Subchronic Inhalation Toxicity Study of n-pentane in Rats

Abstract

ObjectivesThis study was conducted in order to obtain information concerning the health hazards that may result from a 13 week inhalation exposure of n-pentane in Sprague-Dawley rats.MethodsThis study was conducted in accordance with the Organization for Economic Co-operation and Development (OECD) guidelines for the testing of chemicals No. 413 'Subchronic inhalation toxicity: 90-day study (as revised in 2009)'. The rats were divided into 4 groups (10 male and 10 female rats in each group), and were exposed to 0, 340, 1,530, and 6,885 ppm n-pentane in each exposure chamber for 6 hour/day, 5 days/week, for 13 weeks. All of the rats were sacrificed at the end of the treatment period. During the test period, clinical signs, mortality, body weights, food consumption, ophthalmoscopy, locomotion activity, urinalysis, hematology, serum biochemistry, gross findings, organ weights, and histopathology were assessed.ResultsDuring the period of testing, there were no treatment related effects on the clinical findings, body weight, food consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross findings, relative organ weight, and histopathological findings.ConclusionThe no-observable-adverse-effect level (NOAEL) of n-pentane is evaluated as being more than 6,885 ppm (20.3 mg/L) in both male and female rats. n-pentane was not a classified specific target organ toxicity in the globally harmonized classification system (GHS).

Characterization of the toxicological hazards of hydrocarbon solvents

“…The overall no adverse effect level was the analytically determined concentration of 20483 mg/m 3 (approximately 7000 ppm), the highest concentration tested. These results were confirmed in a subsequent study (Kim et al 2012) in which similar exposure levels were tested and similar results were obtained with an overall no adverse effect concentration of 20300 mg/m 3 (approximately 6900 ppm).…”

“…There are specific occupational exposure limits for n-hexane that are related to its neurological properties; for other aliphatic constituents of these solvents, occupational recommendations are set to avoid respiratory irritation and/or acute CNS effects. In repeated exposure studies, liver enlargement is commonly observed; male rat kidney effects associated with a2u-globulin induction are seen in studies of substances containing isoparaffinic and/or cycloparaffinic constituents, and small but statistically significant reductions in hematological parameters have been reported in some studies (Carrillo et al 2013, Carpenter et al 1975d, 1978, Galvin and Marashi 1999a, 1999b, 1999c, Kinkead et al 1985, Kim et al 2012, Malley et al 2000, Schreiner et al 1998, Sung et al 2010). As described above, liver enlargement without pathological changes or elevated levels of marker enzymes (ALT, AST) is considered to be an adaptive response rather than an adverse effect.…”

“…There have also been repeated dose studies in which it has been demonstrated through gross and pathological examinations that repeated exposure to pentanes has no effects on reproductive organs (Galvin and Marashi 1999c, Kim et al 2012, Stadler et al 2001). …”

“…The potential for n-pentane to cause repeated dose toxicity following exposure by inhalation was assessed in 14-day (Stadler et al 2001) and 90-day (Kim et al 2012) toxicity studies. In the 14-day study, rats were exposed by inhalation 6 hours/day and 5 days/week for two weeks at levels of 1000, 3000, or 10000 ppm (2941, 8824, or 29412 mg/ m 3 ).…”

Quantification of pentane in exhaled breath, a potential biomarker of bowel disease, using selected ion flow tube mass spectrometry

“…Pentane excretion in breath has been previously used as an index of lipid peroxidation based on the premise that this hydrocarbon is not metabolized. However, it is now known that pentane is metabolized by the liver in animals into 2‐pentanol and that concentration of exhaled pentane is affected both by its production and by its metabolic loss…”