The present study aims to investigate the current trends in replacing conventional preservatives with multifunctional ingredients with antimicrobial properties for preservation of cosmetics for infants or sensitive population, to decrease their potential for contact dermatitis. We first reviewed the labels of cosmetics purchased from the Chinese market for conventional preservatives and multifunctional ingredients with antimicrobial properties, of which the actual contents were further quantified by chromatographic methods. We identified 7 traditional preservatives (phenoxyethanol, benzoic acid (salts), methylparaben, benzyl alcohol, sorbic acid (salts), propylparaben, and methylisothiazolinone), and 11 alternative ingredients with antimicrobial activities (ethylhexylglycerin, butylene glycol, caprylyl glycol, propylene glycol, 1,2-hexanediol, p-anisic acid, hydroxyacetophenone, pentylene glycol, decylene glycol, caprylhydroxamic acid, and aminomethyl propanol) in descending order of prevalence. The contents of all identified preservatives and ingredients were either below regulatory limits or in the range that is generally regarded to be safe. Further challenge with microorganisms indicated irrespective of the composition of preservation systems, product preservation could be compromised under test conditions. We conclude that multifunctional ingredients with antimicrobial properties in cosmetics have the potential to completely replace or significantly reduce the use of traditional preservatives while retaining comparative preservative efficacy. Future attentions may need to be shifted to the safety of those multifunctional ingredients with antimicrobial properties.

Dermatitis®Vol. 34, No. 5 LettersA Compositional Analysis of Preservative Systems in Cosmetics Intended for InfantsHuailong Chang and Tian ChenHuailong ChangR&D Center, Shanghai Jahwa United Co, Ltd, China.Search for more papers by this author and Tian ChenDivision of Public Health Service and Safety Assessment Shanghai Municipal Center for Disease Control and Prevention China Search for more papers by this authorEmail the corresponding author at [email protected]Published Online:15 Sep 2023https://doi.org/10.1097/DER.0000000000000878AboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View article"A Compositional Analysis of Preservative Systems in Cosmetics Intended for Infants." Dermatitis®, 34(5), pp. 462–463FiguresReferencesRelatedDetails Volume 34Issue 5Oct 2023 Information© 2022 American Contact Dermatitis Society. All Rights Reserved.To cite this article:Huailong Chang and Tian Chen.A Compositional Analysis of Preservative Systems in Cosmetics Intended for Infants.Dermatitis®.Oct 2023.462-463.http://doi.org/10.1097/DER.0000000000000878Published in Volume: 34 Issue 5: September 15, 2023Online Ahead of Print:January 2, 2023PDF download

In recent years, mild baby cleansers have experienced ever-growing demand from caregivers. In the meantime, formulation developers are in practical need for a method(s) to screen mild formulations. In the present study, we aim to repurpose the HET-CAM and SkinEthic™ models to further classify in vivo nonirritant baby cleansing formulations into mild and less mild categories. Both methods were modified to best describe the samples' irritation potential. The results showed that both models successfully classified the formulations into mild and less mild categories according to our customized criteria. For the HET-CAM, the medians of mean irritation scores (IS) were 3.0 for mild formulations (with 0 ≤ mean IS ≤4.5), and 5.0 for less mild formulations (with mean IS values all equaled 5), respectively. And for the SkinEthic™ model, the median relative viabilities were 69.46% for less mild formulations (with 46.80% ≤ mean relative viability ≤84.76%), and 99.96% for mild formulations (with 90.57% ≤ mean relative viability ≤124.58%). Thirty out of 35 formulations were predicted consistently between the HET-CAM and SkinEthic™ model. Statistical analysis of the agreement between predictions made by the two models demonstrated substantial agreement with a Cohen's kappa coefficient of 0.713 (P < 0.001). We conclude that the HET-CAM and SkinEthic™ models are promising in vitro alternatives for screening mild formulations.

The present study aimed to reveal the amount per application of facial sheet masks and its influencing factors in Chinese population to form the base for an accurate exposure assessment. A total of 175 healthy subjects aged 18 years or older were recruited and divided into two subgroups: one group of 35 subjects were asked to apply same mask for 5, 10, 15, 20, 25, and 30 min respectively, and the other 140 subjects were instructed to apply one of four types of facial sheet masks presented in the market for 15 min. Furthermore, phenoxyethanol and methylparaben were measured to reflect actual exposure to chemicals. The sharp increase in the relative exposure to phenoxyethanol (CAS NO.122-99-6) and methylparaben at 25 min and longer suggests applying facial sheet masks for longer than 20 min may drive the exposure to hazardous chemicals to increase significantly. The 90th percentile of amount per application for plant-cellulose, bamboo charcoal fiber, bio-cellulose, and binchotan charcoal fiber-based masks was 5.753, 5.371, 5.017, and 4.821 g respectively. In addition, men and subjects with sebaceous skin demonstrated lower amount per application compared to women and subjects with dry skin, respectively. Finally, our data showed that the larger the contacting area between face and mask, the more amount per application. We concluded that the appropriate time of application should be less than 20 min. And mask fabrics, gender, sebum content, and contacting area could significantly impact the risk assessment of facial sheet masks. Our data for the first time provides insights into a realistic risk assessment of facial sheet masks in Chinese population.

目前风险评估理念已广泛应用于评估化合物对人类健康构成的风险程度,其在化妆品领域的运用也越来越被业界和监管部门所接受.欧盟消费者安全科学委员会(Scientific Committee on Consumer Safety,SCCS)针对欧洲市场上的化妆品原料及风险物质的评估发布了风险评估指南,并定期更新[1].美国化妆品原料评价委员会(Cosmetic Ingredient Review,CIR)则通过化妆品原料综述建立了包含数千种化妆品原料的风险评估报告数据库,该数据库也会定期增补新的原料安全信息.

利用稳转hTRPV1受体SH-SY5Y细胞株评价市售洗发类产品的致刺痛风险,绘制剂量反应关系曲线;然后利用液质联用色谱仪(LC-MS)测定样品中椰油酰胺MEA(CMEA)含量;最后比较鸡胚绒毛尿囊膜试验(HET-CAM)与hTRPV1受体试验评价刺激反应的结果.结果表明,2种洗发产品检测到刺痛反应;刺痛反应与样品中CMEA含量存在相关性;向无刺痛风险的产品中添加质量分数0.5％、1％和1.5％CMEA后可诱导刺痛反应而未在HET-CAM中诱导眼刺激性.综上,基于hTRPV1受体的刺痛评价可在一定程度上弥补传统眼刺激评价方法的不足;CMEA是潜在可引起刺痛的物质,未来产品设计中应考虑避免或减少使用此物质.

介绍一款名为SpheraCosmolife的一站式化妆品风险评估工具,以期为化妆品企业安全评估员的工作提供帮助.分别从软件开发背景、软件所用的数据库和风险评估模型、软件的运行界面和软件运行结果界面等方面介绍SpheraCosmolife软件.SpheraCosmolife软件可根据产品类型,利用数据库中的实测值或预测的未观察到有害作用的最大剂量(NOAEL)定义待测化合物的分离值(POD),并计算安全边际值(MoS).该软件同时提供了其他如致突变性、皮肤致敏性和毒理学关注阈值(TTC)等毒理学特征,从而可总体评价化合物的潜在危害.化妆品安全评估员可将SpheraCosmolife作为支持工具,根据化合物对消费者的潜在风险排定需优先关注的化妆品原料或配方.

Metformin has recently gained attention as an anti-cancer drug and/or a chemoprevention agent because of its roles in inhibiting mTOR, lowering hyperinsulinemia, modulating inflammatory responses, and selectively killing cancer stem cells. However, the key underlying molecular mechanisms for the inhibitory effects of metformin on pancreatic cancer progression remain largely unknown. RET (REarranged during Transfection), a single-pass transmembrane receptor tyrosine kinase and its ligand, glial cell-derived neurotrophic factor (GDNF), were strongly expressed in pancreatic cancer and correlated to invasion and worse survival after surgical resection. In this study, we investigated the roles of RET in the inhibitory effects of metformin on pancreatic cancer cell growth and migration. Real-time PCR and Western blot were used to determine mRNA and protein levels of molecular markers, respectively. siRNAs were adopted to specifically knockdown target genes. Boyden chamber assay was applied to assess cell migration in vitro. We observed that metformin treatment significantly reduced the mRNA and protein expression of RET in a dose-dependent manner in pancreatic cancer cells PANC-1 and MIA PaCa-2. The inhibitory effects of metformin on RET expression were not diminished when AMPK was knockdown by AMPK siRNA or the specific inhibitor, Compound C, suggesting that metformin may suppress RET in an AMPK-independent manner. Metformin treatment or RET knockdown by RET siRNA significantly decreased the phosphorylation of NF-κB and p70S6K, while modestly reduced the phosphorylation of the ERK, AKT, or STAT3. Furthermore, metformin treatment or RET knockdown significantly inhibited GDNF-induced cell migration. These data indicate that targeting RET with metformin may be an attractive and novel strategy for the prevention and treatment of pancreatic cancer progression and metastasis. Further in vitro and in vivo studies are warranted to investigate how metformin modulates RET signaling to inhibit the progression and metastasis of pancreatic cancer. Citation Format: Huailong Chang, Zhiyong Xiao, Tao Li, Lanjing Zhang, Yong Lin, Darren Carpizo, Xianglin Tan. RET signaling in pancreatic cancer: A novel target by metformin to suppress cancer progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2881.

Pregnant women are a unique group undergoing profound structural modifications in uterus, breast, adipose tissue and extracellular fluids. Amino acid metabolic stress is a unique physical process that occurs during pregnancy. Metals constitute a fundamental part of the maternal body and have a universal effect on amino acid metabolism. However, the exact interaction between metals and amino acid metabolism during pregnancy is unknown. The aim of the present study was to determine the correlations of metals with amino acid metabolic intermediates in the urine of 232 healthy pregnant women in their first, second and third trimesters during normal pregnancy. Sixteen metals in the urine of 232 healthy pregnant women in their first, second and third trimesters were quantified using inductively coupled plasma mass spectrometry (ICP-MS). An ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometer (UPLC-QTOFMS)-based metabolomics approach was conducted to detect intermediate products involved in amino acid metabolism during the entire pregnancy period. A panel regression model was established to investigate the relationship between urine metals and amino acid metabolism. Seven metals-cadmium, cobalt, copper, cesium, manganese, thallium and vanadium-showed significant association with amino acid metabolic intermediates, including 2-oxoarginine, 3-indoleacetonitrile, indole, indole-5,6-quinone, N2-succinyl-l-glutamic acid 5-semialdehyde, N-methyltryptamine and N-succinyl-l,l-2,6-diaminopimelate, in the healthy pregnant women. These findings indicated that exposure to cadmium, cobalt, copper, cesium, manganese, thallium and vanadium significantly affected the metabolic status of tryptophan, arginine, proline, tyrosine and lysine metabolism in the maternal body during normal pregnancy.

Increasing evidence indicates that bisphenol A (BPA), a widely manufactured environmental pollutant, can induce changes in DNA methylation paatterns, which is a potential mechanism linking this environmental exposure to disease development. We investigated the influence of developmental exposure to BPA on pancreatic DNA methylation patterns and whether maternal folate supplementation can modify the epigenetic status and pancreatic impairment induced by BPA. Our results showed that maternal dietary folate supplementation in rats exposed to BPA counteracted the observed BPA‐induced pancreatic impairments in the offspring, which included disrupted insulin secretion and glucose intolerance, and impaired morphology and ultrastructure of β cells. Moreover, these pancreatic dysfunctions were shown to be associated with low expression and DNA hypermethylation of insulin‐like growth factor‐2 ( Igf2 ) in islets induced by exposure to BPA during the developmental period. Importantly, maternal dietary folate supplementation was demonstrated to negate this Igf2 DNA hypermethylation in the offspring, which was consistent with the upregulation of Igf2 expression. Overall, our results suggest that early developmental exposure to BPA alters the DNA methylation of Igf2 , that these altered methylation patterns are associated with impaired β‐cell function in the offspring and that these effects can be counteracted by maternal folate supplementation. Copyright © 2017 John Wiley & Sons, Ltd.

Background: Prenatal exposure to bisphenol A (BPA) affects immune system and promotes allergy and asthma in mice, but findings in human studies are limited. We investigated whether prenatal exposure to BPA is associated with increased risk of allergic diseases in infants. Methods: We measured BPA concentrations in maternal urine samples collected at delivery from 412 women in Wuhan, China. The occurrence of allergic diseases including eczema and wheeze were assessed at age 6 mo through questionnaires. We used logistic regression to evaluate the association between urinary BPA levels and the risk of allergic diseases. Results: Mothers of infants with allergic diseases had significantly higher urinary BPA levels than those of infants without allergic diseases (median: 2.35 vs. 4.55 µg/l, P = 0.03). Increased risk of infant allergic diseases was associated with creatinine-adjusted maternal urinary BPA concentrations. And this association was limited to females (odds ratio (OR) = 1.36; 95% confidence interval (CI): 1.10–1.79) rather than males. After stratification by maternal age, the association was only significant in infants of mothers who were younger than 25 y old (OR = 1.90; 95% CI: 1.09–3.29). Conclusion: Prenatal exposure to BPA may potentially increase the risk of allergic diseases at very early life in female infants.

Developmental exposure to bisphenol A (BPA) has been linked to impaired glucose homeostasis and pancreatic function in adulthood, which has been hypothesized to result from the disruption of pancreatic β-cell development at early life. Here we evaluated whether maternal BPA exposure disrupts β-cell development and glucose tolerance and the role of epigenetic modifications of key regulator in this process. We found that maternal exposure to BPA (10 μg kg-1 d-1) reduced the pancreatic β-cell mass and the expression of pancreatic and duodenal homeobox 1 (Pdx1) at birth, as well as the expression of Pdx1 at gestational day (GD) 15.5. In parallel with the decreased expression of Pdx1, histones H3 and H4 deacetylation, along with demethylation of histone 3 lysine 4 (H3K4) and methylation of histone 3 lysine 9 (H3K9), were found at the promoter of Pdx1, while no significant changes in DNA methylation status were detected at this region. Moreover, these alterations were observed in adult life along with impaired glucose tolerance. We conclude that maternal exposure to BPA reduces pancreatic β-cell mass at birth by reducing PDX1+ progenitors during fetal development through altering the histone modifications of Pdx1, which can be propagated to later life and increase the susceptibility to glucose intolerance.

BACKGROUND:Prenatal cadmium (Cd) exposure has been associated with adverse birth outcomes, but the findings of previous studies are inconsistent. The aim of this study was to evaluate the association between prenatal Cd exposure and birth outcomes. METHODS:This study was conducted in 5364 pregnant women with a live singleton birth, who were recruited between September 2012 and October 2014 in the Healthy Baby Cohort (HBC) in Wuhan, China. Gestational age (in days) was estimated using both the woman's last menstrual period (LMP) and ultrasound data. All the birth outcomes including birth weight and birth length were measured in the hospital within one hour after birth through standardized procedures. Cd was measured in maternal urine collected before delivery with inductively coupled plasma mass spectrometry. RESULTS:The geometric mean of Cd concentration in maternal urine was 0.55 (range 0.01-2.85) μg/g creatinine. We found each ln-unit increase in Cd concentration (μg/g creatinine) in maternal urine was associated with decreased gestational age [adjusted β=-0.77day; 95% confidence interval (CI): -1.15, -0.39 for all infants; -0.77; 95% CI: -1.29, -0.25 for boys; and -0.80; 95% CI: -1.35, -0.25 for girls]. Increased likelihood of preterm birth (PTB) was associated with ln-unit increase in urinary Cd (μg/g creatinine) [adjusted odds ratio (OR)=1.78; 95% CI: 1.45, 2.19 for all infants; 1.97; 95% CI: 1.46, 2.65 for boys; and 1.67; 95% CI: 1.24, 2.25 for girls]. Maternal urinary Cd was not significantly associated with low birth weight (LBW) and small for gestational age (SGA). CONCLUSIONS:Maternal exposure to Cd during pregnancy was associated with decreased gestational age and increased likelihood of PTB.

Developmental exposure to bisphenol A (BPA) has been indicated to pose long-lasting effects on brain development and behaviors in adulthood.

Background: Exposure to bisphenol A (BPA), a known endocrine disruptor, has been demonstrated to affect fetal development in animal studies, but findings in human studies have been inconsistent.Objectives: We investigated whether maternal exposure to BPA during pregnancy is associated with an increased risk of infant low birth weight (LBW).Methods: A total 452 mother-infant pairs (113 LBW cases and 339 matched controls) were selected from the participants enrolled in the prospective Health Baby Cohort (HBC) in Wuhan city, China, during 2012-2014. BPA concentrations were measured in maternal urine samples collected at delivery, and the information of birth outcomes was retrieved from the medical records. A conditional logistic regression was used to evaluate the relationship between urinary BPA levels and LBW.Results: Mothers with LBW infants had significantly higher urinary BPA levels (median: 4.70 mu g/L) than the control mothers (median: 2.25 mu g/L) (p < 0.05). Increased risk of LBW was associated with higher maternal urinary levels of BPA [adjusted odds ratio (OR) = 3.13 for the medium tertile, 95% confidence interval (CI): 121,8.08; adjusted OR = 2.49 for the highest tertile, 95% CI: 0.98, 636]. The association was more pronounced among female infants than among male infants, with a statistical evidence of heterogeneity in risk (p = 0.03).Conclusions: Prenatal exposure to higher levels of BPA may potentially increase the risk of delivering LBW infants, especially for female infants. This is the first case-control study to examine the association in China. (C) 2015 Elsevier Ltd. All rights reserved.

Implication of environmental endocrine disruptors, such as bisphenol A (BPA), on the development of cardiopathy has been poorly investigated. The aim of the study was to investigate the effects of long-term exposure to BPA at the reference dose on the myocardium of rats, and the underlying mechanisms. Male rats received corn oil or 50 μg/kg/day of BPA since delactation. At 24 and 48 weeks (wk), cardiac function and mitochondrial function were examined. The mRNA expression and the methylation status of PCG-1α, a major regulator of mitochondrial biogenesis in cardiac muscle, were also tested. At 48 wk, BPA-exposed rats displayed cardiomyopathy, characterized by myocardium hypertrophy, cardiomyocyte enlargement, and impairment of cardiac function. At 24 wk, significantly reduced ATP production, dissipated mitochondrial membrane potential (Ψm) and declined mitochondrial respiratory complex (MRC) activity in cardiomyocytes were observed in BPA-exposed rats compared with the control rats, indicating a decrease in mitochondrial function occurs before the development of cardiomyopathy. Additionally, BPA exposure decreased the expression of PGC-1α and induced hypermethylation of PGC-1 α in heart tissue in 24- and 48-week-old rats. The change in methylation of PGC-1α was observed more pronounced in BPA-exposed rats at 48 wk. Overall, long-term BPA exposure induces cardiomyopathy in male rats, and the underlying mechanism may involve the impairment of cardiac mitochondrial function and the disturbance of methylation of PGC-1α.

Total urinary phthalate metabolites (the free plus glucuronidated forms) have been frequently measured in the general population. However, data are limited on the free forms which may be more bioactive, especially for sensitive population such as pregnant women. Here the data gap was addressed by measuring concentrations of free and total forms of six phthalate metabolites in 293 urine samples from pregnant women at delivery, who were randomly selected from the prospective Healthy Baby Cohort (HBC), China. We observed detectable concentrations of the total amount of phthalate metabolites in all urine samples. The geometric mean (GM) urinary concentrations of free and total mono-butyl phthalate (MBP) (5.20, 54.49ng/mL) were the highest, followed by mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP) (4.52, 7.27ng/mL). For most of phthalate metabolites, urinary concentrations were significantly higher in women who were nulliparous. Significantly higher concentrations of mono-ethyl phthalate (MEP) and mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) were found in women who had higher educational level. To our knowledge, this is the first study to report the free and total forms of phthalate metabolites among pregnant women in China. The results suggest that exposure characteristics may be related to parity and education.

Exposure to endocrine disruptors in utero appears to alter epigenetics in the male germ-line and subsequently promote adult-onset disease in subsequent generations. Fetal exposure to bisphenol A (BPA), a highly prevalent endocrine disruptor in environment, has been shown to alter epigenetic modification and result in glucose intolerance in adulthood. However, whether fetal exposure to BPA can induce epigenetic modification and phenotypic changes in their subsequent offspring are still unclear. The present study was designed to investigate whether exposure to BPA in early life induced glucose intolerance in the offspring through male germ line, and the underlying epigenetic molecular basis. F0 pregnant SD rats were received corn oil or 40 μg/kg/day of BPA during gestation and lactation. F1 male rats were maintained to generate F2 offspring by mating with untreated female rats. Both the F1 rats after weaning and the F2 offspring were not received any other treatments. Our results showed that male F2 offspring in the BPA group exhibited glucose intolerance and β-cell dysfunction. Decreased expression of Igf2 and associated hypermethylation of Igf2 were observed in islets of male F2 offspring. In addition, similar effects were observed in female F2 animals, but the effects were more pronounced in males. Moreover, abnormal expression and methylation of Igf2 was observed in sperm of adult F1 male rats, indicating that epigenetic modification in germ cells can be partly progressed to the next generation. Overall, our study suggests that BPA exposure during early life can result in generational transmission of glucose intolerance and β-cell dysfunction in the offspring through male germ line, which is associated with hypermethylation of Igf2 in islets. The changes of epigenetics in germ cells may contribute to this generational transmission.

Exposure to bisphenol A (BPA), a monomer widely used to manufacture polycarbonate plastics, has been reported to be associated with abnormalities of liver function and hepatic damage. However, the molecular mechanism under the pathogenesis of hepatic injury is unclear. In this study, the effect of perinatal exposure to BPA at the reference dose of 50 µg/kg/day on the apoptotic index in the liver of rat offspring was investigated. Increased levels of ALT and enhanced cell apoptosis were observed in the liver of rat offspring at 15 and 21 weeks, and significantly increased activity of caspase-3 and caspase-9 and elevated levels of cytochrome c were also confirmed. In addition, significant change in the expression levels of Bcl-2 and Bax were found in BPA-treated offspring at 21 weeks. For in vitro experiments, liver mitochondria were isolated from neonatal rats and were treated with BPA. BPA treatment led to a significant increase in mitochondrial permeability transition. Moreover, the supernatant from BPA-treated mitochondria significantly increased apoptotic changes in nuclei isolated from liver tissue. In conclusion, the study demonstrates that BPA induces mitochondria-mediated apoptosis in hepatic cells, which may contribute to long-term hepatotoxicity induced by early-life exposure to BPA.