[Investigation and Improvement of Techniques That Affect the Amount of Dispersal during Preparation of Anticancer Drugs].

Many healthcare workers who handle anticancer drugs are at risk for occupational exposure. However, there are no established permissible limits for occupational exposure to anticancer drugs; thus, in this study, we aimed to search for and improve procedures that have a greater impact on the amount of spatter for handling anticancer drugs in vials, which are frequently used, based on the quantitative evaluation of the amount of exposure. We used sodium riboflavin phosphate (FMN) as a simulated anticancer drug and measured the amount of FMN dispersed to the handling area by the wiping method and the amount of FMN dispersed in both gloves using high-performance liquid chromatography with fluorescence detection (HPLC-FL). In this study, it was suggested that the overall amount of dispersal in the preparation process was affected by the different methods of injecting the drug solution into the infusion bottles and whether recapping. It was also found that the variation in the amount of dispersal differed depending on the selected preparation technique. It was suggested that the amount of dispersal could be reduced by selecting an appropriate dissolution method for multiple vials, recapping, an appropriate method for injecting the drug into the infusion bottle, and properly preparing the internal pressure of the infusion bottle. The results of this study suggest that there are some techniques and procedures in the preparation process of vials that have a significant effect on the amount of dispersal, and that proper implementation of these techniques can contribute to the reduction of dispersal.

Quantitative comparison of anticancer drug dispersal before and after introducing appropriate preparation procedures during anticancer drug preparation.

BACKGROUND: In Japan, engineering controls for preparing injectable anticancer drugs are inadequate and compliance with appropriate preparation procedures is vital. In this study, we evaluated the effects of adherence to appropriate anticancer drug formulation and packaging procedures on reducing anticancer drug dispersal in clinical practice, especially in Japan. METHODS: We quantitatively evaluated the effectiveness of implementing procedures that were experimentally verified to help reduce the amount of anticancer drug dispersed during preparation based on procedures described in the "Anticancer Drug Preparation Manual." The target facilities were four regional hub hospitals in the Kanto area. Contamination of sheets and gloves with 5-fluorouracil (5-FU) and gemcitabine (GEM) in a safety cabinet during formulation was evaluated using wipe tests. Subsequently, the proper preparation procedure was shown on a video, training was provided, and the wipe tests were repeated. RESULTS: Forty-one and 39 pharmacists were engaged in drug preparation before and after intervention, respectively. 5-FU had the highest dispersal per prepared vial on the sheet before intervention. The dispersal amount per prepared vial decreased significantly (P = 0.01) after intervention. The amount of GEM dispersed before and after intervention did not differ significantly. However, the percentage of sheets below the detection limit after intervention was 62%, increasing from 46% before intervention. The amount dispersed on gloves was not significantly reduced by proper preparation technique. Although not explicitly noticeable and quantifiable, pharmacists must consider that a significant amount of anticancer drug is dispersed on gloves despite following appropriate preparation procedures. CONCLUSIONS: Quantitative amounts of anticancer drugs dispersed in the preparations of 5-FU and GEM were found in our study. The difference in the amount of contamination before and after intervention was significantly reduced only for the contamination of sheets with 5-FU. There was no decrease in the amount of glove contamination. There was also no difference between medical facilities. Despite following appropriate preparation procedures, dispersed amounts cannot be maintained below the detection limit, indicating the need for a combination of education and engineering controls.

Effect of secondary particle size of nickel oxide nanoparticles on cytotoxicity in A549 cells.

The effect of nanoparticle type, shape, as well as primary and secondary particle size on toxicity remains poorly characterized. In this study, suspensions of nickel oxide (NiO) nanoparticles with the same primary particle size (< 50 nm) but different secondary particle sizes were prepared, and their cytotoxicity was investigated. A planetary ball mill wet nanopulverizer with zirconium milling balls of decreasing sizes (φ: 0.5, 0.1, and 0.05 mm) yielded NiO nanoparticles of decreasing mean particle size (310.4 ± 6.7, 172.0 ± 2.8, and 102.0 ± 0.5 nm). Stock solutions were diluted to various concentrations in 10% heat-inactivated fetal bovine serum containing minimum essential medium, and shown to have the same primary particle size, but different secondary particle sizes. Tests with A549 cells revealed that cytotoxicity increased with increasing secondary particle size: milling ball diameter φ 0.05 mm (IC50: 148 µg/mL) < φ 0.1 mm (IC50: 83.5 µg/mL) < φ 0.5 mm (IC50: 33.4 µg/mL). Uptake experiments indicated that the intracellular amount of Ni increased with increasing secondary particle size. In summary, the present findings show that differences in secondary particle size affected the cytotoxicity of NiO suspensions, which could be ascribed at least in part to differences in the amount of NiO taken up by the cells.

Evaluation of the sensitization potential of volatile and semi-volatile organic compounds using the direct peptide reactivity assay.

The purpose of this study was to evaluate the sensitization potential of 82 compounds classified as volatile and/or semi-volatile organic compounds using the direct peptide reactivity assay (DPRA), given that these chemical compounds have been detected frequently and at high concentrations in a national survey of Japanese indoor air pollution and other studies. The skin sensitization potential of 81 of these compounds was evaluable in our study; one compound co-eluted with cysteine peptide and was therefore not evaluable. Twenty-five of the evaluated compounds were classified as positive. Although all glycols and plasticizers detected frequently and at high concentrations in a national survey of Japanese indoor air pollution were negative, hexanal and nonanal, which are found in fragrances and building materials, tested positive. Monoethanolamine and 1,3-butanediol, which cause clinical contact dermatitis, and several compounds reported to have weak sensitization potential in animal studies, were classified as negative. Thus, it was considered that compounds with weak sensitization potential were evaluated as negative in the DPRA. Although the sensitization potential of the formaldehyde-releasing preservative bronopol has been attributed to the release of formaldehyde (a well-known contact allergen) by its degradation, its degradation products-bromonitromethane and 2-bromoethanol-were classified as positive, indicating that these degradation products also exhibit sensitization potential. The compounds that tested positive in this study should be comprehensively assessed through multiple toxicity and epidemiological studies.

Skin transferability of phthalic acid ester plasticizers and other plasticizers using model polyvinyl chloride sheets.

The transferability of phthalic acid esters (PAEs) and other plasticizers, from model polyvinyl chloride (PVC) sheets to the skin of 11 subjects was assessed by measuring the amount of substance transferred using PVC sheets containing PAEs and alternative plasticizers of different types and contents. For all subjects, the transferred amount, from sheets containing 28 wt% PAE or from mixed sheets containing 14 wt% each of di (2-ethylhexyl) phthalate (DEHP) and other PAE, was greater than that from sheets containing 15 wt% each of PAE or alternative plasticizer only. A comparison of the transferability of five types of PAE showed that transfer tended to occur more readily as the n-octanol-water partition coefficient increased, suggesting that PAE hydrophobicity affected its transferability. The transferability of the alternative plasticizers di(2-ethylhexyl) terephthalate and 1,2-cyclohexane dicarboxylic acid diisononyl ester showed a similar trend; however, the transferred amount tended to be higher from model PVC sheets containing 28 wt% PAE or mixed with DEHP. The transferability of PAEs and alternative plasticizers was higher for certain subjects, suggesting individual differences in the transferability of chemicals to the subject's skin surface and is the presence of a group of people comparatively more susceptible to such transfer.

Analysis of glycols, glycol ethers, and other volatile organic compounds present in household water-based hand pump sprays.

The aim of this investigation is to clarify the types and concentrations of VOCs present in various commercial household water-based hand pump spray products used in Japan, and to estimate their average concentrations in indoor air when the spray product is used. We selected glycol and glycol ethers as the main target compounds, as these chemicals were detected at high frequencies and concentrations in a national survey of Japanese indoor air pollution. The extraction of these chemicals using graphite carbon cartridges was examined, with good recoveries and reproducibilities being obtained. Eighteen chemicals were analyzed in 54 commercial products and 8 chemicals were detected. More specifically, dipropylene glycol (DPG) was present in 44 samples (1.1 × 101-1.8 × 104 µg/mL); propylene glycol (PG) was present in 22 samples (1.5 × 101-2.9 × 104 µg/mL); diethylene glycol monoethyl ether (DGMEE) was found in 15 samples (trace amount-1.9 × 103 µg/mL); diethylene glycol (DEG) was present in 9 samples (1.0 × 101-2.4 × 103 µg/mL); 1,3-butandiol (13BG) was found in 5 samples (trace amount-7.4 × 103 µg/mL); 2-ethyl-1-hexanol (2E1H) was detected in 5 samples (3.2 × 10-1-4.4 × 101 µg/mL); diethylene glycol monobutyl ether (DGMBE) was present in 4 samples (2.1 × 101-7.1 × 101 µg/mL); and 3-methoxy-3-methylbutanol (MMB) was found in 2 samples (2.4 × 101-4.7 × 102 µg/mL). In addition, the average concentrations of these chemicals in indoor air were estimated using their maximum concentrations observed in the spray product. The estimated average concentrations of the chemicals in indoor air were determined to range between 1.0 × 10-2 and 1.0 mg/m3, with the exception of 2E1H and DGMBE. Furthermore, the estimated average concentrations of PG, 13BG, and DGMEE in indoor air were comparable to or higher than those reported in a national survey of Japanese indoor air pollution. It therefore appeared that household water-based hand pump sprays may contribute to the presence of these chemicals in indoor air. In contrast, estimated average concentrations of 2E1H in indoor air were low, its concentrations observed in a national survey of Japanese indoor air pollution are likely due to the use of plasticizers and paints.

Hepatotoxicity and Drug/Chemical Interaction Toxicity of Nanoclay Particles in Mice.

Nanomaterials are relatively new and unconventional materials with many useful properties, but their effects on biological systems are poorly understood. Nanoclay is a general term for layered mineral silicate nanoparticles that are ideally suited for use in clay-based nanocomposites. The potential biological hazards of nanoclays have not been addressed, however. Therefore, we investigated the in vivo effects and drug interactions of nanoclays. In mice, administration of nanoclay particles via the tail vein led to acute liver injury. Co-administration of nanoclay and carbon tetrachloride, paraquat, or cisplatin resulted in both liver and kidney injury. Our findings thus indicate that nanoclay particles are potentially hepato- and nephrotoxic.

[Polyploidy induction by spherical size standard polystyrene particles in a Chinese hamster cell line CHL].

To investigate relationships between particle (as a model of aggregates) size in a nanomaterial test suspension and its cytotoxicity, a series of eleven sizes of polystyrene (PS) particles were tested in the cytotoxicity test and the chromosome aberration test by using a Chinese hamster cell line CHL. The PS particles were spheres with defined diameters ranging from 0.1 to 9.2 µm. A series of eight sizes of particles with diameters ranging from 0.92 to 4.45 µm showed stronger cytotoxicity than the others. There was a marked difference in cytotoxicity between the 4.45- and 5.26-µm particles. The 0.92- to 4.45-µm particles did not induce structural chromosome aberrations but induced a high frequency of polyploidy in the chromosome aberration test. The 5.26-µm particles showed very weak induction of polyploidy. The incorporation of the 4.45-µm particles into CHL cells was observed by scanning electron microscopy (SEM). Some cells incorporated more than 10 particles. The semi-quantitative measurement of incorporation of particles into cells was performed by flow cytometry with a parameter of side scattered light (SSC) intensity. It showed that CHL cells preferably incorporated the 4.45-µm particles to the 5.26-µm particles. These findings suggest that CHL cells may have a kind of size-recognition ability and incorporate a particular size of particles. The particles may prevent a normal cytokinesis resulting in polyploidy induction. Nanomaterials also may show size-dependent toxicity. Data on particle (or aggregate) size distribution in the test suspension should be provided to evaluate properly the results of toxicity tests of nanomaterials.

Particle size distribution of aerosols sprayed from household hand-pump sprays containing fluorine-based and silicone-based compounds.

Japan has published safety guideline on waterproof aerosol sprays. Furthermore, the Aerosol Industry Association of Japan has adopted voluntary regulations on waterproof aerosol sprays. Aerosol particles of diameter less than 10 µm are considered as "fine particles". In order to avoid acute lung injury, this size fraction should account for less than 0.6% of the sprayed aerosol particles. In contrast, the particle size distribution of aerosols released by hand-pump sprays containing fluorine-based or silicone-based compounds have not been investigated in Japan. Thus, the present study investigated the aerosol particle size distribution of 16 household hand-pump sprays. In 4 samples, the ratio of fine particles in aerosols exceeded 0.6%. This study confirmed that several hand-pump sprays available in the Japanese market can spray fine particles. Since the hand-pump sprays use water as a solvent and their ingredients may be more hydrophilic than those of aerosol sprays, the concepts related to the safety of aerosol-sprays do not apply to the hand pump sprays. Therefore, it may be required for the hand-pump spray to develop a suitable method for evaluating the toxicity and to establish the safety guideline.

Analysis of isothiazolinone preservatives in polyvinyl alcohol cooling towels used in Japan.

Recently, cases of contact dermatitis that were related to the use of polyvinyl alcohol (PVA) cooling towels containing isothiazolinone preservatives were reported in Japan. The aim of this investigation was to analyze the concentrations of five different isothiazolinone compounds present in PVA towels and to assess the effectiveness of washing in removing the preservatives from new towels prior to being used for the first time. Twenty-seven PVA towels were used in this study. Two groups (i.e., laboratory-simulation and volunteer) of washing experiments were conducted to evaluate the effect of washing procedures. Qualitative and quantitative analyses were performed by LC/MS/MS, which detected 2-methyl-4-isothiazolin-3-one (MI) and 5-chloro-2-methyl-4-isothaizolin-3-one (CMI) in 23 samples (MI: 0.29-154 µg g-wet(-1), CMI: 2.2-467 µg g-wet(-1)), 2-n-octyl-4-isothiazolin-3-one (OIT) in one sample (478 µg g-wet(-1)). The compounds 4,5-Dichloro-2-n-octyl-4-isothiazolin-3-one (2Cl-OIT) and 1,2-benzisothiazolin-3-one (BIT) were not detected in all samples. We confirmed the presence of residual MI, CMI, and OIT in the washed towels, and the residual-to-original content ratio of OIT was higher than that of MI and CMI in PVA towels, due to the higher hydrophobicity of OIT than MI and CMI. A concern has been raised about the occurrence of contact dermatitis being caused by the use of PVA towels. It is suggested that a detailed description of isothiazolinone preservatives in PVA towels and an effective washing procedure for the removal of these preservatives should be provided by the manufacturer. Further, alternative non-sensitizing preservatives might be considered for the manufacture of PVA cooling towels in the future.

[In vitro safety evaluation of nanomaterials--cellular response to metal oxide nanoparticles].

Although nanomaterials are already being used for various applications in the industry, the safety of nanomaterials has not yet been sufficiently elucidated. An in vitro cellular toxicological study using well-characterized nanomaterials is conducted for the evaluation of the biological effects of nanomaterials. In this study, the effects of copper oxide nanoparticles on the global gene expression of human lung epithelial A549 cells were analyzed, and the molecular responses of A549 cells to the toxicity of the copper oxide (CuO) nanoparticles were inferred. Furthermore, the cytotoxic effects of silicon dioxide (SiO2) nanoparticles and titanium dioxide (TiO2) nanoparticles coexisting with some metal salts in Chinese hamster lung fibroblast V79 cells were also examined, and SiO2 nanoparticles increased the cytotoxicity of some of the coexisting metal salts as a result. Finally, the importance of in vitro studies in the safety evaluation of nanomaterials was discussed.

Development and performance evaluation of a positive reference material for hemolysis testing.

This study deals with the development and performance evaluation of a positive reference material for hemolysis testing, which is used for evaluating the biological safety of medical devices. Genapol X-080, a nonionic detergent, was selected as a candidate hemolytic substance in a survey of 23 chemical compounds; it showed significant hemolytic activity against rabbit defibrinated blood at concentrations more than 20 µg/mL. A polyvinyl chloride (PVC) sheet spiked with 0.6% (w/w) of the compound exhibited weak hemolytic activity in direct contact and/or extract-based assays after 4 h incubation at 37°C. A PVC sheet containing 5.8% (w/w) Genapol X-080 induced complete hemolysis in both assays. The amount of Genapol X-080 eluted from each PVC sheet during hemolysis testing using the direct contact method increased time-dependently and reached 25.6 (former sheet) or 1154 (later sheet) µg/mL after 4 h incubation, which was similar to or much higher than the critical micelle concentration, respectively. Similar elution behavior was observed using the extract-based method, and the Genapol X-080 content in test solutions prepared by autoclave extraction of both sheets was 22.5 and 358 µg/mL, respectively, indicating a clear relationship between the degree of hemolytic activity and the eluted amount of Genapol X-080. Thus, a PVC sheet spiked with a compound exhibiting different hemolytic activity depending on its concentration may be useful as a positive reference material to validate the hemolysis tests.

[Study for the revision of analytical method for tris (2,3-dibromopropyl) phosphate with restriction in textiles].

The official analytical method for tris(2,3-dibromopropyl)phosphate (TDBPP), which is banned from use in textile products by the "Act on Control of Household Products Containing Harmful Substances", requires revision. This study examined an analytical method for TDBPP by GC/MS using a capillary column. Thermal decomposition of TDBPP was observed by GC/MS measurement using capillary column, unlike in the case of gas chromatography/flame photometric detector (GC/FPD) measurement based on a direct injection method using a capillary megabore column. A quadratic curve, Y=2572X(1.416), was obtained for the calibration curve of GC/FPD in the concentration range 2.0-100 µg/mL. The detection limit was 1.0 µg/mL under S/N=3. The reproducibility for repetitive injections was satisfactory. A pretreatment method was established using methanol extraction, followed by liquid-liquid partition and purification with a florisil cartridge column. The recovery rate of this method was ～100%. TDBPP was not detected in any of the five commercial products that this study analyzed. To understand the cause of TDBPP decomposition during GC/MS (electron ionization; EI) measurement using capillary column, GC/MS (chemical ionization; CI), GC/FPD, and gas chromatography/flame ionization detector (GC/FID) measurements were conducted. It was suggested that TDBPP might thermally decompose both during GC injection, especially through a splitless injection method, and in the column or ion sources. To attempt GC/MS measurement, an injection part comprising quartz liner was used and the column length was halved (15 m); thus, only one peak could be obtained.

Screening study on hemolysis suppression effect of an alternative plasticizer for the development of a novel blood container made of polyvinyl chloride.

The aim of this study is to identify a plasticizer that is effective in the suppression of the autohemolysis of the stored blood and can be used to replace di(2-ethylhexyl) phthalate (DEHP) in blood containers. The results of hemolysis test using mannitol-adenine-phosphate/red cell concentrates (MAP/RCC) spiked with plasticizers included phthalate, phthalate-like, trimeliate, citrate, and adipate derivatives revealed that di-isononyl-cyclohexane-1,2-dicarboxylate (Hexamoll(®) DINCH), di(2-ethylhexyl)-1,2,3,6-tetrahydro-phthalate (DOTP), and diisodecyl phthalate (DIDP) exhibited a hemolysis suppression effect almost equal to that of DEHP, but not other plasticizers. This finding suggested that the presence of 2 carboxy-ester groups at the ortho position on a 6-membered ring of carbon atoms may be required to exhibit such an effect. The hemolytic ratios of MAP/RCC-soaked polyvinyl chloride (PVC) sheets containing DEHP or different amounts of DINCH or DOTP were reduced to 10.9%, 9.2-12.4%, and 5.2-7.8%, respectively (MAP/RCC alone, 28.2%) after 10 weeks of incubation. The amount of plasticizer eluted from the PVC sheet was 53.1, 26.1-36.5, and 78.4-150 µg/mL for DEHP, DINCH, and DOTP, respectively. PVC sheets spiked with DIDP did not suppress the hemolysis induced by MAP/RCC because of low leachability (4.8-6.0 µg/mL). These results suggested that a specific structure of the plasticizer and the concentrations of least more than ∼10 µg/mL were required to suppress hemolysis due to MAP/RCC.

[Examination of identification test of certain aromatic amines originating from azo colorants in textile and leather products using high performance liquid chromatography].

Azo colorants that generate primary aromatic amines (PAAs) have been recently deliberated as a controlled harmful substance by the "Act on the Control of Household Products Containing Harmful Substances" in Japan. Therefore, we examined an identification test for 22 kinds of PAAs originating from the azo colorants in commercial textile products and leather products using high performance liquid chromatography (HPLC). When a PAAs standard solution containing 2,4-xylidine and 2,6-xylidine was analyzed using the condition according to EN14362-1:2012 at 240 nm as a basic condition, we observed enough separation for all the PAAs to identify. However, in the some sample solutions, the peaks of several PAAs were overlapped with the interference peaks, and their identifications were difficult. In these cases, some PAAs were able to identify by alteration to suitable wavelength. Furthermore, the retention time of almost PAAs and interference peaks were changed by using acetonitrile as the organic solvent in eluent or phenyl type column. These modifications were helpful for identification of PAA which was overlapped to interference substances by the basic condition. Thus, we suggest the HPLC condition for an identification test is in accordance to that described in EN14362-1:2013. And we propose that the HPLC condition can be modified as necessary.

[Characterization of cases contravening of regulations regarding primary aromatic amines originating from azo dyes in commercial textile products and leather products in European Union].

Contraventions of regulations regarding primary aromatic amines (PAAs) originating from azo dyes in commercial textile products and leather products in European Union (EU), notified in the period between 2006 and 2012 were collected from the Rapid Alert System for non-food consumer products (RAPEX), were characterized. Various types of products (clothes, footwear, bedding, etc.) and their raw materials (cotton, silk, viscose, leather, etc.) were reported to have contravened the regulations. The contravention frequencies for products made in China and India were higher than those for other countries. Ten percentage of the country in which the reported products were produced was unknown. The notification frequencies for benzidine and 4-aminoazobenzene were higher than those for other PAAs. Contravention of regulations regarding benzidine, 4-aminoazobenzene, and 3,3'-dimethoxybenzidine were notified every year. Contraventions of regulations regarding five PAAs--classified as IARC group 1--were notified one or several times. Since the scale of the survey conducted in Japan were small compared with RAPEX, it is necessary that many kinds and number of products should be surveyed in Japan. In addition, it is also necessary to pay attention to 4-aminoazobenzene, while it has not been detected in the previous studies conducted in Japan.

Calcium-incorporated titanium surfaces influence the osteogenic differentiation of human mesenchymal stem cells.

In this study, a titanium surface was chemically modified with calcium ions and assessed for its influence on osteogenic differentiation and molecular responses of human mesenchymal stem cells (hMSCs). Titanium disks were treated with NaOH (NaOH treatment), NaOH + CaCl2 (CaCl2 treatment), or NaOH + Ca(OH)2 (Ca(OH)2 treatment). Ca(OH)2 treatment caused significantly greater calcium incorporation onto the titanium surface and apatite formation than CaCl2 treatment. The morphology of hMSCs differed on CaCl2- and Ca(OH)2-treated disks. The osteopontin (OPN) expression in hMSCs cultured on CaCl2-treated titanium was significantly higher than that in cells cultured on NaOH-treated disks; OPN expression was significantly higher in cells cultured on Ca(OH)2-treated disks than on un-, NaOH-, and CaCl2-treated disks. Osteocalcin (OCN) protein expression in hMSCs cultured on Ca(OH)2-treated disks was significantly higher than that on all the other disks. Comparative expression profiling by DNA microarray and pathway analyses revealed that calcium modification of the titanium surface induced integrin ß3 after OPN upregulation and promoted Wnt/ß-catenin signaling in hMSCs. In addition, Ca(OH)2 treatment upregulated the expression of bone morphogenetic protein 2, cyclooxygenase 2, and parathyroid hormone-like hormone in comparison to CaCl2 treatment. These observations suggest that calcium-modified titanium surfaces affect osteogenic differentiation in hMSCs and that Ca(OH)2 treatment induced osteogenic differentiation in hMSCs, whereas CaCl2 treatment had a limited effect.

A development and biological safety evaluation of novel PVC medical devices with surface structures modified by UV irradiation to suppress plasticizer migration.

This study examines the chemical, physicochemical, and biological properties of PVC sheets treated with UV irradiation on their surfaces to suppress the elution of a plasticizer, di-(2-ethylhexyl) phthalate (DEHP), for developing novel polyvinyl chloride (PVC) medical devices. The PVC sheets irradiated under conditions 1 (52.5 µW/cm(2), 136 J/cm(2)) and 2 (0.45 mW/cm(2), 972 J/cm(2)) exhibited considerable toxicity in cytotoxicity tests and chromosome aberration tests due to the generation of DEHP oxidants, but no toxicity was detected in the PVC sheet irradiated under condition 3 (8.3 mW/cm(2), 134 J/cm(2)). The release of DEHP from the surface irradiated under condition 3 was significantly suppressed, and mono-(2-ethylhexyl) phthalate (MEHP) converted from a portion of DEHP could be easily removed from the surface by washing with methanol. The physicochemical properties of the surface regarding the suppression of DEHP elution remained stable through all sterilizations tested, but MEHP elution was partially recrudesced by the sterilizations except for gamma irradiation. These results indicated that UV irradiation using a strong UV-source over a short time (condition 3) followed by methanol washing and gamma sterilization may be useful for preparing novel PVC products that did not elute plasticizers and do not exhibit toxicity originating from UV irradiation.

[Examination of analytical method for triphenyltin (TPT) and tributyltin (TBT) to revise the official methods based on "Act on the Control of Household Products Containing Harmful Substances"].

The use of triphenyltin (TPT) and tributyltin (TBT) in some household products is banned by "Act on the Control of Household Products Containing Harmful Substances" in Japan. To revise the official analytical method, the method for detecting these organotin compounds was examined in six laboratories using a textile product, water-based adhesive, oil-based paint, which contained known amounts of TPT and TBT (0.1, 1.0, 10 µg/g). TPT and TBT were measured by GC-MS after ethyl-derivation with sodium tetraethylborate. The TBT recoveries in the samples were 70-120%. The TPT recoveries in the water-based adhesive samples were 80-110%, while its concentrations in the textile product and oil-based paint samples decreased because of dephenylation during storage. However, the precision of the method examined was satisfactory because most coefficients of variation for TPT and TBT in the samples were less than 10%. Furthermore, the revised method was able to detect concentrations lower than the officially regulated value. However, the sample matrix and the condition of analytical instrument might affect the estimated TPT and TBT concentrations. Therefore, the revised method may not be suitable for quantitative tests; rather, it can be employed to judge the acceptable levels of these organotin compounds by comparing the values of control sample containing regulated amounts of TPT and TBT with those for an unknown sample, with deuterated TPT and TBT as surrogate substances. It is desirable that TPT in textile and oil-based paint samples are analyzed immediately after the samples obtained because of the decomposition of TPT.

[Migration of eight harmful elements from metal accessories that infants may swallow by mistake].

The International Standard ISO 8124-3:2010 "Safety of toys--Part 3: Migration of certain elements" controls the levels of migrated eight harmful elements (antimony, arsenic, barium, cadmium, chromium, lead, mercury and selenium) from infants toys. Moreover, the Japanese Food Sanitation Law controls the levels of migrated lead from metal accessory toys. However, the levels of migrated harmful elements from metal accessories that are not infants toys are not controlled, since they are not covered by the ISO Standard or the Food Sanitation Law. Therefore, we investigated the level of eight harmful elements migrated from metal accessories that infants may swallow by mistake. The extraction test of ISO 8124-3:2010 was executed in 117 products (total 184 specimens), and the concentration of these eight elements was measured by inductively coupled plasma mass spectroscopy (ICP-MS). As a result, 28 and one products released lead and cadmium beyond the maximum acceptable levels of the ISO standard, respectively. Metal accessories that infants may swallow by mistake should ideally not release harmful elements such as lead and cadmium.