Risk assessment of cyclohexasiloxane D6 in cosmetic products.

Dodecamethylcyclohexasiloxane (D6) is a siloxane substance mainly used in cosmetics and personal care products. While octamethylcyclotetrasiloxane (D4) and decamethylcyclopentasiloxane (D5) were once commonly used in personal care products, their usage has been restricted due to the classification as persistent, bioaccumulative, and toxic (PBT)/very persistent and very bio-accumulative (vPvB) substances. While D6 has emerged as a substitute for D4 and D5, the risk assessment for D6 remains limited compared to the evaluations for D4 and D5. To address this gap, we conducted a comprehensive risk assessment of D6. In this study, we reviewed the toxicity information on D6 and calculated the exposure level to D6, considering the content of D6 in cosmetic products. No observed adverse effect level (NOAEL) of 1500 mg/kg bw/day was established in a repeated dose toxicity study after oral administration to rats. Negative results were found in tests on the ocular and skin irritation, skin sensitization, and genotoxicity of D6. According to the product content of up to 48% of D6 reported in 2012, the Systemic Exposure Dose (SED) was 5.4E-06 to 7.04 mg/kg bw/day for a 60 kg adult using the exposure factors from Korean cosmetic usage. The Margin of Safety was estimated to be between 35.5 and 4.63E+07, posing a potential health risk of D6 according to the maximum concentration and the product type. Further consideration of the potential of D6 as PBT or vPvB is also required.

Safety assessment of cocamidopropyl betaine, a cosmetic ingredient.

Cocamidopropyl betaine (CAPB) is a surfactant derived from coconut oil that is widely used in cosmetics and personal products for several purposes, such as a surfactant, foam booster, mildness, and viscosity control. Cocamidopropyl betaine is used at concentrations up to 30% in cosmetics. The acute toxicity, skin irritation, eye irritation, skin sensitization, repeated dose toxicity, genotoxicity, carcinogenicity, and phototoxicity of cocamidopropyl betaine were evaluated. Cocamidopropyl betaine was observed to induce mild skin irritation, eye irritation and skin sensitization. The NOAEL of cocamidopropyl betaine was determined to be 250 mg/kg/day based on the results of a 92-day repeated-dose oral toxicity study in rats. The systemic exposure dose of cocamidopropyl betaine was estimated to range from 0.00120 to 0.93195 mg/kg/day when used in cosmetic products. The margin of safety of cocamidopropyl betaine was calculated to be greater than 100 when used at a maximum concentration of 6% in leave-on products and 30% in rinse-off products, suggesting that its use in cosmetic products is safe under current usage conditions.

Economic Inequality, Social Determinants of Health, and the Right to Social Security.

This paper discusses economic inequality as a key social determinant of health. It highlights the potentially transformative role of social protection systems in addressing economic inequality and health inequalities. How to finance social protection and how to distribute benefits among people are key questions in the pursuit of a transformative social protection system that can adequately tackle economic inequalities. This paper argues that a human rights approach can provide a normative orientation in the political process that decides the distribution of burdens and benefits in relation to social protection, calling for an assessment of its impact on socioeconomic inequalities and on disadvantaged groups of people. While the right to social security is at the center of a human rights approach to social protection, the rights to health, education, housing, and work also provide important normative elements for social protection. A human rights-based social protection system requires comprehensive protection for major social risks and challenges throughout the life cycle; universal access to quality services such as health, education, child care, and services for older people or people with disabilities; and a progressive financing mechanism. In this regard, the International Labour Organization's Social Protection Floors Recommendation No. 202 provides strong guidance on the implementation of the right to social security for all.

Suppressing Unfavorable Interfacial Reactions Using Polyanionic Oxides as Efficient Buffer Layers: Low-Cost Li3PO4 Coatings for Sulfide-Electrolyte-Based All-Solid-State Batteries.

The poor electrochemical performance of all solid-state batteries (ASSBs) that use sulfide electrolytes can be attributed to undesirable side reactions at the cathode/sulfide-electrolyte interface; this issue can be addressed via surface coating. Ternary oxides such as LiNbO3 and Li2ZrO3 are generally used as coating materials because of their high chemical stabilities and ionic conductivities. However, their relative high cost discourages their use in mass production. In this study, Li3PO4 was introduced as a coating material for ASSBs, because phosphates possess good chemical stabilities and ionic conductivities. Phosphates also prevent the exchange of S2- and O2- in the electrolyte and cathode and, thus, inhibit interfacial side reactions caused by ionic exchange, because they contain the same anion (O2-) and cation (P5+) species as those present in the cathode and sulfide electrolyte, respectively. Furthermore, the Li3PO4 coatings can be prepared using low-cost source materials such as polyphosphoric acid and lithium acetate. We investigated the electrochemical performance of the Li3PO4-coated cathodes and found that the Li3PO4 coating significantly improved the discharge capacities, rate capabilities, and cyclic performances of the all-solid-state cell. While the discharge capacity of the pristine cathode was ∼181 mAh·g-1, that of 0.15 wt % Li3PO4-coated cathode was ∼194-195 mAh·g-1. And the capacity retention of the Li3PO4-coated cathode over 50 cycles was much superior (∼84-85%) to that of the pristine sample (∼72%). Simultaneously, the Li3PO4 coating reduced the side reactions and interdiffusion at the cathode/sulfide-electrolyte interfaces. The results of this study demonstrate the potential of low-cost polyanionic oxides, such as Li3PO4, as commercial coating materials for ASSBs.

Effect of individuals' forecast for their children's economic environment and satisfaction with their relationships with children on their mortality.

AIM: The aim of this study is to evaluate if the risk of mortality among the elderly Korean individuals is associated with any of the two intergenerational variables: participants' forecast for their children's economic environment (FCEE) and participants' satisfaction with their relationship with their children (SRC). METHODS: Data from the Korean Longitudinal Study of Aging (KLoSA) conducted between 2006 and 2016 were examined. In total, 9937 individuals were included at baseline. The FCEE and SRC were measured using an 11-point Likert scale, which were stratified into four levels: "negative" (0-2), "Moderately negative" (3-5), "moderately positive" (6-8) and "positive" (9, 10). RESULTS: The Cox proportional hazards model was used to calculate hazard ratios of all-cause mortality across different levels of FCEE and SRC while adjusting for other bio-psycho-social variables. Post-hoc subgroup analyses were conducted to examine how potential confounders contribute to the associations found in our study. Multivariate analyses showed that individuals with more negative FCEE were associated with a greater risk of all-cause mortality. Compared with the "positive" FCEE group, the "negative" group showed a 30.6% increase risk of all-cause mortality (hazard ratio = 1.306, 95% confidence interval = 1.066-1.601, P = 0.010). CONCLUSION: The SRC did not exhibit any significant association with the all-cause mortality per multivariate analyses. More negative FCEE was associated with greater all-cause mortality. The FCEE, an individual's appraisal of the financial climate of their children's generation, may be considered a novel correlate of the all-cause mortality in an elderly population. Geriatr Gerontol Int ••; ••: ••-•• Geriatr Gerontol Int 2021; 21: 568-576.

Current opinion on risk assessment of cosmetics.

Risk assessment of cosmetic ingredients is a useful scientific method to characterize potential adverse effects resulting from using cosmetics. The process of risk assessment consists of four steps: hazard identification, dose-response assessment, exposure assessment, and risk characterization. Hazard identification of chemicals refers to the initial stage of risk assessment and generally utilizes animal studies to evaluate toxicity. Since 2013, however, toxicity studies of cosmetic ingredients using animals have not been permitted in the EU and alternative toxicity test methods for animal studies have momentum to be developed for cosmetic ingredients. In this paper, we briefly review the alternative test methods that are available for cosmetic ingredients including read-across, in silico, in chemico, and invitro methods. In addition, new technologies such as omics and artificial intelligence (AI) have been discussed to expand or improve the knowledge and hazard identification of cosmetic ingredients. Aggregate exposure of cosmetic ingredients is another safety issue and methods for its improvement were reviewed. There have been concerns over the safety of nano-cosmetics for a long time, but the risk of nano-cosmetics remains unclear. Therefore, current issues of cosmetic risk assessment are discussed and expert opinion will be provided for the safety of cosmetics.

Clinical assessment of an automated fluorescent plaque index scoring with quantitative light-induced fluorescence.

OBJECTIVE: The aims of this study were to evaluate the clinical applicability of a new fluorescent plaque index scoring (FPI) with the Turesky modified Quigley-Hein plaque index (mQH) and to evaluate its relationship with plaque maturity. METHODS: In total 69 subjects participated in this study. White-light and fluorescent images of anterior teeth were acquired using a Qraycam (AIOBIO, Seoul, Korea). FPI was obtained from fluorescent images using the proprietary software (Q-Ray v.1.39, Inspektor Research System BV, Amsterdam, The Netherlands). Teeth were stained with a two-tone disclosing agent. mQH was used to manually score the combined red and blue disclosed plaque (Combi-mQH) and blue disclosed plaque (Blue-mQH) with the white-light images. Linear relationships between FPI and Combi-mQH (or Blue-mQH) were evaluated by using simple linear regression analysis. Differences of Combi-mQH (or Blue-mQH) with respect to FPI scores were statistically evaluated by using ANOVA with Duncan post hoc correction. RESULTS: FPI showed a moderate positive correlation with Combi-mQH (r = 0.66, P < 0.001) and a high positive correlation with Blue-mQH (r = 0.78, P < 0.001). The model explanatory power (R2) between FPI and Blue-mQH was 60.8 %, which is 16.8 % higher than the explanatory power observed with Combi-mQH (44.0 %). Both Combi-mQH and Blue-mQH increased significantly with increasing FPI score (P < 0.001). CONCLUSION: In this study we found that the FPI scoring system can be used to detect plaque and quantitatively distinguish plaque levels. In addition, FPI was determined to be useful in clinic because of its ability to detect and distinguish old and mature plaque.

Assessment of the 4-week repeated-dose oral toxicity and genotoxicity of GHX02.

Herbal medicines are widely utilized for disease prevention and health promotion. GHX02 consists of mixtures including Gwaruin (Trichosanthes kirilowii), Haengin (Prunus armeniaca), Hwangryeon (Coptis japonica) and Hwangkeum (Scutellaria baicalensis). It has been purported to have therapeutic effectiveness in cases of severe bronchitis. Non-clinical safety testing comprised a single-dose oral toxicity study and a 28-day repeated-dose oral toxicity study with a 14-day recovery period, and genotoxicity was assessed by a bacterial reverse mutation test, in vitro chromosomal aberration test, in vivo mouse bone marrow micronucleus test and single cell gel electrophoresis assay (comet assay). In the single-dose oral toxicity study, the approximate lethal dosage is estimated to be higher than 5000 mg/kg in rats. Thus, the dosage levels were set at 0, 1250, 2500 and 5000 mg/kg/day in the 28-day repeated-dose oral toxicity study, and 10 male rats and 10 female rats/dose were administered GHX02. No clinical signs of toxicological significance were recorded in any animal during the dosing and the observation period in the single-dose study. The no-observed-adverse-effect level of GHX02 was 5000 mg/kg/day when administered orally for 28 days to male and female Sprague-Dawley rats. Despite increases in the frequencies of cells with numerical chromosomal aberration in the in vitro test, the increases were not considered relevant to the in vivo genetic risk. Except for the increase of in vitro numerical chromosomal aberration, clear negative results were obtained from other genetic toxicity studies.

Risk assessment of volatile organic compounds (VOCs) detected in sanitary pads.

Disposable sanitary pads are a necessity for women's health, but safety concerns regarding the use of these products have created anxiety. The aim of this study was to conduct a risk assessment of 74 volatile organic compounds (VOCs), which were expected to be contained within sanitary pads. Of the 74 VOCs, 50 were found in sanitary pads retailed in Korea at concentrations ranging from 0.025 to 3548.09 µg/pad. In order to undertake a risk assessment of the VOCs, the toxicological database of these compounds in the United States Environmental Protection Agency (USEPA), Agency for Toxic Substances and Disease Registry (ATSDR), National Toxicology Program (NTP) and World Health Organization (WHO) was searched. Ethanol was found to exhibit the highest reference dose (RfD) while 1,2-dibromo-3-chloro-propane displayed the lowest RfD. Consequently, a worst-case exposure scenario was applied in this study. It was assumed that there was the use of 7.5 sanitary napkins/day for 7 days/month. In the case of panty liners or overnight sanitary napkins, the utilization of 90 panty liners/month or 21 overnight sanitary napkins/month was assumed, respectively. In addition, 43 kg, the body weight of 12 to 13-year-old young women, and 100% VOCs skin absorption were employed for risk assessment. The systemic exposure dose (SED) values were calculated ranging from 1.74 (1,1,2-trichloroethane) ng/kg/day to 144.4 (ethanol, absolute) µg/kg/day. Uncertainty factors (UFs) were applied ranging from 10 to 100,000 in accordance with the robustness of animal or human experiments. The margin of exposure (MOE) of 34 VOCs was more than 1 (acceptable MOE > 1). Applicable carcinogenic references reported that the cancer risk of five VOCs was below 10-6. Based on our findings, evidence indicates that the non-cancer and cancer risks associated with VOCs detected in sanitary pads currently used in South Korea do not pose an adverse health risk in women.

Risk Assessment of Ethylhexyl Dimethyl PABA in Cosmetics.

Ethylhexyl dimethyl para-aminobenzoic acid (PABA) is an oily yellow liquid derivative of water-soluble PABA commonly used in sunscreen. Ethylhexyl dimethyl PABA is widely used as an ingredient in many cosmetics at an average concentration of 1.25% (0.5-2.0%) in Korea. Previous studies, including those involving animals, have demonstrated that ethylhexyl dimethyl PABA is toxic to the following four organs: testis, epididymis, spleen, and liver. In addition, experiments using human keratinocytes found that ethylhexyl dimethyl PABA inhibits cell growth and DNA synthesis at low concentrations, and halted the cell cycle of MM96L cells (human melanoma cell line) at the G1 phase. Despite limited clinical data in humans, many studies have confirmed increased mutagenicity of ethylhexyl dimethyl PABA following exposure to sunlight, which suggests that this molecule is likely to contribute to onset of sun-induced cancer despite protecting the skin through absorption of UVB. For risk assessment, the no observed adverse effect level (NOAEL) chosen was 100 mg/kg bw/day in a 4 weeks oral toxicity study. Systemic exposure dosage (SED) was 0.588 mg/kg bw/day for maximum use of ethylhexyl dimethyl PABA in cosmetics. Based on the risk assessment and exposure scenarios conducted in this study, the margin of safety (MOS) was calculated to be 180.18 for a sunscreen containing 8% ethylhexyl dimethyl PABA, which is the maximum level allowed by the relevant domestic authorities.

Risk Assessment of 5-Chloro-2-Methylisothiazol-3(2H)-One/2-Methylisothiazol-3(2H)-One (CMIT/MIT) Used as a Preservative in Cosmetics.

The mixture of 5-chloro-2-methylisothiazol-3(2H)-one (CMIT) and 2-methylisothiazol-3(2H)-one (MIT), CMIT/MIT, is a preservative in cosmetics. CMIT/MIT is a highly effective preservative; however, it is also a commonly known skin sensitizer. Therefore, in the present study, a risk assessment for safety management of CMIT/MIT was conducted on products containing 0.0015% of CMIT/MIT, which is the maximum MIT level allowed in current products. The no observed adverse effect level (NOAEL) for CMIT/MIT was 2.8 mg/kg bw/day obtained from a two-generation reproductive toxicity test, and the skin sensitization toxicity standard value for CMIT/MIT, or the no expected sensitization induction level (NESIL), was 1.25 µg/cm2/day in humans. According to a calculation of body exposure to cosmetics use, the systemic exposure dosage (SED) was calculated as 0.00423 mg/kg bw/day when leave-on and rinse-off products were considered. Additionally, the consumer exposure level (CEL) amounted to 0.77512 µg/cm2/day for all representative cosmetics and 0.00584 µg/cm2/day for rinse-off products only. As a result, the non-cancer margin of safety (MOS) was calculated as 633, and CMIT/MIT was determined to be safe when all representative cosmetics were evaluated. In addition, the skin sensitization acceptable exposure level (AEL)/CEL was calculated as 0.00538 for all representative cosmetics and 2.14225 for rinse-off products; thus, CMIT/MIT was considered a skin sensitizer when all representative cosmetics were evaluated. Current regulations indicate that CMIT/MIT can only be used at concentrations 0.0015% or less and is prohibited from use in other cosmetics products. According to the results of this risk assessment, the CMIT/MIT regulatory values currently used in cosmetics are evaluated as appropriate.

Risk Assessment of Triclosan, a Cosmetic Preservative.

Triclosan (TCS) is an antimicrobial compound used in consumer products. The purpose of current study was to examine toxicology and risk assessment of TCS based on available data. Acute toxicities of oral, transdermal and inhalation routes were low, and phototoxicity and neurotoxicity were not observed. Topical treatment of TCS to animal caused mild irritation. TCS did not induce reproductive and developmental toxicity in rodents. In addition, genotoxicity was not considered based on in vitro and in vivo tests of TCS. It is not classified as a carcinogen in international authorities such as International Agency for Research on Cancer (IARC). No-observed-adverse-effect level (NOAEL) was determined 12 mg/kg bw/day for TCS, based on haematoxicity and reduction of absolute and relative spleen weights in a 104-week oral toxicity study in rats. Percutaneous absorption rate was set as 14%, which was human skin absorption study reported by National Industrial Chemicals Notification and Assessment Scheme (NICNAS) (2009). The systemic exposure dosage (SED) of TCS has been derived by two scenarios depending on the cosmetics usage of Koreans. The first scenario is the combined use of representative cosmetics and oral care products. The second scenario is the combined use of rinse-off products of cleansing, deodorants, coloring products, and oral care products. SEDs have been calculated as 0.14337 mg/kg bw/day for the first scenario and 0.04733 mg/kg bw/day for the second scenario. As a result, margin of safety (MOS) for the first and second scenarios was estimated to 84 and 253.5, respectively. Based on these results, exposure of TCS contained in rinse-off products, deodorants, and coloring products would not pose a significant health risk when it is used up to 0.3%.

Risk Assessment of Drometrizole, a Cosmetic Ingredient used as an Ultraviolet Light Absorber.

As the use of cosmetics has greatly increased in a daily life, safety issues with cosmetic ingredients have drawn an attention. Drometrizole [2-(2'-hydroxy-5'-methylphenyl)benzotriazole] is categorized as a sunscreen ingredient and is used in cosmetics and non-cosmetics as a UV light absorber. No significant toxicity has been observed in acute oral, inhalation, or dermal toxicity studies. In a 13-week oral toxicity study in beagle dogs, No observed adverse effect level (NOAEL) was determined as 31.75 mg/kg bw/day in males and 34.6 mg/kg bw/day in females, based on increased serum alanine aminotransferase activity. Although drometrizole was negative for skin sensitization in two Magnusson-Kligman maximization tests in guinea pigs, there were two case reports of consumers presenting with allergic contact dermatitis. Drometrizole showed no teratogenicity in reproductive and developmental toxicity studies in which rats and mice were treated for 6 to 15 days of the gestation period. Ames tests showed that drometrizole was not mutagenic. A long-term carcinogenicity study using mice and rats showed no significant carcinogenic effect. A nail product containing 0.03% drometrizole was nonirritating, non-sensitizing and non-photosensitizing in a test with 147 human subjects. For risk assessment, the NOAEL chosen was 31.75 mg/kg bw/day in a 13-week oral toxicity study. Systemic exposure dosages were 0.27228 mg/kg bw/day and 1.90598 mg/kg bw/day for 1% and 7% drometrizole in cosmetics, respectively. Risk characterization studies demonstrated that when cosmetic products contain 1.0% of drometrizole, the margin of safety was greater than 100. Based on the risk assessment data, the MFDS revised the regulatory concentration of drometrizole from 7% to 1% in 2015. Under current regulation, drometrizole is considered to be safe for use in cosmetics. If new toxicological data are obtained in the future, the risk assessment should be carried out to update the appropriate guidelines.

Application of quantitative light-induced fluorescence technology for tooth bleaching treatment and its assessment: An in vitro study.

OBJECTIVES: This study aimed to determine the efficacy of a combination of photocatalysts-hydrogen peroxide at a low concentration (3.5%) and titanium dioxide (TiO2)-activated at a wavelength of 405 nm using quantitative light-induced fluorescence (QLF) technology, and to quantify their tooth-bleaching efficacy using fluorescence images obtained from QLF technology. MATERIALS AND METHODS: Forty bovine incisors were extrinsically stained according to Stookey's method, and were randomly divided into four groups (n = 10 per group). Two bleaching solutions were prepared by mixing 3.5% H2O2 with 0.05% of anatase and rutile TiO2 powders. These solutions were applied to the stained teeth using a microbrush and then irradiated for 15 min at either 306 or 405 nm to activate the bleaching agent. The color difference (ΔE*) was assessed before and after every 5 min of treatment. The ΔE* and the changes in the fluorescence loss (ΔΔF) were obtained from white-light and fluorescence images, respectively. RESULTS: All of the low-H2O2/TiO2 treatments caused significant tooth-bleaching efficacy after irradiation at 306 and 405 nm (p < 0.05). The results did not differ significantly between the two wavelengths (p > 0.05), but the bleaching efficacy was greater with anatase TiO2 at 306 nm and rutile TiO2 at 405 nm. Analysis of the fluorescence images revealed that the ΔF values increased significantly in all groups with the treatment time (p < 0.05). There was a statistically significant correlation between ΔE* and the change in ΔΔF (r = 0.822, p < 0.001). CONCLUSIONS: Combining low-H2O2/TiO2 with QLF technology at 405 nm has an efficacy of tooth-bleaching as a less harmful and biofriendly method, while the fluorescence images obtained by QLF technology could be used to assess tooth-bleaching.

Risk assessment of zinc oxide, a cosmetic ingredient used as a UV filter of sunscreens.

Zinc oxide (ZnO), an inorganic compound that appears as a white powder, is used frequently as an ingredient in sunscreens. The aim of this review was to examine the toxicology and risk assessment of ZnO based upon available published data. Recent studies on acute, sub-acute, and chronic toxicities of ZnO indicated that this compound is virtually non-toxic in animal models. However, it was reported that ZnO nanoparticles (NP) (particle size, 40 nm) induced significant changes in anemia-related hematologic parameters and mild to moderate pancreatitis in male and female Sprague-Dawley rats at 536.8 mg/kg/day in a 13-week oral toxicity study. ZnO displayed no carcinogenic potential, and skin penetration is low. No-observed-adverse-effect level (NOAEL) ZnO was determined to be 268.4 mg/kg/day in a 13-week oral toxicity study, and a maximum systemic exposure dose (SED) of ZnO was estimated to be 0.6 mg/kg/day based on topical application of sunscreen containing ZnO. Subsequently, the lowest margin of safety (MOS) was estimated to be 448.2, which indicates that the use of ZnO in sunscreen is safe. A risk assessment was undertaken considering other routes of exposure (inhalation or oral) and major product types (cream, lotion, spray, and propellant). Human data revealed that MOS values (7.37 for skin exposure from cream and lotion type; 8.64 for skin exposure of spray type; 12.87 for inhalation exposure of propellant type; 3.32 for oral exposure of sunscreen) are all within the safe range (MOS > 1). Risk assessment of ZnO indicates that this compound may be used safely in cosmetic products within the current regulatory limits of 25% in Korea.

Correlates of oncologist-issued referrals for psycho-oncology services: what we learned from the electronic voluntary screening and referral system for depression (eVSRS-D).

OBJECTIVE: Depression in cancer patients is under-recognized and under-treated. To better identify depression, we designed a voluntary depression screening system. Based on its data, we examined trends in oncologist-issued referrals for the psycho-oncology service (POS). METHODS: The Electronic Voluntary Screening and Referral System for Depression (eVSRS-D) comprises self-screening, automated reporting, and referral guidance. Using touch-screen kiosks at a tertiary hospital in Korea, participants with cancer completed the Patient Health Questionnaire-9 at their convenience, received the results, and reported their willingness to participate in POS. At oncology appointments, oncologists received the screening reports and issued referrals following pre-recommended guidelines. The correlates of actual referrals were examined across all participants and within the willing and non-willing groups. RESULTS: Among the 838 participants, 56.3% reported severe depression symptoms, 30.5% wanted a referral, and 14.8% were actually referred. The correlates of participants' desire for referral were more severe depression symptoms, being unmarried, and being metastasis and recurrence free. Among all participants, the correlates of actual referrals were unemployment, less severe depression symptoms, poorer performance, treatment status, and wanting a referral. The sole correlate of actual referrals within the non-willing group was poorer performance, and no significant correlates existed within the willing group. The non-referrals were mostly (87.1%) because of postponed decisions. CONCLUSIONS: The eVSRS-D cannot definitively diagnose major depression but may efficiently self-select a population with significant depression symptoms. The patients' willingness to engage the POS most strongly predicted the actual referrals. Oncologist reviews of screening reports may not result in further depression severity-specific referrals.

Human rights responsibilities of pharmaceutical companies in relation to access to medicines.

Although access to medicines is a vital feature of the right to the highest attainable standard of health ("right to health"), almost two billion people lack access to essential medicines, leading to immense avoidable suffering. While the human rights responsibility to provide access to medicines lies mainly with States, pharmaceutical companies also have human rights responsibilities in relation to access to medicines. This article provides an introduction to these responsibilities. It briefly outlines the new UN Guiding Principles on Business and Human Rights and places the human rights responsibilities of pharmaceutical companies in this context. The authors draw from the work of the first UN Special Rapporteur on the right to the highest attainable standard of health, in particular the Human Rights Guidelines for Pharmaceutical Companies in Relation to Access to Medicines that he presented to the UN General Assembly in 2008, and his UN report on GlaxoSmithKline (GSK). While the Guiding Principles on Business and Human Rights are general human rights standards applicable to all business entities, the Human Rights Guidelines for Pharmaceutical Companies consider the specific human rights responsibilities of one sector (pharmaceutical companies) in relation to one area of activity (access to medicines). The article signals the human rights responsibilities of all pharmaceutical companies, with particular attention to patent-holding pharmaceutical companies. Adopting a right-to-health "lens," the article discusses GSK and accountability. The authors argue that human rights should shape pharmaceutical companies' policies, and provide standards in relation to which pharmaceutical companies could, and should, be held accountable. They conclude that it is now crucial to devise independent, accessible, transparent, and effective mechanisms to monitor pharmaceutical companies and hold them publicly accountable for their human rights responsibilities.

Issues in combining the categorical and visual analog scale for the assessment of perceived thermal sensation: methodological and conceptual considerations.

Typically, the scales for the measurement of thermal sensation have been formatted as categorical scales (CS). Emerging is the use of CS combined with visual analog scale (VAS) for the measurement of thermal sensation to improve the sensitivity of scales. However, reports are rare comparing the typical CS, standard VAS, and combined CS with VAS. Methodological and conceptual issues are arising with the combining of scales, but there are insufficient reports about the advantages and limitations of different scales. The present study compared 9-points categorical scale (9pts CS), VAS, and CS combined with VAS (graphic CS) through a questionnaire survey (n=988) and a controlled experiment during exercise (17 male subjects). Our results showed that graphic CS was more closely related to indoor air temperature for resting residents rather than VAS or 9pts CS. Around thermal neutral zone indoor environments, sensitivity to discriminate thermal sensation was the greatest for graphic CS. In particular, questionnaire responses to VAS showed a remarkable clustering around the thermal neutral zone. For dynamic exercising subjects, mean skin temperature was more closely related to graphic CS than 9pts CS. Our results indicated that graphic CS seemed to be more valid and sensitive than 9pts CS or VAS for the measurement of thermal sensation, but there are many issues to be considered when combining CS and VAS from the methodological and conceptual view points: definitions of terms, verbalizing with descriptors, number of category, scoring length, unipolar/bipolar construction, language translation, central terms, both anchor terms, orientation, color, etc. The above methodological and conceptual issues were discussed.