Investigation of an acute chemical incident: exposure to fluorinated hydrocarbons.

OBJECTIVES: To assess whether attendance at the site after an incident in a sewer was associated with symptoms in emergency personnel and whether the prevalence of symptoms was associated with estimated levels of exposure to any chemical hazard. METHODS: Symptoms experienced by people attending an incident involving two dead sewer workers suggested the presence of a chemical hazard, before environmental sampling confirmed any toxic agent. Self reported symptoms, estimated exposures, and biomarkers of exposure for likely agents from all 254 people who attended the incident and a referent occupational group matching the 83 emergency personnel who went to the Accident and Emergency department (A and E) in the first 48 hours were recorded. The prevalence of symptoms and concentrations of creatine phosphokinase in serum of the 83 early patients at A and E were compared with their referent occupational group. In all workers who attended the incident, the trends in symptom prevalences and concentrations of creatine phosphokinase in serum were examined by distance from the site and predefined exposure category. RESULTS: Among all workers who attended the incident, symptoms of shortness of breath and sore throat were significantly associated with indirect estimates of exposure but not associated with concentrations of creatine phosphokinase. Freon was detected in two blood samples. The early patients at A and E reported more symptoms than their matched reference group and their median concentrations of creatine phosphokinase were higher. CONCLUSIONS: The association between symptoms and concentrations of creatine phosphokinase with attendance at the site indicated the presence of a continuing hazard at the site and led to extra precautions being taken. Comparison values from the referent occupational group prevented unnecessary medical follow up.

Blood and breath analyses as biological indicators of exposure to trihalomethanes in indoor swimming pools.

In this article, exposure to trihalomethanes (THMs) in indoor swimming pools as a consequence of water chlorination is reported. Environmental and biological monitoring of THMs was performed in order to assess the uptake of these substances after a defined period in five competitive swimmers, regularly attending an indoor swimming pool to train for competition during four sampling sessions. Analyses were performed by gas-chromatography and the following THMs were detected: chloroform (CHC13), bromodichloromethane (CHBrC12), dibromochloromethane (CHBrsC1) and bromoform (CHBr3). CHC13 appeared the most represented compound both in water and in environmental air before and after swimming. CHBrC1w and CHBr2C1 were always present, even though at lower levels than CHC13, CHBr3, was rarely present. In relation to biological monitoring, CHC13, CHBrC12 and CHBr2C1 were detected in all alveolar air samples collected inside the swimming pool. Before swimming, after 1 h at rest at the pool edge, the mean values were 29.4 +/- 13.3, 2.7 +/- 1.2 and 0.8 +/- 0.8 micrograms/m3, respectively, while after spending 1 h swimming, higher levels were detected (75.6 +/- 18.6, 6.5 +/- 1.3 and 1.4 +/- 0.9 micrograms/m3, respectively). Only CHC13 was detected in all plasma samples (mean: 1.4 +/- 0.5 micrograms/1) while CHBrC1x and CHBr2C1 were observed only in few samples at a detection limit of 0.1 micrograms/1. After 1 h at rest, at an average environmental exposure of approx. 100 micrograms/m3, the THM uptake was approx. 30 micrograms/h (26 micrograms/h for CHC1c, 3 micrograms/h for CHBrC12 and 1.5 micrograms/h for CHBr2C1). After 1 h swimming, the THM uptake is approx. seven times higher than at rest: a THM mean uptake of 221 micrograms/h (177 micrograms/h, 26 micrograms/h and 18 micrograms/h for CHC13, CHBrC12 and CHBr2C1, respectively) was evaluated at an environmental concentration of approx. 200 micrograms/m3.

Neurobehavioral and physiologic effects of trifluoromethane in humans.

Nuclear magnetic resonance (NMR) imaging shows promise in the measurement of human cerebral blood flow (CBF) in that nonradioactive indicators may be used. Our earlier investigations with trifluoromethane (FC-23) gas have shown that this compound can be used to safely and effectively measure CBF in anesthetized animal models. In this Phase I dose-escalation study we set out to determine the maximal tolerated concentration (MTC) of FC-23 in normal healthy male volunteers and to assess its feasibility as an NMR indicator. Five subjects were exposed in a blinded fashion to escalating concentrations of FC-23 between 10% and 60%, randomly interleaved with exposures to both room air and 40% nitrous oxide. On each study day, the subjects breathed the test gas for eight pulses of 3 min each with 2-min clearance periods between the pulses. The subjects underwent intensive physiologic and neurobehavioral monitoring throughout the study period. The first subject experienced an anesthetic response to 60% FC-23, and the second subject experienced "discomfort" and requested discontinuation at the initiation of 40% FC-23. The MTC was subsequently determined to be 30% FC-23 (all subjects tolerated the gas), although a small (37.6 vs. 40.5) but statistically significant retention of carbon dioxide was found (p = .003). When one subject received 30% FC-23 during an NMR imaging study, a pronounced anesthetic effect with intolerable hyperacusis was demonstrated. Human studies of FC-23 have been discontinued in our laboratory.

Trihalomethane concentrations in swimmers' and bath attendants' blood and urine after swimming or working in indoor swimming pools.

The influence of working or swimming in indoor swimming pools on the concentrations of four trihalomethanes (haloforms) in blood and urine was investigated. Different groups (bath attendants, agonistic swimmers, normal swimmers, sampling person) were compared. The proportions of trihalomethanes in blood and urine correlated roughly with those in water and ambient air. Higher levels of physical activity were correlated with higher concentrations. Within one night after exposure in the pool the blood concentrations usually were reduced to the pre-exposure values. Secretion of trichloromethane in urine was found to be less than 10%.

Toxicokinetics of inhaled bromotrifluoromethane (Halon 1301) in human subjects.

Bromotrifluoromethane (CBrF3), commonly known as Halon 1301, is used as a fire extinguishant in the Space Shuttle. Several scenarios, such as a fire or a faulty alarm, could lead to its discharge resulting in a Halon 1301 concentration of up to 1% in the spacecraft cabin atmosphere. To examine the effects of Halon 1301 on mental performance and physiologic function, the National Aeronautics and Space Administration sponsored a human inhalation study. Four pairs of adult male subjects were each exposed in a double-blind fashion for 24 hr to 1% (10,000 ppm or 60,875 mg/m3) Halon 1301 and to air in two separate exposures approximately 1 week apart. Mental performance and physiologic function were assessed and the results are reported in a companion paper (D. S. Calkins, J. J. Degioanni, M. N. Tan, J. R. Davis, and D. L. Pierson. Fundam. Appl. Toxicol. 20, in press). Blood and breath samples from the exposed subjects were also collected to provide dosimetric and toxicokinetic information, which is presented here. Blood Halon 1301 levels increased rapidly and approached a steady state within 2 hr of beginning the exposure; the steady-state concentration was approximately 3-4.5 micrograms/ml. Breath samples collected during exposures closely reflected chamber concentrations. Analysis of postexposure blood samples revealed that Halon 1301 was eliminated biphasically with an average t1/2 alpha and t1/2 beta of 4.5 min (range 2.5-8.1 min) and 200 min (range 131-347 min), respectively. Halon 1301 concentrations in fat and soft tissues were also estimated. Subsequently, the end-tidal breath/blood/tissue/fat partition coefficients were calculated to be 17/1/0.5/33.(ABSTRACT TRUNCATED AT 250 WORDS)

[Sudden death caused by freon 22?]. / Morte improvvisa da freon 22?

Case report of a plumber's fatal work accident. Investigations on the causes of death made at post mortem showed that the worker had absorbed a large quantity of freon 22 (chlorodifluoromethane) which is known to be a narcotic agent and capable of inducing cardiac arrhythmia. It is believed freon inhalation was the cause of loss of consciousness with consequent death from drowning in the water issuing from the pipes. It is concluded that preventive measures need to be reinforced by adequate information to the workforce on the risks connected to this type of gas.

Fatal accidental inhalation of bromochlorodifluoromethane (Halon 1211).

Bromochlorodifluoromethane (Halon 1211) is a widely used fire extinguishing agent. Several cases of sudden death in teenagers associated with BCF abuse have been reported. BCF is used as a fire extinguisher in battle tanks. Two young previously healthy male soldiers were accidentally exposed to BCF in a battle tank. The tank driver died, but the gunner survived the event with no medial complications. It is concluded that BCF should be used in confined chambers only after the evacuation of all personnel.

Solubility of Freon 22 in human blood and lung tissue.

The solubility of Freon 22 in human blood and lung tissue was determined using the chromatographic method of Wagner et al. (J. Appl. Physiol. 36: 600-605, 1974). In normal human blood, the mean Bunsen coefficient of solubility (alpha B) was 0.804 cm3 STPD.cm-3.ATA-1 at 37 degrees C. It increased with hematocrit (Hct) according to the equation alpha B = 0.274 Hct + 0.691. Tissue homogenates were prepared from macroscopically normal lung pieces obtained at thoracotomy from eight patients undergoing resection for lung carcinoma. The Bunsen solubility coefficients were 0.537 +/- 0.068 and 0.635 +/- 0.091 in washed and unwashed lung, respectively. These values can be used in the determination of both cardiac output and pulmonary tissue volume in humans by use of the rebreathing technique.

Effects of environmental O2 on blood flow and diffusing capacity in amphibian skin.

The effects of local environmental PO2 on cutaneous blood flow (Q) and the membrane diffusing capacity of the skin (D) were investigated in the leopard frog, Rana pipiens, and the lungless salamander, Desmognathus quadramaculatus. Halothane anesthetized animals were equilibrated with Freon-22 (Fr) and acetylene (Ac) in a box. A gas mixture containing either 0, 20 or 40% O2, respectively, in N2 and initially free of Fr and Ac was drawn through a small sample chamber on the abdomen. The excretion of Fr and Ac into the chamber was analyzed with a mass spectrometer. These conditions allowed the determination of the cutaneous conductance to Fr (GFr) and Ac (GAc) at the 3 levels of local environmental O2. GFr and GAc of the isolated skin and the blood solubilities of the 2 gases were also determined. To estimate Q, DAc and DFr, the data were analyzed with a homogeneous single capillary model. In the frog, Q varied directly with sample chamber [O2], but chamber [O2] had no effect on D. In the salamander, O2 had no effect on either Q or D. The results indicate that regulation of cutaneous gas exchange in the frog by local environmental O2 only involves alterations in Q. Similar control of cutaneous gas exchange is absent in the lungless salamander.

Uptake of trihalomethanes by patients during hemodialysis.

Trihalomethanes (THM) present in tap water were also found in dialysis fluid because they were not eliminated by water treatment. THM, absorbed through the dialyser membranes, increased considerably in blood and in expired air of patients on hemodialysis during the dialysis sessions. The uptake of THM during each dialysis session was about 1 mg.

Solubility of freon-22 in blood and lung tissue.

Despite the frequent use of freon-22 (e.g. to measure pulmonary blood flow), there is no agreement on its solubility in water or body fluids. The values in the literature vary, often quoted without reference to measurement or identification as Ostwald or Bunsen coefficients. We used a Schölander apparatus and determined the Bunsen solubility coefficient (mlgas.(mlfluid.atmosphere)-1) at 37 degrees C as: 0.476 in water; 0.673 in human whole blood; 0.479 in human plasma; 0.662 in canine whole blood; 0.437 in canine plasma; and 1.077 in homogenized canine lung tissue. As pure freon was used, these solubilities may not be applicable if freon-22 does not obey Henry's law. In man, the Ostwald solubility coefficient is calculated as 0.76 ml/ml whole blood at BTPS. These results provide information for further studies involving freon-22, and clear the confusion which has arisen from poorly defined solubility coefficients.

The sloping alveolar plateau of tracer gases washed out from mixed venous blood in man.

We have investigated the slope of the alveolar plateau for inert tracer gases that were washed out from mixed venous blood. Two pairs of tracer gases were used (He, SF6) and (C2H2, Freon 22). The gases of each pair share almost the same blood-gas partition coefficient but they have different diffusive properties in the gas phase. The experiments were performed in healthy subjects at rest and at three levels of exercise (75, 150, 225 W). Each experiment started with the alveolar washin of the tracer gases by adding these gases to inspired air. This washin was continued for several minutes in order to dissolve sufficient amounts of the tracer gases in the body tissues. Subsequently, the tracer gases were washed out. In this paper, the slopes of the alveolar plateaus are defined as the relative increase of the concentration per second. Steeper slopes were found for the heavier gases (SF6 and Freon 22) in comparison with those for the lighter gases of the two pairs (He and C2H2). This finding may be ascribed to the contribution of diffusion-limited gas mixing in the lung to the slope of the alveolar plateau. For each gas, the slope for the first expiration during washout (alveolar washout) was considerably smaller than that for the later part of washout (mixed venous washout), and the difference amounts to about 56% and 76% of the slope during mixed venous washout at rest and at the highest level of exercise, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Multiple deaths resulting from shipboard exposure to trichlorotrifluoroethane.

During the course of dockside ship maintenance, a compartment was partially flooded with tricholotrifluoroethane gas. One sailor entered the compartment, collapsed, and was then rescued by two other men. All three victims then climbed a 11-m (36-ft) ladder and collapsed. They all experienced a rapid development of cardiac arrest. We report on the pathologic, toxicologic, and pathophysiologic aspects of the incident.

Exposure to fluorotrichloromethane (R-11).

Three volunteers were exposed to fluorotrichloromethane (R-11) under experimental conditions. Solvent levels in ambient and alveolar air, in blood and urine were measured. The mean concentration of R-11 in ambient air was 657 ml/m3. The average values of pulmonary retention and solvent levels in alveolar air and blood were 18.2%; 537 ml/m3 and 2.8 mg/l. Inter-individual variations of these parameters are negligible. R-11 concentrations in urine--in contrast to blood or alveolar air--depend on the dose taken up. After termination of exposure, R-11 concentrations in alveolar air and in blood are excreted with biological half-lives of seven and eleven minutes respectively during the first phase of elimination and with 1.8 and 1.0 h respectively during the second phase of elimination. Though ambient monitoring should, in most cases, be sufficient for the prevention of occupational diseases, the R-11 concentration in alveolar air seems to be the best parameter if biological monitoring seems to be necessary.

A report of occupational deaths attributed to fluorocarbon-113.

This study reports two occupational deaths resulting from exposure to fluorocarbon-113 (1,1,2-trichloro-1,2,2-trifluoroethane; FC-113) in enclosed and confined spaces. One incident involved a worker who was exposed to FC-113 after entering a small degreasing tank to clean it. The second case involved a significant spill of FC-113 onboard a marine vessel. The incidents are compared to other fatal exposures.

[Animal experiments on the detection of an exposure to "chemical mace" (author's transl)]. / Tierexperimentelle Untersuchungen zum Nachweis einer Anwendung der "chemischen Keule".

To answer the question whether a negative result of gas chromatographic blood analysis for components of chemical mace proves that no or at most only slight tear gas exposure can have occurred, animal experiments were carried out. In the blood of 10 guinea pigs, which were exposed to the contents of chemical mace for 1--6 h, the solvants 1,1,2-trichloro-1,2,2-trifluorethane (freon 113) and 1,1,1-trichloroethane could easily be detected--even 23 h after the end of exposure or after a storage of the blood samples for 18 weeks--whereas the lacrimator chloracetophenone (CN) could not be found at all. In vitro experiments showed that CN relatively quickly reacts with components of blood. Therefore, blood samples should be analyzed for CN after withdrawal as soon as possible. In case of inhalation of the contents of chemical mace, i.e., after the comparatively mildest form of CN application, most probably no traces of the lacrimator at all can pass into the blood due to the quick reaction of CN with proteins of the respiratory surface of the lung.

Fluorocarbon aerosol propellants XII: Correlation of blood level of trichloromonofluoromethane to cardiovascular and respiratory responses in anesthetized dogs.

Anesthetized mongrel dogs were exposed to various concentrations of trichloromonofluoromethane. Before, during, and after the inhalation, arterial and venous blood samples were obtained for fluorocarbon analysis. After the cessation of fluorocarbon inhalation, a multiexponential decline for the blood was observed. This finding was similar to that of previous study in which the fluorocarbon was administered intravenously to unanesthetized dogs. The half-life calculated from the terminal phase was about 280 min, and the pseudodistribution equilibrium was reached about 100 min after dosing. Study of the relationship between blood fluorocarbon levels and effects on the respiration rate and arterial blood pressure indicates that the sites of these pharmacological activities are located in the blood or central compartment rather than in the peripheral compartment. The effect on the heart rate appears to be quite instantaneous after inhalation. These results might shed some light on the fast effect of the fluorocarbon propellants, which caused sudden deaths after inhalation of a large quantity.

[Cardiac arrhythmia in dogs under the action of adrenaline and difluorodichloromethane (FC 12)]. / Arythmie cardiaque chez le Chien sous l'action de l'ardrénaline et du difluorodichlorométhane (FC 12).

Inhalation of gas mixtures containing different concentrations of FC 12 by anesthetized and normally oxygenated dogs produces blood levels of FC 12 which are stable and proportional to the rate of FC 12 in the mixture. From the arterial concentration of 40 microgram/ml FC 12 (5 % FC 12 mixture) and over, FC 12 alone causes effects proportional to doses: arterial pressure decrease with tachycardia. At high rates of FC 12 tachypnoea and slight morphological alterations of the electrocardiogram can be recorded. Arhythmia never occurs under the action of FC 12 alone even at maximum arterial concentration reached here : 230 microgram/ml (40 % FC 12 mixture). Recorded disturbances are always reversible. The intravenous perfusion of epinephrine alone evokes the appearance of premature contractions at the only dose of 5 microgram/kg/mn. The presence of FC 12 in blood conjoined with epinephrine induces the inhibition of the hypertensive action of epinephrine at high concentration and lowers the arhythmogenic threshold. The dog is clearly more sensitive than the rabbit to the arhythmogenic action of epinephrine and FC 12. The required rates of epinephrine and FC 12 validate the hypothesis of cardiac sensitization by FC 12 to the arhythmogenic action of circulating adrenaline to explain the cases of sudden "sniffing" deaths in man.

Fluorocarbon aerosol propellants. VI: Interspecies differences in solubilities in blood and plasma and their possible implications in toxicity studies.

Solubilities of the three most commonly used fluorocarbon aerosol propellants were determined in the blood and plasma of humans, monkeys, dogs, rats, and mice. Differences as large as approximately fourfold in blood and more than 33-fold in plasma were found in different species. The partitioning of fluorocarbons between blood cells and plasma showed even greater differences between species. An indirect method was suggested for the calculation of plasma concentrations from total blood concentrations. A comparative evaluation was reported for the nonprotein bound fractions of fluorocarbons in the blood samples of various species. A correlation was drawn for the pharmacokinetic properties of the fluorocarbons within and between species, and a rationale was provided for the extrapolation of toxicity data from animals to humans.