A Combined 28-Day Oral Toxicity Study of HFPO-Amidol (CASRN 75888-49-2) With Reproductive/Developmental Toxicity Screening Test in Wistar Han Rats.
HFPO-Amidol (CAS # 75888-49-2) is a new hexafluoropropylene oxide (HFPO)-based intermediate developed as an alternative to longer chain perfluorinated compounds. The repeated-dose toxicity of this material was evaluated in an Organization for Economic Cooperation and Development 422-compliant, 28-day oral exposure study with a concurrent reproductive/developmental toxicity screening test. Wistar rats received doses of 0, 30, 300, or 1000 mg/kg/d by oral gavage. Statistically significant changes in body weight gain of 1000 mg/kg/d females during the postcoitum period were possibly related to treatment but were considered not adverse, given the slight nature of the changes. The lower food consumption of 300 mg/kg/d females during the postcoitum and lactation period was not considered treatment related given the absence of a time- and dose-related trend and because food intake was generally similar to control levels after allowance for body weights. Statistically significant changes in motor activity (total movements and total ambulations) were noted in 1000 mg/kg/d main male and female rats. The changes observed in female rats were considered not treatment related in the absence of a dose-response trend. The higher motor activity of high-dose males was primarily apparent within the first 10 minutes of the 60-minute measurement period and was suggestive of temporary hyperreactivity to a new environment/stimulus. This increased peak motor activity remained present although at an apparent lower magnitude when measured 13 days after withdrawal of treatment. Because the possible toxicological relevance of the temporarily increased motor activity observed in 1000 mg/kg/d males could not be excluded, these changes were considered possibly adverse in nature. No treatment-related or toxicologically relevant effects were noted on the other parental, reproductive, and developmental parameters investigated in this study. The parental systemic no observed adverse effect level (NOAEL) for this study is 300 mg/kg/d (based on increased motor activity in males), while the reproductive and developmental NOAEL is 1000 mg/kg/d.
Medical Department, 3M Company, St Paul, MN, USA lhmoilanen@mmm.com.
Lori H
LH
Moilanen
Medical Department, 3M Company, St Paul, MN, USA.
Bradford D
BD
Bagley
Materials Resource Division, 3M Company, St Paul, MN, USA.
Daniel C
DC
Hakes
Medical Department, 3M Company, St Paul, MN, USA.
Esther F
EF
Hope
Medical Department, 3M Company, St Paul, MN, USA.
Jill E
JE
Reynolds
WIL Research Europe B.V., 's-Hertogenbosch, The Netherlands.
Francois
F
van Otterdijk
D000818:Animals; D001772:Blood Cell Count; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D005260:Female; D005465:Fluorocarbon Polymers / Q000633:toxicity*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D019055:No-Observed-Adverse-Effect Level; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D012098:Reproduction / Q000187:drug effects*; D013723:Teratogens / Q000633:toxicity*; D015430:Weight Gain / Q000187:drug effects
D005465:Fluorocarbon Polymers; D013723:Teratogens; C019223:fomblin Y 04
hexafluoropropylene oxide; rat; repeat-dose toxicity; reproductive toxicity; subacute