Hauser R, Meeker J D, Singh N P, Silva M J, Ryan L, Duty S, Calafat A M
Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115, USA.
Hum Reprod. 2007 Mar;22(3):688-95. doi: 10.1093/humrep/del428. Epub 2006 Nov 7.
The ubiquitous use of phthalate esters in plastics, personal care products and food packaging materials results in widespread general population exposure. In this report, we extend our preliminary study on the relationship between urinary concentrations of phthalate metabolites and sperm DNA damage among a larger sample of men and include measurements of mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), two oxidative metabolites of di-(2-ethylhexyl) phthalate (DEHP).
Among 379 men from an infertility clinic, urinary concentrations of phthalate metabolites were measured using isotope-dilution high-performance liquid chromatography-tandem mass spectrometry. Sperm DNA damage measurements, assessed with the neutral comet assay, included comet extent (CE), percentage of DNA in tail (Tail%) and tail distributed moment (TDM).
Monoethyl phthalate (MEP), a metabolite of diethyl phthalate, was associated with increased DNA damage, confirming our previous findings. Mono-(2-ethylhexyl) phthalate (MEHP), a metabolite of DEHP, was associated with DNA damage after adjustment for the oxidative DEHP metabolites. After adjustment for MEHHP, for an interquartile range increase in urinary MEHP, CE increased 17.3% [95% confidence interval (CI) = 8.7-25.7%], TDM increased 14.3% (95% CI = 6.8-21.7%) and Tail% increased 17.5% (95% CI = 3.5-31.5%).
Sperm DNA damage was associated with MEP and with MEHP after adjusting for DEHP oxidative metabolites, which may serve as phenotypic markers of DEHP metabolism to 'less toxic' metabolites. The urinary levels of phthalate metabolites among these men were similar to those reported for the US general population, suggesting that exposure to some phthalates may affect the population distribution of sperm DNA damage.
邻苯二甲酸酯广泛应用于塑料制品、个人护理产品及食品包装材料中,导致普通人群普遍暴露于其中。在本报告中,我们在更大规模的男性样本中扩展了关于邻苯二甲酸酯代谢物尿浓度与精子DNA损伤之间关系的初步研究,并纳入了单-(2-乙基-5-羟基己基)邻苯二甲酸酯(MEHHP)和单-(2-乙基-5-氧代己基)邻苯二甲酸酯(MEOHP)的测量,这两种是邻苯二甲酸二(2-乙基己基)酯(DEHP)的氧化代谢物。
在一家不孕不育诊所的379名男性中,采用同位素稀释高效液相色谱-串联质谱法测量尿中邻苯二甲酸酯代谢物的浓度。用中性彗星试验评估的精子DNA损伤测量指标包括彗星长度(CE)、尾部DNA百分比(Tail%)和尾部分布矩(TDM)。
邻苯二甲酸二乙酯的代谢物单乙基邻苯二甲酸酯(MEP)与DNA损伤增加有关,证实了我们之前的发现。在对氧化型DEHP代谢物进行校正后,DEHP的代谢物单-(2-乙基己基)邻苯二甲酸酯(MEHP)与DNA损伤有关。在校正MEHHP后,尿中MEHP每增加一个四分位数间距,CE增加17.3%[95%置信区间(CI)=8.7-25.7%],TDM增加14.3%(95%CI=6.8-21.7%),Tail%增加17.5%(95%CI=3.5-31.5%)。
在对DEHP氧化代谢物进行校正后,精子DNA损伤与MEP和MEHP有关,这两种物质可能作为DEHP代谢为“毒性较小”代谢物的表型标志物。这些男性中邻苯二甲酸酯代谢物的尿水平与美国普通人群报告的水平相似,这表明暴露于某些邻苯二甲酸酯可能会影响精子DNA损伤的人群分布。