Henderson W Matthew, Smith Mary Alice
Interdisciplinary Toxicology Program, College of Public Health, University of Georgia, Athens, Georgia 30602, USA.
Toxicol Sci. 2007 Feb;95(2):452-61. doi: 10.1093/toxsci/kfl162. Epub 2006 Nov 8.
8-2 Fluorotelomer alcohol (FTOH) and its metabolites, perfluorooctanoic acid (PFOA) and perfluorononanoic acid (PFNA), are developmental toxicants but metabolism and distribution during pregnancy are not known. To examine this, timed-pregnant mice received a single gavage dose (30 mg 8-2 FTOH/kg body weight) on gestational day (GD) 8. Maternal and neonatal serum and liver as well as fetal and neonatal homogenate extracts were analyzed using gas chromatography coupled with mass spectrometry. During gestation (GD9 to GD18), maternal serum and liver concentrations of PFOA decreased from 789 +/- 41 to 668 +/- 23 ng/ml and from 673 +/- 23 to 587 +/- 55 ng/g, respectively. PFOA was transferred to the developing fetuses as early as 24-h posttreatment with concentrations increasing from 45 +/- 9 ng/g (GD10) to 140 +/- 32 ng/g (GD18), while PFNA was quantifiable only at GD18 (31 +/- 4 ng/g). Post-partum, maternal serum PFOA concentrations decreased from 451 +/- 21 ng/ml postnatal day (PND) 1 to 52 +/- 19 ng/ml (PND15) and PFNA concentrations, although fivefold less, exhibited a similar trend. Immediately after birth, pups were cross-fostered with dams that had been treated during gestation with 8-2 FTOH (T) or vehicle (C) resulting in four treatment groups in which the first letter represents in utero (fetal) exposure and the second represents lactational (neonatal) exposure: C/C, T/C, C/T, T/T. On PND1, neonatal whole-body homogenate concentrations of PFOA from T/T and T/C groups averaged 200 +/- 26 ng/g, decreased to 149 +/- 19 ng/g at PND3 and this decreasing trend was seen in both neonatal liver and serum from PND3 to PND15. Based on detectible amounts of PFOA in neonatal serum in the C/T group on PND3 (57 +/- 11 ng/ml) and on PND15 (58 +/- 3 ng/ml), we suggest that the neonates were exposed through lactation. In conclusion, exposure of neonates to PFOA and PFNA occurs both pre- and postnatally following maternal 8-2 FTOH exposure on GD8.
8-2氟调聚物醇(FTOH)及其代谢产物全氟辛酸(PFOA)和全氟壬酸(PFNA)是发育毒物,但孕期的代谢和分布情况尚不清楚。为了对此进行研究,在妊娠第8天(GD8)给定时怀孕的小鼠经口灌胃单剂量(30毫克8-2 FTOH/千克体重)。使用气相色谱-质谱联用仪分析母体和新生儿的血清、肝脏以及胎儿和新生儿匀浆提取物。在妊娠期(GD9至GD18),母体血清和肝脏中PFOA的浓度分别从789±41降至668±23纳克/毫升以及从673±23降至587±55纳克/克。早在治疗后24小时PFOA就转移到发育中的胎儿体内,其浓度从(GD10)的45±9纳克/克增加到(GD^18)的140±32纳克/克,而PFNA仅在GD18时可检测到(31±4纳克/克)。产后,母体血清中PFOA的浓度从出生后第1天(PND1)的451±21纳克/毫升降至(PND15)的52±19纳克/毫升,PFNA的浓度虽然低五倍,但呈现类似趋势。出生后立即将幼崽与在妊娠期用8-2 FTOH(T)或赋形剂(C)处理过的母鼠进行交叉寄养,从而产生四个处理组,其中第一个字母代表子宫内(胎儿)暴露,第二个字母代表哺乳期(新生儿)暴露:C/C、T/C、C/T、T/T。在PND1时,T/T组和T/C组新生儿全身匀浆中PFOA的浓度平均为200±26纳克/克,在PND3时降至149±19纳克/克,并且从PND3到PND15在新生儿肝脏和血清中均可见这种下降趋势。基于C/T组在PND3(57±11纳克/毫升)和PND15(58±3纳克/毫升)时新生儿血清中可检测到的PFOA量,我们认为新生儿是通过哺乳接触到PFOA的。总之,在妊娠第8天母体暴露于8-2 FTOH后,新生儿在产前和产后均会接触到PFOA和PFNA。