Absence of mutagenicity of acid pyrogallol-containing hair gels.

In the present work, three commercial acid (pH 3.5-4) pyrogallol-containing hair gels, SunSet Alizador Negro (two formulations) and Embelleze Henê Gel, were tested for mutagenicity using two well-established assays. In the Salmonella mutagenicity assay using 648-5000 microg/plate of cosmetic samples, none of the samples reached a 2-fold increase in revertants relative to the controls. Both in the absence and in the presence of S9, the dose-response relation in strains TA98, TA100, TA102, TA1535, and TA1537 was not significant (p>0.01). In the mouse bone marrow micronucleus assay, 10 Swiss male mice were orally administered 2000 mg/kg of sample per body weight/day. The ratio between polychromatic and normochromatic erythrocytes as well as the presence of micronuclei in bone marrow cells were determined. Equal numbers of micronucleated polychromatic erythrocytes were detected between the cells of each treated group and the negative control, using ANOVA and chi-square analyses. Thus, none of the products induced mutagenesis in either assay. Previous studies have shown pyrogallol is mutagenic in various test systems, including Salmonella. However studies have also shown that acidic conditions may repress the reactive-oxygen species (ROS) produced by pyrogallol, and ROS is considered the primary mechanism for the mutagenicity of pyrogallol. Consistent with this are our results, which show that acidic, commercially available pyrogallol-containing hair gels are neither mutagenic in Salmonella nor induce micronuclei in mouse bone marrow in vivo.     

Safety assessment of personal care products/cosmetics and their ingredients

We attempt to review the safety assessment of personal care products (PCP) and ingredients that are representative and pose complex safety issues. PCP are generally applied to human skin and mainly produce local exposure, although skin penetration or use in the oral cavity, on the face, lips, eyes and mucosa may also produce human systemic exposure. In the EU, US and Japan, the safety of PCP is regulated under cosmetic and/or drug regulations. Oxidative hair dyes contain arylamines, the most chemically reactive ingredients of PCP. Although arylamines have an allergic potential, taking into account the high number of consumers exposed, the incidence and prevalence of hair dye allergy appears to be low and stable. A recent (2001) epidemiology study suggested an association of oxidative hair dye use and increased bladder cancer risk in consumers, although this was not confirmed by subsequent or previous epidemiologic investigations. The results of genetic toxicity, carcinogenicity and reproductive toxicity studies suggest that modern hair dyes and their ingredients pose no genotoxic, carcinogenic or reproductive risk. Recent reports suggest that arylamines contained in oxidative hair dyes are N-acetylated in human or mammalian skin resulting in systemic exposure to traces of detoxified, i.e. non-genotoxic, metabolites, whereas human hepatocytes were unable to transform hair dye arylamines to potentially carcinogenic metabolites. An expert panel of the International Agency on Research of Cancer (IARC) concluded that there is no evidence for a causal association of hair dye exposure with an elevated cancer risk in consumers. Ultraviolet filters have important benefits by protecting the consumer against adverse effects of UV radiation; these substances undergo a stringent safety evaluation under current international regulations prior to their marketing. Concerns were also raised about the safety of solid nanoparticles in PCP, mainly TiO₂ and ZnO in sunscreens. However, current evidence suggests that these particles are non-toxic, do not penetrate into or through normal or compromised human skin and, therefore, pose no risk to human health. The increasing use of natural plant ingredients in personal care products raised new safety issues that require novel approaches to their safety evaluation similar to those of plant-derived food ingredients. For example, the Threshold of Toxicological Concern (TTC) is a promising tool to assess the safety of substances present at trace levels as well as minor ingredients of plant-derived substances. The potential human systemic exposure to PCP ingredients is increasingly estimated on the basis of in vitro skin penetration data. However, new evidence suggests that the in vitro test may overestimate human systemic exposure to PCP ingredients due to the absence of metabolism in cadaver skin or misclassification of skin residues that, in vivo, remain in the stratum corneum or hair follicle openings, i.e. outside the living skin. Overall, today's safety assessment of PCP and their ingredients is not only based on science, but also on their respective regulatory status as well as other issues, such as the ethics of animal testing. Nevertheless, the record shows that today's PCP are safe and offer multiple benefits to quality of life and health of the consumer. In the interest of all stakeholders, consumers, regulatory bodies and producers, there is an urgent need for an international harmonization on the status and safety requirements of these products and their ingredients.     

补中益气汤对脑缺血再灌注大鼠神经功能及梗死灶IL-1β和TNF-α表达的影响

目的:观察补中益气汤对脑缺血再灌注大鼠神经功能及梗死灶白细胞介素1β(interleukin-1β,IL-1β)、肿瘤坏死因子α(Tumour necrosis factor-α,TNF-α)表达的影响。方法:将60只SD大鼠随机分为假手术组、模型组、尼莫地平组、补中益气汤高剂量组、补中益气汤中剂量组、补中益气汤低剂量组,每组各10只。假手术组和模型组给予蒸馏水0.003 m L·(g·d)~(-1),尼莫地平组给予尼莫地平混悬液0.003 m L·(g·d)~(-1),补中益气汤高剂量组、补中益气汤中剂量组、补中益气汤低剂量组分别给予临床用药量的25倍、20倍、15倍水煎浓缩液灌胃,用量均按人与大鼠体表面积等效剂量折算,各组等容灌胃每日2次,灌胃6 d后,第7天采用Longa等线栓法复制大脑急性脑缺血再灌注损伤模型,在造模后12h进行神经功能缺损评分,测量脑指数,测定IL-1β、TNF-α含量,光镜下做脑组织病理形态学观察。结果:模型组大鼠脑指数降低、神经体征评分明显高于假手术组(P0.05);与模型组比较,给药组大鼠脑指数降低、神经体征明显改善,差异具有统计学意义(P0.01);与模型组比较,给药组大鼠脑组织IL-1β,TNF-α的含量明显降低,差异具有统计学意义(P0.01);与尼莫地平组比较,补中益气汤高剂量组脑指数明显降低,脑组织IL-1β、TNF-α的含量降低明显,差异均有统计学意义(P0.05)。病理组织学检查发现模型组大鼠脑组织出现不同程度的水肿,神经细胞轴索肿胀、断裂等缺血样改变,给药组大鼠上述病变明显减轻。结论:补中益气汤能明显改善脑缺血再灌注大鼠神经体征,可下调脑指数、降低脑组织IL-1β,TNF-α的含量,对脑缺血再灌注大鼠脑组织病理形态有较强的改善作用。     

针药结合对急性局灶性脑缺血-再灌注大鼠脑组织自由基代谢的影响

目的:观察针药结合治疗对局灶性脑缺血-再灌注大鼠模型脑组织SOD活性、MDA及NO含量的影响,探讨针药结合治疗对缺血性脑血管病病理状态的干预机制。方法:120只大鼠随机分为两组,分别于缺血2 h再灌注后1 h和再灌注后13 h进行治疗,并分别于再灌注后12 h(I2 h/R12 h组)和再灌注后1 d(I2 h/R1 d组)断头开颅取脑,检测脑组织SOD活性及MDA和NO含量。每组又分为4个亚组,分别是模型组、假手术对照组、头针组及针药组。除假手术对照组外,各组大鼠均采用线栓法建立局灶性脑缺血-再灌注模型,头针组以"百会"透"曲鬓"治疗,针药组以补阳还五汤灌胃结合"百会"透"曲鬓"治疗。结果:①在I2 h/R12 h组里,模型组大鼠脑组织SOD活性明显下降,MDA和NO含量显著升高;头针组和针药组大鼠脑组织SOD活性升高,MDA和NO含量降低。②在I2 h/R1 d组里,针药组MDA含量显著低于头针组。结论:对于脑缺血-再灌注模型鼠,头针及针药结合治疗可抑制自由基代谢及改善线粒体功能,减轻氧自由基介导的脂质过氧化反应。     

Guiding principles for the implementation of non-animal safety assessment approaches for cosmetics: Skin sensitisation

Characterisation of skin sensitisation potential is a key endpoint for the safety assessment of cosmetic ingredients especially when significant dermal exposure to an ingredient is expected. At present the mouse local lymph node assay (LLNA) remains the ‘gold standard’ test method for this purpose however non-animal test methods are under development that aim to replace the need for new animal test data. COLIPA (the European Cosmetics Association) funds an extensive programme of skin sensitisation research, method development and method evaluation and helped coordinate the early evaluation of the three test methods currently undergoing pre-validation. In May 2010, a COLIPA scientific meeting was held to analyse to what extent skin sensitisation safety assessments for cosmetic ingredients can be made in the absence of animal data. In order to propose guiding principles for the application and further development of non-animal safety assessment strategies it was evaluated how and when non-animal test methods, predictions based on physico-chemical properties (including in silico tools), threshold concepts and weight-of-evidence based hazard characterisation could be used to enable safety decisions. Generation and assessment of potency information from alternative tools which at present is predominantly derived from the LLNA is considered the future key research area.     

黄芩茎叶总黄酮对大鼠大脑海马区微血管和血脑屏障缺血再灌注损伤的预防作用

目的 探讨黄芩茎叶总黄酮（SSTF）对脑缺血再灌注海马区微血管、血脑屏障（BBB）损伤的预防性保护作用。 方法 SD大鼠90只,随机分为假手术组（sham组）、模型组（IR组）和SSTF预处理组,造模前1周SSTF各组灌胃给药,低、中、高剂量组分别给50、100、200 mg/(kg·d),共7d。IR组和SSTF各组制作脑缺血再灌注模型,术后评价神经功能缺损变化,干湿重法和伊文思蓝法检测脑组织含水量和微血管通透性,单宁酸 氯化铁媒染（TA-Fe）法显示并观测大鼠微血管密度(MVD)和微血管面积比(MVA),Real-time PCR法检测水通道蛋白4（AQP4） mRNA的表达水平,电镜观察血脑屏障完整性。 结果 SSTF各组与IR组比,神经功能缺损评分、脑组织含水量、微血管通透性明显降低（P＜0.01,P＜0.05）,MVD、MVA增加（P＜0.01）, AQP4 mRNA表达增强(P＜0.01),BBB损伤不同程度减轻,内皮细胞肿胀渐消退,紧密连接松解好转,基膜渐连续、清晰,胶质细胞足板胞质溶解减轻,渐接近正常;SSTF 中、高组上述表现较SSTF 低组好转的更明显（P<0.01）,SSTF 中组与SSTF 高组比较差异无统计学意义（P＞0.05）。 结论 SSTF干预对海马区微血管、血脑屏障和神经损伤有预防性保护作用,其作用机制可能是通过增加有效微血管再通数量,维持血脑屏障完整和功能,减轻脑水肿实现的。SSTF的有效预防剂量为100mg/(kg·d)。