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A B Smith

Publications and source records attributed to A B Smith.

At least 145 records · Page 8Linked to original sources
PubMed1989

Mechanistic aspects of the dithiocarbamate-induced mobilization of cadmium.

The examination of some of the species involved in the in vivo processes in which dithiocarbamates mobilize cadmium from its intracellular deposits indicates that several competing reactions occur. Rates of hydrolytic decomposition of a series of dithiocarbamates capable of mobilizing cadmium in vivo have been determined, and the solubility behavior and nuclear magnetic resonance (NMR) spectra of their cadmium complexes have been examined. Some of the dithiocarbamates most effective in this mobilization process are shown to undergo slow conversion to oxazolidine-2-thiones in the presence of cadmium. All of the cadmium complexes involved in the mobilization process are shown to undergo rapid ligand exchange. While dissociative mechanisms based on the turnover of metallothionein are inconsistent with the experimental data, at least two associative mechanisms are possible. These involve attack on the metallothionein by the dithiocarbamate itself or by a compound derived from it by known metabolic processes.

Animals↗
PubMed1989

N,N-disubstituted dithiocarbamates as cadmium antagonists: N-(4-methoxybenzyl)-N-dithiocarboxy-D-glucamine.

The newly synthesized dithiocarbamate analog, N-(4-methoxybenzyl)-N-dithiocarboxy-D-glucamine (MeOBDCG) reduced whole-body cadmium levels 66% in cadmium-laden mice when given as 3 injections at 1.0 mmol/kg. Renal and hepatic Cd concentrations were reduced 78 and 85%, respectively. After 6 injections, the whole-body cadmium burden was reduced 71%, while renal and hepatic levels were lowered 84% and 91%, respectively. Mobilized cadmium was excreted almost exclusively by the fecal route. There was no evident toxicity consequent to treatment as judged by mouse body weights and by gross appearance of organs upon dissection. On a molar dose basis, MeOBDCG was more effective than N-benzyl-N-dithiocarboxy-D-glucamine (BDCG) in removing cadmium from both renal and hepatic deposits. An in-vitro assessment of the interaction of MeOBDCG, BDCG and N-methyl-N-dithiocarboxy-D-glucamine with murine cadmium-metallothionein (Cd-MT) revealed a direct relationship between the extent of cadmium depletion from Cd-MT and the relative in-vivo efficacies of the 3 analogs.

Animals↗
PubMed1989

Mobilization of lead by esters of meso-2,3-dimercaptosuccinic acid.

An examination was made of the relative efficacies of 2,3-dimercapto-1-propanol (BAL) and three diesters ( [CH(SH)COOR]2; DMDMS, R = CH3; DEDMS, R = C2H5; and Di-PDMS, R = CH(CH3)2] of meso-2,3-dimercaptosuccinic acid (DMSA) in mobilizing freshly injected lead from mice. These diesters, like BAL, reduced the lead levels resulting from freshly injected lead in both the soft tissues (liver, kidneys, spleen, and brain) and the bone (tibia). After treatment with the dimethyl (DMDMS), the diethyl (DEDMS), and the diisopropyl (Di-PDMS) esters the lead content of each of the organs was significantly less than that present in the untreated controls. Each of the diesters reduced lead levels in the kidneys, liver, and spleen significantly below those levels found after BAL treatment. The action of the diesters in reducing brain lead levels was comparable to that of BAL. Di-PDMS was the most effective of these compounds and was significantly superior to BAL. Each of the esters was also significantly more effective than BAL in reducing the whole body level of lead.

Animals↗
PubMed1989

Effect of chelating agent structure on the mobilization of cadmium from intracellular deposits.

An examination of the efficacy of several structural types of chelating agents in the removal of cadmium from its intracellular deposits in mouse liver and kidneys reveals that of the structural types examined, only dithiocarbamates and a vicinal dithiol were able to mobilize cadmium from such intracellular sites. Esters of L-cysteine, a macrocyclic thioether, and a disulfide of a dithiocarbamate were unable to cause any appreciable decrease in either renal or hepatic cadmium levels. Charged groups such as carboxylic acid groups reduce the efficacy as well as the toxicity of the structural types that can otherwise mobilize such cadmium. It was also found that the administration of a cadmium-binding polymer ip leads to only a very slight net excretion of cadmium, while the po administration of this polymer leads to no net additional cadmium excretion. Of the compounds newly reported here, some are approximately equal in cadmium-mobilizing efficacy to the most effective of previously reported compounds.

Animals↗
PubMed1989

Occupational exposure to zeranol, an animal growth promoter.

Zeranol (3,4,5,6,7,8,9,10,11,12-Decahydro-7,14,16-trihydroxy-3-methyl-1H-2 - benzoxacyclotetradecin-1-one) is a synthetic oestrogenic agent used as an animal growth promoter. The effects of occupational exposure to zeranol in 11 exposed workers from a pelletising plant and 14 nonexposed subjects were assessed. A questionnaire showed that more breast symptoms were reported by male and female plant workers compared with non-exposed subjects, although the difference was not statistically significant. Clinical assessment showed no cases of gynaecomastia in all the male participants. Blood samples analysed by high performance liquid chromatography for zeranol, its precursor zearalenone, and its main metabolites did not show any of these compounds above the laboratory limit of detection. Serum levels of follicle stimulating hormone (FSH), luteinising hormone (LH), prolactin, and oestradiol showed no striking differences between the exposed and the non-exposed subjects. Total and low density lipoprotein cholesterol (LDL cholesterol) levels did not significantly differ between the two groups but mean high density lipoprotein cholesterol (HDL cholesterol) levels were higher in the exposed group; this could be due to relatively high HDL cholesterol in two women exposed to zeranol or relatively low HDL cholesterol in three non-exposed men.

Adult↗
PubMed1989

Reducing knee morbidity among carpetlayers.

Carpetlayers have a high prevalence of occupational knee morbidity, partly attributable to their use of the knee kicker to stretch carpet for wall-to-wall installation. While a mechanical alternative "power stretcher" is available, knee kickers are still widely used. A questionnaire survey indicated that unavailability of the mechanical stretcher at installation sites was a major factor for continued use of the knee kicker. Strategies to reduce use of the knee kicker are discussed.

Floors and Floorcoverings↗
PubMed1989

Comparative effects of disulfiram and diethyldithiocarbamate on cadmium distribution in mice.

It has been reported that disulfiram (DSF) and diethyldithiocarbamate (DDTC) have similar actions on cadmium (Cd) distribution in maternal and fetal organs when given to pregnant mice prior to and again immediately after iv administration of Cd (Arch. Toxicol. 55, 161-167, 1984). We have now examined Cd distribution in mice in which virtually all of the Cd was bound to metallothionein (MT) in an attempt to simulate more closely the condition of low level, chronic Cd exposure. When DSF was incorporated into food and ingested by mice over a 4-hr period on each of four days, hepatic and pulmonary Cd levels were reduced significantly. When given ip at 500 mg/kg, DDTC lowered hepatic, renal, splenic, and pancreatic Cd levels, but increased Cd concentrations in brain, testes, heart, and lungs. When DSF was given at 500 mg/kg ip, it lowered hepatic, splenic, testicular, and pancreatic Cd levels, but increased Cd concentrations in heart and brain. In contrast to DDTC, DSF had no effect on pulmonary or renal Cd. When given as a bolus dose po for five days at 1.0 mmole/kg, DDTC lowered renal, splenic, testicular, and pancreatic Cd levels, but increased Cd concentrations in brain and heart. There was no effect on hepatic or pulmonary Cd. When given at the same dose po, DSF did not alter the Cd concentration of any organ assessed. We suggest that studies of interactions of various xenobiotics with Cd in vivo should be done with an animal model which simulates chronic Cd exposure rather than acute Cd intoxication.

Animals↗
PubMed1988

Esters of meso-dimercaptosuccinic acid as cadmium-mobilizing agents.

The dimethyl, diethyl, di-n-propyl, diisopropyl (Di-PDMS), and di-n-butyl esters of meso-2,3-dimercaptosuccinic acid were prepared by esterification of the parent acid and were subsequently purified and characterized. Their relative ability to mobilize cadmium from its aged (greater than 30 days) deposits was evaluated in mice in comparison with 2,3-dimercapto-1-propanol (BAL). All but the dimethyl ester were superior to BAL in reducing the hepatic cadmium levels, though none was superior in reducing renal cadmium levels. Their efficacy in reducing hepatic cadmium levels had the result that all except the dimethyl ester were significantly more effective than BAL in reducing total cadmium body burdens in mice. The most effective of these compounds, Di-PDMS, caused a reduction of whole body cadmium of 59% (i.e., to 41% of control values) under conditions where the corresponding reduction found for BAL was only 18% (i.e., to 82% of control value). The predominant route of excretion of cadmium subsequent to administration of these compounds is via the fecal route (greater than 99%). A synergistic effect was found in the reduction of whole body and kidney cadmium burdens when Di-PDMS was used in combination with trisodium calcium diethylenethriaminepentaacetate.

Animals↗
PubMed1988

N-alkyl-N-dithiocarboxy-D-glucamine analogs as cadmium antagonists: synthesis and evaluation of the n-propyl, n-butyl, and n-amyl derivatives.

N-(n-Propyl)-, N-(n-butyl)-, and N-(n-amyl)-N-dithiocarboxy-D-glucamine were newly synthesized by (a) addition of each n-alkylamine to glucose, (b) high-pressure catalytic reduction of each glucosamine thus formed to the corresponding glucamine, and (c) reaction of the resultant secondary amines with CS2 to form the dithiocarboxy derivatives. Each compound was evaluated as an antagonist of acute cadmium (Cd) toxicity and as a complexing agent for intracellular metallothionein-bound Cd (Cd-MT) in mice. N-Benzyl-N-dithiocarboxy-D-glucamine (BDCG) was used as a positive control compound. Each congener afforded partial or complete protection against the lethal effects of 10.0 mg/kg CdCl2.2.5 H2O, and retarded accumulation of Cd in livers and kidneys when given 2 h after the acutely toxic dose of Cd. Each derivative was also effective in mobilizing Cd from MT-bound sites in livers and kidneys of mice which had received a sub-lethal dose of CdCl2 along with 109CdCl2 2 weeks earlier. Excretion of mobilized Cd was almost exclusively by the fecal route. Potency of the analogs, as well as the octanol/aqueous partition coefficients, increased with the overall length of the N-(n-alkyl) carbon chain. Each compound readily complexed Cd from partially purified Cd-MT in vitro. Serum Cd from mice treated with BDCG was associated principally with proteins of high molecular weight.

Animals↗
PubMed1988

Dithiocarbamate treatment of chronic cadmium intoxication in mice.

The dithiocarbamate analogs, N-benzyl-N-dithiocarboxy-D-glucamine (BDCG) and N-cyclohexyl-N-(2-hydroxy-3-sulfonatopropyl)dithiocarbamate (CAPSO-DTC), were evaluated as cadmium (Cd) antagonists in mice which had received repetitive injections of Cd to effect accumulation of substantial levels of metallothionein-bound Cd in kidneys and livers. BDCG was highly effective in lowering whole body Cd stores and renal Cd concentrations. While the percent of renal Cd mobilized decreased with increasing Cd concentrations, the total amount of Cd mobilized increased. CAPSO-DTC was also effective in reducing whole body Cd levels, but appeared to have less affinity for renal Cd than did BDCG. Treatment of Cd-laden mice with BDCG provoked only a modest elevation of serum creatinine levels, suggesting that the complex of Cd with BDCG may be less nephrotoxic than the complex of Cd with EDTA or dimercaprol. The log of the percent reduction of renal Cd by BDCG was found to be a linear function of the pretreatment renal Cd concentration, and reductions of whole body Cd burdens correlated closely with reductions of liver and kidney Cd concentrations. It was suggested that a Cd complexing agent of the dithiocarbamate class may have ultimate application in a provocative methodology to estimate body or organ Cd stores based upon the amount of Cd excreted following a standard dose of the chelator.

Animals↗
PubMed1988

Mobilization of cadmium in mice by combined treatment with N-benzyl-N-dithiocarboxy-D-glucamine and diesters of meso-2, 3-dimercaptosuccinic acid.

Mice which had received a non-lethal injection of cadmium (Cd) as CdCl2 nine days prior to therapy were treated with N-benzyl-N-dithiocarboxy-D-glucamine (BDCG) alone or in combination with either di(iso-butyl)dimercaptosuccinate (DiBDMS) or di(iso-amyl)-dimercaptosuccinate (DiADMS). Seven injections of BDCG (1.0 mmole/kg), DiBDMS (0.4 mmole/kg), and DiADMS (0.4 mmol/kg) reduced whole body Cd burdens 50%, 54% and 37%, respectively; coadministration of BDCG + DiBDMS and BDCG + DiADMS produced respective reductions of 65% and 61%. Seven injections of BDCG lowered renal Cd concentrations an average of 82%, but reduced hepatic Cd concentrations only 53%. The DMSA diesters were more effective in lowering hepatic Cd than in reducing the levels of Cd in the kidneys. The respective hepatic and renal Cd reductions were 50% and 20% after treatment with DiADMS, and were 73% and 30% after treatment with DiBDMS. Coadministration of BDCG with DiADMS reduced hepatic and renal Cd concentrations 74% and 82%, respectively, while BDCG co-administered with DiBDMS yielded respective reductions of 80% and 82%. It is suggested that combined use of these newer Cd complexing agents in studies of experimental Cd poisoning may now permit resolution of the issue of reversibility of Cd-induced nephrotoxicity.

Animals↗
PubMed1988

Dermatitis from plastic tote boxes impregnated with an antistatic agent.

An outbreak of dermatitis occurred among employees of a microelectronics firm. In a cross-sectional epidemiologic investigation, we found that dermatitis of the hands or arms had occurred among 14 of 29 (48.3%) employees of the incoming inspection department where plastic tote boxes recently purchased from one manufacturer had been used, compared to only one case among 17 (5.9%) employees in another department which had not used these boxes. Affected workers could detect an oily film on the surfaces of these new boxes, but not on older ones. We identified the oily film to be a surface accumulation of bis-hydroxyethyl-tallow amine (BHETA), an antistatic agent with which the tote boxes had been impregnated. Subsequent toxicologic investigation established that BHETA could provoke both follicular and nonfollicular irritant dermatitis, and was also a potential skin sensitizer. Antistatic agents should be considered as potential causes of dermatitis among employees who handle electrical parts transported in plastic boxes, particularly when affected employees can detect an oily film on the box surfaces.

Amines↗
PubMed1988

Interaction of caffeine with acetaminophen in mice: schedule dependency of the antagonism by caffeine of acetaminophen hepatotoxicity and the effects of caffeine metabolites, allopurinol, and diethyl ether.

Administration of caffeine (CAF) to mice as early as 6 hr prior to injection of a hepatotoxic but nonlethal dose of acetaminophen (ACM) significantly antagonized the hepatotoxic action of ACM as judged by serum levels of alanine aminotransferase (ALT) activity. Administration of CAF after ACM produced complete antagonism only when CAF was given no later than 1 hr after ACM. Administration of CAF daily for 3 days prior to injection of ACM enhanced ACM toxicity markedly, but little or no toxicity ensued when CAF-pretreated mice received ACM followed immediately by CAF. The four primary metabolites of CAF, 1,3-dimethylxanthine (theophylline), 3,7-dimethylxanthine (theobromine), 1,7-dimethylxanthine (paraxanthine), and 1,3,7-trimethyluric acid were effective and virtually complete antagonists of ACM-induced hepatotoxicity when given immediately after ACM, as were the secondary metabolites, 1-methylxanthine and 1,3-dimethyluric acid. Allopurinol, which reduces theophylline clearance, increases the rate of oxidative N-demethylation of theophylline to 1-methylxanthine, and inhibits conversion of 1-methylxanthine to 1-methyluric acid, was also a dose-dependent antagonist of ACM-induced hepatotoxicity. The hepatotoxic response of mice to ACM is exaggerated by a brief period of diethyl ether anesthesia; CAF given immediately after ACM to previously anesthetized mice suppressed this response and maintained serum ALT levels at control values. It is suggested that CAF and its primary metabolites compete with ACM for biotransformation by the cytochrome P-450 mixed function oxidase system, thereby reducing the rate of formation of the hepatotoxic ACM metabolite.

Acetaminophen↗
PubMed1987

Benzene and leukemia. An epidemiologic risk assessment.

To assess quantitatively the association between benzene exposure and leukemia, we examined the mortality rate of a cohort with occupational exposure to benzene. Cumulative exposure for each cohort member was estimated from historical air-sampling data and, when no sampling data existed, from interpolation on the basis of existing data. The overall standardized mortality ratio (a measure of relative risk multiplied by 100) for leukemia was 337 (95 percent confidence interval, 154 to 641), and that for multiple myeloma was 409 (95 percent confidence interval, 110 to 1047). With stratification according to levels of cumulative exposure, the standardized mortality ratios for leukemia increased from 109 to 322, 1186, and 6637 with increases in cumulative benzene exposure from less than 40 parts per million-years (ppm-years), to 40 to 199, 200 to 399, and 400 or more, respectively. A cumulative benzene exposure of 400 ppm-years is equivalent to a mean annual exposure of 10 ppm over a 40-year working lifetime; 10 ppm is the currently enforceable standard in the United States for occupational exposure to benzene. To examine the shape of the exposure-response relation, we performed a conditional logistic-regression analysis, in which 10 controls were matched to each cohort member with leukemia. From this model, it can be calculated that protection from benzene-induced leukemia would increase exponentially with any reduction in the permissible exposure limit.

Adult↗
PubMed1987

Occupational asthma from inhaled egg protein.

We evaluated workers and performed an industrial hygiene assessment at a plant where raw eggs are processed into powdered egg yolk and whole egg. Egg dust levels in the packaging room straddled the American Conference of Governmental Industrial Hygienists' (ACGIH) exposure guideline of 10 mg/m3 for nuisance dust. We obtained medical histories from 25 workers, and performed physical examinations, spirometry, and serial determinations of peak expiratory flow rate (PEFR) by portable meter every 3 hrs (while awake) for 7 days. We defined symptomatic bronchial lability to be a decrement in PEFR on any one day of 20% or more of the day's maximum, with concurrent symptoms. Skin-prick tests and serum assays for specific IgE by the radioallergosorbent (RAST) method were performed to assess sensitivity to commercial egg proteins, egg protein fractions, and freshly prepared extracts of whole egg powder and yolk. We classified participants as definite cases of asthma if both the examining physician diagnosed asthma and symptomatic bronchial lability was demonstrated by serial PEFR determinations. Definite noncases of asthma were those participants in whom the physician did not diagnose asthma and in whom symptomatic bronchial lability was not demonstrated by PEFR. All five definite cases, compared to three of 16 definite noncases of asthma, had one or more positive skin-prick tests to egg proteins. Four of five cases, compared to 0 of 14 noncases, who had serum determinations, had an elevated RAST to one or more of the egg proteins. This study demonstrates that occupational asthma associated with IgE-mediated allergy to egg proteins occurs among workers exposed to inhaled egg proteins.

Air Pollutants, Occupational↗
PubMed1987

4,4'-Methylenebis (2-chloroaniline): an unregulated carcinogen.

4,4'-Methylenebis (2-chloroaniline) (MBOCA) is a confirmed animal carcinogen. It is used commercially as a curing agent for polymers containing isocyanate. There are no adequate studies documenting a carcinogenic risk for MBOCA in humans; however, studies in rats and dogs have shown that MBOCA is a carcinogen. Also, MBOCA is structurally similar to aromatic amines, which cause bladder cancer in workers with occupational exposure. Manufacture of MBOCA in the United States ceased in 1979. However, estimates of the number of workers potentially exposed range from 1,400 to 33,000 in the manufacture of MBOCA-cured products. Presently, there are no federal regulations limiting occupational exposure to MBOCA. An occupational standard for MBOCA proposed by the Occupational Safety and Health Administration was remanded by the Third Circuit Court of Appeals on procedural grounds in 1974. NIOSH recommended in 1978 that MBOCA be treated as a potential human carcinogen and that worker exposure be controlled so that it does not exceed 3 micrograms/m3 of air determined as a time-weighted average concentration for up to a 10-hour workshift (the lowest level that can be reliably measured). In this paper, we will review the literature in regard to MBOCA's carcinogenicity, describe industrial use and extent of worker exposure, and review MBOCA's status in relation to occupational regulations in the United States and abroad.

Animals↗
PubMed1987

Clinical and immunologic studies among egg-processing workers with occupational asthma.

Twenty-five workers in an egg-processing factory were evaluated for respiratory sensitization to inhaled egg proteins by a physician evaluation, serial peak expiratory flow rate (PEFR) measurements for a 1-week period, and immunologic tests. Immunologic studies included skin prick tests, serum-specific IgE (RAST), and specific IgG (ELISA) to solutions prepared from commercial food allergens: factory-powdered egg white and yolk products and purified egg white fractions, including ovalbumin, ovomucoid, lysozyme, and conalbumin. Six workers had significant daily PEFR lability (greater than 20%) of whom five had associated cutaneous reactivity to at least one egg allergen. A diagnosis of "definite asthma" was established in five workers suspected by the physician of having asthma. These five workers exhibited significant decrements in daily PEFR that were accompanied by bronchial symptoms. Occupational asthma was diagnosed by the physician in four of the five latter workers. Definite asthma was significantly associated with both cutaneous reactivity to egg allergens (p less than 0.01) and RAST binding (p less than 0.01). Of eight workers with cutaneous reactivity to at least one egg reagent, four workers (50%) were positive to only purified egg white fractions. The highest levels of RAST binding were detected in four workers, and the best binding activity was to ovomucoid and ovalbumin fractions. Elevated specific IgG responses were significantly higher in egg-factory workers to whole egg (p less than 0.005), lysozyme (p less than 0.002), and conalbumin (p less than 0.002) allergens compared to responses of nonexposed control subjects. However, no differences in specific IgG were detected between symptomatic and asymptomatic workers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗