"Spice"-related deaths in and around Munich, Germany: A retrospective look at the role of synthetic cannabinoid receptor agonists in our post-mortem cases over a seven-year period (2014-2020).

Synthetic cannabinoid receptor agonists (SCRAs, "Spice") are a diverse group of recreational drugs, with their structural and pharmacological variability still evolving. Forensic toxicologists often rely on previous reports to assess their role in intoxication cases. This work provides detailed information on the "Spice"-related fatalities around Munich, Germany, from 2014 to 2020. All cases underwent an autopsy. Pharmaceutical and illicit drugs were detected and quantified in post-mortem peripheral blood or liver by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Based on circumstantial evidence, only those cases for which a prior consumption was suspected underwent additional analyses for SCRAs and other new psychoactive substances in post-mortem blood, liver or antemortem specimens. Drug concentrations, pathological findings at autopsy and case histories were considered to assess and rank the SCRAs' involvement in each death. Concentration ranges for the individual substances in blood were defined and their distribution patterns over the investigated period were determined and correlated with their legal status and local police seizures. We identified 41 different SCRAs among 98 fatalities. 91.8% were male, at a median age of 36 years. SCRAs played a causative role in 51%, contributory role in 26%, and an insignificant role in 23% of cases. In correlation with local police seizures and legal status, 5F-ADB was the most prevalent in our cases, followed by 5F-MDMB-PICA and AB-CHMINACA. Cumyl-CBMICA and 5F-MDMB-P7AICA were among the least frequently detected SCRAs. "Spice"-related fatalities and SCRAs' causative role have significantly decreased among our cases since the German New Psychoactive Substances Act.

Unexpected results found in larvae samples from two postmortem forensic cases.

PURPOSE: In forensics, entomological specimens can be used as additional/alternative matrices to detect xenobiotics when human specimens are limited in their application. Despite some advantages over implementing putrefied human remains, most medico-legal laboratories do not include entomotoxicological procedures as routine analytical methods. We thus applied two authentic cases to evaluate necrophagous larvae's potential as complementary matrices for toxicological analysis after extensive postmortem decomposition. METHODS: Larvae and postmortem human samples, including hair, stomach contents, pericardial fluid, liver, lung, and skeletal muscle, were collected at autopsy. Samples were analyzed by liquid chromatography-tandem mass spectrometry and liquid chromatography-quadrupole time-of-flight mass spectrometry for pharmaceutical substances, illicit drugs, and new psychoactive substances, including synthetic cannabinoids, benzodiazepines, new synthetic opioids, and stimulants. RESULTS: Nearly all substances detected in human specimens, including several benzodiazepines and synthetic cannabinoids, were also detected in larvae. Surprisingly, some drugs, including the new psychoactive substances EAM-2201 and U-47700, were found exclusively in larvae and hair. The benzodiazepine etizolam was detected only in liver, lungs, and stomach contents, possibly resulting from characteristic tissue distribution in humans and/or larvae. CONCLUSIONS: Antemortem external hair contamination with synthetic cannabinoids from side-stream smoke and postmortem hair contamination with substances in putrefaction fluids can be supposed in these cases. Our findings suggest that supplementary information can indeed be gained from analyzing larvae additional to those human specimens that are typically used for toxicological analysis after extensive postmortem decomposition. Nevertheless, these results represent merely two cases, requiring in-depth studies to determine whether such findings can identify acute intoxications as possible causes of death.

Infants and mothers levels of mercury in breast milk, urine and hair, data from an artisanal and small-scale gold mining area in Kadoma / Zimbabwe.

In Kadoma (Zimbabwe) gold is extracted from ore based on a simple technology using mercury. Women are exposed whilst living in an exposed area, or even more working directly with mercury. Breast fed infants are exposed via mercury contaminated milk and the general environmental mercury exposure. The aim of the study was to measure infants and mothers levels of mercury in urine and hair, as well as in breast milk. In 2006, an environmental epidemiological field study with 120 mother - child pairs was conducted. A non exposed control group (n = 42) was compared with a medium exposed group (n = 51) and a high exposed group (occupational exposure, n = 27). Urine and hair samples from mother and infants plus breast milk samples were analyzed for total mercury. 120 breast milk samples were analyzed, median (maximum) concentrations [µg Hg/l] were (i) control group < 0.50 (1.55), (ii) medium exposed group 1.10 (10.48), (iii) high exposed group 1.20 (24.80) (p < 0,001). Urine and hair results were distributed similarly for infants and mothers, with higher levels according to the exposure subgroup. All specimen results correlated very well with another, indicating there is a pathway between breast milk and infant's level of mercury. The daily uptake of mercury via breast milk was calculated. The reference dose of 0.3°[µg Hg/kg BW/d] was used to compare the burden of the infants. No infant from the control group, but 17.6% of the medium and 18.5% of the high exposed group were above the reference dose. Mercury in breast milk is generally higher in artisanal and small scale gold mining areas. Breast fed infants were burdened with toxic mercury via breast milk and via the general environment, both are important public health issues.

Postmortem concentrations of the synthetic opioid U-47700 in 26 fatalities associated with the drug.

Most recently, the synthetic opioid U-47700 has emerged on the illicit drug market and is sold on the Internet as a "research chemical". Its structure is closely related to the synthetic opioid AH-7921. U-47700 is a µ-opioid receptor agonist with a potency of approximately 7.5 times that of morphine. In this study, postmortem concentrations of U-47700 are presented in 26 fatalities which occurred between April 2016 and August 2017 in the southern part of Germany. In 18 of these cases, quantitative analyses of U-47700 were carried out in femoral blood, heart blood, liver, urine, vitreous humor, pericardial fluid, and gastric content. In five cases, concentrations of U-47700 were determined in femoral blood, whereas in one case, the concentration of U-47700 was analyzed in heart blood. Due to advanced putrefaction, the analysis of U-47700 could only be performed in putrefaction fluid in two cases. Quantification of U-47700 was carried out using liquid chromatography-quadrupole-time-of-flight mass spectrometry (LC-QTOF-MS) with electrospray ionization operated in positive mode. The median femoral blood concentration of U-47700 (n = 23) was 610 ng/mL (range: 27-2200 ng/mL). Except for one female, all decedents were male and aged between 23 and 56 years (mean age: 34 years). In all fatalities, the cause of death was attributed to an intoxication with U-47700 either alone or in combination with other psychoactive substances. In 15 of the 26 cases, there was a combined use of U-47700 with other new psychoactive substances (NPS). Therefore, not only new synthetic opioids but also additional NPS including synthetic cannabinoids, new stimulant drugs, and designer benzodiazepines should be included in the routine toxicological screening methods.

Two fatalities associated with synthetic opioids: AH-7921 and MT-45.

In this study, two fatalities associated with the synthetic opioids AH-7921 and MT-45 are reported. Within the last few years, both compounds have emerged on the recreational drug market and are sold as "research chemicals" on the internet. In the first case, a 22-year-old woman was found dead in the bedroom of her apartment by two of her friends. A plastic bag labeled "AH-7921" was found in the apartment and the two friends stated that the deceased had consumed AH-7921 prior to her death. The woman was a known drug addict. In the second case, a 24-year-old man was found dead in his room by his mother. The deceased was sitting on a chair in front of his desk slumped over. Several bags of white powder labeled "MT-45", "Methoxmetamine" and "Methoxphenidine" were found in his room. Toxicological analyses of femoral blood, heart blood, liver, pericardial fluid, urine, vitreous humor and stomach content of the deceased were performed using liquid chromatography-quadrupole-time-of-flight mass spectrometry (LC-QTOF-MS). Time-of-flight mass spectrometry was carried out on an LC-Triple TOF 5600 system (AB Sciex) with electrospray ionization operated in positive mode. In the first case, additional hair analysis was performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and LC-QTOF-MS. In both cases, the relevant synthetic opioid could be detected in all analyzed samples. The concentration of AH-7921 was determined to be 450µg/L in femoral blood. MT-45 was present at a concentration of 2900µg/L in femoral blood. Besides methoxmetamine which could qualitatively be detected in femoral blood, urine and stomach content no methoxphenidine was found. In summary, deaths of the young individuals could be, by exclusion of other causes of death, attributed to the consumption of an overdose of AH-7921 and MT-45, respectively.

Signs and symptoms of mercury-exposed gold miners.

OBJECTIVES: Gold miners use mercury to extract gold from ore adding liquid mercury to the milled gold-containing ore. This results in a mercury-gold compound, called amalgam. Miners smelt this amalgam to obtain gold, vaporizing it and finally inhaling the toxic mercury fumes. The objective was to merge and analyze data from different projects, to identify typical signs and symptoms of chronic inorganic mercury exposure. MATERIAL AND METHODS: Miners and community members from various artisanal small-scale gold mining areas had been examined (Philippines, Mongolia, Tanzania, Zimbabwe, Indonesia). Data of several health assessments were pooled. Urine, blood and hair samples were analyzed for mercury (N = 1252). Questionnaires, standardized medical examinations and neuropsychological tests were used. Participants were grouped into: Controls (N = 209), living in an exposed area (N = 408), working with mercury as panners (N = 181), working with mercury as amalgam burners (N = 454). Chi2 test, linear trend test, Mann-Whitney test, Kruskal-Wallis test, correlation coefficient, Spearman's rho, and analysis of variance tests were used. An algorithm was used to define participants with chronic mercury intoxication. RESULTS: Mean mercury concentrations in all exposed subgroups were elevated and above threshold limits, with amalgam burners showing highest levels. Typical symptoms of chronic metallic mercury intoxication were tremor, ataxia, coordination problems, excessive salivation and metallic taste. Participants from the exposed groups showed poorer results in different neuropsychological tests in comparison to the control group. Fifty-four percent of the high-exposed group (amalgam burners) were diagnosed as being mercury-intoxicated, compared to 0% within the control group (Chi2 p < 0.001). CONCLUSIONS: Chronic mercury intoxication, with tremor, ataxia and other neurological symptoms together with a raised body burden of mercury was clinically diagnosed in exposed people in artisanal small-scale mining areas. The mercury exposure needs to be urgently reduced. Health care systems need to be prepared for this emerging problem of chronic mercury intoxication among exposed people. Int J Occup Med Environ Health 2017;30(2):249-269.

Mitragynine concentrations in two fatalities.

Two cases of fatalities are reported of which the recreational use of Mitragyna speciosa ("kratom") could be confirmed. One of these cases presents with one of the highest postmortem mitragynine concentrations published to date. Our results show that even extremely high mitragynine blood concentrations following the consumption of kratom do not necessarily have to be the direct cause of death in such fatalities as a result of an acute overdose. The two cases are compared with regard to the differences in mitragynine concentrations detected and the role of mitragynine in the death of the subjects. Irrespective of the big differences in mitragynine concentrations in the postmortem blood samples, mitragynine was not the primary cause of death in either of the two cases reported here. Additionally, by rough estimation, a significant difference in ratio of mitragynine to its diastereomers in the blood and urine samples between the two cases could be seen.

Concentrations of cyanide in blood samples of corpses after smoke inhalation of varying origin.

Cyanide (CN) blood concentration is hardly considered during routine when evaluating smoke gas intoxications and fire victims, although some inflammable materials release a considerable amount of hydrogen cyanide. CN can be significant for the capacity to act and can in the end even be the cause of death. Systematic data concerning the influence of different fire conditions, especially those of various inflammable materials, on the CN-blood concentration of deceased persons do not exist. This study measured the CN level in 92 blood samples of corpses. All persons concerned were found dead in connection with fires and/or smoke gases. At the same time, the carboxyhemoglobin (COHb) level was determined, and the corpses were examined to detect pharmaceutical substances, alcohol and drugs. Furthermore, we analysed autopsy findings and the investigation files to determine the inflammable materials and other circumstances of the fires. Due to the inflammable materials, the highest concentration of CN in the victims was found after enclosed-space fires (n = 45) and after motor-vehicle fires (n = 8). The CN levels in these two groups (n = 53) were in 47 % of the cases toxic and in 13 % of the cases lethal. In victims of charcoal grills (n = 17) and exhaust gases (n = 6), no or only traces of CN were found. Only one case of the self-immolations (n = 12) displayed a toxic CN level. The results show that CN can have considerable significance when evaluating action ability and cause of death with enclosed-space fires and with motor-vehicle fires.

Detection of methaemoglobinaemia and its application in 'poppers' abuse: maintaining the right balance between reduction and autooxidation during storage.

In our study, we analysed the effect of a variety of storage conditions on the methaemoglobin (MetHb) content of blood samples obtained from altogether 110 deceased subjects with diverse causes of death, including three 'poppers'-related fatalities. The obtained results were compared to data from blood samples of six living, healthy subjects. Results obtained from the spectrophotometric measurement of blood MetHb content suggest that storage at room temperature (RT) and storage at -20 °C result in either highly fluctuating values, as was the case for the RT samples, or values much higher than the initial MetHb concentrations when stored at -20 °C. Blood samples at 4 °C showed more stable MetHb levels, which, however, increased with up to 4 % of the initial value after only 3 weeks of storage. These factors pose a problem in forensic toxicology, especially in nitrite abuse cases, where the involvement of such substance abuse is often unknown at the time of blood sampling and thus often requires longer storage times. Nevertheless, even after the storage of blood samples over several months at 4 and -20 °C, 'poppers' cases still show a significantly higher MetHb concentration as compared to non-'poppers' samples that were stored for the same time period under identical conditions.

Influence of Surface Coating on Metal Ion Release: Evaluation in Patients With Metal Allergy.

Nickel, chromium, and cobalt in stainless steel and Cobalt-chrome-molybdenum (CoCrMo) alloys may induce allergy. The objectives of this study were to evaluate surface coating regarding ion release, patch test reactivity, and arthroplasty performance. Materials and methods included patch test in 31 patients with metal allergy and 30 patients with no allergy to stainless steel and CoCrMo disks that are uncoated or coated by titanium nitride/zirconium nitride (TiN/ZrN). Assessment include atomic absorption spectrometry of released nickel, cobalt, and chromium from the disks after exposure to distilled water, artificial sweat and culture medium. Results showed that both coatings reduced the nickel and chromium release from stainless steel and CoCrMo disks and mostly the cobalt release from the disks (maximally 11.755 µg/cm(2)/5 d to 1.624 by Ti-N and to 0.442 by ZrN). Six of the 31 patients with metal allergy reacted to uncoated disks, but none reacted to the coated disks. The current authors report on exemplary patients with metal allergy who had symptom relief by revision with surface-coated arthroplasty. The authors concluded that the surface coating may prevent cutaneous and peri-implant allergic reactions. [Orthopedics. 2016; 39(3):S24-S30.].

Quantification of aconitine in post-mortem specimens by validated liquid chromatography-tandem mass spectrometry method: three case reports on fatal 'monkshood' poisoning.

The diester-diterpene alkaloid aconitine was quantified by liquid chromatography-tandem mass spectrometry in post-mortem specimens of three cases where suicidal ingestion of Aconitum napellus L. ('monkshood') was supposed. In an attempt at rationalization, sample preparation and chromatographic conditions of plasma/serum drug analysis routine were utilized. Linearity was established from 0.5 to 20 µg L⁻¹ using newborn calf serum (NCS) as a surrogate calibration matrix for all sample types and mesaconitine as an internal standard. Validation (selectivity, sensitivity, precision, accuracy, recovery of the extraction procedure, matrix effect, processed sample stability) confirmed the applicability of the analytical method to various post-mortem matrices. Internal standard selection was based on multi-matrix process efficiency data. In human post-mortem peripheral blood a lower limit of quantification of 0.51 µg L⁻¹ and a limit of detection of 0.13 µg L⁻¹ were accomplished (0.1 ml sample aliquots). Aconitine was degraded to a large extent in different sample types when being stored at +20 °C for 30 days, while at -20 °C and for some matrices also at +4 °C no appreciable degradation occurred. Aconitine concentrations in real samples were 10.3-17.9 µg L⁻¹ (peripheral blood, n = 3), 14.9-87.9 µg L⁻¹ (heart blood, n = 3), 317-481 µg L⁻¹ (urine, n = 2), 609-4040 µg L⁻¹ (stomach content, n = 3), 139-240 µg L⁻¹ (bile, n = 2), 8.4 µg L⁻¹ (vitreous humor, n = 1), 54.7 µg L⁻¹ (pericardial fluid, n = 1), 492 µg kg⁻¹ (liver, n = 1), 15.2-19.7 mg L⁻¹ (unknown liquids secured onsite, n = 3). Together with concomitant circumstances the analytical data provided compelling evidence for acute Aconitum poisoning as being the cause of death.

Applicability of two mobile analysers for mercury in urine in small-scale gold mining areas.

Mercury is still used in developing countries to extract gold from the ore in small-scale gold mining areas. This is a major health hazard for people living in mining areas. The concentration of mercury in urine was analysed in different mining areas in Zimbabwe, Indonesia and Tanzania. First the urine samples were analysed by CV-AAS (cold vapour atomic absorption spectrometry) during the field projects with a mobile mercury analyser (Lumex(®) or Seefelder(®)) and secondly, in a laboratory with a stationary CV-AAS mercury analyser (PerkinElmer(®)). Caused by the different systems (reduction agent either SnCl(2) (Lumex(®) or Seefelder(®))) or NaBH(4) (PerkinElmer(®)), with the mobile analysers only the inorganic mercury was obtained and with the stationary system the total mercury concentration was measured. The aims of the study were whether the results obtained in field with the mobile equipments can be compared with the stationary reference method in the laboratory and allow the application of these mobile analysers in screening studies on concerned populations to select those, who are exposed to critical mercury levels. Overall, the concentrations obtained with the two mobile systems were approximately 25% lower than determined with the stationary system. Nevertheless, both mobile systems seem to be very useful for screening of volunteers in field. Moreover, regional staff may be trained on such analysers to perform screening tests by themselves.

Mercury exposure in female artisanal small-scale gold miners (ASGM) in Mongolia: An analysis of human biomonitoring (HBM) data from 2008.

BACKGROUND: Many poor in developing countries have turned to artisanal small-scale gold mining (ASGM) in an attempt to improve their situation. However, the mercury used to extract gold from ore is discharged in vaporized form into the environment, where it poses a hazard for human health. METHODS: As part of an environmental epidemiological study in Mongolia-to evaluate the burden of environmental mercury contamination-urine, blood and hair samples were collected from residents of areas with or without mercury contamination. A total of 200 blood, urine and hair samples were analyzed for mercury and divided into three subgroups according to mercury content: (1) occupational exposure (high/medium); (2) environmental exposure (low); and (3) no exposure. Internal mercury distributions of the subgroups were compared using the Kruskal-Wallis and Mann-Whitney U-test. The Chi-square test and likelihood ratio proportion were used to compare the findings with threshold limits. RESULTS: The highest values and greatest differences were seen in the urine samples (p<0.001, Kruskal-Wallis). The occupational group showing the highest exposure with a median mercury level of 4.36µg/l (control group: 0.10µg/l, p<0.001), 7.18µg/g creatinine and 12 results above the threshold limit HBM I (Human Biomonitoring I). Even participants from the low-exposure subgroup showed elevated mercury levels (median 2.88µg/l urine and 2.98µg/g creatinine, p<0.001), with 10 individuals above the HBM I threshold limits. DISCUSSION: The body burden resulting from the use of mercury in artisanal gold mining is high not only in the miners themselves, an increased mercury hazard was also found for inhabitants of mining areas who were not actively involved in mining. Public health support measures are urgently needed to alleviate the situation.

Health assessment of artisanal gold miners in Indonesia.

Small scale miners use mercury to extract gold from ore in many countries. An environmental and health assessment was performed in Indonesia in two regions, Galangan in Central Kalimantan and Talawaan in Northern Sulawesi. The environmental assessment showed severe mercury contamination of the sediments, and increased mercury levels in local fish. For the health investigation 281 volunteers were recruited and examined by a standardized questionnaire, a neurological examination and neuro-psychological tests. A medical score was used consisting of significant factors of mercury intoxication. Mercury exposed workers showed typical symptoms of mercury intoxication, such as movement disorders (ataxia, tremor, dysdiadochokinesia, etc.). Blood, urine and hair samples were taken from any participant and analyzed for mercury. The mercury concentration in the biomonitors was high, partly extreme high in the working population, increased in the population living in the same habitat and low in the control group. By a standard protocol which includes a combination of threshold values of mercury in the biomonitors and a medical sum score the diagnosis of chronic mercury intoxication was made for highly burdened workers (amalgam smelters) in 55% in Sulawesi and in 62% in Kalimantan. Less exposed mineral processors and the general population in the mining areas were also intoxicated to a high percentage.

Health assessment of artisanal gold miners in Tanzania.

In 2003 UNIDO (United Nations Industrial Development Organization) conducted an environmental and health assessment in a small-scale mining area in Tanzania. BGS (British Geological Survey) performed the environmental assessment. The Institute of Forensic Medicine - University of Munich performed the health assessment. The results of the medical, neurological and neuro-psychological examination of 180 participants from the affected area of Rwamagasa and 31 controls were analyzed. Urine, blood and hair samples were analyzed to detect the level of mercury body burden. Mercury concentrations in the bio-monitors urine, blood and hair were statistically significantly higher in the exposed population from Rwamagasa compared to the control group from Katoro. Only amalgam burners showed mercury levels above the toxicological threshold limits. A speciation of mercury in hair indicated that mainly elemental mercury vapor contributed to the high body burden of the artisanal miners. 104 amalgam-burners, the most exposed population group, were examined. 25 of these workers were found to be intoxicated. Small-scale mining is a serious health hazard for amalgam burners. Reduction of the exposure is essential to prevent further damage.

Mercury in breast milk - a health hazard for infants in gold mining areas?

Breast-feeding can be a source of mercury exposure for infants. The main concern up to now is methyl-mercury exposure of women at child-bearing age. Certain fish species have high levels of methyl-mercury leading to consumer's advisory guidelines in regard of fish consumption to protect infants from mercury exposure passing through breast milk. Little is known about the transfer of inorganic mercury passing through breast milk to infants. Epidemiological studies showed negative health effects of inorganic mercury in gold mining areas. Small-scale gold miners use mercury to extract the gold from the ore. Environmental and health assessments of gold mining areas in Indonesia, Tanzania and Zimbabwe showed a high exposure with inorganic mercury in these gold mining areas, and a negative health impact of the exposure to the miners and the communities. This paper reports about the analysis and the results of 46 breast milk samples collected from mercury-exposed mothers. The median level of 1.87mug/l is fairly high compared to other results from literature. Some breast milk samples showed very high levels of mercury (up to 149mug/l). Fourteen of the 46 breast milk samples exceed 4mug/l which is considered to be a "high" level. US EPA recommends a "Reference Dose" of 0.3mug inorganic mercury/kg body weight/day [United States Environmental Protection Agency, 1997. Volume V: Health Effects of Mercury and Mercury Compounds. Study Report EPA-452/R-97-007: US EPA]. Twenty-two of the 46 children from these gold mining areas had a higher calculated total mercury uptake. The highest calculated daily mercury uptake of 127mug exceeds by far the recommended maximum uptake of inorganic mercury. Further systematic research of mercury in breast milk from small-scale gold mining areas is needed to increase the knowledge about the bio-transfer of mercury from mercury vapour-exposed mothers passing through breast milk to the breast-fed infant.

Frequency of different anti-depressants associated with suicides and drug deaths.

From each case of suicide and drug-related death autopsied in the Institute of Forensic Medicine, Munich during the years 2001--2005, a toxicological investigation on anti-depressants (AD) was performed. In 180 suicides and 72 narcotic drug death cases, ADs were detected: 4 different classic tricyclic anti-depressants (TCAs), 6 other non-selective monoamine re-uptake inhibitors (NSMRIs), 5 selective serotonin re-uptake inhibitors (SSRIs) and 3 other ADs. The suicides were grouped further according to the type of suicide (violent or non-violent). The prescription frequency of the ADs in Germany, expressed as the defined daily dosages (DDDs), during the investigated years served for comparison. There were serious differences in the frequency of different ADs regarding to the manner of suicide. In cases associated with doxepin and trimipramine, non-violent suicides were distinctly over-represented, as in cases in which the drug itself was responsible for the death as in cases of non-violent suicides in other manners. In contrast, in cases with citalopram or opipramol, violent forms of suicides were significantly over-represented. For amitriptyline, the ratio was approximately balanced. For the remainder of the ADs, the case numbers were too low for a valid evaluation. The different frequency distributions of the ADs, associated with violent and non-violent suicides may be explained by their different pharmacological active profiles and the different lethality of overdoses of the different ADs. There was no indication at all for a special suicidal problem of SSRIs in juveniles. Amongst 1,127 suicides within 5 years, in an area with approximately 5 million people, the youngest suicide victim with SSRIs was 28 years old. In drug death cases, citalopram was obviously over-represented.

Patch test reactivity to a cobalt-chromium-molybdenum alloy and stainless steel in metal-allergic patients in correlation to the metal ion release.

Nickel, chromium, and cobalt released from stainless steel and CoCrMo alloys have been postulated to trigger hypersensitivity reactions. The objective of this study was to assess the ion release from a CoCrMo alloy and stainless steel in vitro and the cutaneous reactivity to it by patch test. 52 metal-allergic patients and 48 non-allergic controls were patch tested to stainless steel and CoCrMo discs. In addition, using atomic absorption spectrometry, the release of nickel, cobalt, and chromium from both materials was assessed upon 2-day exposure to distilled water, artificial sweat (AS), and cell culture medium. There was low nickel ion release from stainless steel (0.3-0.46 microg/cm(2)/2 days) and CoCrMo discs (up to 0.33 microg/cm(2)/2 days) into the different elution media. Chromium release from the 2 materials was also very low (0.06-0.38 microg/cm(2)/2 days from stainless steel and 0.52-1.36 microg/cm(2)/2 days from CoCrMo alloy). In contrast, AS led to abundant cobalt release (maximally 18.94 microg/cm(2)/2 days) from the CoCrMo discs, with concomitant eczematous reaction upon patch testing: 0 of the 52 metal-allergic patients reacted to stainless steel discs and 5 of the 52 patients to CoCrMo discs (all 5 patients were cobalt allergic and 3 also nickel and chromium allergic). None of the controls reacted to the discs. Apart from nickel being a focus of allergological research, our results point to the possibly underestimated association of cobalt release and potential hyperreactivity to CoCrMo alloy.