Risk Assessment and Risk Reduction of Ptaquiloside in Bracken Fern.

This study was conducted to determine the optimal boiling time to reduce ptaquiloside (PTA) and to carry out a risk assessment for PTA, a representative toxic substance found in bracken fern (BF; Pteridium aquilinum), which is frequently consumed as food in East Asian countries. High-performance liquid chromatography showed that the concentration of PTA in BF was reduced by up to 99% after boiling for 20 min. Risk assessment results showed that the cancer margin of exposure (MOE; ≥ 25,000 = safe) to PTA for an average daily exposure scenario after boiling BF for 20 min was considered safe. In addition, the non-cancer MOE (≥ 300 = safe) to PTA under an average daily exposure scenario after BF boiling for 20 min was considered safe. However, human exposure to PTA was considered unsafe under the non-boiled BF exposure and maximum daily exposure scenarios. Therefore, boiling BF for at least 20 min is recommended before consumption, to reduce exposure to PTA as much as possible.

Micro-ultrasonic Assessment of Early Stage Clot Formation and Whole Blood Coagulation Using an All-Optical Ultrasound Transducer and Adaptive Signal Processing Algorithm.

Abnormal formation of solid thrombus inside a blood vessel can cause thrombotic morbidity and mortality. This necessitates early stage diagnosis, which requires quantitative assessment with a small volume, for effective therapy with low risk to unwanted development of various diseases. We propose a micro-ultrasonic diagnosis using an all-optical ultrasound-based spectral sensing (AOUSS) technique for sensitive and quantitative characterization of early stage and whole blood coagulation. The AOUSS technique detects and analyzes minute viscoelastic variations of blood at a micro-ultrasonic spot (<100 µm) defined by laser-generated focused ultrasound (LGFU). This utilizes (1) a uniquely designed optical transducer configuration for frequency-spectral matching and wideband operation (6 dB widths: 7-32 MHz and d.c. ∼ 46 MHz, respectively) and (2) an empirical mode decomposition (EMD)-based signal process particularly adapted to nonstationary LGFU signals backscattered from the spot. An EMD-derived spectral analysis enables one to assess viscoelastic variations during the initiation of fibrin formation, which occurs at a very early stage of blood coagulation (1 min) with high sensitivity (frequency transition per storage modulus increment = 8.81 MHz/MPa). Our results exhibit strong agreement with those obtained by conventional rheometry (Pearson's R > 0.95), which are also confirmed by optical microscopy. The micro-ultrasonic and high-sensitivity detection of AOUSS poses a potential clinical significance, serving as a screening modality to diagnose early stage clot formation (e.g., as an indicator for hypercoagulation of blood) and stages of blood-to-clot transition to check a potential risk for development into thrombotic diseases.

Risk assessment of unintentional phthalates contaminants in cosmetics.

A risk assessment was performed for three types of phthalates, benzyl butyl phthalate (BBP), dibutyl phthalate (DBP), and di(2-ethylhexyl)phthalate (DEHP) unintentionally contaminated in cosmetics. A total of 100 products of 8 types of cosmetics were analyzed employing gas chromatography-mass spectrometry (GC-MS). By applying the maximum detected values of phthalates based on the worst exposure cases, their systemic exposure dosage (SED) was calculated. Accordingly, DEHP was identified as the main unintentional phthalates contaminants (0.10-600.00 ppm) in the cosmetics, with an SED of 3.37 × 10-9-3.75 × 10-4 mg/kg/day. In the non-cancer risk assessment, a margin of safety (MOS ≥ 100, safe) of 1.28 × 104-1.42 × 109 was estimated. In the cancer risk assessment, the lifetime cancer risk (LCR ≤ 10-5, safe) was determined to be 8.81 × 10-12-9.79 × 10-7. Based on the results of both risk assessments, the levels of unintentional phthalates contaminants in cosmetics were deemed safe. Some phthalates are widely used as plasticizers and are essential for daily life; however, various toxicities, including endocrine disruption, have been reported. Therefore, even under these "worst case" assumptions, an adequate margin of safety is shown such that this might be a low priority for further work although exposure to unintentional phthalates contaminants through cosmetics should be considered as part of cumulative exposure.

Acute cholecystitis: predictive clinico-radiological assessment for conversion of laparoscopic cholecystectomy.

BACKGROUND: Previous studies evaluating predictive factors for the conversion from laparoscopic to open cholecystectomy have reported conflicting conclusions. PURPOSE: To create a risk assessment model to predict the conversion from laparoscopic to open cholecystectomy in patients with acute calculous cholecystitis. MATERIAL AND METHODS: A retrospective review of patients with acute calculous cholecystitis with available preoperative contrast-enhanced computed tomography (CT) findings who underwent laparoscopic cholecystectomy was performed. Forty-four parameters-including demographics, clinical history, laboratory data, and CT findings-were analyzed. RESULTS: Among the included 581 patients, conversion occurred in 113 (19%) cases. Multivariate analysis identified obesity (odd ratio [OR] 2.58, P = 0.04), history of abdominal surgery (OR 1.78, P = 0.03), and prolonged prothrombin time (OR 1.98, P = 0.03) as predictors of conversion. In preoperative CT findings, the absence of gallbladder wall enhancement (OR 3.15, P = 0.03), presence of a gallstone in the gallbladder infundibulum (OR 2.11, P = 0.04), and inflammation of the hepatic pedicle (OR 1.71, P = 0.04) were associated with conversion. Inter-observer agreement for CT study interpretation was very good (range 0.81-1.00). A model was created to calculate the risk for conversion, with an area under the receiver operating characteristic curve of 0.87. The risk for conversion, estimated based on the number of factors identified, was in the range of 5.3% (with one factor) to 86.4% (with six factors). CONCLUSION: Obesity, history of abdominal surgery, prolonged prothrombin time, absence of gallbladder wall enhancement, presence of a gallstone in the gallbladder infundibulum, and inflammation of the hepatic pedicle are associated with conversion of laparoscopic to open cholecystectomy.

Quantitative structure-activity and quantitative structure-property relationship approaches as alternative skin sensitization risk assessment methods.

This study aimed to predict skin sensitization potency of selected chemicals by quantitatively analyzing their physicochemical properties by employing quantitative structure-activity relationship (QSAR) and quantitative structure-property relationship (QSPR) approaches as alternative risk assessment methods to animal testing. Correlations between effective concentration for a stimulation index of 3 (EC3) (%), the amount of a chemical required to elicit a threefold increase in lymph node cell proliferative activity (stimulation index, ≥3), were calculated using local lymph node assay (LLNA) and physicochemical properties of 212 skin sensitizers and 38 non-sensitizers were investigated. The correlation coefficients between melting point (MP) and EC3 and between surface tension (ST) and EC3 were 0.65 and 0.69, respectively. The correlation coefficient for MP + ST and EC3 was estimated to be 0.72. Thus, correlation coefficients between EC3 and MP, ST, and MP + ST reliably predicted the skin sensitization potential of the chemicals with sensitivities of 72% (126/175), 70% (122/174), and 73% (116/158); specificities of 77% (27/35), 69% (22/32), and 81% (26/32); and accuracies of 73% (153/210), 70% (144/206), and 75% (142/190), respectively. Our findings suggest that the EC3 value may be more accurately predicted using the ST values of chemicals as opposed to MP values. Thus, information on MP and ST parameters of chemicals might be useful for predicting the EC3 values as not only an alternative approach to animal testing, but as a risk assessment method for skin sensitization.

Risk assessment of phthalates in pharmaceuticals.

Phthalates are used for industrial plasticizers to impart flexibility and durability to polyvinyl chloride. Despite widespread use of phthalates, reported endocrine-disrupting properties raise safety concerns for consumers. Since phthalates are permitted as excipients in controlled-release capsules and enteric coatings, patients taking drugs containing these chemicals may potentially be at some health risk. In this study, 102 distinct pharmaceutical products were analyzed by gas chromatography/mass spectrometry to determine phthalate content and maximal phthalate exposure rate was calculated. In 102 drug samples, di(2-ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP), and diethyl phthalate (DEP) were detected in 9.8, 27.45, and 5.88% of cases, respectively. The highest level of DEP was found in extended-release (ER) capsules with concentrations ranging from 935.5 to 1535.37 ppb. The highest levels of DBP (1.32-7.07 ppb) were detected in tablets, whereas highest level (7.07 ppb) of DEHP was found in suspension preparations. The phthalate hazard index (HI) (human exposure tolerable daily intake) was calculated for each sample, but no sample exhibited an HI value exceeding 1; the minimum value taken to indicate a serious health risk. Thus, no apparent serious health risk from phthalate exposure arises from taking these medications. The low HI values suggest that phthalate contamination in pharmaceuticals may not pose an apparent significant risk to humans. However, the sources of phthalate present in pharmaceutical products still needs to be investigated and verified through on-site inspections in manufacturing processes in order to minimize human exposure. It is recommended that measures be taken to prevent phthalate contamination in pharmaceuticals.

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.

Alternative skin sensitization prediction and risk assessment using proinflammatory biomarkers, interleukin-1 beta (IL-1ß) and inducible nitric oxide synthase (iNOS).

As an alternative to animal tests for skin sensitization potency and risk assessment, cell viability and biomarkers related to skin sensitization were analyzed in THP-1 human monocytic leukemia cells. Cell viabilities of 90% (CV90) and 75% (CV75) were determined for 24 selected test chemicals. Further biomarkers related to skin sensitization were also determined under equivalent comparative conditions. In cell viability analyses, potent skin sensitizers exhibited high cytotoxicity, but non-sensitizers did not display this tendency. In biomarker analyses, interleukin-I beta (IL-1ß), inducible nitric oxide synthase (iNOS), IL-1ß+iNOS, and THP-1 IL-1ß+Raw 264.7 IL-1ß were found to be suitable for prediction of skin sensitization potency following classification as either skin sensitizers or non-sensitizers (accuracies of 91.7%, 87.5%, 83.3%, and 82.6%, respectively). A significant positive correlation was found between biomarkers and skin sensitization potency, with a correlation coefficient (R) of 0.7 or more (correlation coefficients of 0.77, 0.72, 0.7, and 0.84, respectively). Finally, the skin sensitization potency effective threefold concentration (EC) 3% was predicted using a biomarker equation, with resulting prediction rates (match rate with actual data) of 58.3%, 54.2%, 62.5%, and 60.9%, respectively. The prediction accuracy for the EC3 value obtained from animal data was calculated as 83.3%, 79.2%, 79.2%, and 73.9%, respectively. Thus, these biomarkers, IL-1ß and iNOS, may be alternatively used to predict skin sensitization potency and risk assessment.

IL-1α and IL-1ß as alternative biomarkers for risk assessment and the prediction of skin sensitization potency.

Potential biomarkers of skin sensitization in RAW264.7 mouse macrophages were investigated as alternatives to animal experiments and risk assessment. The concentrations that resulted in a cell viability of 90% (CV90) and 75% (CV75) were calculated by using a water-soluble tetrazolium salt (WST)-1 assay and used to analyze the skin sensitization potency of 23 experimental materials under equivalent treatment conditions. In addition, the expression of interleukin (IL)-1α, IL-1ß, IL-31, tumor necrosis factor (TNF)-α, inducible nitric oxide synthase (iNOS), prostaglandin E2 (PGE2), and cyclooxygenase-2 (COX-2) was analyzed utilizing Western blotting. In the cell viability analysis, skin sensitizers were generally more cytotoxic and exhibited increased skin sensitization potency. However, nonsensitizers did not show any marked cytotoxic tendency. Biomarker analysis demonstrated that IL-1α, IL-1ß, and the combination of IL-1α and IL-1ß (IL-1α + IL-1ß) predicted reliably skin sensitization potential (1) sensitivities of 94.4%, 83.3%, and 83.3%, specificities of 100%, 100%, and 100%, and (2) accuracies of 95.7%, 87%, and 87%, respectively. These observations correlated most reliably as indicators for skin sensitization potency. Data suggest that IL-1α and IL-1ß may serve as potential biomarkers for skin sensitization and provide an alternative method to animal experiments for prediction of skin sensitization potency and risk assessment.

Risk assessment of N-nitrosodiethylamine (NDEA) and N-nitrosodiethanolamine (NDELA) in cosmetics.

N-nitrosamines and their precursors found in cosmetics may be carcinogenic in humans. Thus the aim of this study was to carry out risk assessment for N-nitrosamines (N-nitrosodiethanolamine [NDELA], N-nitrosodiethylamine [NDEA]) and amines (triethanolamine [TEA], diethanolamine [DEA]) levels in cosmetics determined using validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) procedures. NDELA and NDEA concentrations were present at levels of "not detected" (N.D.) to 596.5 µg/kg and N.D. to 40.9 µg/kg, respectively. TEA and DEA concentrations ranged from N.D. to 860 µg/kg and N.D. to 26.22 µg/kg, respectively. The nitrite concentration (3-2250 mg/l), number of nitrosating agents to a maximum 5, and pH (3.93-10.09) were also assessed. The impact of N-nitrosamine formation on the levels of TEA, DEA, nitrite, and other nitrosating agents was also examined. N-nitrosamine concentrations correlated with the number of nitrosating agents and nitrite concentrations. Data demonstrated that higher nitrite concentrations and a greater number of nitrosating agents increased NDELA and NDEA yields. Further, the presence of TEA and DEA exerted a significant influence on N-nitrosamine formation. Risk assessments, including the margin of exposure (MOE) and lifetime cancer risk (LCR) for N-nitrosamines and margin of safety (MOS) for amines, were calculated using product type, use pattern, and concentrations. Exposure to maximum amounts of NDELA and NDEA resulted in MOE > 10,000 (based upon the benchmark dose lower confidence limit 10%) and LCR <1 × 10-5, respectively. In addition, TEA and DEA concentrations in cosmetic samples resulted in MOS values >100. Therefore, no apparent safety concerns were associated with cosmetic products containing NDELA, NDEA, TEA, and DEA in this study. However, since amines and nitrosating agents produce carcinogenic nitrosamines, their use in cosmetics needs to be minimized to levels as low as technically feasible.

Non-cancer, cancer, and dermal sensitization risk assessment of heavy metals in cosmetics.

The heavy metal content of cosmetics may be a cause for concern in that exposure to these metals is associated with adverse consequences. Thus, the aim of this study was to assess consequences attributed to exposure to heavy metals in cosmetics as determined by non-cancer, cancer, and sensitization risks methodologies. The quantification and exposure assessments of aluminum (Al), chromium (Cr), manganese (Mn), iron (Fe), cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), lead (Pb), mercury (Hg), cadmium (Cd), antimony (Sb), and titanium (Ti) were performed by inductively coupled plasma-mass spectrometry. The non-cancer risk assessment of Al, Cr3+, Mn, Fe, Co, Ni, Cu, Zn, Cd, Sb, and Ti in cosmetic samples resulted in a margin of safety (MOS) greater than 100 or a hazard index (HI) of less than 1. However, the probability of lifetime cancer risk (LCR) resulting from dermal exposure to heavy metals from cosmetics exceeded the acceptable risk levels (LCR > 10-5). An exposure-based sensitization quantitative risk assessment determined that the ratios of acceptable exposure level to consumers for Ni, Co, Cu, or Hg were above 1, suggesting an absence of skin-sensitizing potential. For an average daily user of lip cosmetics, the estimated intakes of heavy metals were within the acceptable daily intake (ADI). The percentage of heavy users for which metal intakes exceeded ADIs were 20.37% for Pb, 9.26% for Mn, 1.85% for Cr3+, and 1.85% for Cr6+, respectively. Data suggested that the heavy metals present in cosmetics do not appear to pose a serious risk to health. However, for heavy users of lip cosmetics, contamination with some heavy metals, such as Pb, Mn, and Cr needs to be minimized.

Risk assessment of benzalkonium chloride in cosmetic products.

A risk assessment of benzalkonium chloride (BAC) was conducted based upon its toxicological profile and exposure evaluation. Since 1935, BAC has been used in a wide variety of products such as disinfectants, preservatives, and sanitizers. It is well-established that BAC is not genotoxic nor does it display tumorigenic potential, but safety concerns have been raised in local usage such as for ocular and intranasal applications. The Foundation of Korea Cosmetic Industry Institute (KCII) reported that in a hair conditioner manufactured as a cosmetic or personal product in South Korea, BAC was present at concentrations of 0.5-2%. The systemic exposure dosage (SED) was determined using the above in-use concentrations and a risk assessment analysis was conducted. The Margin of Safety (MOS) values for hair conditioners were calculated to be between 621 and 2,483. The risk of certain personal and cosmetic products was also assessed based upon assumptions that BAC was present at the maximal level of regulation in South Korea and that the maximal amount was used. The MOS values for the body lotion were all above 100, regardless of the application site. Collectively, data indicate that there are no safety concerns regarding use of products that contain BAC under the current concentration restrictions, even when utilized at maximal permitted levels. However, a chronic dermal toxicity study on BAC and comprehensive dermal absorption evaluation needs to be conducted to provide a more accurate prediction of the potential health risks to humans.

Risk assessment of lithium-ion battery explosion: chemical leakages.

Use of lithium-ion batteries has raised safety issues owing to chemical leakages, overcharging, external heating, or explosions. A risk assessment was conducted for hydrofluoric acid (HF) and lithium hydroxide (LiOH) which potential might leak from lithium-ion batteries. The inhalation no-observed-adverse-effect-level (NOAEL) for HF was 0.75 mg/kg/d. When a lithium-ion battery explodes in a limited space, HF emissions amount to 10-100 ppm. Assuming the worst-case scenario, the conversion rate was calculated to be 81.8 mg/m3, and the average daily dose (ADD) was 19.5 mg/kg/d. Consequently, the margin of exposure (MOE = NOAEL/ADD) was 0.034, a value which constitutes an unsafe inhalation exposure for HF. Conversely, skin toxicity NOAEL for LiOH was 41.35 mg/kg/d-. This LiOH value reflects the amount of lithium in the lithium-ion battery, which is generated upon contact between water and the electrolyte. The quantity of lithium in a mobile phone is approximately 295 mg, and systemic exposure dose (SED) was 4.92 mg/kg/d. Accordingly, the MOE (NOAEL/SED) value was 8.41, and skin exposure of LiOH was deemed as safe for humans. However, it is important that Energy Storage System batteries still require safety measures and technologies for next-generation batteries, to prevent any potential explosions of lithium-ion batteries.

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.

Photomechanical effect on Type I collagen using pulsed diode laser.

BACKGROUND: As the most abundant protein in human tissues, the use of collagen is essential in the fields of biological science and medicine. OBJECTIVE: The aim of this study is to investigate the mechanical effect of pulsed laser irradiation on collagen tissue. METHODS: With various laser parameters such as peak power, pulse width, and repetition rate, the induced stresses on samples were measured and analyzed. Monte Carlo simulation was performed to investigate the effect of laser parameters on the collagen sample. RESULTS: The results indicated that the magnitude of mechanical stress could be controlled by various laser parameters. CONCLUSIONS: This study can be used in biostimulation for therapy and mechanoreceptor stimulation for tactile application.

Potential application of benzo(a)pyrene-associated adducts (globin or lipid) as blood biomarkers for target organ exposure and human risk assessment.

In order to investigate the potential application of blood biomarkers as surrogate indicators of carcinogen-adduct formation in target-specific tissues, temporal formation of benzo[a]pyrene (BaP)-associated DNA adducts, protein adducts, or lipid damage in target tissues such as lung, liver, and kidney was compared with globin adduct formation or plasma lipid damage in blood after continuous intraperitoneal (ip) injection of [(3)H]BaP into female ICR mice for 7 d. Following treatment with [(3)H]BaP, formation of [(3)H]BaP-DNA or -protein adducts in lung, liver, and kidney increased linearly, and persisted thereafter. This finding was similar to the observed effects on globin adduct formation and plasma lipid damage in blood. The lungs contained a higher level of DNA adducts than liver or kidneys during the treatment period. Further, the rate of cumulative adduct formation in lung was markedly greater than that in liver. Treatment with a single dose of [(3)H]BaP indicated that BaP-globin adduct formation and BaP-lipid damage in blood reached a peak 48 h after treatment. Overall, globin adduct formation and lipid damage in blood were significantly correlated with DNA adduct formation in the target tissues. These data suggest that peripheral blood biomarkers, such as BaP-globin adduct formation or BaP-lipid damage, may be useful for prediction of target tissue-specific DNA adduct formation, and for risk assessment after exposure.

Risk assessment of volatile organic compounds benzene, toluene, ethylbenzene, and xylene (BTEX) in consumer products.

Exposure and risk assessment was performed by evaluating levels of volatile organic compounds (VOC) benzene, toluene, ethylbenzene, and xylene (BTEX) in 207 consumer products. The products were categorized into 30 different items, consisting of products of different brands. Samples were analyzed for BTEX by headspace-gas chromatography/mass spectrometry (headspace-GC/MS) with limit of detection (LOD) of 1 ppm. BTEX were detected in 59 consumer products from 18 item types. Benzene was detected in whiteout (ranging from not detected [ND] to 3170 ppm), glue (1486 ppm), oil-based ballpoint pens (47 ppm), and permanent (marking) pens (2 ppm). Toluene was detected in a leather cleaning product (6071 ppm), glue (5078 ppm), whiteout (1130 ppm), self-adhesive wallpaper (15-1012 ppm), shoe polish (806 ppm), permanent pen (609 ppm), wig adhesive (372 ppm), tapes (2-360 ppm), oil-based ballpoint pen (201 ppm), duplex wallpaper (12-52 ppm), shoes (27 ppm), and air freshener (13 ppm). High levels of ethylbenzene were detected in permanent pen (ND-345,065 ppm), shoe polish (ND-277,928 ppm), leather cleaner (42,223 ppm), whiteout (ND-2,770 ppm), and glue (ND-792 ppm). Xylene was detected in permanent pen (ND-285,132 ppm), shoe polish (ND-87,298 ppm), leather cleaner (12,266 ppm), glue (ND-3,124 ppm), and whiteout (ND-1,400 ppm). Exposure assessment showed that the exposure to ethylbenzene from permanent pens ranged from 0 to 3.11 mg/kg/d (men) and 0 to 3.75 mg/kg/d (women), while for xylene, the exposure ranges were 0-2.57 mg/kg/d and 0-3.1 mg/kg/d in men and women, respectively. The exposure of women to benzene from whiteout ranged from 0 to 0.00059 mg/kg/d. Hazard index (HI), defined as a ratio of exposure to reference dose (RfD), for ethylbenzene was 31.1 (3.11 mg/kg/d/0.1 mg/kg/d) and for xylene (2.57 mg/kg/d/0.2 mg/kg/d) was 12.85, exceeding 1 for both compounds. Cancer risk for benzene was calculated to be 3.2 × 10(-5) based on (0.00059 mg/kg/d × 0.055 mg/kg-d(-1), cancer potency factor), assuming that 100% of detected levels in some products such as permanent pens and whiteouts were exposed in a worst-case scenario. These data suggest that exposure to VOC via some consumer products exceeded the safe limits and needs to be reduced.

Development and application of risk management system for consumer products in compliance with global harmonization.

Exposure to the wide variety of chemicals used for manufacturing consumer products commonly occurs daily and the consequences to health are beneficial. However, some of these products are hazardous and exert deleterious effects on humans and the ecosystem. To protect consumers from exposure to hazardous chemicals, appropriate risk management systems are needed. Developed countries such as the United States and Canada have developed their own risk management systems for regulating hazardous agents. However, the risk management systems prepared by developed countries may not be readily applicable to developing or underdeveloped countries because of certain economic, political, cultural, or social factors in each country. In general, a risk management framework includes evaluation components of risk assessment, risk confrontation, risk intervention, risk communication, and risk management, but these may differ in specifics. The European Commission (EC) requires a socioeconomic analysis for formulating restrictions suggested by the European Chemicals Agency (ECHA). The EC has an early warning system for safety management termed the Rapid Alert System (RAPEX). Korea, Australia, and Japan also developed integrated network systems for risk management of consumer products. Monitoring entails the collection of information and evaluation. The risk assessment process includes scientific evaluation of potential adverse health effects. Risk communication tasks are to (1) identify stakeholders, (2) develop stakeholder analysis, (3) assess stakeholder acceptability, (4) consult with stakeholders, (5) inform stakeholders about their options, (6) evaluate control options, and (7) monitor changing issues. The risk management process involves weighing policy options and selecting regulatory options. The decision-making step is related to the determination of governmental or voluntary actions. This review examines the critical points of risk management system in Korea to effectively control hazardous agents for human safety and compliance with global harmonization.

Safety evaluation and risk assessment of d-Limonene.

d-Limonene, a major constituent of citrus oils, is a monoterpene widely used as a flavor/fragrance additive in cosmetics, foods, and industrial solvents as it possesses a pleasant lemon-like odor. d-Limonene has been designated as a chemical with low toxicity based upon lethal dose (LD50) and repeated-dose toxicity studies when administered orally to animals. However, skin irritation or sensitizing potential was reported following widespread use of this agent in various consumer products. In experimental animals and humans, oxidation products or metabolites of d-limonene were shown to act as skin irritants. Carcinogenic effects have also been observed in male rats, but the mode of action (MOA) is considered irrelevant for humans as the protein α(2u)-globulin responsible for this effect in rodents is absent in humans. Thus, the liver was identified as a critical target organ following oral administration of d-limonene. Other than the adverse dermal effects noted in humans, other notable toxic effects of d-limonene have not been reported. The reference dose (RfD), the no-observed-adverse-effect level (NOAEL), and the systemic exposure dose (SED) were determined and found to be 2.5 mg/kg/d, 250 mg/kg//d, and 1.48 mg/kg/d, respectively. Consequently, the margin of exposure (MOE = NOAEL/SED) of 169 was derived based upon the data, and the hazard index (HI = SED/RfD) for d-limonene is 0.592. Taking into consideration conservative estimation, d-limonene appears to exert no serious risk for human exposure. Based on adverse effects and risk assessments, d-limonene may be regarded as a safe ingredient. However, the potential occurrence of skin irritation necessitates regulation of this chemical as an ingredient in cosmetics. In conclusion, the use of d-limonene in cosmetics is safe under the current regulatory guidelines for cosmetics.