Mitochondrial uncoupler BAM15 reverses diet-induced obesity and insulin resistance in mice.

Obesity is a health problem affecting more than 40% of US adults and 13% of the global population. Anti-obesity treatments including diet, exercise, surgery and pharmacotherapies have so far failed to reverse obesity incidence. Herein, we target obesity with a pharmacotherapeutic approach that decreases caloric efficiency by mitochondrial uncoupling. We show that a recently identified mitochondrial uncoupler BAM15 is orally bioavailable, increases nutrient oxidation, and decreases body fat mass without altering food intake, lean body mass, body temperature, or biochemical and haematological markers of toxicity. BAM15 decreases hepatic fat, decreases inflammatory lipids, and has strong antioxidant effects. Hyperinsulinemic-euglycemic clamp studies show that BAM15 improves insulin sensitivity in multiple tissue types. Collectively, these data demonstrate that pharmacologic mitochondrial uncoupling with BAM15 has powerful anti-obesity and insulin sensitizing effects without compromising lean mass or affecting food intake.

Second basic pKa: An overlooked parameter in predicting phospholipidosis-inducing potential of diamines.

In this paper, we present the phospholipidosis-inducing potential (PLIP) of forty fragment-sized diamines derived from N-benzyl-4-(methylamino)piperidine and discuss the relationship between their PLIP and the physicochemical properties. Our results demonstrate that the previously reported methods are not suitable for predicting the PLIP of fragment-sized diamines; the second basic pKa can distinguish PLIP-positive diamines from PLIP-negative diamines more accurately than ClogP or most basic pKa. To the best of our knowledge, this is the first report describing the relationship between PLIP and second basic pKa.

Safety lead-in of the MEK inhibitor trametinib in combination with GSK2141795, an AKT inhibitor, in patients with recurrent endometrial cancer: An NRG Oncology/GOG study.

OBJECTIVE: We sought to determine safety and efficacy of the AKT inhibitor, GSK2141795, combined with the MEK inhibitor, trametinib, in endometrial cancer. METHODS: Patients with measurable recurrent endometrial cancer were eligible. One to two prior cytotoxic regimens were allowed; prior use of a MEK or PI3K pathway inhibitor was excluded. Initial trial design consisted of a KRAS mutation stratified randomized phase II with a safety lead-in evaluating the combination. For the safety lead in, the previously recommended phase 2 dose (RP2D; trametinib 1.5 mg, GSK2141795 50 mg) was chosen for Dose Level 1 (DL1). RESULTS: Of 26 enrolled patients, 14 were treated on DL1 and 12 were treated on DL-1 (trametinib 1.5 mg, GSK2141795 25 mg). Most common histologies were endometrioid (58%) and serous (27%). Four of 25 (16%) patients were KRAS mutant. Dose limiting toxicities (DLTs) were assessed during cycle 1. DL1 had 8 DLTs (hypertension (n = 2), mucositis (2), rash (2), dehydration, stroke/acute kidney injury). DL1 was deemed non-tolerable so DL-1 was explored. DL-1 had no DLTs. Sixty-five percent of patients had ≥ grade 3 toxicity. There were no responses in DL1 (0%, 90%CI 0-15%) and 1 response in DL-1 (8.3%, 90%CI 0.4-33.9%). Proportion PFS at 6 months for DL1 is 14%, and 25% for DL-1. CONCLUSION: The combination of trametinib and GSK2141795 had high levels of toxicity in endometrial cancer at the previously RP2D but was tolerable at a reduced dose. Due to insufficient preliminary efficacy at a tolerable dose, the Phase II study was not initiated.

Results from a single arm, single stage phase II trial of trametinib and GSK2141795 in persistent or recurrent cervical cancer.

BACKGROUND: Improved treatment for advanced cervical cancer is needed; currently, treatment options include combined chemotherapy and bevacizumab or pembrolizumab monotherapy for PD-L1 positive disease. PIK3CA and KRAS mutations have been reported in cervical cancers; this study therefore tested dual inhibition of PI3K and RAS signaling by combining the MEK inhibitor trametinib and the AKT inhibitor GSK2141795 in recurrent cervical cancer. METHODS: This was an investigator-initiated phase II study combining trametinib and GSK2141795 in patients with recurrent cervical cancer. Primary endpoint was best tumor response; secondary endpoints included progression free survival, overall survival, and safety assessment. Translational objectives included characterization of molecular alterations in PI3K and RAS signaling pathway genes. RESULTS: Planned accrual was 35 patients; 14 patients were enrolled and received at least one dose of study drug before the study was terminated due to discontinuation of GSK2141795 development. There were no confirmed responses; 1 patient had an unconfirmed PR, 8 had stable disease, 3 had progression as best response, and 2 were unevaluable. Toxicities were mostly grade 1 and 2, although 57% of patients experienced grade 3/4 adverse events and 50% patients required a dose reduction. CONCLUSIONS: The combination of trametinib and GSK2141795 was feasible but required dose holds and modifications for adverse events; however, anti-cancer activity was minimal, even in patients with PI3K or RAS pathway alterations. Although the study was terminated early after GSK2141795 development was halted, the findings in these 14 patients do not support further development of this combination in cervical cancer.

Chronic effects of platinum(IV) complex and its diamine ligand on rat heart function: comparison with cisplatin.

The aim of the present study was to compare the cardiodynamic parameters in the isolated rat heart in animals chronically treated with cisplatin, platinum(IV) complex and its diamine ligand. Sixty Wistar albino rats (8 weeks old) were divided into five groups: three experimental and two control groups. Animals in all groups were treated with a dose of 4 mg/kg body weight once a week for 4 weeks with different substances; experimental groups received cisplatin, ligand and octahedral platinum(IV) complex, and control groups received saline and dimethyl sulfoxide. After sacrificing the animals, hearts were isolated and perfused according to the Langendorff technique at gradually increased coronary perfusion pressures (40-120 cmH2O). The following parameters of cardiac function were continuously recorded: maximum and minimum rate of change of pressure in the left ventricle, systolic and diastolic left ventricular pressure, heart rate and coronary flow. The results showed statistically significant differences between all experimental groups in maximum and minimum rate of pressure development as well as in systolic pressure of the left ventricle, whereas cisplatin, ligand and the platinum(IV) complex had effects on heart contractility without significant influences on coronary circulation. The findings of the present study could be important for a better understanding of anticancer drug cardiac side effects. Our results indicate that compared to cisplatin as a "gold standard", novel platinum complexes and ligands do not possess fewer negative effects on the heart, indicating insufficient safety for their usage in terms of affecting cardiac function, a result that can be of great interest for further investigations.

A phase I, open-label, two-stage study to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of the oral AKT inhibitor GSK2141795 in patients with solid tumors.

Background We sought to determine the recommended phase II dose (RP2D) and schedule of GSK2141795, an oral pan-AKT kinase inhibitor. Patients and Methods Patients with solid tumors were enrolled in the dose-escalation phase. Pharmacokinetic (PK) analysis after a single dose (Cycle 0) informed dose escalation using accelerated dose titration. Once one grade 2 toxicity or dose-limiting toxicity was observed in Cycle 1, the accelerated dose titration was terminated and a 3 + 3 dose escalation was started. Continuous daily dosing was evaluated along with two intermittent regimens (7 days on/7 days off and 3 times per week). In the expansion phase at RP2D, patients with endometrial or prostate cancer, as well as those with select tumor types with a PIK3CA mutation, AKT mutation or PTEN loss, were enrolled. Patients were evaluated for adverse events (AEs), PK parameters, blood glucose and insulin levels, and tumor response. Results The RP2D of GSK2141795 for once-daily dosing is 75 mg. The most common (>10%) treatment-related AEs included diarrhea, fatigue, vomiting, and decreased appetite. Most AEs were low grade. The frequency of hyperglycemia increased with dose; however, at the RP2D, grade 3 hyperglycemia was only reported in 4% of patients and no grade 4 events were observed. PK characteristics were favorable, with a prolonged half-life and low peak-to-trough ratio. There were two partial responses at the RP2D in patients with either a PIK3CA mutation or PTEN loss. Conclusion GSK2141795 was safe and well-tolerated, with clinical activity seen as monotherapy at the RP2D of 75 mg daily. NCT00920257.

Sensitization and cross-reactivity patterns of contact allergy to diisocyanates and corresponding amines: investigation of diphenylmethane-4,4'-diisocyanate, diphenylmethane-4,4'-diamine, dicyclohexylmethane-4,4'-diisocyanate, and dicylohexylmethane-4,4'-diamine.

BACKGROUND: Isocyanates are used in polyurethane production. Dermal exposure to isocyanates can induce contact allergy. The most common isocyanate is diphenylmethane diisocyanate used for industrial purposes. The isomer diphenylmethane-4,4'-diisocyanate (4,4'-MDI) is used in patch testing. Diphenylmethane-4,4'-diamine (4,4'-MDA) is its corresponding amine. Concurrent reactions to 4,4'-MDI and 4,4'-MDA have been reported, as have concurrent reactions to 4,4'-MDI and dicyclohexylmethane-4,4'-diisocyanate (4,4'-DMDI). OBJECTIVES: To investigate the sensitization capacities and the cross-reactivity of 4,4'-MDI, 4,4'-MDA, 4,4'-DMDI, and dicyclohexylmethane-4,4'-diamine (4,4'-DMDA). METHODS: The guinea-pig maximization test (GPMT) was used. RESULTS: The GPMT showed sensitizing capacities for all investigated substances: 4,4'-MDI, 4,4'-MDA, 4,4'-DMDI, and 4,4'-DMDA (all p < 0.001). 4,4'-MDI-sensitized animals showed cross-reactivity to 4,4'-MDA (p < 0.001) and 4,4'-DMDI (all p < 0.05). 4,4'-MDA-sensitized animals showed cross-reactivity to 4,4'-DMDA (p = 0.008). CONCLUSION: All of the investigated substances were shown to be strong sensitizers. Animals sensitized to 4,4'-MDI showed cross-reactivity to 4,4'-MDA and 4,4'-DMDI, supporting previous findings in the literature. The aromatic amine 4,4'-MDA showed cross-reactivity to the aliphatic amine 4,4'-DMDA.

Exposure of hairdressers to aromatic diamines: an interventional study confirming the protective effect of adequate glove use.

OBJECTIVES: Many hairdressers leave their profession due to health problems, including occupational hand eczema, which has been associated with skin exposure to sensitising hair dye components such as paraphenylenediamine (PPD) and paratoluenediamine (PTD). Since the use of protective gloves is advised but without the short-term effect being known, our main goal was to attribute a significant biomarker reduction to adequate glove use, in a real work situation. METHODS: 11 hairdressers were studied over 2 weeks. In the first week, they worked as usual and (re)used their gloves. Thereafter, we intervened to improve glove use during the second week. In both weeks, workplace exposure data were collected through observations, and systemic exposure was quantified by biomonitoring of PPD and PTD. The effect of improved glove use and other exposure determinants was studied through mixed models analysis. RESULTS: We showed that improved glove use significantly reduced mean PTD concentrations from 24.1 before to 4.2 µg/g creatinine after the intervention (n=11, third day postshift). In addition, mean PTD concentrations increased during the first week (14 times elevated after three consecutive shifts), but not during the second week. For PPD, no effect of improved glove use and no accumulation effect were detected. CONCLUSIONS: Our study is the first to deliver evidence for a significant reduction in systemic exposure to PTD through improved glove use. Disposable gloves should never be reused. PTD biomonitoring is shown to be a practical tool to quantify recent dermal exposure to oxidative hair dye components.

Skin testing of gallic acid-based hair dye in paraphenylenediamine/paratoluenediamine-reactive patients.

Incidence of allergic contact dermatitis (ACD) to para-phenylenediamine (PPD)/paratoluenediamine (PTD) hair dyes is increasing. Hair dyes utilizing gallic acid (GA) may be a safe alternative. However, pretesting is recommended. We investigated the contact sensitivity to ingredients of a dye product; GA, monoethanolamine thioglycolate (MT), l-cystein and ferrous sulfate, and an appropriate pretest method in 31 patients reactive to PPD and/or PTD. An open test was performed with the test dye following the patch test. Subsequently, a use test was performed twice, with a 4-week interval. One subject showed a positive reaction to ferrous sulfate in the patch test. Another subject reacted to the first compound alone in the open test. Thirteen subjects manifesting cutaneous lesions from previous regular hair dyeing, showed reactions at the first use of the test dye; and six had reactions with reduced severity at the second test. GA and MT are safe for use in ACD patients reactive to PPD and/or PTD. For predicting contact allergy to hair dyes, the open test appeared to be a better pretest method than the patch test.

Dose-Finding Quantitative 18F-FDG PET Imaging Study with the Oral Pan-AKT Inhibitor GSK2141795 in Patients with Gynecologic Malignancies.

UNLABELLED: AKT (a serine/threonine-specific protein kinase) regulates many cellular processes contributing to cytotoxic drug resistance. This study's primary objective examined the relationship between GSK2141795, an oral, pan-AKT inhibitor, and (18)F-FDG PET markers of glucose metabolism in tumor tissue to determine whether (18)F-FDG PET could be used to guide personalized dosing of GSK2141795. Biomarker analysis of biopsies was also undertaken. METHODS: Twelve patients were enrolled in 3 cohorts; all underwent dynamic (18)F-FDG PET scans and serial pharmacokinetic sampling at baseline, week 2, and week 4 with tumor biopsies before treatment and at week 4. Response was evaluated by RECIST v1.1 and Gynecologic Cancer Intergroup criteria. Biopsy samples were analyzed for mutations and protein expression. RESULTS: GSK2141795 did not significantly influence blood glucose levels. No dose-response relationship was observed between GSK2141795 pharmacokinetics and (18)F-FDG PET pharmacodynamic measures; however, an exposure-response relationship was seen between maximum drug concentrations and maximal decrease in (18)F-FDG uptake in the best-responding tumor. This relationship also held for pharmacokinetic parameters of exposure and 1,5-anhydroglucitol (a systemic measure of glucose metabolism). Phospho-AKT upregulation at week 4 in biopsies confirmed AKT inhibition by GSK2141795. Single-agent activity was observed with a clinical benefit rate of 27% (3/11) and 30% (3/10) CA125 response in the study's platinum-resistant ovarian patients. AKT pathway activation by PIK3CA/PIK3R1 mutation did not correlate with clinical activity, whereas RAS/RAF pathway mutations did segregate with resistance to AKT inhibition. CONCLUSION: GSK2141795 demonstrated an exposure-response relationship with decreased (18)F-FDG uptake and is active and tolerable. This study's design integrating (18)F-FDG PET, pharmacokinetics, and biomarker analyses demonstrates the potential for clinical development for personalized treatment.

Testing Penetration of Epoxy Resin and Diamine Hardeners through Protective Glove and Clothing Materials.

Efficient, comfortable, yet affordable personal protective equipment (PPE) is needed to decrease the high incidence of allergic contact dermatitis arising from epoxy resin systems (ERSs) in industrial countries. The aim of this study was to find affordable, user-friendly glove and clothing materials that provide adequate skin protection against splashes and during the short contact with ERS that often occurs before full cure. We studied the penetration of epoxy resin and diamine hardeners through 12 glove or clothing materials using a newly developed test method. The tests were carried out with two ERS test mixtures that had a high content of epoxy resin and frequently used diamine hardeners of different molar masses. A drop (50 µl) of test mixture was placed on the outer surface of the glove/clothing material, which had a piece of Fixomull tape or Harmony protection sheet attached to the inner surface as the collection medium. The test times were 10 and 30 min. The collecting material was removed after the test was finished and immersed into acetone. The amounts of diglycidyl ether of bisphenol A (DGEBA), isophorone diamine (IPDA), and m-xylylenediamine (XDA) in the acetone solution were determined by gas chromatography with mass spectrometric detection. The limit for acceptable penetration of XDA, IPDA, and DGEBA through glove materials was set at 2 µg cm(-2). Penetration through the glove materials was 1.4 µg cm(-2) or less. The three tested chemical protective gloves showed no detectable penetration (<0.5 µg cm(-2)). Several affordable glove and clothing materials were found to provide adequate protection during short contact with ERS, in the form of, for example, disposable gloves or clothing materials suitable for aprons and as additional protective layers on the most exposed parts of clothing, such as the front of the legs and thighs and under the forearms. Every ERS combination in use should be tested separately to find the best skin protection material, and this can be done by using this simple test method.

A new orally active, aminothiol radioprotector-free of nausea and hypotension side effects at its highest radioprotective doses.

PURPOSE: A new aminothiol, PrC-210, was tested for orally conferred radioprotection (rats, mice; 9.0 Gy whole-body, which was otherwise lethal to 100% of the animals) and presence of the debilitating side effects (nausea/vomiting, hypotension/fainting) that restrict use of the current aminothiol, amifostine (Ethyol, WR-2721). METHODS AND MATERIALS: PrC-210 in water was administered to rats and mice at times before irradiation, and percent-survival was recorded for 60 days. Subcutaneous (SC) amifostine (positive control) or SC PrC-210 was administered to ferrets (Mustela putorius furo) and retching/emesis responses were recorded. Intraperitoneal amifostine (positive control) or PrC-210 was administered to arterial cannulated rats to score drug-induced hypotension. RESULTS: Oral PrC-210 conferred 100% survival in rat and mouse models against an otherwise 100% lethal whole-body radiation dose (9.0 Gy). Oral PrC-210, administered by gavage 30-90 min before irradiation, conferred a broad window of radioprotection. The comparison of PrC-210 and amifostine side effects was striking because there was no retching or emesis in 10 ferrets treated with PrC-210 and no induced hypotension in arterial cannulated rats treated with PrC-210. The tested PrC-210 doses were the ferret and rat equivalent doses of the 0.5 maximum tolerated dose (MTD) PrC-210 dose in mice. The human equivalent of this mouse 0.5 MTD PrC-210 dose would likely be the highest PrC-210 dose used in humans. By comparison, the mouse 0.5 MTD amifostine dose, 400 µg/g body weight (equivalent to the human amifostine dose of 910 mg/m(2)), when tested at equivalent ferret and rat doses in the above models produced 100% retching/vomiting in ferrets and 100% incidence of significant, progressive hypotension in rats. CONCLUSIONS: The PrC-210 aminothiol, with no detectable nausea/vomiting or hypotension side effects in these preclinical models, is a logical candidate for human drug development to use in healthy humans in a wide variety of radioprotection settings, including medical radiation, space travel, and nuclear accidents.

[Methodical aspects of hygienic safety assessment of polymeric materials in contact with foodstuffs].

It was purposed new technique by capillary gas chromatography (GC) for the low level determination of monomer hexamethylenediamine (HMDA) in food simulants water from polymeric materials in contact with foodstuffs. Hexamethylenediamine, HN2-(CH2)6-NH2, is a monomer used in the manufacture of certain of polyamide plastic materials and articles intended to come into contact with foodstuffs. Compound exhibits all the chemical properties of aliphatic amines, is an irritant, causing dermatitis, can accumulate in the body, the degree of human exposure to HMDA assigned to the 2nd class of hazard - the substance is highly dangerous. There was studied two methodological approaches pre-derivatization of compound for GC determination. The first approach involves conversion of the free diamine using ethyl chloroformate as derivatizing agent followed by analysis of the resulting diurethan by gas chromatography using a flame ionization and mass selective detection (HMDA was quantitated by selective ion monitoring at m/z 102, the lower detection limit of 1 ng). According to second methodological approach the water samples were mixed with sodium chloride and extracted with toluene, then derivatized with trifluoroacetic anhydride (60 min, 55 degrees C) to diamide, 1 M potassium phosphate buffer (pH 7,0) was add to remove excess derivatizing agent, followed by analysis of resulting diamide by gas chromatography with electron capture detection (lower limit value 0,01 ng). Conformation of HMDA levels is carried out by combined gas chromatography/mass spectrometry (HMDA was quantitated by selective ion monitoring at m/z 126, the lower limit value of 0,1 ng). The optimal pre-derivatization of the second approach for the determination of low levels of HMDA in the water extracts. The range of measured concentrations of 0,005-0,5 mg/dm3, recovery 88-101%, the total error of measurement is 16%, the relative standard deviation is 1,85%. The method was tested in the study of aqueous extracts of the 10 random samples intended for food purchased in the consumer market. Shows the corresponding output level hexamethylenediamine requirements for products of this type.

An intranasal irritation assessment of antibacterial ointment alone or in combination with mupirocin versus Bactroban Nasal in rabbits.

The purpose of this study was to evaluate the potential irritating effects and the systemic exposure level of an antibacterial ointment containing REP8839 as a single agent or in combination with mupirocin versus Bactroban Nasal in rabbits. Additionally, the reversibility of REP8839 effects during a 14-day recovery period was assessed. Five treatment groups of six male and six female New Zealand White rabbits received dose levels of 1%, 2%, and 4% REP8839, 2% Bactroban Nasal, or 2% REP8839/2% mupirocin combination. One additional group of six animals/sex served as the control and received the vehicle, Petrolatum/Softisan 649. The test article or vehicle was administered to all groups via topical administration to the external nares, twice a day (approx. 8h intervals between the doses) for 21 consecutive days, at a dose volume of 100 microL per nare/dose for a total of 400 microL per day (200 microL per nare). Two animals/sex/group were maintained for a 14-day recovery period. The external nares were reflected back and the mucosal lining was evaluated and scored for erythema and edema within 30-60 min following the first dose each day. Blood samples were collected from all animals at designated time points on Day 21 of the study to assess systemic exposure levels. Cross-sectioning of the nasal tract was conducted in all the groups for microscopic evaluation. Mucosal scoring of the nares did not reveal any edema or erythema in any of the dose groups with the antibacterial alone, with the combination product, or with Bactroban Nasal. Mean body weights and food consumption were not adversely impacted by the test articles. Minimal plasma exposure was observed in the rabbits (<5 ng/mL). The REP8839 groups did appear to have dose-responsive exposure (from below the limit of quantitation to 5 ng/mL with 1%, 2%, and 4% REP8839, respectively). Microscopic changes on the nasal sectioning noted in these animals were infrequent and considered incidental findings unrelated to administration of the test articles. In conclusion doses of up to 4% of REP8839 ointment as a single agent or 2% in the combination product, as well as 2% Bactroban Nasal, were not found to induce mucosal irritation when applied topically to the external nares twice a day for 21 consecutive days. Additionally, no delayed effects were observed in the recovery animals.

Pro-inflammatory activity in rats of thiocyanate, a metabolite of the hydrocyanic acid inhaled from tobacco smoke.

OBJECTIVE: To seek a mechanism linking tobacco smoking with the increased incidence and severity of rheumatoid arthritis, deduced from many retrospective surveys, by studying arthritis/fibrosis development in rats. METHODS: Rats (>300) received low levels of sodium/potassium thiocyanate (10 or 25 mmol/l) in their drinking water to raise their blood thiocyanate levels, mimicking the elevated levels of blood, salivary and urinary thiocyanate found in smokers. RESULTS: Thiocyanate supplements increased the severity of experimental arthritis induced by tailbase injection of (1) Freund's complete adjuvants (mycobacteria plus various adjuvant-active oils), (2) collagen type-II with Freund's incomplete adjuvant (no mycobacteria), (3) the synthetic lipid amine, avridine in an oil and (4) the natural hydrocarbons squalene (C(30)H(50)) and pristane (C(19)H(40)). This pro-arthritic effect was independent of sex, rat strain or changing diet and housing facilities. Thiocyanate supplements also amplified the acute/persisting inflammatory responses to paw injections of pristane, zymosan and microcrystalline hydroxyapatite. Iodide salts also mimicked some of these effects of thiocyanate. CONCLUSION: Thiocyanate, a detoxication product of HCN present in tobacco smoke, increased (or even induced) inflammatory responses to several agents causing arthritis or fibrotic inflammation in rats. It, therefore, can act as a co-arthritigen, or 'virulence factor' and could be a therapeutic target to reduce arthritis expression and morbidity.

A study of the sensitization rate to cocamidopropyl betaine in patients patch tested in a university hospital of Beijing.

BACKGROUND: The prevalence of sensitization to cocamidopropyl betaine (CAPB) in China has not been reported. OBJECTIVE: This study is to evaluate the prevalence of CAPB sensitization in patients patch tested in Peking University Third Hospital, Beijing. METHODS: 429 consecutive patients with suspected allergic contact dermatitis were patch tested with CAPB 1.0% aqueous, 3-dimethylaminopropylamine (DMAPA) 1.0% aqueous as well as a modified European standard series of allergens from June 2005 to August 2006. RESULTS: 42 patients (9.8%) had a positive reaction to CAPB. 25 of them (59.5%) were considered relevant. Of those, 7 were head and/or neck dermatitis, 4 hand dermatitis, 1 cheilitis, and the other 13 patients were widespread dermatitis. 10 out of 429 (2.3%) patients reacted to DMAPA. Of those, 8 were relevant and 6 of them also reacted to CAPB. CONCLUSION: The rate of CAPB sensitization in our study is higher than previously reported elsewhere. CAPB is a common cosmetic allergen in Beijing. Both CAPB and DMAPA should be tested in patients with suspected cosmetic dermatitis.