Motor activity effects in female Fischer 344 rats exposed to isopropanol for 90 days

Abstract

In a previous subchronic neurotoxicity study, increases in motor activity were observed for female rats after 9 and 13 weeks of exposure to 5000 ppm of isopropanol vapor.1 The present study was conducted to evaluate the reproducibility of these effects and, if reproducible, to assess the potential for reversibility following cessation of exposure. Two groups, each containing 30 female Fischer 344 rats, were exposed to concentrations of zero (control) and 5000 ppm of isopropanol vapor for 6 h per day, 5 days per week. Fifteen of the animals in the control and 5000 ppm groups were exposed for 9 weeks (designated as the 9‐week subgroup), while the other 15 animals in each group were exposed for 13 weeks (designated as the 13‐week subgroup). Motor activity was assessed for both subgroups prior to exposure and following 4, 7 and 9 weeks of exposure. Motor activity was also measured for rats in the 13‐week subgroup following 11 and 13 weeks of exposure. These motor activity measurements were made 18–20 h following the end of the last exposure for that week. In addition, to evaluate the reversibility of motor activity effects, measurements were made on three occasions during the week following the final exposure for rats in both the 9‐week and 13‐week subgroups and weekly thereafter for five additional weeks for rats in the 13‐week subgroup. Increases in cumulative test session motor activity counts were observed following 4, 7 and 9 weeks of exposure for rats in the 9‐week subgroup. Increases in cumulative test session motor activity counts were also observed following 4, 7, 9, 11 and 13 weeks of exposure for rats in the 13‐week subgroup. Reversibility of this effect was observed for rats in the 9‐week subgroup within 2 days following the last exposure. Reversibility was also noted for rats in the 13‐week subgroup but not until Study Week 15 (2 weeks following the last exposure). Minor changes were observed in the shape of the motor activity habituation curves for isopropanol‐exposed animals in the 9‐week and 13‐week subgroups at ca. 50% of the measurement intervals beginning at Study Week 4. While most of these statistical changes were observed in conjunction with increases in cumulative test session motor activity, some were observed following time points where recovery of the cumulative test session motor activity counts had occurred. No change in the shape of the motor activity habituation curve was observed at 42 days following the last exposure, indicating that complete recovery of motor activity effects had occurred. Thus, repeated exposure of female rats to 5000 ppm of isopropanol produced reversible increases in motor activity. © 1998 John Wiley & Sons, Ltd.

Review of reproductive and developmental toxicity studies with isopropanol

“…Questions continue to arise regarding the interpretation of the data from the Bevan et al (1995) study particularly with regards to classification criteria for labeling. The repeated exposure studies with IPA do not describe any effects to the male reproductive organs (Burleigh‐Flayer et al, 1994, 1997, 1998), and therefore a plausible explanation for the decrease in male mating index described by Bevan et al (1995) has not been provided. In an attempt to better understand the decrease in male mating index and decreased postnatal survival reported by Bevan et al (1995), the original study report (including appendices) from the testing laboratory was reviewed.…”

Richtwerte für 2-Propanol in der Innenraumluft

“…Ein Geruchsschwellenwert für 2-Propanol in Höhe von 26 ml/m 3 (65 mg/m 3 ) wurde von Nagata (2003) [40] mittels der Triangle-Bag-Methode ermittelt, bei der jeweils 6 Freiwillige nacheinander den Inhalt von 3 Luftsäcken inhalierten, von denen zwei Luft und einer die Testsubstanz enthielten. Dies wurde in 3 Replikaten für jeweils verschiedene Substanzverdünnungen durchgeführt.…”

“…Bemerkenswert ist der bei Nagata (2003) [40] berichtete große Unterschied zum entsprechenden Wert für 1-Propanol, der mit 0,094 ml/m 3 (0,235 mg/m 3 ) angegeben wird.…”