of their exposures and general health status. The presence of dust and other substances from cattle feedlots also causes some neighbors to voice concerns about the impact on their health but this exposure has been studied less extensively than exposure to substances released from CAFOs where hogs are raised. Further research needs to be done to look for measurable health effects attributable to living near all CAFOs in order to better understand the impact of these farms.

Air Pollutants↗
PubMed1994

Fatality associated with inhalation of a pyrethrin shampoo.

A fatality associated with the inhalational exposure to a pyrethrin insecticide is described. Death was attributed to sudden irreversible bronchospasm. While less severe allergic reactions have been reported, this is the first death associated with pyrethrin inhalation.

Administration, Inhalation↗
PubMed2003

[Neurological effects of chemical and biological weapons].

Neurological manifestations of chemical and biological weapons are reviewed. Nerve agents in current use, storage, or production include tabun, sarin, soman and VX. The initial effects of exposure to a nerve agent depend on the dose and on the route of exposure. Sarin, the agent studied most thoroughly in man in Matumoto and Tokyo attacked by Aum shinrikyo will cause miosis, rhinorrehea and shortness of breath are initial complaints immediately after inhalation exposure of the vapor. The severe cases showed loss of consciousness and convulsions. Respiratory arrest may occur. The most toxic of the nerve agents is VX. It is thought to be 100 times as toxic as sarin for humans by the percutaneous rout. The similar findings to sarin exposure are also observed in cases exposured to VX. Atropin and PAM will be effective in the early stage. BZ (benzilate) is a delayed onset incapacitation agent. It causes severe hallucination. The cyanide compounds are among the most rapidly acting of war gases, resulting in death. Anthrax has been the most attractive biological weapon for a long time. Anthrax is an acute bacterial infection of the skin and lungs in man and animals. Meningoencephalitis has been reported in the terminal stage in anthrax infection. In autopsy, it is really confirmed in the characteristic findings of the meningeal abnormality. The potential weaponization of variola virus continues to pose a military threat because the aerosol infectivity of the virus and the development of susceptible populations. A high rate of lethality, a staunch resistance to treatments and a rapid onset of severe generalised muscle weakness make botulinum toxin a suitable agent for biological warfare particularly by oral administration.

Animals↗
PubMed2001

Point mutations of K-ras and H-ras genes in forestomach neoplasms from control B6C3F1 mice and following exposure to 1,3-butadiene, isoprene or chloroprene for up to 2-years.

1,3 Butadiene (BD), isoprene (IP) and chloroprene (CP) are structural analogs. There were significantly increased incidences of forestomach neoplasms in B6C3F1 mice exposed to BD, IP or CP by inhalation for up to 2-years. The present study was designed to characterize genetic alterations in K- and H-ras proto-oncogenes in a total of 52 spontaneous and chemically induced forestomach neoplasms. ras mutations were identified by restriction fragment length polymorphism, single strand conformational polymorphism analysis, and cycle sequencing of PCR-amplified DNA isolated from paraffin-embedded forestomach neoplasms. A higher frequency of K- and H-ras mutations was identified in BD-, IP- and CP-induced forestomach neoplasms (83, 70 and 57%, respectively, or combined 31/41, 76%) when compared to spontaneous forestomach neoplasms (4/11, 36%). Also a high frequency of H-ras codon 61 CAA-->CTA transversions (10/41, 24%) was detected in chemically induced forestomach neoplasms, but none were present in the spontaneous forestomach neoplasms examined. Furthermore, an increased frequency (treated 13/41, 32% versus untreated 1/11, 9%) of GGC-->CGC transversion at K-ras codon 13 was seen in BD-, and IP-induced forestomach neoplasms, similar to the predominant K-ras mutation pattern observed in BD-induced mouse lung neoplasms. These data suggest that the epoxide intermediates of the structurally related chemicals (BD, IP, and CP) may cause DNA damage in K-ras and H-ras proto-oncogenes of B6C3F1 mice following inhalation exposure and that mutational activation of these genes may be critical events in the pathogenesis of forestomach neoplasms induced in the B6C3F1 mouse.

Animals↗