ABSTRACT
The Norwegian Scientific Committee for Food Safety (Vitenskapskomiteen for mattrygghet, VKM) has, at the request of the Norwegian Food Safety Authority (Mattilsynet; NFSA), assessed the risk of "other substances" in food supplements and energy drinks sold in Norway. VKM has assessed the risk of doses in food supplements and concentrations in energy drinks given by NFSA. These risk assessments will provide NFSA with the scientific basis while regulating the addition of "other substances" to food supplements and other foods. "Other substances" are described in the food supplement directive 2002/46/EC as substances other than vitamins or minerals that have a nutritional and/or physiological effect. It is added mainly to food supplements, but also to energy drinks and other foods. VKM has not in this series of risk assessments of "other substances" evaluated any claimed beneficial effects from these substances, only possible adverse effects. The present report is a risk assessment of specified doses of L-aspartic acid in food supplements, and it is based on previous risk assessments and articles retrieved from literature searches. According to information from NFSA, L-aspartic acid is an ingredient in food supplements sold in Norway. NFSA has requested a risk assessment of 3000, 3500, 4000, 4500, 5000 and 5700 mg/day of L-aspartic acid in food supplements. L-aspartic acid is a dispensable dicarboxylic amino acid that can be produced by the transamination of oxaloacetic acid, an intermediate in the metabolism of e.g. glucose and some amino acids. L-aspartic acid is present in frequently consumed foods of animal and plant origin and is also a component of the sweetener aspartame. Dietary intake of aspartic acid in Norway is not known, but data from NHANES III (USA) suggest a mean dietary intake of about 6.5 g/day in adults. The highest intake was seen in men 31 through 50 years of age at the 99th percentile of 15.4 g/day. In the literature review we did not identify any long-term studies in human individuals that could be used for risk assessment. Short-term human studies found no adverse health effect when L-aspartic acid was given in acute doses ranging from 1 to 10 g/day, for time periods between one single dose and four weeks. None of these studies were undertaken to assess the toxicity of L-aspartic acid. In the literature search, two animal studies were identified of which one was a 90-day subchronic toxicity study. In that study, a no observed adverse effect level (NOAEL) of 697 mg/kg bw per day in male rats and 715 mg/kg bw per day in female rats was established. No neurotoxicity was found, however a toxic effect on kidneys and possibly salivary glands was observed at 1400 mg/kg bw per day (lowest observed adverse effect level, LOAEL). For the risk characterisation, the NOAEL of 697 mg/kg bw per day derived from the abovementioned subchronic toxicity study in rats was used for comparison with the estimated exposures from food supplements. The calculated Margin of Exposure (MOE) values for this NOAEL ranged from 5 to 16 for a daily intake of 3000-5700 mg/day of Laspartic acid. These low MOE-values may not be regarded as acceptable since L-aspartic acid has caused toxic effects on the kidneys (regenerative renal tubules with tubular dilation) and acinar cell hypertrophy of salivary glands in rats. Further, direct information regarding potential adverse health effects in humans is not available due to absence of long-term studies. In adults (≥18 years), adolescents (14 to < 18 years) and children (10 to < 14 years), the specified doses 3000, 3500, 4000, 4500, 5000 and 5700 mg/day L-aspartic acid in food supplements may represent a risk of adverse health effects. Children younger than 10 years were not within the scope of the present risk assessment.
ABSTRACT
This study aimed to develop a UPLC-MS/MS method for determining plasma levels of L-aspartic acid and L-asparagine and the activity of L-asparaginase. L-aspartic acid, L-asparagine, and L-aspartic acid-2,3,3-d3 were extracted from human plasma by protein precipitation with sulfosalicylic acid (30%, v/v). The plasma samples were analyzed using an Imtakt Intrada amino acid analysis column with 25 mM ammonium formate and 0.5% formic acid in acetonitrile as the mobile phase with step gradient method at a flow rate of 0.5 mL/min. The injection volume was 5 µL, and the total run time was 15 min. Inter- and intra-batch accuracies (%) ranged from 96.62–106.0% for L-aspartic acid and 89.85–104.8%, for L-asparagine, and the coefficient of variation (CV%) did not exceed 7%. The validation results for L-aspartic acid and L-asparagine satisfied the specified criterion, however, the results for L-asparaginase activity assay showed a borderline validity. This study could be a foundation for further development of therapeutic drug monitoring systems using UPLC-MS/MS.
Subject(s)
Humans , Ammonium Compounds , Asparagine , Aspartic Acid , Drug Monitoring , Methods , PlasmaABSTRACT
The electrocatalytic oxidation of dopamine (DA) was studied by electrochemical approaches at a carbon ionic liquid electrode (CILE) modified with the composite film of nafion and L-aspartic acid (NL-CILE). The CILE was fabricated by replacing non-conductive organic binders with a room-temperature hydrophobic ionic liquid, 1-butyl-3-methyl-imidazolium hexafluorophosphate. The composite film of NL was used as matrix to adsorb DA and catalyze the oxidation of DA in phosphate buffer solution (PBS). The electrochemical response of DA was investigated at the NL-CILE, the traditional carbon paste electrode (TCPE), CILE and the nafion modified CILE (N-CILE) in 0.1 M PBS (pH 7.4), respectively. The results showed the superiority of NL-CILE to N-CILE, CILE and TCPE in terms of provision of higher sensitivity, faster electron transfer and better reversibility. Under optimum condition, the oxidation peak current was rectilinear with DA concentration range from 0.1 μM to 0.1 mM, with a detection limit of 0.03 μM (S/N=3) by differential pulse voltammetry. The proposed method was applied to determine DA in samples successfully.
ABSTRACT
The electrocatalytic oxidation of dopamine (DA) was studied by electrochemical approaches at a carbon ionic liquid electrode (CILE) modified with the composite film of nafion and L-aspartic acid (NL-CILE). The CILE was fabricated by replacing non-conductive organic binders with a room-temperature hydrophobic ionic liquid, 1-butyl-3-methyl-imidazolium hexafluorophosphate. The composite film of NL was used as matrix to adsorb DA and catalyze the oxidation of DA in phosphate buffer solution (PBS). The electrochemical response of DA was investigated at the NL-CILE, the traditional carbon paste electrode (TCPE), CILE and the nafion modified CILE (N-CILE) in 0.1M PBS (pH 7.4), respectively. The results showed the superiority of NL-CILE to N-CILE, CILE and TCPE in terms of provision of higher sensitivity, faster electron transfer and better reversibility. Under optimum condition, the oxidation peak current was rectilinear with DA concentration range from 0.1μM to 0.1mM, with a detection limit of 0.03μM (S/N=3) by differential pulse voltammetry. The proposed method was applied to determine DA in samples successfully.
ABSTRACT
The silver doped poly(L-aspartic acid) modified electrode was prepared by cyclic voltammetric method. The voltammetric behavior of dopamine and cyclic voltammetric method for the determination of dopamine were studied on the silver doped poly(L-aspartic acid) modified electrode. In pH 7.0 phosphate buffer solution, the peak potential was 0.191 V of Epa and 0.161 V of Epc(vs.Ag/AgCl) at the scan rate of 50 mV/s. The linear ranges for the determination of dopamine were 3.0×10-7-1.0×10-5 mol/L and 1.0×10-5-5.0×10-4 mol/L. The detection limit was 5.0×10-8 mol/L. The method was applied to the determination of dopamine in drug and urine with satisfactory results.