Recently, we discovered that the cosmetic preservatives, benzalkonium chloride and formaldehyde, are especially toxic to human meibomian gland epithelial cells (HMGECs). Exposure to these agents, at concentrations approved for human use, leads within hours to cellular atrophy and death. We hypothesize that these effects are not unique, and that other cosmetic preservatives also exert adverse effects on HMGECs. Such compounds include parabens, phenoxyethanol and chlorphenesin, which have been reported to be toxic to corneal and conjunctival epithelial cells, the liver and kidney, as well as to irritate the eye. To test our hypothesis, we examined the influence of parabens, phenoxyethanol and chlorphenesin on the morphology, signaling, survival, proliferation and lipid expression of immortalized (I) HMGECs. These cells were cultured under proliferating or differentiating conditions with varying concentrations of methylparaben, ethylparaben, phenoxyethanol and chlorphenesin for up to 5 days. We monitored the signaling ability, appearance, number and neutral lipid content of the IHMGECs, as well as their lysosome accumulation. Our findings show that a 30-min exposure of IHMGECs to these preservatives results in a significant reduction in the activity of the Akt pathway. This effect is dose-dependent and occurs at concentrations equal to (chlorphenesin) and less than (all others) those dosages approved for human use. Further, a 24-h treatment of the IHMGECs with concentrations of methylparaben, ethylparaben, phenoxyethanol and chlorphenesin close to, or at, the approved human dose induces cellular atrophy and death. At all concentrations tested, no preservative stimulated IHMGEC proliferation. Of particular interest, it was not possible to evaluate the influence of these preservatives, at close to human approved dosages, on IHMGEC differentiation, because the cells did not survive the treatment. In summary, our results support our hypothesis and show that methylparaben, ethylparaben, phenoxyethanol and chlorphenesin are toxic to IHMGECs.

中文翻译：

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化妆品防腐剂对羟基苯甲酸酯，苯氧乙醇和氯酚素对人睑板腺上皮细胞的毒性。

最近，我们发现化妆品防腐剂苯扎氯铵和甲醛对人睑板腺上皮细胞（HMGEC）尤其有毒。暴露于允许人类使用的浓度的这些药物，可在数小时内导致细胞萎缩和死亡。我们假设这些作用不是唯一的，并且其他化妆品防腐剂也对HMGEC产生不利影响。此类化合物包括对羟基苯甲酸酯，苯氧乙醇和氯酚素，据报导它们对角膜和结膜上皮细胞，肝脏和肾脏有毒性，并刺激眼睛。为了检验我们的假设，我们检查了对羟基苯甲酸酯，苯氧乙醇和氯酚素对永生化（I）HMGECs的形态，信号传导，存活，增殖和脂质表达的影响。将这些细胞在增殖或分化条件下用不同浓度的对羟基苯甲酸甲酯，对羟基苯甲酸乙酯，苯氧乙醇和氯酚素培养长达5天。我们监测了IHMGECs的信号传导能力，外观，数量和中性脂质含量，以及它们的溶酶体积累。我们的发现表明，IHMGECs暴露于这些防腐剂30分钟会导致Akt途径活性显着降低。这种作用是剂量依赖性的，并且浓度等于（氯酚素）且小于（所有其他）批准用于人类的剂量。此外，用接近或等于批准剂量的对羟基苯甲酸甲酯，对羟基苯甲酸乙酯，苯氧乙醇和氯酚的浓度对IHMGEC进行24小时治疗会引起细胞萎缩和死亡。在所有测试浓度下 没有防腐剂刺激IHMGEC增殖。特别令人感兴趣的是，由于细胞无法在治疗中存活，因此不可能以接近人类批准的剂量评估这些防腐剂对IHMGEC分化的影响。总而言之，我们的结果支持了我们的假设，并表明对羟基苯甲酸甲酯，对羟基苯甲酸乙酯，苯氧乙醇和氯苯甲醛对IHMGEC有毒性。