US EPA

2829149 

Book/Book Chapter 

n-Heptane 

Laine, R 

1999 

Nordic Council of Ministers 

Copenhagen, Denmark 

Health effects of selected chemicals. Vol. 4-5 

15 

253-268 

English 

is also published as 1008138 [Health effects of selected chemiclas 4-5.]
is a chapter of 3160596 Health effects of selected chemicals

The primary concern associated with n-heptane intoxication in man is the potential effect on the central nervous system. The electrophysiological data confirmed the clinical impression of minimal polyneuropathy in workers exposed to fumes of nearly pure n-heptane. n-Heptane is transformed by liver microsomal enzymes to 2,5-heptanedione, the known neurotoxin. It is, however, a minor metabolite, The effectiveness in transforming n-heptane is higher in man than in rats. In the urine of workers exposed to alkane mixture containing n-heptane, small amounts of 2,5-heptanedione was detected, but the small amount is very unlikely to cause clinical damage to the peripheral nervous system. In most workplace situations workers will be exposed to a mixture of hydrocarbon solvent vapors. Components of a n-heptane containing alkane mixture, especially methyl ethyl ketone, may exert additive neurotoxic effects, but the mechanism is not clear. Occupational exposure to n-heptane containing solvent vapours caused slight hematological disorders; anemia, leukopenia and neutropenia. Respiratory absorption of about 25-28% has been suggested. At high vapour concentrations mucous membrane irritation may occur. Absorption through the skin is poor. n-Heptane is a degreasing agent that can cause irritation and dermatitis with prolonged contact. n-Heptane has a low acute toxicity in experimental animals. High vapour concentrations caused irritation of the respiratory tract. The target organ after repeated intraperitoneal administration of n-heptane was the liver based on clinical chemistry and microscopy results. The animals did not show any overt toxic symptoms. Subchronic inhalation toxicity was demonstrated by increased serum alkaline phosphatase levels. Neurotoxicity was not observed in rats in acute, subacute or subchronic inhalation tests using pure n-heptane. The neurotoxic metabolite 2,5- heptanedione was detected in small amounts in the urine, but the serum concentrations were not high enough to produce a peripheral neuropathy. n- Heptane had a similar affinity for the brain tissue as for other tissues tested. No pathological or electrophysiological alterations of the nerve tissues were observed in n-heptane treated rats in contrast to n-hexane treated rats. Technical heptane caused damage in nerves, but constituents other than n- heptane may also have contributed to the results observed. n-Heptane was not mutagenic. Carcinogenicity and teratogenicity of n-heptane have not been studied. There are indications of neuropathy in exposed humans. The neurotoxic metabolite 2,5-heptanedione has been detected in humans at higher levels than in rats. This metabolic difference may explain the lack of positive neurotoxic data in rats. n-Heptane was ototoxic in rats. n-Heptane presents an aspiration hazard in humans because of its low viscosity; the kinematic viscosity derived from rotational viscometry is less than 7 x 10-6 m2/s and the mean surface tension is less than 25 mN, and thereby warrant a classification with R65. 

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