Loveless Scott E, Finlay Carol, Everds Nancy E, Frame Steven R, Gillies Peter J, O'Connor John C, Powley Charles R, Kennedy Gerald L
DuPont Haskell Laboratory for Health and Environmental Sciences, Newark, DE 19714, United States.
Toxicology. 2006 Mar 15;220(2-3):203-17. doi: 10.1016/j.tox.2006.01.003. Epub 2006 Jan 31.
The purpose of this study was to compare the toxicity of linear/branched ammonium perfluorooctanoate (APFO) with that of linear and branched APFO. Linear/branched APFO (approximately 80% linear and 20% branched isomers) was formerly used in the production of commercial products. The extensive toxicologic database for APFO has been developed essentially using this mixture of isomers. The trend now is to use APFO containing only the linear isomer. The current study was performed to determine if the toxicological database developed for the linear/branched isomer is applicable to the linear isomer. To determine the contribution of branched APFO to the toxicity of linear/branched APFO, a form of APFO that was 100% branched was synthesized. Rats and mice were given doses by oral gavage ranging from 0.3 to 30 mg/kg of either the linear/branched, linear, or branched APFO for 14 days. Clinical signs, body weights, food consumption, selected hematology and serum lipid parameters, liver and kidney weights, hepatic peroxisomal beta-oxidation, and serum PFOA concentrations were evaluated. Mean body weights were about 20% lower in rats and mice dosed with 30 mg/kg of linear/branched or linear APFO compared to controls, and 3-5% lower in animals dosed with 30 mg/kg of branched APFO. In rats, all three forms reduced lipids. In mice, all three forms reduced total and HDL cholesterol similarly but triglycerides were increased at lower doses. Increased peroxisomal beta-oxidation activity and serum PFOA concentrations were seen in both species but these effects were least pronounced in rats dosed with the branched material. In rats, serum PFOA levels were 20-51 ppm at Lowest Observed Effect Levels (LOEL) of 0.3-1 mg/kg, based primarily upon lipid parameters. In mice, serum PFOA levels were 10-14 ppm at the LOEL of 0.3 mg/kg, based primarily upon relative liver weight. In both rats and mice, the overall responses to the linear/branched and the linear forms of PFOA were similar, but the branched form appears to be less potent. Based on these results, and for the endpoints evaluated in this study, the toxicological database developed primarily from testing linear/branched APFO is applicable to linear APFO.
本研究的目的是比较直链/支链全氟辛酸铵（APFO）与直链和支链APFO的毒性。直链/支链APFO（约80%为直链异构体，20%为支链异构体）以前用于商业产品的生产。APFO广泛的毒理学数据库基本上是使用这种异构体混合物建立的。现在的趋势是使用仅含直链异构体的APFO。进行本研究以确定为直链/支链异构体建立的毒理学数据库是否适用于直链异构体。为了确定支链APFO对直链/支链APFO毒性的贡献，合成了一种100%支链的APFO形式。通过口服灌胃给予大鼠和小鼠0.3至30mg/kg的直链/支链、直链或支链APFO，持续14天。评估临床体征、体重、食物摄入量、选定的血液学和血清脂质参数、肝脏和肾脏重量、肝脏过氧化物酶体β氧化以及血清全氟辛酸（PFOA）浓度。与对照组相比，给予30mg/kg直链/支链或直链APFO的大鼠和小鼠的平均体重降低了约20%，给予30mg/kg支链APFO的动物体重降低了3 - 5%。在大鼠中，所有三种形式都降低了脂质。在小鼠中，所有三种形式对总胆固醇和高密度脂蛋白胆固醇的降低作用相似，但在较低剂量下甘油三酯增加。在两个物种中都观察到过氧化物酶体β氧化活性增加和血清PFOA浓度升高，但这些影响在给予支链物质的大鼠中最不明显。在大鼠中，基于脂质参数，最低观察到有害作用水平（LOEL）为0.3 - 1mg/kg时，血清PFOA水平为20 - 51ppm。在小鼠中，基于相对肝脏重量，LOEL为0.3mg/kg时，血清PFOA水平为10 - 14ppm。在大鼠和小鼠中，对直链/支链和直链形式的PFOA的总体反应相似，但支链形式的效力似乎较低。基于这些结果，对于本研究中评估的数据终点，主要通过测试直链/支链APFO建立的毒理学数据库适用于直链APFO。
