Subacute oral toxicity of 2‐butyne‐1,4‐diol in rats

Abstract

2-Butyne-1,4-diol was given to male and female Wistar Imp:DAK rats by oral gavage for 28 consecutive days in daily doses of 1, 10 or 50 mg kg-1 day-1. After 28 days all animals were necropsied. Blood samples were obtained and selected organs were weighed and prepared for histological examination. Treatment-related effects in the high-dose group consisted of: fatal cases in both sexes; depressed body weight gain in males; increase of absolute and/or relative weights of liver and kidneys in both sexes; decreased red blood cell count, haematocrit value and haemoglobin concentration in female rats and elevated reticulocyte count and leukocyte count in both sexes; increased total serum protein content in females, elevated glucose concentration in males and higher activity of sorbitol dehydrogenase in both sexes; and histopathological evidence of hepatotoxicity and nephrotoxicity in decedents, and hepatic and splenic changes in survivors. Minor hepatic, splenic and erythrocytic changes were also found in some females given the middle dose. The dose of 1 mg kg-1 day-1 was considered to be the no-observed-effect level (NOEL), and 10 mg kg-1 day-1 the lowest-observed-effect level (LOEL).

A review of evidence leading to the prediction that 1,4-butanediol is not a carcinogen

“…Body weights were lower in the 400 and 800 mg kg −1 groups, and food consumptions were also decreased. In contrast to the Jedrychowski et al (1990b) study, histopathologic findings were limited to diffuse transitional epithelial hyperplasia and fibrosis of the lamina propria of the urinary bladder at 400 and 800 mg kg −1 . There were no adverse reproductive effects other than reduced pup weight attributed to maternal weight deficits.…”

“…However, the rapid conversion of 1,4-butanediol to γ-hydroxybutyric acid makes it unlikely that the steady state concentration of aldehyde would reach toxic levels. None of the toxicology studies of 1,4-butanediol have identified consistent organ specific toxicity or other significant affects associated with exposure to this chemical, except for behavioral changes (Jedrychowski et al, 1990a(Jedrychowski et al, , 1990bTaberner and Pierce, 1974;Zabic et al, 1974;Kinney et al, 1985;Japan MHW, 1999). Zabic et al (1974) demonstrated a reduction of spontaneous motor activity in rats with i.p.…”

“…Hematological parameters determined on blood samples obtained at the end of the study indicated small differences not considered to represent chemical related toxicity. Mild to moderate inflammation of the liver and proliferation of bile ducts was observed in some dosed animals, primarily from the 500 mg kg −1 groups, but the increase over control was not statistically significant in either males or females (Jedrychowski et al, 1990b). …”

“…Repeated dose studies have been conducted by oral (Jedrychowski et al, 1990b) and inhalation (Kinney et al, 1991) exposure. Groups of male and female Wistar rats were administered 1,4-butanediol by gavage at doses of 5, 50 or 500 mg kg −1 for 28 days.…”

Scientific Opinion on the evaluation of the substances currently on the list in the Annex to Commission Directive 96/3/EC as acceptable previous cargoes for edible fats and oils - Part I of III

“…In a 28-day oral toxicity study in Wistar rats 1,4-butanediol was administered by gavage at doses of 5, 50 or 500 mg/kg per day (Jedrychowski et al, 1990a, as reported by OECD, 2000. A statistically significant increase in activities of sorbitol dehydrogenase and alanine aminotransferase was observed at 500 mg/kg per day in males.…”