Derivation of subacute guidance values for chemical contaminants of drinking water quality standard in Japan.

The concentration of chemicals in drinking water may transiently and accidently exceed the Drinking Water Quality Standard (DWQS). If the level of a contaminant is not expected to cause adverse effects for a limited period of exposure, immediate suspension of the water supply may not be necessary. Assessments should be conducted using subacute guidance values (SGVs). In this study, we assessed 26 chemicals for the DWQS to establish the SGVs. Principally, a key study was selected from subacute studies to derive a Subacute Reference Dose (saRfD). The SGV was calculated from the saRfD for adults (drinking water intakes: 40 mL/kg/day) and children (drinking water intakes: 150 mL/kg/day). No allocation factor was applied to derive the SGV. We established the SGV for 20 chemicals, which were 2-38 times higher than the corresponding DWQS. However, SGVs for six chemicals were the same as the corresponding DWQS. Therefore, immediate action will be required for these six accidental contaminants. Our established SGVs are useful for assessing accidental contamination.

Prevalence of common aneuploidy in twin pregnancies.

The incidence of chromosomal abnormalities in twin pregnancies is not well-studied. In this retrospective study, we investigated the frequency of chromosomal abnormalities in twin pregnancies and compared the incidence of chromosomal abnormalities in dichorionic diamniotic (DD) and monochorionic diamniotic (MD) twins. We used data from 57 clinical facilities across Japan. Twin pregnancies of more than 12 weeks of gestation managed between January 2016 and December 2018 were included in the study. A total of 2899 and 1908 cases of DD and MD twins, respectively, were reported, and the incidence of chromosomal abnormalities in one or both fetuses was 0.9% (25/2899) and 0.2% (4/1908) in each group (p = 0.004). In this study, the most common chromosomal abnormality was trisomy 21 (51.7% [15/29]), followed by trisomy 18 (13.8% [4/29]) and trisomy 13 (6.9% [2/29]). The incidence of trisomy 21 in MD twins was lower than that in DD twins (0.05% vs. 0.5%, p = 0.007). Trisomy 21 was less common in MD twins, even when compared with the expected incidence in singletons (0.05% vs. 0.3%, RR 0.15 [95% CI 0.04-0.68]). The risk of chromosomal abnormality decreases in twin pregnancies, especially in MD twins.

Formation and evaluation of mechanism-based chemical categories for regulatory read-across assessment of repeated-dose toxicity: A case of hemolytic anemia.

The aim of this study is to define chemical categories that can be applied to regulatory read-across assessments for repeated-dose toxicity, by classifying toxic substances based on their structures and mechanism of actions (MoAs). Hemolytic anemia, which often appears primarily, was examined as an example. An integrated database was constructed by collecting publicly available datasets on repeated-dose toxicity, in which 423 out of a total of 1518 chemicals were identified as capable of inducing hemolytic anemia. Subsequently, by grouping these chemicals based on their chemical structures and plausible MoAs on hemolytic substances, we identified the following categories: (i) anilines, (ii) nitrobenzenes, (iii) nitroanilines, (iv) dinitroanilines, (v) ethylene glycol alkyl ethers, (vi) hydroquinones, (vii) oximes, and (viii) hydrazines. In these categories, the toxicant and the measurable key events leading to hematotoxicity were identified, thereby allowing us to justify the categories and to discriminate the category substances. Moreover, toxicokinetics seems to critically affect the hemolytic levels of the category substances. Overall, the categories were validated through a comprehensive analysis of the collected information, while the utility was demonstrated by conducting a case study on the selected category. Further endeavors with this approach would attain categories for other organ toxicity endpoints.

Initial hazard assessment of ethyl(dimethyl)(tetradecyl)ammonium ethyl sulfate: Genotoxicity tests and combined repeated-dose and reproductive/developmental toxicity screening in rats.

Ethyl(dimethyl)(tetradecyl)ammonium ethyl sulfate, used in laundry detergents, shampoos, and body soaps, is classified by the Japanese Chemical Substances Control Law as a priority assessment chemical substance for environmental effects. However, its toxicity data for human health are insufficient. This study evaluated this chemical under the Safety Examination of Existing Chemicals and Safety Programmes of the Ministry of Health, Labour and Welfare (MHLW). The MHLW conducted bacterial reverse mutation (Ames test), in vitro chromosomal aberration, and combined repeated-dose and reproductive/developmental toxicity screening tests. We performed a screening assessment of ethyl(dimethyl)(tetradecyl)ammonium ethyl sulfate for human health. The chemical showed a negative reaction in the Ames test and a positive reaction in the in vitro chromosomal aberration test with metabolic activation in rats. The combined repeated-dose and reproductive/developmental toxicity screening test showed significantly decreased food consumption at 50 mg/kg body weight/day, but no reproductive and developmental toxicity was observed. The no-observed-effect level of 15 mg/kg/day was obtained as a screening value. Therefore, this chemical was classified as hazard class 3, with a derived-no-effect level of 0.025 mg/kg/day. The results of this study will be useful for risk assessment of groups of structurally similar alkyl quaternary ammonium surfactants.

Ultra-morphological characteristics of dentin surfaces after different preparations and treatments.

Using transmission electron microscopy (TEM), this study investigated the characteristics of smear layers after preparation of dentin surfaces using different methods. In addition, this study analyzed, using scanning electron microscopy (SEM), the interactions of smear layers with the various acidic agents used subsequently to treat the dentin surface. Mid-coronal dentin surfaces were prepared according to one of five instrumentation methods: fracture; grinding with carbide bur; grinding with regular-grit diamond bur; grinding with superfine-grit diamond bur; or grinding with 600-grit silicon carbide (SiC) abrasive paper. Then, each prepared dentin surface was further divided into control (no further treatment) or treatment with one of the following agents: phosphoric acid solution (PAS); phosphoric acid gel (PAG); Clearfil SE Bond 2 Primer (SE2); or Scotchbond Universal Adhesive (SBU). Longitudinal ultra-thin sections were made for TEM observations. Dentin discs, representing each surface preparation and treatment method described above, were created, and the morphology was examined by SEM. The TEM results revealed differences in thickness and denseness of the smear layer, according to the different methods of instrumentation used to prepare the dentin surface. The two forms of phosphoric acid completely removed the smear layer in all groups. Agglomerated silica particles were observed on the top of the collagen layer after etching with PAG. For all dentin surfaces, except for that prepared with SiC, SE2 demonstrated better etching efficacy on different smear layers, whereas SBU provided only superficial interaction.

Initial hazard assessment of 1,4-dichlorobutane: Genotoxicity tests, 28-day repeated-dose toxicity test, and reproductive/developmental toxicity screening test in rats.

1,4-Dichlorobutane (1,4-DCB) is used as raw materials for drugs, pesticides, fragrances, and chemical fibers, and being used as a solvent. Its toxicity data was insufficient for screening assessment under the Japanese Chemical Substances Control Law. We conducted toxicity tests and hazard classification for screening assessment 1,4-DCB showed negative in the Ames test, positive in the in vitro chromosomal aberrations test with metabolic activation, and negative in the in vivo mouse bone-marrow micronucleus test. The 28-day repeated-dose toxicity study, where male and female rats were administered 1,4-DCB by gavage at 0, 12, 60, and 300 mg/kg/day, showed significant effects on the liver and pancreas from 12 mg/kg/day and kidney at 300 mg/kg/day. Based on periportal hepatocellular hypertrophy and decreased zymogen granules in pancreas, the lowest observed adverse effect level (LOAEL) of 12 mg/kg/day was obtained. The reproductive/developmental toxicity screening study, in which male and female rats were administered 1,4-DCB by gavage at dose of 0, 2.4, 12, and 60 mg/kg/day for 42-46 days, showed that the delivery index was decreased at 60 mg/kg/day without maternal toxicity. Based on the general toxicity, we classified this chemical as hazard class 2, with a D-value (Derived No Effect Level) of 0.002 mg/kg/day.

Variable Smear Layer and Adhesive Application: The Pursuit of Clinical Relevance in Bond Strength Testing.

The removal or modification of smear layers that cover the dentin is critical to allow the penetration of adhesive molecules and to ensure a strong bond between resin and dentin. Aiming to establish a model for clinically-relevant dentin-bond testing, we evaluated the effects of smear layers created by abrasives having similar coarseness (180-grit SiC paper; fine-grit diamond bur) and application modes (single application; double application) on the microtensile bond strengths (µTBS) of two currently available universal adhesives (G-Premio Bond; Scotchbond Universal Adhesive) and a two-step self-etch adhesive (Clearfil Megabond 2). Sixty extracted human third molars were used for the µTBS test. Data were analyzed by three-way ANOVA and Tukey's test (α = 0.05). Fracture modes were determined using stereomicroscopy. An additional 24 third molars were prepared for observation of the resin-dentin interface by TEM and adhesive-smear layer interaction by SEM. µTBS was significantly affected by the adhesives and their application modes (p < 0.001), implying that the double application of universal adhesives should be recommended to improve their performance. The effect of smear layers was not significant (p > 0.05), indicating that 180-grit SiC papers could be used to prepare dentin as a substitute for fine-grit diamond burs for dentin-bond testing in laboratory settings.

Initial hazard assessment of benzyl salicylate: In vitro genotoxicity test and combined repeated-dose and reproductive/developmental toxicity screening test in rats.

Benzyl salicylate is used as a fragrance ingredient and an ultraviolet light absorber, but its toxicity is unknown. Therefore, toxicity tests and hazard classification were conducted for screening assessment under the Japanese Chemical Substances Control Law. Benzyl salicylate was found to be non-genotoxic in vitro based on the chromosomal aberration test using Chinese hamster lung cells. However, the combined repeated-dose and reproductive/developmental screening toxicity test, in which male and female rats were administered benzyl salicylate by gavage at 0, 30, 100, or 300 mg/kg/day for 42 and 41-46 days, respectively, from 14 days before mating until postnatal Day 4, showed that repeated doses had major effects on the thymus, liver, epididymis, and femur at 100 and/or 300 mg/kg/day. Furthermore, although benzyl salicylate had no effect on the estrus cycle, fertility, corpus lutea, or implantation rate, embryonic resorption, offspring mortality, and neural tube defects were observed at 300 mg/kg/day, and the offspring had lower body weights at 30 and 100 mg/kg/day, suggesting teratogenicity similar to other salicylates. Based on the developmental toxicity, this chemical was classified as hazard class 2, with a lowest observed adverse effect level (LOAEL) of 30 mg/kg/day and a D-value of 0.003 mg/kg/day.

Initial hazard assessment of 4-benzylphenol, a structural analog of bisphenol F: Genotoxicity tests in vitro and a 28-day repeated-dose toxicity study in rats.

4-Benzylphenol (CAS No. 101-53-1), a structural analog of bisphenol F, has estrogenic activity in vitro and in vivo, as is the case with bisphenol F. 4-Benzylphenol is used in plastics and during organic synthesis. Since its safety is largely unknown, we conducted toxicity tests as part of screening risk assessment in an existing chemical safety survey program. Based on results of the Ames test and the chromosomal aberration test using Chinese hamster lung cells (OECD TG 471 and 473), 4-benzylphenol was determined to be non-genotoxic in vitro. In a 28-day repeated-dose toxicity study, Crl:CD (SD) rats were administrated 4-benzylphenol by gavage at 0, 30, 150, or 750 mg/kg/day (OECD TG 407). Consequently, body weight was lower in males at 750 mg/kg/day. In the liver, relative organ weights were increased in both sexes at 750 mg/kg/day, and centrilobular hepatocellular hypertrophy was observed in males at 150 and 750 mg/kg/day. In the forestomach, hyperkeratosis and hyperplasia of squamous cells were observed in males at 150 and 750 mg/kg/day, and in females at 750 mg/kg/day. Based on these results, we identified the NOAEL for 4-benzylphenol as 30 mg/kg/day, with a hazard assessment value (D-value) of 0.05 mg/kg/day corresponding to hazard class 3.

Mature cystic teratoma coexisting with clear-cell carcinoma in the ovary.

Mature cystic teratoma (MCT) is the most common benign ovarian tumor; clear-cell carcinoma (CCC) is a relatively common malignant ovarian tumor in Japan, but there are few reports on the coexistence of MCT and CCC. Here we report a case of simultaneous MCT and CCC in the ovary and review the relevant literature. The patient was a 49-year-old woman. A 5-cm MCT was found in the left ovary on initial gynecological examination, and she was referred to hospital for treatment because it was expanding. Magnetic resonance imaging showed a multilocular cystic tumor 16 × 10 × 9.5 cm in the left ovary, and surgery was performed. The final pathological diagnosis was MCT, endometriotic cyst, clear-cell adenofibroma, clear-cell borderline tumor, and CCC in the left ovary.

Bonding effectiveness and multi-interfacial characterization of two direct buildup resin core systems bonded to post-space dentin.

OBJECTIVES: The aim of the present study was to evaluate the bonding effectiveness of two resin core buildup systems using conventional methods in the field of adhesive dentistry and a new non-destructive method. MATERIALS AND METHODS: Twenty-four single-rooted human teeth were built up with dual-cure one-step self-etch adhesive and composite systems (SY1: Clearfil DC bond and Clearfil DC core automix, SY2: Clearfil bond SE one and Clearfil DC core automix one). The prepared samples were sectioned into approximately 1 × 1-mm-thick beams and subjected to micro-tensile bond strength (µTBS) testing (n = 24). The fractured beams after µTBS testing were analyzed by SEM and energy-dispersive X-ray (EDX) spectrometry. The three teeth filled with each resin core system were sectioned and embedded in epoxy resin to observe the dentin-bonding interface under TEM (n = 6). Moreover, three of each resin core-filled teeth without any processing were examined using µCT (n = 6). RESULTS: Two-way ANOVA revealed that the two factors "root region" (p < 0.001, F = 15.22) and "system" (SY1 < SY2; p < 0.001, F = 22.52) had a significant influence. The µTBS gradually decreased from the coronal side to the apical side of the root canal. Morphological evaluation revealed that SY2 was superior in terms of resin curing at the apical side. µCT non-destructive evaluation clearly revealed gap formation in SY1. CONCLUSION: SY2, which included a new light-independent catalyst, showed better bonding effectiveness and adhesive interface to dentin compared to that of SY1. CLINICAL RELEVANCE: The new catalyst, which is activated by contact with adhesive and resin composite, can be used for resin core buildup restorations.

USP15 stabilizes the transcription factor Nrf1 in the nucleus, promoting the proteasome gene expression.

The transcriptional factor Nrf1 (NF-E2-related factor 1) sustains protein homeostasis (proteostasis) by regulating the expression of proteasome genes. Under physiological conditions, the transcriptional activity of Nrf1 is repressed by its sequestration into the endoplasmic reticulum (ER) and furthermore by two independent ubiquitin-proteasome pathways, comprising Hrd1 and ß-TrCP in the cytoplasm and nucleus, respectively. However, the molecular mechanisms underlying Nrf1 activation remain unclear. Here, we report that USP15 (Ubiquitin-Specific Protease 15) activates Nrf1 in the nucleus by stabilizing it through deubiquitination. We first identified USP15 as an Nrf1-associated factor through proteome analysis. USP15 physically interacts with Nrf1, and it markedly stabilizes Nrf1 by removing its ubiquitin moieties. USP15 activates the Nrf1-mediated expression of a proteasome gene luciferase reporter and endogenous proteasome activity. The siRNA-mediated knockdown of USP15 diminishes the Nrf1-induced proteasome gene expression in response to proteasome inhibition. These results uncover a new regulatory mechanism that USP15 activates Nrf1 against the ß-TrCP inhibition to maintain proteostasis.

Risk assessment of skin lightening cosmetics containing hydroquinone.

Following reports on potential risks of hydroquinone (HQ), HQ for skin lightening has been banned or restricted in Europe and the US. In contrast, HQ is not listed as a prohibited or limited ingredient for cosmetic use in Japan, and many HQ cosmetics are sold without restriction. To assess the risk of systemic effects of HQ, we examined the rat skin permeation rates of four HQ (0.3%, 1.0%, 2.6%, and 3.3%) cosmetics. The permeation coefficients ranged from 1.2 × 10-9 to 3.1 × 10-7 cm/s, with the highest value superior than the HQ aqueous solution (1.6 × 10-7 cm/s). After dermal application of the HQ cosmetics to rats, HQ in plasma was detected only in the treatment by highest coefficient cosmetic. Absorbed HQ levels treated with this highest coefficient cosmetic in humans were estimated by numerical methods, and we calculated the margin of exposure (MOE) for the estimated dose (0.017 mg/kg-bw/day in proper use) to a benchmark dose for rat renal tubule adenomas. The MOE of 559 is judged to be in a range safe for the consumer. However, further consideration may be required for regulation of cosmetic ingredients.

Laparoscopic management for prenatally diagnosed choledochal cysts.

PURPOSE: The aim of this study was to validate our laparoscopic management strategy for asymptomatic and symptomatic patients with prenatally diagnosed choledochal cysts (CCs). METHODS: Thirteen prenatally diagnosed CC patients from 1997 to 2015 were included. Seven patients (1997-2008) underwent open surgery (OS group), and 6 (2009-2015) underwent laparoscopic surgery (LS group). In the asymptomatic patients, LS was performed when the patients weighed over 5 kg. When the patient had clinical manifestations, early LS was performed irrespective of body weight. A retrospective comparison was conducted between the LS and OS groups in terms of the operative time, blood loss, postoperative fasting period, hospital stay, and intra- and postoperative complications. RESULTS: There was no difference between the demographics of both groups. The operative time was significantly longer (380 vs. 288 min) and blood loss was significantly lower (4 vs. 30 mL) in the LS group. Additionally, the postoperative fasting period (3 vs. 6 days) and hospital stay (11 vs. 20 days) were significantly shorter in the LS group. Intraoperative events and early postoperative complications were not encountered in either group. Small bowel obstruction requiring surgery occurred in two patients, 10 and 13 years after OS, respectively. CONCLUSIONS: LS is as safe and feasible as OS in small children with prenatally diagnosed CC, although sufficient pediatric laparoscopic expertise is mandatory.

Repeated dose and reproductive/developmental toxicity of perfluorododecanoic acid in rats.

Perfluoroalkyl carboxylic acids (PFCAs) are a series of environmental contaminants that have received attention because of their possible adverse effects on wildlife and human health. Although many toxicological studies have been performed on perfluorooctanoic acid with carbon chain length C8, available toxicity data on PFCAs with longer chains are still insufficient to evaluate their hazard. A combined repeated dose and reproductive/developmental toxicity screening study for perfluorododecanoic acid (PFDoA; C12) was conducted in accordance with OECD guideline 422 to fill these toxicity data gaps. PFDoA was administered by gavage to male and female rats at 0.1, 0.5, or 2.5 mg/kg/day. The administration of PFDoA at 0.5 and 2.5 mg/kg/day for 42-47 days mainly affected the liver, in which hypertrophy, necrosis, and inflammatory cholestasis were noted. Body weight gain was markedly inhibited in the 2.5 mg/kg/day group, and a decrease in hematopoiesis in the bone marrow and atrophic changes in the spleen, thymus, and adrenal gland were also observed. Regarding reproductive/developmental toxicity, various histopathological changes, including decreased spermatid and spermatozoa counts, were observed in the male reproductive organs, while continuous diestrous was observed in the females of the 2.5 mg/kg/day group. Seven of twelve females receiving 2.5 mg/kg/day died during late pregnancy while four other females in this group did not deliver live pups. No reproductive or developmental parameters changed at 0.1 or 0.5 mg/kg/day. Based on these results, the NOAELs of PFDoA were concluded to be 0.1 mg/kg/day for repeated dose toxicity and 0.5 mg/kg/day for reproductive/developmental toxicity.

Summary information of human health hazard assessment of existing chemical substances (I).

Under the Chemical Substances Control Law (CSCL) in Japan, initial hazard information tor existing chemical substances has been collected by the Ministry of Health, Labour and Welfare, Japan (MHLW) to assess potential initial risks to human health. We have reviewed all collected toxicity information pertaining to acute toxicity, repeated dose toxicity, genotoxicity, and/or reproductive/developmental toxicity and performed hazard assessments. Approximately 150 substances are currently undergoing review and assessment. For clarification and evaluation of each toxicity study, we have created a dossier (a collection of study data containing a detailed summary of the methods, results, and conclusions of each study) in English using the International Uniform Chemical Information Database (IUCLID) version 5. The IUCLID dossier format is widely used and has been accepted as one of the most beneficial formats for providing summarized chemical substance toxicity assessments. In this report, as a contribution to our ongoing hazard assessment activity, we present summary hazard information related to the potential human health effects of the following 5 chemical substances: 4-chlorobenzoyl chloride (CAS: 122-01-0); benzenesulfonic acid, 4-hydroxy-, tin (2+) salt (CAS: 70974- 33-3); chlorocyclohexane (CAS: 542-18-7); 1,3-cyclohexanedimethanamine (CAS: 2579-20-6); and 1,3,5-triazine-2,4,6 (1H,3H,5H) -trithione (CAS: 638-16-4). The IUCLID dossiers created for these 5 chemical substances will be made available via the Japan Existing Chemical Data Base (JECDB) at . Additional human health hazard information on existing chemical substances will be provided using the same methodology and website when it is available.

[The Roles of Aß in Alzheimer's Disease: In Light of the Latest Findings].

The 'amyloid hypothesis', initially put forward in 1992, posits that amyloid ß protein (Aß) contributes to neurodegeneration through aberrant aggregation. In the process of this aberrant aggregation, Aß forms oligomers, protofibrils, and mature fibrils, ultimately developing plaques. These mature fibrils and plaques were believed to be the culprits behind the neurotoxicity and neurodegeneration seen in Alzheimer's disease (AD). However, growing evidence in recent years has led to the 'Aß oligomer hypothesis', which suggests that the intermediate forms of aggregates, such as oligomers and protofibrils, exhibit stronger neurotoxicity than the mature forms. Consequently, efforts have been made to develop anti-Aß antibody drugs that specifically target these intermediate aggregates. Such interventions hold promise as disease-modifying treatments for AD.

Effect of Silver Diamine Fluoride on Bonding Performance and Ultra-morphological Characteristics to Sound Dentin.

OBJECTIVES: This study aimed to evaluate microtensile bond strength (µTBS) and ultra-morphological characteristic changes in sound dentin resulting from silver diamine fluoride (SDF) when using adhesives. METHODS: Ninety-six extracted human third molars were divided into the SDF-contaminated dentin group and the sound dentin group. In the SDF-contaminated dentin group, 38% SDF was agitated for 1 min, left undisturbed for 2 min, and rinsed with distilled water for 30 s. Then, each group was further subdivided into six subgroups (n = 8 / group) according to application modes: self-etch mode (SE) and etch-and-rinse mode (ER) followed by three adhesives: (1) Scothbond Universal Plus Adhesive (SUP); (2) G2-Bond Universal Adhesive (G2B); and (3) Clearfil Mega Bond 2 (MB2). All specimens were restored with resin composite and were stored in distilled water for 24 h before µTBS testing. Data from the µTBS test were analyzed using Three-way ANOVA and Duncan test (p < 0.05). The morphology of fractured surface and adhesive-dentin interfaces were evaluated by SEM, TEM, and STEM. Further elemental analysis was done by EDX. RESULTS: All SDF-contaminated dentin groups demonstrated significantly lower µTBS than sound dentin groups. All ER groups had higher µTBS than SE groups, except for G2B in the sound dentin group. STEM/EDX revealed an SDF-dentin-reacted layer in the SDF-contaminated dentin group. SIGNIFICANCE: SDF had an adverse effect on adhesives. Additionally, ER mode is preferable when bonded to SDF-contaminated dentin. A calcium and fluoride-contained layer was observed in all SDF-contaminated dentin.

Lack of in vivo mutagenicity of carbendazim in the liver and glandular stomach of MutaMice.

BACKGROUND: Carbendazim (methyl 2-benzimidazolecarbamate, CASRN: 10605-21-7) exhibits spindle poisoning effects and is widely used as a fungicide. With respect to genotoxicity, carbendazim is deemed to be non-mutagenic in vitro, but it causes indicative DNA damage in vivo and chromosome aberrations in vitro and in vivo. In this study, we examined the mutagenicity of carbendazim in vivo. RESULTS: MutaMice were treated with carbendazim orally at doses of 0 (corn oil), 250, 500, and 1,000 mg/kg/day once a day for 28 days. A lacZ assay was used to determine the mutant frequency (MF) in the liver and glandular stomach of mice. MutaMice were administered up to the maximum dose recommended by the Organization for Economic Co-operation and Development Test Guidelines for Chemicals No. 488 (OECD TG488). The lacZ MFs in the liver and glandular stomach of carbendazim-treated animals were not significantly different from those in the negative control animals. In contrast, positive control animals exhibited a significant increase in MFs in both the liver and glandular stomach. CONCLUSIONS: Carbendazim is non-mutagenic in the liver and glandular stomach of MutaMice following oral treatment.

Effect of filler contents on the bond strength of CAD/CAM resin crowns: New resin primer versus conventional silane agents.

Purpose This study aims to evaluate the effects of resin primers containing methyl methacrylate (MMA) and silane agent on the bonding effectiveness of indirect resin composite blocks with three different filler contents.Methods A commercially available computer-aided design/computer-aided manufacturing (CAD/CAM) resin composite block and two experimental resin composite blocks with different filler contents were alumina-blasted and two surface treatments (primer and silane agent) were applied. The resin cement was built up, and the micro-tensile bond strength (µTBS) was measured after 24 hours, 1 month or 3 months of water storage (n = 24 per group). The fracture surfaces after µTBS measurements and resin block/cement interface were observed by scanning electron microscopy (SEM).Results The primer treatment group showed a significantly higher bond strength than the silane group only in F0 (filler content 0 wt%) group (P < 0.001). In the primer group, F0 and F41 (filler content 41 wt%) groups showed significantly higher bond strengths than F82 (filler content 82 wt%) group (P < 0.001). In contrast, in the silane group, F41 group showed significantly higher bond strength than F0 and F82 groups (P < 0.001), and F82 group showed significantly higher bond strength than F0 group (P < 0.001). SEM revealed that the matrix resin was partially destroyed on the fracture surface of the primer group, and an uneven interface surface was observed compared with that of the silane group.Conclusions MMA-containing primers showed higher bonding effectiveness to CAD/CAM resin composite blocks than the silane treatment.