Evaluation of propargyl alcohol toxicity and carcinogenicity in F344/N rats and B6C3F1/N mice following whole-body inhalation exposure

Abstract

Propargyl alcohol (PA) is a high production volume chemical used in synthesis of many industrial chemicals and agricultural products. Despite the potential for prolonged or accidental exposure to PA in industrial settings, the toxicity potential of PA was not well characterized. To address the knowledge gaps relevant to the toxicity profile of PA, the National Toxicology Program (NTP) conducted 2-week, 14-week and 2-year studies in male and female F344/N rats and B6C3F1/N mice. For the 2-week inhalation study, the rats and mice were exposed to 0, 31.3, 62.5, 125, 250 or 500 ppm. Significant mortality was observed in both rats and mice exposed to ≥ 125 ppm of PA. The major target organ of toxicity in both mice and rats was the liver with exposure-related histopathological changes (250 and 500 ppm). Based on the decreased survival in the 2-week study, the rats and mice were exposed to 0, 4, 8, 16, 32 or 64 ppm of PA in the 14-week study. No treatment-related mortality was observed. Mean body weights of male (≥ 8 ppm) and female mice (32 and 64 ppm) were significantly decreased (7–16%). Histopathological changes were noted in the nasal cavity, and included suppurative inflammation, squamous metaplasia, hyaline droplet accumulation, olfactory epithelium atrophy, and necrosis. In the 2-year inhalation studies, the rats were exposed to 0, 16, 32 and 64 ppm of PA and the mice were exposed to 0, 8, 16 and 32 ppm of PA. Survival of male rats was significantly reduced (32 ppm and 64 ppm). Mean body weights of 64 ppm male rats were significantly decreased relative to the controls. Both mice and rats showed a spectrum of non-neoplastic changes in the nose. Increased neoplastic incidences of nasal respiratory/transitional epithelial adenoma were observed in both rats and mice. The incidence of mononuclear cell leukemia was significantly increased in male rats. In conclusion, the key findings from this study indicated that the nose was the primary target organ of toxicity for PA. Long term inhalation exposure to PA led to nonneoplastic changes in the nose, and increased incidences of respiratory/transitional epithelial adenomas in both mice and rats. Increased incidences of harderian gland adenoma may also have been related to exposure to PA in male mice.

Quantitative Survey and Structural Classification of Hydraulic Fracturing Chemicals Reported in Unconventional Gas Production

“…For example, methanol is classified as toxic in the EU, but it is rapidly metabolized and not expected to persist in the environment over longer time scales . Propargyl alcohol in pure form is toxic to humans, highly toxic to aquatic organisms and was found to be carcinogenic in rats. , However, propargyl alcohol is further transformed in the subsurface (1,3-hydroxyl shift and tautomerization to 1-propenal, subsequent polymerization or oxidation) and is readily biodegradable according to OECD criteria . It is, therefore, expected to persist in the environment for weeks rather than months after application, similar to other reactive monomers (see acrylamide, epichlorhydrin, etc., in Table ).…”

A censorious appraisal of the oil well acidizing corrosion inhibitors

“…For instance, propargyl alcohol-formaldehyde mixture, propargyl alcohol-propylene mixture (de Queiroz Baddini et al, 2007;Perry et al, 1990) as well as propargyl alcohol-benzyl quinolinium chloride (BQC) formulation are highly effective acidizing inhibitors. Nevertheless, the high toxicity of propargyl alcohol is of serious concern as it is capable of posing serious negative effect on the environment and on human lives (Thakur et al, 2013). The current research drive is to have effective inhibitor devoid of propargyl alcohol.…”

Oxygen-functionalized alkyne precursors in carbon nanotube growth

“…Both are liquids at standard conditions, with low vapor pressures (15.6 and 3.52 mm Hg, respectively, at 25°C; see Table S1). Though the reactivity and small size of these two alkynes can present health hazards, [18][19][20] their usage in synthesis could produce a net benefit by eliminating the need for ex situ CNT functionalization via acid reflux, potentially reducing material and energy consumption. Finally, we note that while acetylene and propargyl alcohol are both bulk commodity chemicals (priced at $6.21 per mol (Airgas) and $4.22 per mol (Sigma-Aldrich), respectively; non-bulk pricing) that can be readily deployed for use in CNT fabrication, propiolic acid is quite expensive ($157.50 per mol, Sigma-Aldrich), and thus might be limited in its commercial potential.…”