A. Human StudiesInhalation is the major route of occupational exposure to carbon disulfide. Investigations in volunteers and occupationally exposed workers suggest that equilibrium between inhaled and exhaled CS2 is generally attained during the first 2 hr of Initially, the fraction of inhaled CS2 absorbed was relatively constant over a wide range of exposure concentrations, with approximately 70 to 80% of the inhaled carbon disulfide a b s~r b e d .~' .~~~~~~~ At equilibrium, retention of inhaled CS2 declined to approximately 15 to 45% of the inhaled vapor.61,2239289 It is interesting to note a report that described retention of inhaled CS2 in individuals not previously exposed to this agent that was greater than in those who were chronically exposed to CS2.289 Although the mechanism of the decreased retention with chronic exposure is not known, this observation does suggest caution in extrapolation of acute human exposure data to the chronic exposure situation.Percutaneous absorption is a second potential source of occupational exposure to CS2. Dutkiewicz and Baranowska" evaluated skin absorption by immersion of the hand in aqueous CS2 solutions (0.33 to 1.67 g/Q) for 1 hr. Absorption of CS2 was quantitated by two methods: indirectly by determining CS;? elimination by the lung; and by measurement of the CS2 concentration in the aqueous solutions before and after immersion of the hand. Absorption rates determined by solution analysis were found to range from 0.232 to 0.789 mg/cm2/ hr and were approximately 10 times higher than rates calculated from lung excretion of CS2. Further calculations indicated that only 3% of cutaneously absorbed CS2 was eliminated by the lung. Using the solution data, these investigators also calculated that immersion of a hand for 1 hr in a viscose rayon washing bath containing 0.1 mg/g CS2 would result in a total dose of 17.5 mg. One potential difficulty with this study, however, was that no precautions were described to prevent loss of CS2 from the solutions due to volatilization. Failure to adequately control for this variable would result in an overestimate of percutaneous absorption.Following inhalation exposure the primary route of excretion for unmetabolized CS2 is exhalation from the lung. In 1943, McKee et a1.'56 estimated that 6 to 10% of exposure. 148,156,250,254,296 Volume 11, Issue 3 CRC Critical Reviews in Toxicologyidentification of metabolite(s) responsible for the hepatotoxic effects of high-dose exposure to CS2, particularly in phenobarbital pretreated rats. The formation of the toxic metabolite(s) is thought to involve activation of CS2 by the microsomal mixed function oxidase system. Formation of Water-Soluble MetabolitesAn early study by Strittmatter et a1.226 characterized the overall disposition of the radiolabel in guinea pigs after inhalation of 35S-carbon disulfide. A small fraction (8 to 17%) of the total radioactivity recovered during the 48 hr after various inhalation exposures (13.6 ppm for 8 hr; 20.6 ppm for 16 hr, 25.7 ppm for 40 hr) was exhaled as CS2. ...

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Occupational exposure to inorganic acid mists containing sulfuric acid has been associated with increased laryngeal cancer. The primary objective of this review was to compile the literature regarding chronic toxicity and carcinogenicity of inorganic acid mists in laboratory animals. Several chronic toxicity studies had exposures of 1 year or longer. Whereas numbers of animals were limited, no evidence of neoplastic or preneoplastic lesions was reported. Two studies evaluated the carcinogenicity of inorganic acid mists in rats; however, one was limited by a short duration of exposure and the other did not achieve a maximum tolerated dose. A large lifetime study in hamsters evaluated the carcinogenicity of 100 mg/M3 sulfuric acid mist, as well as its ability to act as a promoter or co-carcinogen for benzo(a)pyrene. No evidence of carcinogenic potential was shown. Although an increase in papillomas was noted in the benzo(a)pyrene + H2SO4 group, the co-carcinogenic or promoting potential was considered equivocal. Thus, no evidence from experimental animals strongly supports or refutes the induction of cancer by inorganic acid mists. A possible mechanism that could be associated with inorganic acid mist carcinogenicity relates to the genetic consequences of lowering the pH. Reduced pH can induce chromosomal aberrations, enhance depurination, and deamination of cytidine in DNA. This mechanism has not been evaluated in tissues of the respiratory tract.

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Experimental N-Bis-(2-cyanoethyl)-acetamide.-A solution of 25 g. (0.203 mole) of /S, d'-iminodipropionitrile in 30 ml. of chloroform was cooled and rapidly stirred during the addition of 7.85 g. (0.1 mole) of acetyl chloride. A vigorous reaction set in instantly, causing the precipitation of a white solid.After stirring for about one hour, the solid was removed by suction filtration. The solid melted at 147°, the melting point of the hydrochloride of ß, 5 '-iminodipropionitrile, and it was obtained in 95-100% of the theoretical amount.The filtrate was a clear yellow solution, and when hydrogen chloride gas was bubbled through it, more of the hydrochloride formed. In addition, the yellow color was discharged, giving rise to a yellow gum and a water-white solution. The solid and gum were removed by filtration, and the chloroform solvent was evaporated from the clear filtrate. A solid began to crystallize out, and even before the entire product had solidified, it was poured into boiling ethyl acetate. Upon cooling, white plates crystallized slowly; a dried sample of this material melted at 50°( cor.). The yield of product was 82%.