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1008137 
Technical Report 
Occupational exposure limits: Criteria document for heptane 
European Commission :: EC 
1996 
Office for Official Publications of the European Communities 
Luxembourg 
Riskline/1998070013 
Occupational exposure limits
Vol 
1996 
English 
Heptane depresses the central nervous system. Human data shows that a concentration of 1000 ppm (4170 mg/m3) leads to slight vertigo within 6 minutes, and increasing concentrations and exposure time cause increasing vertigo, hilarity and increasing duration of symptoms after the end of exposure. Heptane is narcotic in mice and rats in concentrations greater than 8,000 ppm (33,360 mg/m3) and concentrations greater than 20,000 ppm (83,400 mg/m3) causes death due to paralysis of the respiratory centre. The concentration leading to a 50% decrease in the breathing rate in mice (RD50) have been determined to 17,400 ppm (72,558 mg/m3). The possible role of heptane in the development of peripheral polyneuropathy has been investigated in rats and humans. None of the animal studies found signs of polyneuropathy by clinical or histopathological investigations after exposure to concentrations up to 3000 ppm (12,510 mg/m3); which are concentrations similar to those that lead to polyneuropathy after exposure to hexane. In a single study in humans, electrophysiological findings indicating a marginal effect were found, but the quality of the study was dubious. The 18 exposed individuals had subjective symptoms, but neurological examination did not show any signs of polyneuropathy. It was not noted to which concentration the subjects had been exposed. Based on data from experimental animals it does not seem probable that 2,5-heptanedione will be formed in amounts that are able to cause an adverse effect. Thus, occupational exposure to heptane is not likely to produce peripheral polyneuropathy. Heptane has been tested by Brooks and coworkers (1988) in a number of in vitro assays with bacteria, yeast, and cultured mammalian cells. Heptane did not show mutagenic activity in any of these tests. Thus, nothing is indicating that heptane should be genotoxic. No long-term animal bioassays exist, and immunotoxic properties have not been investigated either. Recommendations. The available data for the establishment of an OEL for heptane are inadequate. No dose-response relationship can be established from human data, and the available animal data are not sufficient. No long-term bioassays exist, but the available in vitro assays do not indicate that heptane should be genotoxic. The critical effect by inhalation of vapours of heptane is respiratory irritation. No human data is elucidating this effect. The RD50 (the concentration leading to a 50% decrease in breathing rate) in mice is 17,400 ppm (72,558 mg/m3). Alarie (1981) has suggested that 0.03 x RD50 gives a value corresponding to a low degree of sensory irritation and this should be the maximum which should be accepted in industrial situations. For heptane this gives a value of 520 ppm (2168 mg/m3). Kristiansen and Nielsen (1988) suggest that for substances with a low slope of the concentration-response curves (such as heptane) a better approach is to use the RDo and multiply this with 0.2. Based on their data a threshold for sensory irritation of 1090 ppm (4543 mg/m3) is likely. Other investigators who have investigated the relationship between RD50 and respiratory irritation in humans have suggested that OEL should be in the range 0.1 - 0.01 RD50. This is based on a comparison between RD50's in mice and human data, which has shown that 0.1 x RD50 is uncomfortable but tolerable in humans, and that 0.01 x RD50 gives minimal or no respiratory irritation (Alarie, 1973; Kane et al., 1979). Based on this assumption the threshold for respiratory irritation for heptane is above 175 ppm (730 mg/m3). Since data concerning RD50 and its relation to respiratory irritation in humans is limited, it is not possible to determine which approach is the best. Since data concerning RD50 and its relation to respiratory irritation in humans is inadequate, a factor in the lowest end of the suggested range seems prudent. Since this factor include human experience, no further safety factor should be applied. Therefore, an OEL of 200 ppm (835 mg/m3) is suggested.