Developmental toxicity of perfluorononanoic acid in mice
Developmental toxicity of perfluorononanoic acid in mice
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DOI：
10.1016/j.reprotox.2014.12.012
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发表时间：
2015-01-01
影响因子：
3.3
通讯作者：
Lau, Christopher
中科院分区：
文献类型：
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作者：
Das, Kaberi P.;Grey, Brian E.;Lau, Christopher
全氟农酸(PFNA)是一种普遍存在的持久性环境污染物。尽管其在环境和人体中的水平低于全氟辛烷磺酸(PFOS)或全氟辛酸(PFOA)，但近年来总体人口的稳步上升趋势引起了相当大的兴趣和关注。之前对全氟辛烷磺酸和全氟辛烷磺酸的研究表明，在实验室啮齿动物模型中存在发育毒性。目前的研究将这些不良后果的评估扩展到小鼠的PFNA。分时妊娠CD-I小鼠于妊娠第1~17天每日经口灌胃1、3、5、10 mg/kg的PFNA，对照组灌胃水。给母鼠注射10 mg/kg PFNA不能成功妊娠，未观察到该剂量组的效果。与全氟辛烷磺酸和全氟辛烷磺酸相似，5 mg/kg或更低剂量的全氟辛烷磺酸在妊娠母鼠体内产生肝肿大，但不影响植入数量、胎儿存活率或胎儿体重。1 mg/kg组和3 mg/kg组仔鼠存活时间与对照组无明显差异。相比之下，尽管在5 mg/kg PFNA组中，大多数幼崽也是活着出生的，但这些新生儿中有80%在出生后10天内死亡。全氟辛烷酸致新生儿死亡的模式与全氟辛烷磺酸或全氟辛烷磺酸引起的有所不同。大多数暴露于全氟辛烷磺酸或全氟辛烷磺酸的幼崽在出生后几天内存活的时间比暴露于全氟辛烷磺酸或全氟辛烷磺酸的幼崽长，后者通常在出生后2天内死亡。暴露于PFNA的存活新生儿在睁眼和青春期开始方面表现出剂量依赖性的延迟。此外，暴露于PFNA的后代肝脏重量增加持续到成年，可能与该化学物质在组织中的持久性有关。对胎儿和新生儿肝脏基因表达的评估显示，通过PFNA，PPARα靶基因被激活，这与PFOA的反应相似。我们的结果表明，全氟辛烷酸对小鼠的发育毒性与全氟辛烷磺酸和全氟辛酸相当，这些不良影响很可能是体内持续存在的全氟烷基酸的共同作用。由爱思唯尔公司出版。
Perfluorononanoic acid (PFNA) is a ubiquitous and persistent environmental contaminant. Although its levels in the environment and in humans are lower than those of perfluorooctane sulfonate (PFOS) or perfluorooctanoic acid (PFOA), a steady trend of increases in the general population in recent years has drawn considerable interest and concern. Previous studies with PFOS and PFOA have indicated developmental toxicity in laboratory rodent models. The current study extends the evaluation of these adverse outcomes to PFNA in mice. PFNA was given to timed-pregnant CD-I mice by oral gavage daily on gestational day 1-17 at 1, 3, 5 or 10 mg/kg; controls received water vehicle. Dams given 10 mg/kg PFNA could not carry their pregnancy successfully and effects of this dose group were not followed. Similar to PFOS and PFOA, PFNA at 5 mg/kg or lower doses produced hepatomegaly in the pregnant dams, but did not affect the number of implantations, fetal viability, or fetal weight. Mouse pups were born alive and postnatal survival in the I and 3 mg/kg PFNA groups was not different from that in controls. In contrast, although most of the pups were also born alive in the 5 mg/kg PFNA group, 80% of these neonates died in the first 10 days of life. The pattern of PFNA-induced neonatal death differed somewhat from those elicited by PFOS or PFOA. A majority of the PFNA-exposed pups survived a few days longer after birth than those exposed to PFOS or PFOA, which typically died within the first 2 days of postnatal life. Surviving neonates exposed to PFNA exhibited dose-dependent delays in eye opening and onset of puberty. In addition, increased liver weight seen in PFNA-exposed offspring persisted into adulthood and was likely related to the persistence of the chemical in the tissue. Evaluation of gene expression in fetal and neonatal livers revealed robust activation of peroxisome proliferator-activated receptor-alpha (PPAR alpha) target genes by PFNA that resembled the responses of PFOA. Our results indicate that developmental toxicity of PFNA in mice is comparable to that of PFOS and PFOA, and that these adverse effects are likely common to perfluoroalkyl acids that persist in the body. Published by Elsevier Inc.