Carbon tetrachloride inhalation

Levels of Significant Exposure to Carbon Tetrachloride— Inhalation 2-2 Levels of Significant Exposure to Carbon Tetrachloride—Oral 2-3 Pathways of Carbon Tetrachloride Metabolism ... 

FIGURE 2-1 Levels of Signtfleant Exposure to Carbon Tetrachloride - Inhalation... 

Dermal/Ocular Effects. Very few reports mention any effect of carbon tetrachloride inhalation on the skin. Inhalation exposure to carbon tetrachloride for several days in the workplace caused a blotchy, macular rash in one man (but not in six others) (McGuire 1932). Similarly, a hemorrhagic rash occurred in a woman exposed to carbon tetrachloride fumes for several days in the workplace (Gordon 1944), and black and blue marks were seen in a patient exposed intermittently to carbon tetrachloride vapors for several years (Straus 1954). Because observations of dermal effects are so sporadic, it is difficult to judge whether these effects are related to carbon tetrachloride exposure, or are incidental. Conceivably, they may have been secondary to reduced synthesis of blood coagulation factors resulting from carbon tetrachloride-induced hepatotoxicity. No studies were located regarding ocular effects in humans or animals after inhalation exposure to carbon tetrachloride. 

Although there are many cases of human overexposure to carbon tetrachloride vapor, there are few quantitative studies of pulmonary absorption of carbon tetrachloride in humans. Based on the difference in carbon tetrachloride concentration in inhaled and exhaled air, absorption across the lung was estimated to be about 60% in humans (Lehmann and Schmidt-Kehl 1936). In animals, monkeys exposed to 50 ppm absorbed an average of 30.4% of the total amount of carbon tetrachloride inhaled, at an average absorption rate of 0.022 mg carbon tetrachloride/kg/minute (McCollister et al. 1951). The concentration of carbon tetrachloride in the blood increased steadily, but did not reach a steady-state within 344 minutes of exposure. 

Ethanol. Alcohol (ethanol) ingestion has repeatedly been associated with potentiation of carbon tetrachloride-induced hepatic and renal injury in humans. In two cases in which men cleaned furniture and draperies with carbon tetrachloride, one man, a heavy drinker, became ill and died (Smetana 1939). His coworker, a nondrinker, suffered a headache and nausea but recovered quickly after breathing fresh air. Both men were subjected to the same carbon tetrachloride exposure, as they had been working in the same room for the same amount of time. In 19 cases of acute renal failure due to carbon tetrachloride inhalation or ingestion, 17 of 19 patients had been drinking alcoholic beverages at about the time of their carbon tetrachloride exposure (New et al. 

Sakata T, Watanabe A, Hobara N, et al. 1987. Chronic liver injury in rats by carbon tetrachloride inhalation. Bull Environ Contam Toxicol 38 959-961. 

Vazquez C, Bujan J, Vallejo D. 1990. Blood coagulation variations induced by carbon tetrachloride inhalation in wistar rats. Toxicol AppI Pharmacol 103 206-213. 

Other mixtures which may be employed are carbon tetrachloride (b.p. 77°) and toluene (b.p. 110-111°) chloroform (b.p. 61°) and toluene methyl alcohol (b.p. 65°) and water (b.p. 100°). The last example is of interest because almost pure methyl alcohol may be isolated no constant boiling point mixture (or azeotropic mixture) is formed (compare ethyl alcohol and water, Sections 1,4 and 1,5). Attention is directed to the poisonous character of methyl alcohol the vapour should therefore not be inhaled. 

The most serious ha2ard of repeated exposure to chloroform inhalation is injury to the Hver and kidneys. Evidence indicates that in humans, repeated exposure to atmospheric concentrations well below the odor threshold may cause such injury. Industrial experience has shown that daily exposure to concentrations below 100 ppm may result in a variety of nervous system and alimentary tract symptoms, in the absence of demonstrable evidence of injury (39). Injury to the Hver is similar to but somewhat less severe than that caused by carbon tetrachloride. Kidney injury is usually associated with but less severe than Hver injury. 

Carbon tetrachloride is toxic by inhalation of its vapor and oral intake of the Hquid. Inhalation of the vapor constitutes the principal ha2ard. Exposure to excessive levels of vapor is characterized by two types of response an anesthetic effect similar to that caused by compounds such as diethyl ether and chloroform and organic injury to the tissues of certain organs, in particular the Hver and kidneys. This type of injury may not become evident until 1—10 days after exposure. The nature of the effect is deterrnined largely by the vapor concentration but the extent or severity of the effect is deterrnined principaHy by the duration of exposure (38). 

Prendergast JA, Jones RA, Jenkins LJ Jr, et al. 1967. Effects on experimental animals of long-term inhalation of trichloroethylene, carbon tetrachloride, 1,1,1-trichloroethane, dichlorodifluoromethane, and 1,1-dichloroethylene. Toxicol Appl Pharmacol 10 270-289. 

This rule holds reasonably well when C or t varies within a narrow range for acute exposure to a gaseous compound (Rinehart and Hatch, 1964) and for chronic exposure to an inert particle (Henderson et al., 1991). Excursion of C or / beyond these limits will cause the assumption Ct = K to be incorrect (Adams et al., 1950, 1952 Sidorenko and Pinigin, 1976 Andersen et al., 1979 Uemitsu et al., 1985). For example, an animal may be exposed to 1000 ppm of diethyl ether for 420 min or 1400 ppm for 300 min without incurring any anesthesia. However, exposure to 420,000 ppm for lmin will surely cause anesthesia or even death of the animal. Furthermore, toxicokinetic study of fiver enzymes affected by inhalation of carbon tetrachloride (Uemitsu et al., 1985), which has a saturable metabolism in rats, showed that Ct = K does not correctly reflect the toxicity value of this compound. Therefore, the limitations of Haber s rule must be recognized when it is used in interpolation or extrapolation of inhalation toxicity data. 

Uemitsu, N., Minobe, Y. and Nakayoshi, H. (1985). Concentration-time-response relationship under conditions of single inhalation of carbon tetrachloride. Toxicol. Appl. Pharmacol. 77 260-266. 

Its effects on the body are widespread. Inhalation of the vapor is the most common mode of entry, and when the chemical is inhaled in sufficient concentration, it has an immediate effect on the brain (hence the high that Harry was partial to) and ultimately, over longer periods, it causes damage to the liver and kidneys. Now it so happened, that although Harry had been working for five years with concentrations of carbon tetrachloride above the recommended limit, any obvious damage to his brain, liver, and kidneys at that time was no more than he would have derived from knocking back a six pack of beer several times a week. So what was the trouble ... 

Carbon tetrachloride is absorbed through the skin of humans, although much less readily than from the lung. After use as a shampoo or as a solvent for removal of adhesives from skin, a number of fatal or near-fatal cases have been reported. It has been noted that these exposures must have also involved high levels of inhalation exposure as well as dermal exposure. It has been estimated that immersion of both hands in the liquid for 30 minutes would yield an exposure equivalent to breathing 100-500 ppm for 30 minutes. 

Schwetz DW et al Embryo- and fetotoxicity of inhaled carbon tetrachloride, 1,1-dichloroethane and methyl ethyl ketone in rats. Toxicol Appl Pharmacol 28 452-464, 1974... 

Hepatic Effects. Data in humans are limited to one study which reported significant dose-related increases in the concentration of serum bile acids in workers after inhalation exposure to hexachlorobutadiene (0.005-0.02 ppm) (Driscoll et al. 1992). The practical importance of this finding is reduced because workers were also potentially exposed to other solvents (carbon tetrachloride and perchloroethylene) and background information on other confounding variables was minimal. No studies were located regarding other hepatic effects in humans. 

Estimates of exposure levels posing minimal risk to humans (Minimal Risk Levels or MRLs) have been made for carbon tetrachloride. An MRL is defined as an estimate of daily human exposure to a substance that is likely to be without an appreciable risk of adverse effects (noncarcinogenic) over a specified duration of exposure. MRLs are derived when reliable and sufficient data exist to identify the target organ(s) of effect or the most sensitive health effect(s) for a specific duration within a given route of exposure. MRLs are based on noncancerous health effects only and do not consider carcinogenic effects. MRLs can be derived for acute, intermediate, and chronic duration exposures for inhalation and oral routes. Appropriate methodology does not exist to develop MRLs for dermal exposure. 

In the past, when industrial and household use of carbon tetrachloride was still common, inhalation exposure to carbon tetrachloride resulted in a considerable number of deaths in humans (e.g., Norwood et al. 1950 Umiker and Pearce 1953). However, quantitative estimates of the exposure... 

No studies were located regarding musculoskeletal effects in humans or animals after inhalation exposure to carbon tetrachloride. Studies have been conducted in both humans and animals to evaluate the respiratory, cardiovascular, hematological, hepatic, and renal effects of inhalation exposure to carbon tetrachloride. Gastrointestinal and dermal/ocular effects have been studied in humans but not in animals. These effects are discussed below. The highest NOAEL values and all LOAEL values from each reliable study for systemic effects in each species and duration category are recorded in Table 2-1 and plotted in Figure 2-1. 

Cardiovascular Effects. Most studies of humans exposed to carbon tetrachloride by inhalation have not detected significant evidence of cardiovascular injury, even at exposure levels sufficient to markedly injure the liver and/or kidney. Changes in blood pressure, heart rate, or right- sided cardiac dilation have sometimes, but not always, been observed (Ashe and Sailer 1942 Guild et al. 1958 Kittleson and Borden 1956 Stewart et al. 1961 Umiker and Pearce 1953), and are probably secondary either to fluid and electrolyte retention resulting from renal toxicity, or to central nervous system effects on the heart or blood vessels. Carbon tetrachloride also may have the potential to induce cardiac arrhythmias by sensitizing the heart to epinephrine, as has been reported for various chlorinated hydrocarbon propellants (Reinhardt et al. 1971). 

Similarly, except for what are likely secondary effects following acute lethal exposures, significant cardiovascular injury has not accompanied hepato/renotoxic inhalation exposure to carbon tetrachloride in a variety of experimental animals (Adams et al. 1952 Prendergast et al. 1967 ... 

Hematological Effects. Significant effects on the hematological system are not usually observed in humans exposed to carbon tetrachloride by inhalation (Heimann and Ford 1941 Norwood et al. 

Hepatic Effects. Carbon tetrachloride has been known for many years to be a powerful hepatotoxic agent in humans and in animals. The principal clinical signs of liver injury in humans who inhale carbon tetrachloride are a swollen and tender liver, elevated levels of hepatic enzyme (aspartate aminotransferase) in the serum, elevated serum bilirubin levels and the appearance of jaundice, and decreased serum levels of proteins such as albumin and fibrinogen (Ashe and Sailer 1942 McGuire 1932 New et al. 1962 Norwood et al. 1950 Straus 1954). In cases of acute lethal exposures, autopsy generally reveals marked liver necrosis with pronounced steatosis (Jennings 1955 Markham 1967 Smetana 1939), and repeated or chronic exposures leads in some cases to fibrosis or cirrhosis (McDermott and Hardy 1963). 

---