Propargyl alcohol is a commercially available acetylenic primary alcohol. It is also a by-product in the industrial synthesis of butynediol from
acetylene and
formaldehyde with
copper acetylide as catalyst.
Propargyl alcohol is used as a reactant/chemical intermediate,
pharmaceutical intermediate,
agricultural chemical intermediate, soil fumigant, corrosion inhibitor,
solvent stabilizer, and
polymer modifier. It has also been used to prevent the
hydrogen embrittlement of steel.
Propargyl alcohol was nominated by the National Cancer Institute for study because of the potential for human exposure in occupational settings through inhalation and dermal contact. Male and female F344/N rats and B6C3F1 mice were exposed to
propargyl alcohol (greater than 99% pure) by inhalation for 2 weeks, 3 months, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium and mouse peripheral blood erythrocytes. 2-WEEK STUDY IN RATS: Groups of five male and five female rats were exposed to
propargyl alcohol vapor at concentrations of 0, 31.3, 62.5, 125, 250, or 500 ppm, 6 hours plus T(90 )(12 minutes) per day, 5 days per week for 16 days. All males exposed to 125 ppm or greater and all females exposed to 250 or 500 ppm died by the end of day 3 of the study, and one 125 ppm female died on day 5. Mean
body weights were significantly decreased in 62.5 ppm males and 125 ppm females. Clinical findings in the 125 and 250 ppm groups included
lethargy,
ataxia, abnormal breathing, and nasal/eye discharge. Right kidney weights of 62.5 and 125 ppm females and liver weights of 125 ppm females were significantly greater than those of the chamber controls. All 250 and 500 ppm males and females had moderate to marked periportal
necrosis, congestion, and erythrophagocytosis of the liver. 2-WEEK STUDY IN MICE: Groups of five male and five female mice were exposed to
propargyl alcohol vapor at concentrations of 0, 31.3, 62.5, 125, 250, or 500 ppm, 6 hours plus T(90) (12 minutes) per day, 5 days per week for 17 days. All mice exposed to 125 ppm or greater died by day 3 of the study. Mean
body weights of mice exposed to 62.5 ppm were significantly less than those of the chamber controls. Clinical findings in the 62.5 and/or 125 ppm groups included abnormal breathing, nasal/eye discharge,
thinness, and
lethargy. Right kidney weights of 31.3 ppm mice were significantly greater, and thymus weights of 62.5 ppm males were significantly less than those of the chamber controls. The livers of all males and females exposed to 250 or 500 ppm exhibited marked periportal
necrosis, congestion, and erythrophagocytosis; these lesions also occurred in all 125 ppm males with less severity. 3-MONTH STUDY IN RATS: Groups of 10 male and 10 female rats were exposed to
propargyl alcohol vapor at concentrations of 0, 4, 8, 16, 32, or 64 ppm, 6 hours plus T(90) (12 minutes) per day, 5 days per week for 14 weeks. All rats survived to the end of the study. Mean
body weights of all exposed groups were similar to those of the chamber control groups. The incidences of minimal to mild
hyperplasia of respiratory epithelium of the nose were significantly increased in all exposed groups except 8 ppm males and 4 ppm females. Squamous
metaplasia of the respiratory epithelium was noted in a few males and most females exposed to 64 ppm.
Necrosis of olfactory epithelium was present in half of the males and females exposed to 64 ppm and in a few males and females exposed to 32 ppm. 3-MONTH STUDY IN MICE: Groups of 10 male and 10 female mice were exposed to
propargyl alcohol vapor at concentrations of 0, 4, 8, 16, 32, or 64 ppm, 6 hours plus T(90) (12 minutes) per day, 5 days per week for 14 weeks. All mice survived to the end of the study. Mean
body weights of males exposed to 8 ppm or greater and 32 and 64 ppm females were significantly less than those of the chamber control groups. Histopathologic changes occurred in the nasal cavity of mice and involved both the respiratory and olfactory epithelium in groups exposed to 16 ppm or greater. Lesions included minimal to moderate suppurative
inflammation, minimal to moderate squamous
metaplasia of the respiratory epithelium, minimal to mild hyaline degeneration (accumulation) in the respiratory epithelium, minimal to moderate olfactory epithelial
atrophy, minimal to moderate
hyperplasia of glands in the olfactory region, minimal
necrosis of olfactory epithelium, and minimal to moderate turbinate
atrophy. There were no biologically significant differences in organ weights between exposed and chamber control groups. Reproductive tissue parameters of exposed males were similar to those of the chamber controls. Only 2/9 female mice in the 64 ppm group exhibited regular estrous cyclicity compared to 6/10 in the controls. Females exposed to 16 ppm differed from chamber controls in the relative time in the estrous stages, and 64 ppm females had a significantly increased probability of extended estrus. No gross lesions were observed at necropsy. 2-YEAR STUDY IN RATS: Groups of 50 male and 50 female rats were exposed to
propargyl alcohol vapor at concentrations of 0, 16, 32, or 64 ppm, 6 hours plus T(90) (14 minutes) per day, 5 days per week for 105 weeks. Survival of 32 and 64 ppm males was significantly less than that of the chamber control group. Mean
body weights of males exposed to 64 ppm were less than those of the chamber controls after week 24 of the study. Nasal respiratory epithelial
adenomas were present in three 64 ppm males and one 32 ppm female; the incidence in 64 ppm males exceeded the historical control ranges. A spectrum of nonneoplastic lesions occurred in the respiratory and olfactory epithelium of rats at all exposure concentrations. The incidences of respiratory epithelial
hyperplasia, respiratory glandular
hyperplasia, and olfactory basal cell
hyperplasia were significantly increased in all exposed groups of rats. The incidences of lesions of the olfactory epithelium including
hyperplasia, glandular
hyperplasia,
atrophy, respiratory
metaplasia, degeneration,
necrosis, hyaline droplet accumulation, and chronic active
inflammation were significantly increased in one or more exposed groups of males and/or females. The incidence of mononuclear cell
leukemia was significantly increased in males exposed to 64 ppm, and the incidence exceeded the historical control ranges. 2-YEAR STUDY IN MICE: Groups of 50 male and 50 female mice were exposed to
propargyl alcohol vapor at concentrations of 0, 8, 16, or 32 ppm, 6 hours plus T(90) (14 minutes) per day, 5 days per week for 105 weeks. Survival of exposed groups was similar to that of the chamber control groups. Mean
body weights of 16 and 32 ppm females were less than those of the chamber control group after weeks 73 and 21, respectively.
Eye abnormality (unspecified) was observed after one full year of exposure with the incidence increasing in an exposure concentration-related manner. The incidences of nasal respiratory epithelial
adenoma increased with a positive trend and were significantly increased in groups exposed to 32 ppm. A spectrum of nonneoplastic lesions occurred in the nasal respiratory and olfactory epithelium of mice at all exposure concentrations. The incidences of respiratory epithelial
hyperplasia, respiratory glandular
hyperplasia, and squamous
metaplasia were significantly increased in most exposed groups of mice. Suppurative
inflammation was often associated with the squamous
metaplasia, and turbinate
atrophy was present in all exposed mice (except one 16 ppm male). The incidences of olfactory epithelial
atrophy and respiratory
metaplasia were increased in the 16 and 32 ppm groups. Significantly increased incidences of Harderian gland
adenoma occurred in 8 and 32 ppm males.
GENETIC TOXICOLOGY: