Derivation of Biomonitoring Equivalents for aluminium for the interpretation of population-level biomonitoring data.

Aluminium is widely used in many consumer products, however the primary source of aluminium exposure to the Canadian general population is through food. Aluminium can cause neurotoxicity and reproductive toxicity at elevated exposure levels. Health-based exposure guidance values have been established for oral exposure to aluminium, including a Minimal Risk Level (MRL) by the Agency for Toxic Substances and Disease Registry (ATSDR), a Provincial Tolerable Weekly Intake (PTWI) by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) and a Tolerable Weekly Intake (TWI) by the European Food Safety Authority (EFSA). Aluminium concentration in blood and urine can be used as a tool for exposure characterization in a population. A pharmacokinetic (PK) model was developed based on human dosing data to derive blood Biomonitoring Equivalents (BEs), whereas a mass balance approach was used to derive urine BEs for the above guidance values. The BEs for blood for daily intake consistent with the MRL, PTWI and TWI were 18, 16 and 8 µg/L, respectively. BEs for urine for the same guidance values were 137, 123 and 57 µg/L, respectively. The derived BEs may be useful in interpreting population-level biomonitoring data in a health risk context and thereby screening and prioritizing substances for human health risk assessment and risk management.

Impact of Daily Antiperspirant Use on the Systemic Aluminum Exposure: An Experimental Intervention Study.

BACKGROUND AND OBJECTIVES: Adverse health effects such as neurotoxic and carcinogenic effects through aluminum from cosmetic products have been repeatedly discussed. The dermal uptake and impact on the systemic aluminum load is still poorly understood. Therefore, we investigated the effect of daily antiperspirant use on the systemic aluminum load under real-life conditions. METHODS: 21 healthy subjects meeting certain selection criteria to ensure a low systemic aluminum background load were asked to use a commercial aluminum-containing antiperspirant for 14 days. A questionnaire enquired about shaving habits and other sources of aluminum. Aluminum levels were measured before and after the exposure in 24-h urine and plasma using atomic absorption spectroscopy. Urine samples (n = 6) with <700 mg/day creatinine excretion or more than 30% difference in 24-h creatinine excretion were excluded from further analysis. RESULTS: No significant increase in plasma aluminum concentration or total excreted aluminum per day before and after exposure was measurable. No sample exceeded the reference values of the general population (maximum: 9.42 µg/g creatinine and 2.1 µg/L plasma). Shaving habits did not have a significant influence on the systemic aluminum load. Also, no correlation between the total amount of antiperspirant applied and the systemic aluminum level could be demonstrated. CONCLUSIONS: No measurable contribution to the overall systemically available aluminum load due to daily use of an antiperspirant for 14 days could be shown, but real-life data concerning long-term use or higher concentrations are still lacking. Considering toxicological occupational exposure data, adverse neurotoxic changes are unlikely in the case of urinary excretion of <50 µg aluminum/g creatinine (= no observed adverse effect level), even following long-term exposure.

Human biomonitoring of aluminium after a single, controlled manual metal arc inert gas welding process of an aluminium-containing worksheet in nonwelders.

PURPOSE: Several existing field studies evaluate aluminium welding works but no thoroughly controlled exposure scenario for welding fume has been described yet. This study provides information about the uptake and elimination of aluminium from welding fumes under controlled conditions. METHODS: In the Aachen Workplace Simulation Laboratory, we are able to generate welding fumes of a defined particle mass concentration. We exposed 12, until then occupationally unexposed participants with aluminium-containing welding fumes of a metal inert gas (MIG) welding process of a total dust mass concentration of 2.5 mg/m(3) for 6 h. Room air filter samples were collected, and the aluminium concentration in air derived. Urine and plasma samples were collected directly before and after the 6-h lasting exposure, as well as after 1 and 7 days. Human biomonitoring methods were used to determine the aluminium content of the samples with high-resolution continuum source atomic absorption spectrometry. RESULTS: Urinary aluminium concentrations showed significant changes after exposure compared to preexposure levels (mean t(1) (0 h) 13.5 µg/L; mean t(2) (6 h) 23.5 µg/L). Plasma results showed the same pattern but pre-post comparison did not reach significance. CONCLUSIONS: We were able to detect a significant increase of the internal aluminium burden of a single MIG aluminium welding process in urine, while plasma failed significance. Biphasic elimination kinetic can be observed. The German BAT of 60 µg/g creatinine was not exceeded, and urinary aluminium returned nearly to baseline concentrations after 7 days.

Reference values for metal(loid)s concentrations in the urine samples of healthy Iranian adults: Results from the first nationally representative human biomonitoring study.

BACKGROUND: This study measured the concentrations of arsenic (As), aluminum (Al), cadmium (Cd), chromium (Cr), mercury (Hg), nickel (Ni), and lead (Pb) in the urine samples of the Iranian adult population. METHODS: This nationally representative study was conducted on 490 participants in six provinces of Iran who were selected based on the clustering method. Participants included healthy Iranian adults aged above 25 years without a history of illness and non-smokers. Fasting urine sampling, body composition, and demographic measurements were performed for each participant. Urine samples were analyzed by acid digesting method using Inductively Coupled Plasma Mass Spectrometry (ICP-MS). The analysis included descriptive statistics and multiple linear regression using Python programming language. RESULTS: The geometrical mean (with corresponding reference values, µg/l) concentrations of metal(loid)s in urine for women, men, and both were 198.2 (625.3), 163.5 (486.1), and 192.5(570.4) for Al, 15.6(51.7), 28.8(71.1), and 21.9 (61.64) for As, 18.5(55.2), 20.7(56.5), and 19.22(55.75) for Pb, 17.9(57.6), 17.9 (53.9), and 17.9(56) for Ni, 13.95(47.5), 20.3(62.2) and 16(51.6) for Cr, 3.5(12.2), 2.9(11.5), and 3.3(12) for Hg, 0.74(2.7), 0.95 (3.6), and 0.81(3.1) for Cd. There was a direct relationship between the concentration of metal(loid)s and demographic indicators and body composition (P<0.05). Moreover, there was a direct relationship between the concentration of As, Cr, Hg, Ni, and Pb with age and wealth index (P<0.05). CONCLUSIONS: The concentrations found could be used as the reference range for As, Al, Cd, Cr, Hg, Ni, and Pb for human biomonitoring studies on the Iranian adult population.

Effect of an aluminum foil-processed diet on internal human aluminum burden.

BACKGROUND AND PURPOSE: Aluminum can be released into food by aluminum-containing food-contact materials (Al-FCM) during preparation or storage. There is considerable concern that extra aluminum intake may have negative effects on public health, especially with regard to its high background exposure and neurotoxic properties of aluminum in high exposures. Human in-vivo data on the additional aluminum load from Al-FCM, however, are lacking. As such, the objective of this study was to explore whether the consumption of a diet highly exposed to such products leads to an increased systemic Al load in real-world conditions. MATERIALS AND METHODS: An exploratory, single-arm intervention study with a partially standardized diet was designed and carried out with 11participants. The same 10-day sequence of dishes was repeated three times. Participants were exposed to Al-FCM from Days 11 to 20, whereas control-phase meals were prepared without Al-FCM during the first and last 10-day periods. Spot urine samples were collected each morning and evening and analyzed for their aluminum concentration; appropriate contamination countermeasures were taken. PRINCIPAL RESULTS: Urinary aluminum excretion showed a strong dependency on the creatinine concentration in urine and required adjustment in further analyses. The creatinine-adjusted aluminum excretion during the exposure phase (median 1.98 µg/g creatinine) was higher than in both control phases (1.78 µg/g creatinine each). Two different mixed-effects regression models showed a significant effect in the exposure phase. Considering a discrete time effect, the creatinine-adjusted mean increase in the exposure phase was estimated to be 0.19 µg/L (95% CI: 0.07-0.31; p = 0.0017). MAJOR CONCLUSIONS: This study demonstrated a measurable but fully reversible additional Al burden in humans from subacute Al-FCM exposure under real-world conditions. The estimated increase from Al-FCM corresponds to 8% of the baseline concentration. These data enable a more robust assessment of human health risks by Al-FCM.

Chelation of aluminum by combining deferasirox and deferiprone in rats.

The hypothesis that two known chelators deferasirox and deferiprone (L1) might be more efficient as combined treatment than as single therapies in removing aluminum from the body was tested in a new acute rat model. Seven-week-old male Wistar rats received chelators: deferasirox (orally [p.o.]), L1 (p.o.) or deferasirox + L1 as 100 or 200 mg/kg dose half an hour after a single intraperitoneal administration of 6 mg Al/kg body weight in the form of chloride. Serum aluminum concentration, urinary aluminum and iron excretions were determined by graphite furnace atomic absorption spectrometry. Both chelators were effective only at the higher dose level. While deferasirox was more effective than L1 in enhancing urinary aluminum excretion, L1 was more effective than deferasirox in enhancing urinary iron excretion. In the combined treatment group, deferasirox did not increase the L1 effect on aluminum and L1 did not increase the effect of deferasirox on iron elimination. Our results support the usefulness of this animal model for preliminary in vivo testing of aluminum chelators. Urinary values were more useful due to the high variability of serum results.

Biological effect markers in exhaled breath condensate and biomonitoring in welders: impact of smoking and protection equipment.

PURPOSE: The objective of this study was to investigate the effect of welding as well as the impact of smoking and protection measures on biological effect markers in exhaled breath condensate. Additionally, biomonitoring of chromium, aluminium and nickel in urine was performed to quantify internal exposure. METHODS: Exhaled breath condensate (EBC) and urine samples of 45 male welders and 24 male non-exposed control subjects were collected on Friday pre-shift and after 8 h of work post-shift. In EBC, biological effect markers such as malondialdehyde, nitrite, nitrate, 3-nitrotyrosine, tyrosine, hydroxyproline, proline, H(2)O(2) and pH-value were measured while aluminium, nickel, and chromium were measured in the urine samples. RESULTS: Although internal exposure to aluminium, nickel and chromium in this study was low, welders showed significantly increased concentrations of all these parameters at baseline compared to non-exposed controls. Moreover, welders had higher nitrate concentrations in EBC at baseline and after shift. Nitrate concentration was considerably lower after shift if personal protection equipment was used. H(2)O(2) was increased only when subjects smoked during shift. CONCLUSION: It has been shown that welding-associated long-term and short-term health effects could be detected in a population of welders. The results also showed that using personal protection equipment is of high importance and H(2)O(2) may be an effect marker associated with smoking rather than with welding fumes, while nitrate in EBC seems to be sensitive to welding fume exposure.

Health risk assessment of workers exposed to metals from an aluminium production plant.

OBJECTIVE: Foundry is an industry involved various kinds of metals and chemicals. Workers who work in foundry industry are at risk of exposure to these metals and chemicals. Objective of this study was to conduct quantitative health risk assessment for workers who exposed to metals from an aluminium production industry. MATERIAL AND METHOD: The U.S. National Academy of Sciences' four steps of health risk assessment were used to conduct quantitative health risk assessment in this study. RESULTS: This study showed that there were 6 types of metals involved in the aluminium foundry in this study. These metals could cause various health effects but not cancers. Workers were mostly exposed to these metals by inhalation. Calculated reference dose (RfD) for inhalation of aluminium used in this assessment was 0.000015 mg/kg/day. Calculated RID for inhalation of manganese used in this assessment was 0.000002 mg/kg/day. Calculated RfD for inhalation of copper used in this assessment was 0.000028 mg/kg/day. Calculated RID for inhalation of zinc used in this assessment was 0.000083 mg/ kg/day. Calculated RID for inhalation of magnesium used in this assessment was 0.949833 mg/kg/day. Calculated RID for inhalation of iron used in this assessment was 10.6219 mg/kg/day. Maximum daily doses (MDDs) for workers who exposed to metals measured in this foundry were 0, 0, 0.000463, 0.0000927, 0.000162 and 0 mg/kg/day for manganese, zinc, aluminium, iron, magnesium and copper, respectively. Finally, risk characterization for workers exposed to metals in this aluminium foundry showed that workers in this foundry had 31 times higher risk of developing diseases from aluminium than persons who were not exposed to aluminium. These workers had the same risk of developing diseases from other metals and chemicals as persons who were not exposed to those metals and chemicals. CONCLUSION: Workers who exposed to aluminium in this aluminium production plant had 31 times risk of developing non-carcinogenic effects from aluminium compared with normal persons. Therefore, appropriate preventive measures should be applied to protect workers.

Biomonitoring of Aluminum in Urine of Young Lebanese Children Living in Beirut.

BACKGROUND Aluminum (Al) is a ubiquitous, toxic metal to which infants and young toddlers are highly vulnerable. High Al exposure has been associated with various human pathologies. The aim of the present biomonitoring (BM) study was to provide a background for the levels of urinary aluminum (Al) in children ages 7 months to 4 years living in Beirut. MATERIAL AND METHODS We collected and analyzed 120 urine specimens using the Shimadzu Atomic Absorption Spectrophotometer-6300 system equipped with an electrothermal atomization, and using a GFA-EX7i graphite furnace. RESULTS The mean and standard deviation of Al level in urine revealed 8.978±12.275 µg/L, which is within the lower range of each of populations in Germany, Taiwan, and Poland. Vitamin intake, powder rice, and the use of Al utensils proved to be major determinants for Al level in urine (significant at 95%). CONCLUSIONS The Shimadzu Atomic Absorption Spectrophotometer-6300 system proved again to be an optimal and reliable instrument that can be used for the determination of Al level in urine, especially if using a GFA-EX7i pyrolytic graphite furnace. High levels of Al were found in the urine of Lebanese children. However, the frequent consumption of canned food did not prove to be a significant factor in determining the Al level in urine.

Longitudinal study on potential neurotoxic effects of aluminium: II. Assessment of exposure and neurobehavioral performance of Al welders in the automobile industry over 4 years.

OBJECTIVES: This is the second of two parallel longitudinal studies investigating Al exposure and neurobehavioral health of Al welders over 4 years. While the first published study in the trail and truck construction industry examined the neurobehavioral development of Al welders from age 41-45 in the group mean (Kiesswetter et al. in Int Arch Occup Environ Health 81:41-67, 2007), the present study in the automobile industry followed the development from 35 to 39. Although no conspicuous neurobehavioral developments were detected in the first study, which furthermore exhibited the higher exposure, it cannot be excluded that exposure effects appear in earlier life and exposure stages. METHODS: The longitudinal study is based on a repeated measurement design comprising 4 years with three measurements in 2 years intervals. 92 male Al welders in the automobile industry were compared with 50 non-exposed construction workers of the same industry and of similar age. The repeated measurements included total dust in air, and Al pre- and post-shift plasma and urine samples. Neurobehavioral methods comprised symptoms, verbal intelligence, logic thinking, psychomotor behavior, memory, and attention. The computer aided tests came from the Motor Performance Series and the European Neurobehavioral Evaluation System. The courses of neurobehavioral changes were analyzed with multivariate covariance-analytical methods considering the covariates age, indicators of 'a priori' intelligence differences (education or markers of 'premorbid' intelligence), and alcohol consumption (carbohydrate-deficient transferrin in plasma). Additionally, the interrelationship, reliability and validity of biomonitoring measures were examined. RESULTS: The mean environmental dust load during welding, 0.5-0.8 mg/m(3), and the mean internal load of the welders (pre-shift: 23-43 microg Al/g creatinine in urine; 5-9 microg Al/l plasma) were significantly lower than in the parallel study. Under low exposure, the stability of biomonitoring measures was reduced, but the Al load differed significantly between Al welders and referents. It could not be shown that the development of neurobehavioral performances over the 4-year period differed between both groups. Mainly, markers of premorbid intelligence and age were related to neurobehavioral performance differences but not Al exposure. CONCLUSIONS: The biomonitoring and neurobehavioral results are in line with the results of the first published study. The repeated measurement models of both studies showed no adverse neurobehavioral effects of Al welding. A modular lifetime-oriented research concept is outlined aiming at the investigation of sequential periods of exposure life with special focus on the biologically most sensitive phases like first exposure and old age.

A role for the body burden of aluminium in vaccine-associated macrophagic myofasciitis and chronic fatigue syndrome.

Macrophagic myofasciitis and chronic fatigue syndrome are severely disabling conditions which may be caused by adverse reactions to aluminium-containing adjuvants in vaccines. While a little is known of disease aetiology both conditions are characterised by an aberrant immune response, have a number of prominent symptoms in common and are coincident in many individuals. Herein, we have described a case of vaccine-associated chronic fatigue syndrome and macrophagic myofasciitis in an individual demonstrating aluminium overload. This is the first report linking the latter with either of these two conditions and the possibility is considered that the coincident aluminium overload contributed significantly to the severity of these conditions in this individual. This case has highlighted potential dangers associated with aluminium-containing adjuvants and we have elucidated a possible mechanism whereby vaccination involving aluminium-containing adjuvants could trigger the cascade of immunological events which are associated with autoimmune conditions including chronic fatigue syndrome and macrophagic myofasciitis.

[Changes of some elements in rat's tissues except nerve centre with both ovariectomy and chronic aluminum toxication and the effects of estrogen supplement].

OBJECTIVE: To reveal the influence of ovariectomy and chronic Aluminum toxication in combination on the distribution in tissues except nerve centre and excretion in urine of somel elements. The study will supply the basis for study of Alzheimers disease. METHODS: Forty 6-month-old female S-D rats were divided randomly into 4 groups: group OVX, group OVX + Al and group OVX + Al + E2. After 3 months, urine of 24 h were collected by metabolic cages; liver, kidney, heart, bone, tibia and skeletal muscle, were got from the rats. The content of the elements in these tissues and urine was detected by ICP-AES. RESULTS: Compared of group OVX with group sham, the content of Zn decreased (P < 0.001). Compared of group OVX + Al + E2 with group sham, the content of Al, Cd, Si and Se in heart increased (P < 0.05, P < 0.01, P < 0.01, P < 0.001). The content of Se and Cd in tibia increased (P < 0.01, P < 0.001). The content of Al in kidney increased (P < 0.05). The content of Mn and Cu increased (P < 0.05, P < 0.001), Se decreased (P < 0.001) in skeletal muscle. The content of Al, Se and Ca in spinal cord decreased (P < 0.05, P < 0.01, P < 0.05). The content of Mn, Zn and Si in liver increased (P < 0.01, P < 0.05, P < 0.05). The content of Cd, Mg, Se, Al and Ca in urine increased (P < 0.05, P < 0.05, P < 0.01, P < 0.001, P < 0.001). Compared of group OVX + Al + E2 with group OVX + Al, the content of Cd, Mn and Se in heart increased (P < 0.05, P < 0.05, P < 0.01). The content of Al, Mg, Se, Cd and Mn in tibia increased (P < 0.05, P < 0.01, P < 0.001, P < 0.001, P < 0.001). The content of Mn and Cu increased (P < 0.05, P < 0.001), Se decreased (P < 0.001), in skeletal muscle. The content of Se in spinal cord decreased (P < 0.05). The content of Al and Ca decreased (P < 0.05, P < 0.01), the content of Cu, Si, Fe, Mg, Mn and Zn incraesed(P <0.05, P < 0.05, P <0.01, P < 0.01, P < 0.001, P < 0.001), in liver. The content of Se, Al, Cd, Mg, Si and Ca in urine increased (P < 0.05, P < 0.05, P < 0.05, P < 0.05, P < 0.05, P < 0.01). CONCLUSION: Zn in heart can transfer to other tissues after a long time ovariectomy. Heart, skeletal muscle and liver, are mainly affected tissues except nerve centre by ovariectomy and chronic aluminum toxication in combination; and mainly affected elements are Zn, Si, Cu and Se. Chronic aluminum toxication make Si transfer to heart of ovariectomized rats, and facilitate Zn in heart transfer to other tissues. Supply estrogen can promote aluminum excretion in urine. distribution in tissues except nerve centre and excretion in urine of somel elements. The study will supply the basis for study of Alzheimers disease. METHODS: Forty 6-month-old female S-D rats were divided randomly into 4 groups: group OVX, group OVX + Al and group OVX + Al + E2. After 3 months, urine of 24h were collected by metabolic cages; Liver, kidney, heart, bone, tibia and skeletal muscle, were got from the rats. The content of the elements in these tissues and urine was detected by ICP-AES. RESULTS: Compared of group OVX with group sham, the content of Zn decreased (P < 0.001). Compared of group OVX + Al + E2 with group sham, the content of Al, Cd, Si and Se in heart increased (P < 0.05, P < 0.01, P < 0.01, P < 0.001). The content of Se and Cd in tibia increased (P < 0.01, P < 0.001). The content of Al in kidney increased (P < 0.05). The content of Mn and Cu increased (P < 0.05, P < 0.001),Se decreased (P < 0.001) in skeletal muscle. The content of Al, Se and Ca in spinal cord decreased (P < 0.05, P < 0.01, P < 0.05). The content of Mn, Zn and Si in liver increased (P < 0.01, P < 0.05, P < 0.05). The content of Cd, Mg, Se, Al and Ca in urine increased (P < 0.05, P < 0.05, P < 0.01, P < 0.001, P < 0.001). Compared of group OVX + Al + E2 with group OVX + Al, the content of Cd, Mn and Se in heart increased (P < 0.05, P < 0.05, P < 0.01). The content of Al, Mg, Se, Cd and Mn in tibia increased (P < 0.05, P < 0.01, P < 0.001, P < 0.001, P < 0.001). The content of Mn and Cu increased (P < 0.05, P < 0.001), Se decreased (P < 0.001), in skeletal muscle. The content of Se in spinal cord decreased (P < 0.05). The content of Al and Ca decreased (P < 0.05, P < 0.01), the content of Cu, Si, Fe, Mg, Mn and Zn incraesed(P <0.05, P < 0.05, P <0.01, P < 0.01, P < 0.001, P < 0.001), in liver. The content of Se, Al, Cd, Mg, Si and Ca in urine increased (P < 0.05, P < 0.05, P < 0.05, P < 0.05, P < 0.05, P < 0.01). CONCLUSION: Zn in heart can transfer to other tissues after a long time ovariectomy. Heart, skeletal muscle and liver, are mainly affected tissues except nerve centre by ovariectomy and chronic aluminum toxication in combination; and mainly affected elements are Zn, Si, Cu and Se. Chronic aluminum toxication make Si transfer to heart of ovariectomized rats, and facilitate Zn in heart transfer to other tissues. Supply estrogen can promote aluminum excretion in urine.

Aluminium levels in hair and urine are associated with overweight and obesity in a non-occupationally exposed population.

BACKGROUND: Data on the association between aluminium (Al) exposure and obesity and/or metabolic syndrome are insufficient. The objective of the present study was to investigate the association between hair and urine Al levels and obesity. METHODS: A total of 206 lean and 205 obese non-occupationally exposed subjects (30-50 y.o.) were enrolled in the study. Hair and urine Al levels were assessed with ICP-MS. Laboratory quality control was performed using the certified reference materials of human hair, plasma, and urine. RESULTS: Hair and urinary Al levels in obese subjects were significantly higher by 31% and 46% compared to the control levels, respectively. The presence of hypertension (41% cases), atherosclerosis (8%), type 2 diabetes mellitus (10%), and non-alcoholic fatty liver disease (NAFLD) (53%) in obese patients were not associated with Al levels in the studied subjects. An overall multiple regression model established urinary Al levels (ß = 0.395; p < 0.001), hypertension (ß = 0.331; p < 0.001) and NAFLD (ß = 0.257; p = 0.003) were significantly and directly associated with BMI. Hair Al levels were found to be border-line significantly related to BMI after adjustment for several confounders (ß = -0.205; p = 0.054). CONCLUSIONS: Aluminium body burden is associated with increased body weight, although the causal relationship between Al exposure and obesity is not clear. Both clinical and experimental studies are required to further investigate the impact of Al exposure on metabolic parameters in obesity and especially direct effects of Al in adipose tissue.

Association Between Exposure to Heavy Metals and Systemic Sclerosis: the Levels of Al, Cd, Hg, and Pb in Blood and Urine of Patients.

Systemic sclerosis (SSc) is a multisystem connective tissue disease; exogenous factors-including heavy metals-may have a role in the disease pathogenesis. In this context, a study on the quantification of Al, Cd, Hg, and Pb in blood and urine of 27 SSc patients and 30 controls was carried out. Main findings were that Al was significantly depleted in blood and increased in urine of SSc patients respect to controls; and Pb was found slightly increased in blood and significantly decreased in SSc group. In addition, higher Hg levels in urine were found in SSc subjects with the higher severity of the disease. Females showed the most marked differences in the levels of blood Al, blood Pb, and urine Cd between patients and controls. Smoking, hobby, ingestion of contaminated food, job exposure may contribute to the bodily levels of Al, Hg, Pb in SSc patients. The results indicated that low, chronic, and multiple exposures to heavy metals-also through habits, diet, and environment-may influence the risk for SSc.

Prenatal aluminum exposure is associated with increased newborn mitochondrial DNA copy number.

Aluminum is a widely distributed metal that has been reported to have embryotoxicity and fetotoxicity in animal studies. However, there has been no study of the association between prenatal aluminum exposure and newborn mitochondrial DNA copy number (mtDNAcn). We aimed to investigate the effect of prenatal aluminum exposure on newborn mtDNAcn. A total of 762 mother-newborn pairs were recruited between November 2013 and March 2015 in Wuhan city, China. We measured maternal urinary aluminum concentrations at three trimesters of pregnancy. Relative mtDNAcn was measured in DNA extracted from umbilical cord blood samples. We used generalized estimating equations to assess the relationship between prenatal aluminum exposure and newborn mtDNAcn. The geometric means of creatinine corrected aluminum concentrations were 31.0 µg/g Cr (95% CI: 27.6, 34.7), 40.9 µg/g Cr (95% CI: 35.7, 46.8) and 58.4 µg/g Cr (95% CI: 51.2, 67.4) for the first, second and third trimesters, respectively. After adjustment for potential confounding factors, a doubling of maternal urinary aluminum concentrations during the second and third trimesters was related to 3.16% (95% CI: 0.88, 5.49) and 4.20% (95% CI: 1.64, 6.81) increases in newborn mtDNAcn, respectively, while the association between maternal urinary aluminum concentration during the first trimester and newborn mtDNAcn was not significant (percent difference: 0.70%, 95% CI: -2.25, 3.73). Prenatal aluminum exposure during the second and third trimesters was positively associated with newborn mtDNAcn. Further studies are essential to elucidate on the potential health consequences of newborn mtDNAcn.

Increased urinary excretion of aluminium after ingestion of the food additive sodium aluminium phosphate (SALP) - a study on healthy volunteers.

Food is an important source of human aluminium (Al) exposure and regular consumption of foods containing Al-based food additives may result in high Al intakes above health-based tolerable intakes. However, some additives are Al salts with low solubility, and little is known about bioavailability of Al in these additives. We investigated urine Al concentrations in healthy adult volunteers (N = 18, women/men) before (base-line) and after 7 days of ingestion of pancakes with a low Al content (median: <0.5 mg Al/kg) and high Al content (median: 860 mg/kg). The high-Al pancakes contained the common additive sodium aluminium phosphate (SALP). The participants did not know if the pancakes contained SALP or not during the experiment. After adjusting for creatinine content of the urine samples, median base-line Al concentrations before pancake ingestion were in the range 30-40 µmol Al/mol creatinine. Urine Al concentrations after ingestion of low-Al pancakes (average intake: <0.042 Al mg/day) did not differ significantly from the base-line levels. After ingestion of high-Al pancakes (72 mg Al/day) the median Al concentration in urine was more than 2-fold higher than at the base-line sampling before the high-Al pancake ingestion. At the end of the experiment the volunteers ingested an Al-containing antacid (Al-OH, 1800 mg Al/day) for 7 days as a positive control of Al absorption. This caused a 10-fold increase in median urine Al concentration compared to base-line. Our results strongly suggest that Al in the form of SALP in a pancake mix is bioavailable for absorption in humans, which should be taken into account in risk assessment of Al in food in countries with a high use of SALP as a food additive.

Behavior of aluminum in aluminum welders and manufacturers of aluminum sulfate--impact on biological monitoring.

OBJECTIVES: The suitability of determining aluminum in serum or urine as a form of biological monitoring was critically assessed. METHODS: Airborne and internal aluminum exposure was assessed for 12 aluminum welders in a shipyard and 5 manufacturers of aluminum sulfate. Particles were characterized with X-ray diffraction and scanning electron microscopy. Aluminum in air and biological samples was analyzed using electrothermal atomic absorption spectrometry. Basic toxicokinetic features were inferred from the data. RESULTS: The mean 8-hour time-weighted average concentration of aluminum was 1.1 (range 0.008-6.1) mg/m(3) for the shipyard and 0.13 (range 0.02-0.5) mg/m(3) for the aluminum sulfate plant. Welding fume contained aluminum oxide particles <0.1 microm in diameter and their agglomerates, whereas bauxite and aluminum sulfate particles ranged from 1 to 10 microm in diameter. The shipyard welders' mean postshift serum and urinary concentrations of aluminum (S-Al and U-Al, respectively) were 0.22 and 3.4 micromol/l, respectively, and the aluminum sulfate workers' corresponding values were 0.13 and 0.58 micromol/l. Between two shifts, the welders' S-Al concentration decreased by about 50% (P<0.01), but their U-Al concentration did not change (P=0.64). No corresponding temporal changes occurred among the aluminum sulfate workers. After aluminum welding at the shipyard had ceased, the median S-Al concentration decreased by about 50% (P=0.007) within a year, but there was no change (P=0.75) in the corresponding U-Al concentration. CONCLUSIONS: About 1% of aluminum in welding fume appears to be rapidly absorbed from the lungs, whereas an undetermined fraction is retained and forms a lung burden. A higher fractional absorption of aluminum seems possible for aluminum sulfate workers without evidence of a lung burden. After rapid absorption, aluminum is slowly mobilized from the lung burden and dominates the S-Al and U-Al concentrations of aluminum welders. For kinetic reasons, S-Al or U-Al concentrations cannot be used to estimate the accumulation of aluminum in the target organs of toxicity. However, using U-Al analysis to monitor aluminum welders' lung burden seems practical.

Determination of trace aluminum in biological and water samples by cloud point extraction preconcentration and graphite furnace atomic absorption spectrometry detection.

A cloud point extraction (CPE) method for the preconcentration of trace aluminum prior to its determination by graphite furnace atomic absorption spectrometry (GFAAS) has been developed. The CPE method is based on the complex of Al(III) with 1-phenyl-3-methyl-4-benzoyl-5-pyrazolone (PMBP), and then entrapped in non-ionic surfactant Triton X-114. PMBP was used not only as chelating reagent in CPE preconcentration, but also as chemical modifier in GFAAS determination. The main factors affecting CPE efficiency, such as pH of sample solution, concentration of PMBP and Triton X-114, equilibration temperature and time, were investigated in detail. An enrichment factor of 37 was obtained for the preconcentration of Al(III) with 10 mL solution. Under the optimal conditions, the detection limit of this method for Al(III) is 0.09 ng mL(-1), and the relative standard deviation is 4.7% at 10 ng mL(-1) Al(III) level (n=7). The proposed method has been applied for determination of trace amount of aluminum in biological and water samples with satisfactory results.

Evaluation of toxic metals in blood and urine samples of chronic renal failure patients, before and after dialysis.

The determination of toxic elements in the biological samples of human beings is an important clinical screening procedure. The aim of this work was to determine total content of toxic elements-aluminum (Al), cadmium (Cd), and lead (Pb)-in whole blood and urine samples of male chronic renal failure patients (CRFPs) on maintenance hemodialysis from 2006 to 2007. The study included 100 CRFPs, plus 150 healthy volunteers in the control group. The concentration of toxic elements (TEs) were determined in blood sample before and after hemodialysis, while urine sample was determined once, before dialysis. Toxic elements were analyzed by electrothermal atomic absorption spectrometer, prior to microwave-induced acid digestion. The accuracy of the total Al, Cd, and Pb measurements was tested by simultaneously analyzing certified reference materials. No significant differences were established between the analytical results and the certified values (paired t-test at p > 0.05). The levels of TEs in blood samples of patients before dialysis were found to be higher than blood samples after dialysis session. In the control group, the blood levels of Al, Cd, and Pb were significantly lower than the chronic renal failure patients. Moreover, the study shows that analyzing levels of Al, Cd, and Pb may be useful in hemodialysis patients in evaluating TEs status.

Aluminium (Al) speciation in serum and urine after subcutaneous venom immunotherapy with Al as adjuvant.

BACKGROUND: Aluminium is associated with disorders and is the commonly used vaccine adjuvant. Understanding the mechanisms of how Al is transported, metabolized or of its toxicity depends on the knowledge of Al-interactions with bioligands, i.e. Al-species. Al-speciation in serum is difficult because of low concentration and the risk of exogenous Al contamination. Furthermore, Al-measurements may be hampered according to various interferences. This study aims for developing quality controlled protocols for reliable Al- and Al-species determination and for investigating probable differences in Al (-speciation) after Al-containing subcutaneous immunotherapy (SIT). METHODS: Sample donors were recruited either for the control group ("class-0", they never had been treated with SIT containing an Al-depot extract) or for the SIT-group ("class-1", they previously had been treated with SIT for insect venom allergy with an Al-depot extract). Blood was drawn for medical reasons and serum prepared. Additionally, some sample donors collected 24-h-urine. They had been informed (and they consented) about the scientific use of their samples. The study was approved by the ethic committee of the "Medical Association Westphalia-Lippe" and of the University of Münster, evaluating the study positively (No. 2013-667-f-S). We applied quality controlled sample preparation and interference-free Al detection by ICP sectorfield-mass spectrometry. Al-species were analysed using size-exclusion-chromatography-ICP-qMS. FINDINGS: Al-concentrations or speciation in urine samples showed no differences between class-0 and class-1. Al-citrate was the main uric Al-species. In serum elevated Al-concentrations were found for both classes, with class-1 samples being significantly higher than class-0 (p = 0.041), but class-0 samples being approximately 10-fold too high compared to reference values from non-exposed persons. We identified gel-monovettes as contamination source. In contamination-free samples from HNO3-prewashed gel-free monovettes (n = 27) there was no difference in the serum Al concentration between the two patient groups (p = 0.669) INTERPRETATION: Thorough cleaning of sample preparation ware and use of gel-free monovettes is decisive for an accurate Al analysis in serum. Without these steps, wrong analysis and wrong conclusions are likely. We conclude that gel-monovettes are unsuitable for blood sampling with subsequent Al-analysis. Whether Al in serum is elevated after SIT treatment containing an Al-depot extract, or not, remains inconclusive as the non-contaminated sample size was small.