Animal toxicity studies with ammonium perfluorooctanoate

Griffith, F. D.; Long, James E.

doi:10.1080/15298668091425301

Cited by 119 publications

(61 citation statements)

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“…PFAAs are known to affect the liver, causing hypertrophy and in some cases necrosis, in rodents (Chengelis et al, 2009;Goldenthal, 1978;Griffith and Long, 1980;Kawashima et al, 1995;Kennedy, 1987;Lieder et al, 2009b;Mertens et al, 2010;van Otterdijk, 2007avan Otterdijk, , 2007bZhang et al, 2008). Hepatocyte hypertrophy was observed at as low as 0.064~0.23 mg/kg/day in a 2-year dietary study of PFOS (Thomford, 2002) and 0.64 mg/kg/day in a 13-week dietary study of PFOA (Perkins et al, 2004) in rats.…”

Section: Discussionmentioning

confidence: 99%

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

Hirata-Koizumi¹,

Fujii

Furukawa

et al. 2012

J. Toxicol. Sci.

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-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.

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Section: Discussionmentioning

confidence: 99%

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

Hirata-Koizumi¹,

Fujii

Furukawa

et al. 2012

J. Toxicol. Sci.

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“…However, Oat2 expression is not gender-predominant in mouse kidney. Interestingly, perfluoro-octanoic acid (PFOA), a chemical used in the production of nonstick cookware and protective finishes on carpets, is excreted into urine by female rats at a greater rate than by male rats (Griffith and Long, 1980;Hanhijärvi et al, 1982;Kudo et al, 2002). Additionally, PFOA induces liver toxicity in male rats, but not in female rats, presumably due to differences in the urinary excretion rate (Griffith and Long, 1980).…”

Section: Discussionmentioning

confidence: 99%

RAT AND MOUSE DIFFERENCES IN GENDER-PREDOMINANT EXPRESSION OF ORGANIC ANION TRANSPORTER (OAT1–3;SLC22A6–8) mRNA LEVELS

Buist

Klaassen²

2004

Drug Metab Dispos

132

112

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ABSTRACT:Organic anion transporters (Oats) mediate the initial step of active renal excretion, specifically substrate uptake into proximal tubule cells. Despite extensive characterization of rat Oats, mouse Oat expression patterns are virtually unknown. This study was designed to identify basal expression patterns of mouse Oat1 (Slc22a6), Oat2 (Slc22a7), and Oat3 (Slc22a8) mRNA, compare these patterns with those in rat, and characterize postnatal development of mouse Oat mRNA. Tissues were collected from adult male and female 129J and C57BL/6 mice, and male and female C57BL/6 mice 0 to 40 days of age. Oat mRNA levels were determined by branched DNA signal amplification. Mouse Oat1 mRNA was primarily expressed in kidney of both strains, with male predominance. Mouse Oat2 mRNA levels were highest in kidney of both strains without gender predominance. In both strains, Oat3 mRNA was highest in kidney, and liver expression was male-predominant. However, only 129J mice had higher Oat3 mRNA levels in female kidney than in male kidney. During postnatal development, both Oat1 and Oat2 mRNA levels began to rise after 25 days of age. Oat3 mRNA levels rose gradually from birth through 40 days of age. Oat2 mRNA increased 30-fold during the first 40 days, whereas Oat1 and Oat3 increased about 2-fold. The most notable species differences in Oat mRNA expression were a lack of Oat2 female predominance in mouse kidney and a less dramatic Oat3 male predominance in mouse liver. With the exception of a significant species difference in Oat2 expression, many similarities were found between rat and mouse Oat mRNA levels.

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“…In contrast to PAH, renal clearance of PFOA is greater in female than male rats (Griffith and Long, 1980;Hanhijärvi et al, 1982;Kudo et al, 2002). Griffith and Long (1980) demonstrated that male rats developed hepatotoxicity at lower PFOA treatment levels than did females, and corresponding serum levels were 75-226 fold greater in males than in females.…”

Section: Fig 3 Effects Of Hx and Gh Treatments On Oat Mrna In Kidnementioning

confidence: 99%

“…Griffith and Long (1980) demonstrated that male rats developed hepatotoxicity at lower PFOA treatment levels than did females, and corresponding serum levels were 75-226 fold greater in males than in females. These differences were attributed to relatively slow urinary excretion in male as compared with female rats, and led to the conclusion that female rats possess an active secretory mechanism which is lacking or inactive in male rats (Hanhijärvi et al, 1982).…”

Section: Fig 3 Effects Of Hx and Gh Treatments On Oat Mrna In Kidnementioning

confidence: 99%

Endocrine Regulation of Rat Organic Anion Transporters

Buist¹,

Cherrington²,

Klaassen³

2003

Drug Metab Dispos

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This article is available online at http://dmd.aspetjournals.org ABSTRACT:Messenger RNA levels of rat organic anion transporter 1 (Oat1; Slc22a6) and Oat2 (Slc22a7) in kidney and Oat3 (Slc22a8) in liver are gender-predominant. Oat1 and Oat3 are male-predominant, whereas Oat2 is female-predominant. Gonadectomized and hypophysectomized (HX) rats were studied to determine whether sex steroids and/or growth hormone (GH) are responsible for these gender-divergent patterns. GH was administered to HX rats by two daily injections (simulating male secretion) or continuous infusion (simulating female secretion). Oat1 mRNA levels, normally higher in male than female kidney, were lowered by gonadectomy and HX in male rats, but not in females. Additionally, GH injections or infusion did not alter Oat1 levels in HX rats. Oat2 mRNA levels, typically much higher in female than in male kidney, were unaffected by gonadectomy. However, HX dramatically decreased Oat2 in female kidney without altering male levels. GH administered by continuous infusion increased Oat2 in kidneys of both HX male and female rats, whereas injections had no affect. Gonadectomy reduced Oat3 mRNA levels in male livers without affecting levels in female livers. In contrast, HX decreased male and elevated female Oat3 mRNA. GH injections did not significantly change Oat3 mRNA levels in HX rats, but infusion decreased Oat3 mRNA in liver. In conclusion, androgens, but not GH, are responsible for the Oat1 mRNA gender difference in kidney; the female GH secretion pattern is responsible for the Oat2 mRNA gender difference in kidney; and both androgens and the female GH secretion pattern are responsible for the Oat3 mRNA gender difference in liver.Metabolism and excretion both determine elimination of endogenous and exogenous compounds. Liver is the primary site of metabolism, and liver and kidney are important organs in the process of excretion. Increasing or decreasing metabolism or excretion can lead to a respective decrease or increase of xenobiotic half-life, thus altering disposition. Expression of phase I [e.g., cytochromes P450 (P450s 1 )] and phase II enzymes [e.g., glucuronosyltransferases and sulfotransferases (STs)] is critical to metabolic processes, whereas transport proteins are vital for excretion. Interestingly, some enzymes and transporters are expressed in a gender-specific manner.

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Animal toxicity studies with ammonium perfluorooctanoate

Cited by 119 publications

References 0 publications

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

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

RAT AND MOUSE DIFFERENCES IN GENDER-PREDOMINANT EXPRESSION OF ORGANIC ANION TRANSPORTER (OAT1–3;SLC22A6–8) mRNA LEVELS

Endocrine Regulation of Rat Organic Anion Transporters

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