Toxicology update isoparaffinic hydrocarbons: A summary of physical properties, toxicity studies and human exposure data

Publisher Website
Google Scholar
Abstract
The Isoparaffins covered in this manuscript are branched aliphatic hydrocarbons with a carbon skeleton length ranging from approximately C10 to C15. They are used in the manufacture of liquid imaging toners, paint formulations, charcoal lighter fluid, furniture polishes and floor cleaners. Potential exposure exists in the petroleum, printing and paint industries. Isoparaffins have a very low order of acute toxicity, being practically non‐toxic by oral, dermal and inhalation routes. However, aspiration of liquid isoparaffins into the lungs during oral ingestion could result in severe pulmonary injury. Dermally, isoparaffins have produced slight to moderate irritation in animals and humans under occluded patch conditions where evaporation cannot freely occur. However, they are not irritating in non‐occluded tests, which are a more realistic simulation of human exposure. They have not been found to be sensitizers in guinea pig or human patch testing. However, occasional rare idiosyncratic sensitization reactions in humans have been reported. Instillation of isoparaffins into rabbit eyes produces only slight irritation. Several studies have evaluated sensory irritation in laboratory animals or odor or sensory response in humans. When evaluated by a standard procedure to assess upper airway irritation, isoparaffins did not produce sensory irritation in mice exposed to up to 400 ppm isoparaffin in air. Human volunteers were exposed for six hours to 100 ppm isoparaffin. The subjects were given a self‐administered questionnaire to evaluate symptoms, which included dryness of the mucous membranes, loss of appetite, nausea, vomiting, diarrhea, fatigue, headache, dizziness, feeling of inebriation, visual disturbances, tremor, muscular weakness, impairment of coordination or paresthesia. No symptoms associated with solvent exposure were observed. With a human expert panel, odor from liquid imaging copier emissions became weakly discernible at approximately 50 ppm. Numerous long‐term exposures have been conducted in animals with only one major finding observed. Renal tubular damage has been found in kidneys of male rats upon repeated exposures to isoparaffins. It does not occur in mice or in female rats. This male rat nephropathy has been observed with a number of hydrocarbons, including wholly vaporized unleaded gasoline. The phenomenon has been attributed to reversible binding of hydrocarbon to α2μ‐globulin. Since humans do not synthesize α2μ‐globulin or a similar protein, the finding is not considered to be of biological significance to man. No clinically significant renal abnormalities have been found in refinery workers exposed to hydrocarbons. When evaluated for developmental toxicity in rats, isoparaffins were neither embryotoxic nor teratogenic. Isoparaffins were consistently negative on standard bacterial genotoxicity assays. They were also non‐genotoxic in in vivo mammalian testing for somatic or germ cell mutations (mouse micronucleus test and rat dominant lethal assay, respectively).