Polymorphism of metabolic genes and susceptibility to occupational chronic manganism.

In this study we investigated genetic polymorphisms of five metabolizing genes and their association with occupational chronic manganism. We recruited 49 patients with chronic manganism and 50 unrelated healthy control subjects who were welders and ferromanganese smelters and occupationally exposed to manganese dust and fume in the same workshops from three metallurgical industries. The controls were matched to the cases by sex, age, cigarette and alcohol intake, as well as the manganese exposure duration. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to genotype the cytochrome P450 2D6L gene (CYP2D6L) and the NAD(P)H:quinone oxidoreductase gene (NQO1). Allele-specific PCR was used to detect the cytochrome P450 1A1 gene (CYP1A1), and the glutathione-S-transferase mu and theta genes (GSTM and GSTT). The frequency of polymorphic alleles, a mutation of CYP2D6L, was significantly lower in patients with chronic manganism (16.3%) than in controls (29.0%). Individuals with the homozygote polymorphism (L/L) of CYP2D6 had a 90% decreased risk of chronic manganism compared with the wild-type (Wt/Wt) (odds ratio =0.10, 95% confidence interval = 0.01-0.82). A significant association between the CYP2D6 genotype subgroup and the latency of chronic manganese poisoning was also found. Patients who had homozygous (L/L) or heterozygous (Wt/L) mutant alleles developed manganism an average of 10 years later than those who were homozygous wildtype (Wt/Wt). However, the allele and genotype frequencies of CYP1A1 and NQO1 genes were distributed similarly in cases and controls. In addition, no difference in the frequencies of GSTM1 and GSTT1 null genotypes were observed between cases and controls. The results suggest that CYP2D6L gene polymorphism might influence susceptibility to manganese-induced neurotoxicity. However, because of limited sample size, our results should be validated in large-scale studies.

Background exposure of urban populations to lead and cadmium: comparison between China and Japan.

OBJECTIVES: To assess and compare the background exposure of the general population to lead (Pb) and cadmium (Cd) in China and in Japan. METHODS: Food duplicates and peripheral blood samples were collected from nonoccupationally exposed subjects, viz 202 Chinese women in four Chinese cities (Beijing, Shanghai, Nanning, and Tainan) and 72 Japanese women in three Japanese cities (Tokyo, Kyoto, and Sendai) in the years 1993-1995. Wet-ashing and graphite furnace atomic absorption spectrometric methods were used for the determination of Pb and Cd levels in food and blood samples. RESULTS: Geometric mean (GM) dietary Pb intake (25.8 micrograms/day) and the GM Pb concentration in blood (56.7 micrograms/l) in Chinese were significantly higher than in Japanese women (11.6 micrograms/day in food and 32.1 micrograms/l in blood), whereas Cd in food (32.1 micrograms/day) and Cd in blood (1.92 micrograms/l) in Japanese were significantly higher than in Chinese women (9.9 micrograms/day in food and 1.07 micrograms/l in blood). The intake of Pb and Cd via boiled rice accounted for 3.6% and 31.1% of the total dietary burden in Chinese, and 12.1% and 32.7% in Japanese, respectively. The Cd burden was acquired almost exclusively through the dietary route, whereas the Pb burden came from both air and food, especially in the case of the Chinese population. CONCLUSIONS: The background Pb exposure in the Chinese population was higher than that in the Japanese population, whereas Cd exposure was lower in Chinese women than in their Japanese counterparts.

Lipid peroxidation in rats intoxicated with 3-nitropropionic acid.

Using an electron spin resonance technique, free radical signals were observed to be increased in liver of rats 15, 30 and 45 min after orally dosing with 80 mg/kg 3-nitropropionic acid (3-NPA). Concentrations of 3-NPA from 595 to 2380 mg/litre enhanced the formation of adrenochrome from adrenaline in mitochondria and microsome suspensions of liver and brain. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) as well as the content of malonidialdehyde (MDA) were significantly increased in liver of rats dosed with 80 mg/kg 3-NPA. There was also a cerebral increase of activity of SOD and content of MDA. These results suggest that 3-NPA is able to produce lipid peroxidation both in vivo and in vitro.

[Synthesis and antibacterial action of 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(4-aroylthiocarbamoyl-1-piperaziny l)-3-quinoline carboxylic acids].

Thirteen new 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(4-aroyl-thiocarbamoyl-1-piperazinyl)-3- quinoline carboxylic acids were prepared. Their structures were characterized by elemental analysis, IR, HNMR and MS spectra. Preliminary pharmacological tests indicated that some of compounds Ia-m possess strong inhibiting activity against Escherichia coli, Bacillus subtilis and Proteus at concentration of 100 micrograms/ml.

An epidemiological study on occupational acute pyrethroid poisoning in cotton farmers.

A cross sectional survey on the prevalence of acute pyrethroid poisoning in cotton farmers was conducted in 1987 and 1988. A total of 3113 pyrethroid spraymen (2230 men (71.6%) and 883 women (28.4%] were interviewed after spraying and followed up for 72 hours. Adverse effects of pyrethroid exposure were found in 834 of them (26.8%) manifested as abnormal facial sensations, dizziness, headache, fatigue, nausea, or loss of appetite. Only 10 subjects, who developed significant systemic symptoms and had signs of listlessness or muscular fasciculation, were diagnosed as having mild occupational acute pyrethroid poisoning with a prevalence of 0.31% in subjects exposed to pure pyrethroids and 0.38% in subjects exposed to pyrethroid organophosphate mixtures. Measurements of pyrethroid concentrations in the air of the breathing zone, in skin pads, and in urine samples showed that dermal contamination is the main route of exposure to pyrethroids in cotton growers. Preventive measures are recommended.

Levels of exposure and biological monitoring of pyrethroids in spraymen.

To assess the exposure response relation of pyrethroids in spraymen, 50 adult male cotton growers were selected and divided into three groups, one group to spray pyrethroids for one day, two groups to spray for three days. Deltamethrin, fenvalerate, and a deltamethrin methamidophos mixture were sprayed by appropriate subgroups for five hours a day. Exposure levels were evaluated by measuring the air concentration, dermal exposure concentration, and urinary content of pyrethroids by gas chromatography. Air concentrations of deltamethrin at the breathing zone were 0.01-0.89 microgram/m3 in the deltamethrin exposed group. For fenvalerate, air concentrations were 0.06-1.98 micrograms/m3. Dermal exposure, particularly on the legs, feet, and hands was appreciable and indicated that this was the main route of absorption. In those spraying for one day, urinary deltamethrin was not detectable by 12 hours after the beginning of exposure whereas fenvalerate was still detectable up to 24 hours after first exposure. Both pyrethroids could be detected two days after the end of three day spraying. Health effects were investigated by interview and physical examination. Twenty nine spraymen complained of abnormal facial sensations that developed mostly two to three hours from the start of pyrethroid spraying and that disappeared by 24 hours after exposure ceased. Some had dizziness, headache, and nausea, but no subject was diagnosed as having acute pyrethroid poisoning. The symptoms showed no significant correlation with urinary pyrethroid excretion. Blood cholinesterase activity of spraymen using the pyrethroid methamidophos mixture did not change.

Changes of nerve excitability and urinary deltamethrin in sprayers.

The nerve excitability of median nerve as well as the urinary deltamethrin and its metabolite dibromovinyl-dimethyl-cyclopropane carboxylic acid (Br2A) were detected in 24 deltamethrin sprayers in an assessment of the exposure and effect of deltamethrin. Twenty-nine male, unexposed referents of the same age range were also selected. The urinary deltamethrin and its metabolite Br2A were detectable by GC and HPLC in the sprayers after exposure. The nerve excitability detected with an electromyograph and pairs of stimuli at variable intervals showed that there was a prolongation of supernormal period in median nerve of the exposed group after a 3-d spraying compared with that before spraying which became more significant 2 d after cessation of exposure. In the mean time, no change of supernormal period in the median nerve of reference group was found at the 3-d interval. Nearly half of the sprayers had a supernormal period prolonged by more than 4 ms after spraying, whereas nearly none of the reference group showed similar changes after repeated examinations. Although there was neither correlation between the nerve excitability changes and the urinary deltamethrin or Br2A excretion, nor was a case of acute deltamethrin poisoning diagnosed, the non invasive technique used for nerve excitability detection in this study seems to be valuable in studying deltamethrin toxicity on human.

Neurological and electroneuromyographic assessment of the adverse effects of acrylamide on occupationally exposed workers.

Seventy-one acrylamide workers and fifty-one unexposed referents were studied. Weak legs and numb hands and feet, preceded by skin peeling from the hands, were the early symptoms of the acrylamide workers; their early signs were impairment of vibration sensation in their toes and loss of ankle reflexes. Three cases had cerebellar involvement followed by polyneuropathy due to heavy exposure. Electroneuromyographic changes, including a decrease in the sensory action potential amplitude, neurogenic abnormalities in electromyography, and prolongation of the ankle tendon reflex latency, are of greater importance in the early detection of acrylamide neurotoxicity since they can precede the neuropathic symptoms and signs. The diagnostic criteria for occupational acrylamide intoxication of this study revealed three severe poisonings, six moderate poisonings, and 43 mild poisonings. The total prevalence of acrylamide poisoning was 73.2%. The prevention of dermal exposure to acrylamide should be emphasized.

Training and education in occupational health in China.

Training programmes in Occupational Health in the People's Republic of China have been expanded and improved tremendously since 10 years ago. There are 26 faculties of Public Health in the medical schools taking undergraduate students for a six-year basic training which leads to the degree of Bachelor of Medicine and Public Health. A three-year postgraduate course leading to the Master's degree in Occupational Health and two more years' specialist course for the doctorate degree in Occupational Health are offered by the Institute of Occupational Medicine, Chinese Academy of Preventive Medicine and six training centres for occupational health. Continuing education at multi-level seems to be of great benefit, yet needs further development.

Observations on renal function in workers exposed to lead.

Renal function was studied in 40 workers chronically exposed to lead at a smelter. The geometric means of lead were 40 (range 24.0 - 63.0) micrograms/dl in blood and 47 (range 19 - 115) micrograms/g creatinine or 71 (range 20 - 250) micrograms/l in urine, respectively. There were no significant differences between the lead-exposed group and a control group in the concentrations of beta 2-microglobulin in serum, urinary total protein and IgG, whereas the level of beta 2-microglobulin in urine was significantly higher in the lead-exposed group (p less than 0.01). No individual lead worker showed abnormally increased level of urinary beta 2-microglobulin. The significance of increased excretion of beta 2-microglobulin on the basis of the group remains to be elucidated.

An electroneurographic assessment of subclinical lead neurotoxicity.

While heavy exposure to inorganic lead is capable of inducing symptomatic neuropathy in man, the subclinical neuropathy due to low levels of occupational lead exposure remains to be proved. The reported results of electroneurographic studies on lead workers, however, have been controversial. In this study, 40 lead smeltery workers and 50 non-exposed referents were investigated. The air concentrations of lead at worksites were 0.25 to 42.5 mg/m3. The geometric means of PbB, PbU and delta-ALAU in lead exposed group were 40.03 micrograms/dl, 71 micrograms/l and 4.68 mg/l respectively, which were significantly higher (P less than 0.001) than those (7.01 micrograms/dl, 6.0 micrograms/l and 1.81 mg/l respectively) in the reference group. There were no clinical symptoms or signs of nerve damage in either group. Alcoholism and diabetes were excluded in both groups. Nerve conduction velocity was measured by a DISA 1500 electromyograph in both groups. Eleven electroneurographic parameters, including motor nerve conduction velocity (MCV) and distal latency (DML) of median, ulnar and peroneal nerves as well as sensory nerve conduction velocity (SCV) and distal latency (DSL) of median, ulnar and sural nerves, showed statistically significant differences between the two groups. However, the results of electroneurographic measurements of each individual in the lead-exposed group were all within the normal range. There was no correlation between the blood-lead levels and the neurophysiological measurements except for the median MCV. No correlation was seen between the median MCV and the exposure duration.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of allyl chloride on occupationally exposed subjects.

Effects of allyl chloride on occupationally exposed subjects were studied in two factories manufacturing sodium allyl sulfonate. Twenty-six subjects in factory A and 27 workers in factory B were exposed to allyl chloride at levels of 2.6-6 650 mg/m3 for 2.5 months--6 years and 0.2-25.13 mg/m3 for 1-4.5 years, respectively. Most subjects of factory A had weakness, paresthesia, and numbness in extremities with sensory impairment in the glove-stocking distribution, as well as reduced ankle reflexes. Electroneuromyography showed neurogenic abnormalities in 10 of the 19 subjects examined, the prevalence of neuropathy therefore being 52.6%. Similar symptoms of workers in factory B were clinically much milder, and there were few abnormal neurological signs--yet electromyographic findings indicating mild neuropathy were found in 13 of the 27 subjects. No significant abnormalities of other organs were noted. Possible etiologic factors other than exposure to allyl chloride were excluded. All the evidence obtained indicates that chronic exposure to allyl chloride mainly causes toxic polyneuropathy. The neurotoxicity of allyl chloride has also been confirmed by experimental neuropathological studies.

Chronic allyl chloride poisoning. An epidemiology, clinical, toxicological and neuropathological study.

It was previously reported that chronic exposure to allyl chloride resulted in liver and kidney damage. No neurotoxic effect of allyl chloride had been noticed until two outbreaks of polyneuropathy without liver and kidney dysfunction due to exposure to allyl chloride in China in the early 1970's. Epidemiological and clinical studies done within 1973-1982 revealed that the main risk of industrial exposure to allyl chloride is damage to the peripheral nervous system. Polyneuropathy is thought to be the main clinical manifestation of chronic allyl chloride poisoning. Electroneuromyography is essential and valuable for early diagnosis and biological monitoring. Toxicological and neuropathological studies in rabbits and mice have given the evidence of a pattern of central-peripheral distal axonopathy in peripheral nervous system which has further confirmed the neurotoxicity of allyl chloride found in man. Based on the above results, the maximum allowable concentration of allyl chloride and diagnostic criteria for chronic allyl chloride poisoning are proposed.

Prognosis of mercury poisoning in mercury refinery workers.

The prognosis of chronic metallic mercury poisoning in two groups of patients from the mercury refinery of a mercury mine was evaluated by reexamination which included an interview, physical and neurological examination and determination of urinary mercury. Group I consisted of 70 male patients, who had been exposed to metallic mercury for 1.6-17.8 years, 15 of whom had been diagnosed 10 years earlier as having severe chronic metallic mercury poisoning, and the rest moderate chronic metallic mercury poisoning. At the time of reexamination, they had been removed from mercury exposure for 2 months-17 years. None of them had been treated with any chelating agent. Group 2 comprised 84 male patients from the same mercury mine, who had been exposed to metallic mercury for 2-10 years after 1962 and had been previously diagnosed as having mild chronic metallic mercury poisoning. They were reexamined after 2 months of hospital admission and chelation treatment with unithiol or sodium dimercaptosuccinate (Na-DMS). Based on clinical evaluation, the condition of the patients in both groups had all improved, even in the severe cases. The overall prognosis of chronic metallic mercury poisoning in mercury refinery workers was encouraging after termination of mercury exposure. Chelation therapy with unithiol or Na-DMS was evidently beneficial for reducing urine mercury and some symptoms, but not for neurological and stomal signs.