Repeated dose and reproductive/developmental toxicity of perfluorooctadecanoic acid in rats

Abstract

-Male and female rats were given perfluorooctadecanoic acid (PFOdA) by gavage at 40, 200 or 1,000 mg/kg/day, and each female was mated with a male in the same dose group after 14-day administration. Males were dosed for 42 days and females were dosed throughout the gestation period until day 5 of lactation. One female given 1,000 mg/kg/day was euthanized on day 18 of gestation due to a moribund condition; however, no other treatment-related clinical signs of toxicity were observed. Body weights fell at 1,000 mg/kg/day from day 28 through the administration period in males and throughout gestation and lactation in females. Red blood cell count, hemoglobin level and hematocrit were decreased at 200 and 1,000 mg/kg/day in males and activated partial thromboplastin time was prolonged at 1,000 mg/kg/ day in females. Histopathological examination revealed hepatic changes, such as centrilobular hypertrophy and necrosis, in males given 200 and 1,000 mg/kg/day and in females given 1,000 mg/kg/day. Pancreatic zymogen granule was decreased in both sexes at 1,000 mg/kg/day. As for reproductive and developmental toxicity, there were decreases in the number of corpora lutea, implantation, total number of pups born and the number of live pups on postnatal days 0 and 4 at 1,000 mg/kg/day. At this dose, birth weights of pups were decreased and postnatal body weight gain was inhibited. Based on these findings, the NOAEL of PFOdA was considered to be 40 mg/kg/day for repeated dose toxicity and 200 mg/kg/day for reproductive/developmental toxicity.

Repeated dose and reproductive/developmental toxicity of perfluoroundecanoic acid in rats

“…This is because hydrophobicity, which increases as carbon length increases, seems to favor biliary enterohepatic recirculation, resulting in more protracted toxicity (ATSDR, 2009). In contrast, 42-day administration of PFOdA (C18) increased liver (Hirata-Koizumi et al, 2012). In comparison with other PFAAs (C8-C12), including PFUA (C11), PFOdA induced liver toxicity at higher doses, and this may be due to the low absorption of PFOdA into the body.…”

“…Perfluoroalkyl acids (PFAAs) are environmental contaminants that have received attention because of their possible effects on wildlife and human health in recent years; PFAAs are very stable in the environment, have bioaccumulation potential, and have been detected in environmental media and biota in many parts of the world, including oceans and the Arctic; and many researchers have revealed their toxic effects, including hepatotoxicity and reproductive/developmental toxicity in laboratory animals, as reviewed by ATSDR (2009) and Hirata-Koizumi et al (2012). In particular, perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are the most effective surfactants among PFAAs , and many toxicological effects of PFOS and PFOA have been revealed (reviewed in ATSDR, 2009, and fully introduced in Hirata- Koizumi et al, 2012).…”

“…In particular, perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are the most effective surfactants among PFAAs , and many toxicological effects of PFOS and PFOA have been revealed (reviewed in ATSDR, 2009, and fully introduced in Hirata- Koizumi et al, 2012). PFOS and PFOA have now been regulated worldwide, and the manufacture, import and use of PFOS were essentially prohibited in the EU in 2008 (DIRECTIVE 2006/122/EC) and in Japan in 2010 (Japanese law, 2009).…”

“…In order to obtain initial risk information on the toxicity of PFCAs, which have a longer chain than PFOA (C8), we have carried out a series of screening tests on the toxicity of PFCAs (C11-C18), and the result for perfluorooctadecanoic acid (PFOdA, C18) has been already published (Hirata-Koizumi et al, 2012). Here, we show initial risk information on the repeated dose and reproductive/developmental toxicity of PFUA (C11).…”

Combined repeated dose and reproductive/developmental toxicity screening test of <i>tert</i>-butylhydrazine monohydrochloride in rats

“…38 No. 2 177 Information Data Sets of the OECD chemical assessment.Recently the safety assessments of several chemicals performed using this test guideline have been reported in toxicological journals (Tanaka et al, 1992;Malley et al, 2002;Sato et al, 2005;Matsumoto et al, 2008;Chung et al, 2009;Hirata-Koizumi et al, 2012). A number of toxicity information on hydrazine (CAS No.…”