Absence of toxicity and genotoxicity in an extract of Rubus coriifolius.

Rubus coriifolius Focke is a wild plant from the Rosaceae family. It grows in both Guatemala and Mexico. The polar extract of the aerial parts of this plant has antibacterial, anti-inflammatory, and anti-protozoal activities. These properties may explain the traditional use of this plant. In vivo and in vitro assays were used to assess the genotoxic and toxic effects of an ethanol extract of the aerial parts of R. coriifolius. Three groups of rats were orally administered the R. coriifolius extract diluted in ethanol (5%) at doses of 1.89 mg/kg body weight (low dose), 4.72 mg/kg body weight (medium dose), and 9.44 mg/kg body weight (high dose) for 3 weeks. Genotoxic/cytotoxic effects induced by the R. coriifolius ethanol extract were evaluated in vivo by a micronuclei (MN) test in rat's bone marrow cells and in vitro by MN and sister chromatid exchange (SCE) in human lymphocyte cultures. In vivo genotoxicity analyses revealed that the average number of micronucleated polychromatic erythrocytes and the polychromatic erythrocyte/red blood cell ratio at all doses were not significantly different from those of the negative control. In vitro genotoxicity analyses showed that MN, SCE, and proliferative index frequencies in a human lymphocyte cell culture were not significantly different from those of the negative control. These results demonstrate that the ethanol extract of R. coriifolius aerial parts is not toxic or mutagenic (in vitro and in vivo) and does not affect cell proliferation at the concentrations analyzed.

Occurrence of monomethylarsonous acid in urine of humans exposed to inorganic arsenic.

Monomethylarsonous acid (MMA(III)) has been detected for the first time in the urine of some humans exposed to inorganic arsenic in their drinking water. Our experiments have dealt with subjects in Romania who have been exposed to 2.8, 29, 84, or 161 microg of As/L in their drinking water. In the latter two groups, MMA(III) was 11 and 7% of the urinary arsenic while the monomethylarsonic acid (MMA(V)) was 14 and 13%, respectively. Of our 58 subjects, 17% had MMA(III) in their urine. MMA(III) was not found in urine of any members of the group with the lowest level of As exposure. If the lowest-level As exposure group is excluded, 23% of our subjects had MMA(III) in their urine. Our results indicate that (a) future studies concerning urinary arsenic profiles of arsenic-exposed humans must determine MMA(III) concentrations, (b) previous studies of urinary profiles dealing with humans exposed to arsenic need to be re-examined and re-evaluated, and (c) since MMA(III) is more toxic than inorganic arsenite, a re-examination is needed of the two hypotheses which hold that methylation is a detoxication process for inorganic arsenite and that inorganic arsenite is the major cause of the toxicity and carcinogenicity of inorganic arsenic.

DMPS (2,3-dimercaptopropane-1-sulfonate, dimaval) decreases the body burden of mercury in humans exposed to mercurous chloride.

DMPS (2,3-dimercaptopropane-1-sulfonate, Na salt), when used as a challenge test for mercury in workers involved in the production of a calomel skin-bleaching lotion and in direct contact with mercurous chloride, elevated urine levels of mercury. A DMPS treatment regimen was devised and initiated. Three days after the challenge test, DMPS was administered p.o. (400 mg per day) for 8 days, followed by a no-treatment period of five days. A new cycle of DMPS treatment for 7 days was initiated and followed by 5 days without treatment. A third period of treatment was begun for 6 days, followed by a 5-day no-treatment period. The urinary mercury greatly increased during those periods when DMPS was administered (1754, 314, and 173 microgram/24 h for the periods 1, 2 and 3, compared with 106, 48 and 53 microgram/24 h on the corresponding no-treatment periods). One of the workers presented signs of drug intolerance and was discharged after receiving the first cycle of treatment. DMPS treatment was effective in lowering the body burden of mercury and in decreasing the urinary mercury concentration to normal levels.

DMPS-arsenic challenge test. I: Increased urinary excretion of monomethylarsonic acid in humans given dimercaptopropane sulfonate.

The purpose of the present study was to evaluate in a novel manner the arsenic exposure of humans living in two towns in Northeastern Chile. Residents of one town drink water containing 593 microg As/l. Those in the control town drink water containing 21 microg As/l. Our hypothesis was that the administration of the chelating agent, 2,3-dimercaptopropane-1-sulfonic acid, Na salt (DMPS, DIMAVAL) would increase the urinary excretion of arsenic, alter the urinary profile of arsenic species and thus result in a better indication of the body load of arsenic and a better biomarker for arsenic exposure. The method used to evaluate these subjects was to give them 300 mg DMPS by mouth, after an overnight fast, and collect urine at specified time periods. The urine samples were analyzed for inorganic arsenic, monomethylarsonic acid (MMA), dimethylarsinic acid (DMA) and total arsenic by hydride generation and atomic absorption spectrophotometry. The results indicated that: 1) During the 2-hr period after DMPS administration, MMA represented 42%, inorganic As, 20 to 22% and DMA, 37 to 38% of the total urinary arsenic. The usual range of the MMA percentage in human urine has been 10 to 20%. The % MMA increased almost equally for both the arsenic-exposed and control subjects. 2) The exposed subjects had a greater urinary excretion of total arsenic, before and after DMPS administration, than the control subjects. 3) Although buccal cells were obtained only from a few subjects, the prevalence of mononucleated buccal cells, an indication of genotoxicity, was 5-fold greater for those who consumed drinking water with the higher arsenic content than among control subjects. Our conclusions are that 1) DMPS has a highly specific effect in humans on MMA metabolism and/or urinary excretion; 2) the human body stores substantial amounts of arsenic; and 3) the urinary arsenic concentration after DMPS administration may be more indicative of the body burden of arsenic because it was greater than that found before DMPS was given.

Sodium 2,3-dimercaptopropane-1-sulfonate challenge test for mercury in humans. III. Urinary mercury after exposure to mercurous chloride.

The sodium salt of 2,3-dimercaptopropane-1-sulfonic acid (Dimaval; DMPS) challenge test has been given previously to humans exposed to elemental mercury (vapor) or mercuric salts, but not mercurous salts. The test (300 mg p.o., after an 11-hr fast) was given to 11 factory workers who make a skin lotion that contains mercurous chloride, eight users of the skin lotion and nine controls. Urines were analyzed for total mercury by using cold vapor atomic absorption spectrophotometry. The mercury excreted for 6 hr before and 6 hr after DMPS treatment was 113 micrograms +/- 26 and 5037 micrograms +/- 682 S.E.M. for the skin lotion makers; 16.2 micrograms +/- 3.4 and 1410 micrograms +/- 346 S.E.M. for the skin lotions users; and 0.49 micrograms +/- 0.11 and 18.4 micrograms +/- 7.1 S.E.M. for the controls, respectively. The increases in urinary mercury resulting from the DMPS challenge test were 45-, 87- and 38-fold, respectively. The results demonstrate that, in humans exposed to mercurous chloride, DMPS increases the urinary excretion of mercury and that the DMPS/mercury challenge test is of value for a more realistic estimation of mobilizable mercury. An attempt to associate genotoxicity, as indicated by micronuclei content in buccal cells, with mercury exposure was inconclusive, perhaps because of the small number of subjects.

Mobilization of heavy metals by newer, therapeutically useful chelating agents.

Four chelating agents that have been used most commonly for the treatment of humans intoxicated with lead, mercury, arsenic or other heavy metals and metalloids are reviewed as to their advantages, disadvantages, metabolism and specificity. Of these, CaNa2EDTA and dimercaprol (British anti-lewisite, BAL) are becoming outmoded and can be expected to be replaced by meso-2,3-dimercaptosuccinic acid (DMSA, succimer) for treatment of lead intoxication and by the sodium salt of 2,3-dimercapto-1-propanesulfonic acid (DMPS, Dimaval) for treating lead, mercury or arsenic intoxication. Meso-2,3-DMSA and DMPS are biotransformed differently in humans. More than 90% of the DMSA excreted in the urine is found in the form of a mixed disulfide in which each of the sulfur atoms of DMSA is in disulfide linkage with an L-cysteine molecule. After DMPS administration, however, acyclic and cyclic disulfides of DMPS are found in the urine. The Dimaval-mercury challenge test holds great promise as a diagnostic test for mercury exposure, especially for low level mercurialism. Urinary mercury after Dimaval challenge may be a better biomarker of low level mercurialism than unchallenged urinary mercury excretion.

Sodium 2,3-dimercaptopropane-1-sulfonate challenge test for mercury in humans: II. Urinary mercury, porphyrins and neurobehavioral changes of dental workers in Monterrey, Mexico.

The sodium salt of 2,3-dimercaptopropane-1-sulfonic acid (DMPS) challenge test (300 mg p.o. after an 11-hr fast) was given in Monterrey, Mexico to dental and nondental personnel. Urine samples were collected and analyzed for total mercury. The mean mercury urinary excretion (+/- S.E.) for 6 hr before and 6 hr after DMPS administration for 10 dental technicians, who formulate amalgam, was 4.84 micrograms +/- 0.742 and 424.0 micrograms +/- 84.9; for 5 dentists, who use amalgam in their practice, 3.28 micrograms +/- 1.11 and 162.0 micrograms +/- 51.2; and for 13 nondental personnel, 0.783 microgram +/- 0.189 and 27.3 micrograms +/- 3.19. The urinary coproporphyrin levels before DMPS administration, which are indicative of renal mercury content, were quantitatively associated with the urinary mercury levels among the three study groups after DMPS administration. This was not so if the urinary mercury level before DMPS administration was compared with the urinary coproporphyrin concentration. The urinary mercury level after DMPS administration is a better indicator of exposure and renal mercury burden than is the mercury level measured in the urine before DMPS is given. Regression analysis showed that the coefficient of urinary mercury was statistically and adversely associated with complex attention (switching task), the perceptual motor task (symbol-digit substitution), symptoms and mood. The easily performed DMPS-mercury challenge test is useful for monitoring dental personnel for mercury vapor exposure.

Penicillamine produces changes in the acute blood elimination and tissue accumulation of thallium.

D-penicillamine (PCA) is used by some physicians in human thallium intoxication. With the aim of learning how the blood thallium altered kinetics and the modifications produced on the tissue accumulation, we administered PCA to white male thallium dosed rabbits. The method consisted of intravenous (i.v.) administration of thallium (10 mg/kg) to three groups of rabbits. The first group (control) received only the metal, the second group (treatment A) received PCA (25 mg/kg) at the 70th minute after thallium dose, the third group (treatment B) received the PCA at the same dose, 30 sec before the metal was administered. For kinetics studies, blood samples were collected in all groups at minutes 65, 70, 71, 73, 75, 80, 85 and 90. For thallium accumulation studies, bile, urine and tissue samples were collected. Thallium analyses were made by atomic absorption spectrophotometry. The results showed that in treatment A rabbits, the blood thallium concentration raised significantly at the 71st and 73rd minutes. Concerning metal in tissues, muscle mass accumulated significantly more thallium by the B-treatment, while brain accumulation was significantly greater with treatment A. In conclusion, the PCA modifies the blood thallium elimination acute kinetics for a few minutes and changes its accumulation in some tissues, suggesting that PCA extracts the metal from tissues and then re-distributes it throughout the organism.

[Mobilization of lead in patients with chronic poisoning by that metal. Oral penicillamine]. / Movilización de plomo en pacientes con intoxicación crónica por el metal. Penicilamina oral.

Penicillamine was administered, per os, in patients who had been working with lead for several years, showing signs and symptoms suggesting chronic lead intoxication, so as to evaluated the test of lead chelation. A positive response allowed further treatment. Daily elimination of urinary lead, delta-aminolevulinic acid and coproporphyrin were evaluated. Weekly assays of hematic lead, protoporphyrin IX and the activity of the enzyme delta-aminolevulinic acid dehydratase were performed. The result show penicillamine to be an alternative to ethylene diamine tetra acetic acid in the chelatable lead mobilization test and prove that it is an excellent alternative in the treatment of chronic lead intoxication.

Probable alteracion en la transmision neuromuscular en un caso de saturnismo. / Probable change in the neuromuscular transmission in a case of saturnism

Se examino a un nino de cuatro anos y medio de edad quien habia vivido desde su nacimiento en un ambiente contaminado con plomo. Dos meses antes de su admision hospitalaria el menor presento una crisis que sugeria ataque al sistema nervioso central y que fue seguido de una manifestacion de neuropatia periferica (marcha en "estepaje"). En examenes especificos de laboratorio, radiograficos y electrofisiologicos se observaron alteraciones compatibles con un cuadro grave de saturnismo infantil que cursaba con trastornos bilaterales de la funcion neuromuscular en la region del nervio ciatico popliteo externo. Tres semanas despues de iniciado el tratamiento a base de EDTA calcico disodico, se observo notable mejoria en la dorsiflexion de ambos pies; se observo tambien mejoria concurrente en los resultados de los examenes electrofisiologicos y de laboratorio que son especificos para el saturnismo. Los resultados sugieren que la transmision neuromuscular en el hombre puede verse afectada de manera reversible por el plomo