Yearly measurements of blood lead in Swedish children since 1978: an update focusing on the petrol lead free period 1995-2001

Methods: In the south of Sweden, each year from 1995 to 2001, B-Pb was measured in 329 boys and 345 girls, aged 7–11 years.

Results: The geometric mean (GM) of B-Pb was 21 (range 6–80) µg/l. There was no consistent change of B-Pb from 1995 to 2001. Children living near a lead smelter had raised B-Pb (GM 24 µg/l, range 11–80). Passive smoking, but not age and sex, influenced B-Pb significantly.

Conclusions: B-Pb in Swedish children, no longer exposed to petrol lead, seems to have stabilised at an average level close to 20 µg/l (provided there is no nearby industrial lead emission).

     

The inhibition of mercury absorption by dietary ethanol in humans: cross-sectional and case-control studies

Aims: To investigate this phenomenon in a large scale human study with low level Hg exposed dentists.

Methods: Data were collected for a sample of 1171dentists, and both cross sectional and case-control methods were utilised to examine the data.

Results: Abstainers (n = 345) had significantly higher urinary mercury concentrations (HgU) than drinkers (n = 826): 5.4 µg/l v 4.8 µg/l. Multiple linear regression showed a significant effect of ethanol dose on HgU after adjusting for potential confounders. A case-control analysis in which cases were defined as those individuals with urinary Hg concentrations of 15 µg/l (≈ top 5%), and controls as those with concentrations of <1.0 µg/l (≈ bottom 5%), showed a clear protective dose-response relation; there was a decreasing risk of being a "case" (having an HgU 15 µg/l) with increasing ethanol consumption. The significance of the adjusted model is p<0.001, and the χ² test for trend across ethanol consumption categories in the adjusted model is p<0.05, confirming the dose-response relation.

Conclusion: We believe that this straightforward investigation provides the first specific confirmation in a large scale human study of the inhibitory effect of ethanol on urinary mercury concentration, and by inference, on mercury absorption.

     

Exposure to traffic exhausts and oxidative DNA damage

Aims: To assess the relations between exposure to traffic exhausts and indicators of oxidative DNA damage among highway toll station workers.

Methods: Cross-sectional study of 47 female highway toll station workers exposed to traffic exhausts and 27 female office workers as a reference group. Exposure assessment was based on average and cumulative traffic density and a biomarker of exposure, urinary 1-hydroxypyrene-glucuronide (1-OHPG). Urinary 8-hydroxydeoxyguanosine (8-OHdG) was used as a biomarker of oxidative DNA damage. Plasma nitric oxide (NO) was measured as an indicator of oxidative stress related to traffic exhaust exposure.

Results: The mean concentration of urinary 8-OHdG was substantially higher among the exposed non-smokers (13.6 µg/g creatinine) compared with the reference non-smokers (7.3 µg/g creatinine; difference 6.3, 95% CI 3.0 to 9.6). The mean concentration of NO among the exposed (48.0 µmol/l) was also higher compared with the reference non-smokers (37.6 µmol/l; difference 10.4, 95% CI –0.4 to 21.2). In linear regression adjusting for confounding, a change in log(8-OHdG) was statistically significantly related to a unit change in log(1-OHPG) (ß = 0.372, 95% CI 0.081 to 0.663).

Conclusions: Results indicate that exposure to traffic exhausts increases oxidative DNA damage. Urinary 8-OHdG is a promising biomarker of traffic exhaust induced oxidative stress.

     

Cytotoxicity and Mutagenicity of 2,4,6-Trinitrotoluene and Its Metabolites

Composting has been advocated and is being used as an economical method for remediating 2,4,6-trinitrotoluene (TNT)-contaminated soils. However, evidence suggests that TNT is transformed into products of unknown toxicity during the process. This study was undertaken to examine thein vitrocytotoxicity and mutagenicity of TNT and several of its degradation products/metabolites. TNT was equally cytotoxic to H4IIE cells and Chinese hamster ovary-K1 (CHO) cells (LC₅₀of 4 g/ml vs 24 μg/ml, with overlapping 95% prediction intervals), indicating that TNT does not need to be metabolized to exhibit cytotoxicity. Four metabolites studied, 4-hydroxylamino-2,6-dinitrotoluene; 2-amino-4,6-dinitrotoluene; 4,4′,6,6′-tetranitro-2,2′-azoxytoluene; and 2,2′,6,6′-tetranitro-4,4′-azoxytoluene, were equally cytotoxic to both H4IIE and CHO cells. The LC₅₀s were in the 3- to 18-μg/ml range and were not significantly different from TNT cytotoxicity in both cell lines. 4-Amino-2,6-dinitrotoluene (4-A) was moderately less cytotoxic than TNT to H4IIE cells, but was noncytotoxic to CHO cells. This result indicates that 4-A is metabolized to a cytotoxic compound. Both TNT and its metabolites exhibited only slight mutagenicity at high doses in one or both of the mutagenicity assays. While composting may reduce the levels of TNT in composted material, the hazard associated with TNT-contaminated soils is probably lower, but still uncertain.     

Genotoxicity and potential carcinogenicity of 2,4,6-TNT trinitrotoluene: structural and toxicological considerations

Environmental contamination with 2,4,6-TNT (trinitrotoluene) represents a worldwide problem. Concern for carcinogenicity can be derived from chemically related compounds, especially the dinitrotoluenes. In the metabolism of TNT, the reductive routes are preponderant. The main urinary metabolites of TNT are 4-amino-2,6-dinitrotoluene and 2-amino-4,6-dinitrotoluene. In humans exposed to TNT, the formation of hemoglobin adducts of the amino-dinitrotoluenes is in general concordance with the ratio of urinary excretion. The variations in quantities of excreted metabolites among the different occupational cohorts studied are likely explained by the different routes of exposure to TNT, including dermal uptake. Most studies show that urinary excretion of the amino-dinitrotoluenes (4-amino-dinitrotoluene plus 2-amino-dinitrotoluene) in a range of 1 to 10 mg L(-1) (5-50 microM) are not uncommon--for instance in persons employed with the disposal of military waste. Trinitotoluene is mutagenic in Salmonella typhimurium strains TA98 and TA100, with and without exogenous metabolic activation. Mutagenic activity has been found in urine from workers who were occupationally exposed to TNT. An unpublished 2-year study was reported in 1984 by the IIT Research Institute, Chicago, IL. Fischer 344 rats were fed diets containing 0.4, 2.0, 10, or 50 mg/kg TNT per day. In the urinary bladder, hyperplasia (12 of 47 animals p < .01) and carcinoma (11 of 47 animals, p < .05) were observed at significant levels in high-dose (50 mg kg(-1)) females and in one or two females, respectively, at 10 mg kg(-1). Taking all the available evidence together, the appropriate precautions should be taken.     

Acute toxicity of 2,4,6-trinitrotoluene, 2,4-dinitrotoluene, and 2,6-dinitrotoluene in the adult bullfrog (Lithobates catesbeiana)

2,4,6-Trinitrotoluene (TNT) is one of the most prevalent high explosives in the environment. 2,4-Dinitrotoluene (2,4-DNT) and 2,6-dinitrotoluene (2,6-DNT) are the most common isoforms of dinitrotoluene. The goal of this study was to determine the acute toxic effects of TNT, 2,4-DNT, and 2,6-DNT in adult male bullfrogs. The LD(50) for TNT was 1,060 mg/kg BW while the LD(50 )for 2,4-DNT and 2,6-DNT was 1,098 mg/kg BW. All three compounds elicited similar symptoms of toxicity including changes of skin color, body weight, development of seizures, liver and kidney necrosis, and lung cyanosis. Relative organ weights did not show significant change.     

Effect of trihalomethane exposure on fetal development

Aims: To examine the effect of trimester specific and pregnancy average total trihalomethane (TTHM) exposure on infant birth weight, low birth weight, and intrauterine growth retardation in term births, as well as gestational age and preterm delivery in all births.

Methods: Cross sectional analysis of 56 513 singleton infants born to residents of Massachusetts during 1990. City specific aggregate data were used to estimate maternal exposure to TTHM concentration; individual maternal information was used to adjust for confounding.

Results: Increased pregnancy average and second trimester TTHM exposure were associated with small for gestational age and reductions in birth weight after adjusting for potential confounding variables. Compared to ≤60 µg/l, pregnancy average TTHM exposure over 80 µg/l was associated with a 32 g reduction in birth weight. There was a 23 g reduction in birth weight in infants born to mothers exposed to greater than 80 µg/l TTHM during the second trimester. For each 20 µg/l increase in TTHM, the estimated reduction in birth was 2.8 g for pregnancy average exposure and 2.6 g for second trimester exposure. An increased risk of small for gestational age births was found for pregnancy average (odds ratio (OR) 1.14; 95% CI 1.02 to 1.26) and second trimester (OR 1.13, 95% CI 1.03 to 1.24) TTHM levels greater than 80 µg/l. There was no evidence of an association between preterm delivery and increased TTHM levels, but there were slight increases in gestational duration associated with TTHM concentrations.

Conclusions: Maternal exposure to THMs may be associated with fetal growth retardation. Our findings are consistent with most previous work, although we generally found smaller effects of TTHMs on low birth weight and intrauterine growth retardation.

     

Benzene and naphthalene in air and breath as indicators of exposure to jet fuel

Aims: To estimate exposures to benzene and naphthalene among military personnel working with jet fuel (JP-8) and to determine whether naphthalene might serve as a surrogate for JP-8 in studies of health effects.

Methods: Benzene and naphthalene were measured in air and breath of 326 personnel in the US Air Force, who had been assigned a priori into low, moderate, and high exposure categories for JP-8.

Results: Median air concentrations for persons in the low, moderate, and high exposure categories were 3.1, 7.4, and 252 µg benzene/m³ air, 4.6, 9.0, and 11.4 µg benzene/m³ breath, 1.9, 10.3, and 485 µg naphthalene/m³ air, and 0.73, 0.93, and 1.83 µg naphthalene/m³ breath, respectively. In the moderate and high exposure categories, 5% and 15% of the benzene air concentrations, respectively, were above the 2002 threshold limit value (TLV) of 1.6 mg/m³. Multiple regression analyses of air and breath levels revealed prominent background sources of benzene exposure, including cigarette smoke. However, naphthalene exposure was not unduly influenced by sources other than JP-8. Among heavily exposed workers, dermal contact with JP-8 contributed to air and breath concentrations along with several physical and environmental factors.

Conclusions: Personnel having regular contact with JP-8 are occasionally exposed to benzene at levels above the current TLV. Among heavily exposed workers, uptake of JP-8 components occurs via both inhalation and dermal contact. Naphthalene in air and breath can serve as useful measures of exposure to JP-8 and uptake of fuel components in the body.

     

Dimethyl sulphate; a hidden problem in occupational medicine

Background: In a chemical plant, alkylating agents (mainly ethylene oxide and propylene oxide, but also dimethyl sulphate) are utilised for the production of special surfactants.

Aims: To determine possible uptakes of dimethyl sulphate by workers using N-methylvaline.

Methods: Sixty two workers in a chemical plant (38 smokers, 24 non-smokers) with potential exposure to dimethyl sulphate were monitored with respect to their blood levels of N-methylvaline. Ten laboratory workers without exposure to methylating agents were controls. Blood samples of eight workers from a specific working area were analysed for N-methylvaline in a follow up investigation four months later.

Results: The 95th centile for N-methylvaline was 80.7 µg/l blood in the exposed workers compared to 12.4 µg/l blood in controls. In a hot spot area, 10 workers exceeded the German exposure equivalent value for dimethyl sulphate (40 µg/l blood) up to fourfold. In contrast, dimethyl sulphate has not been detectable in workplace air in this area. In a follow up investigation of eight of these 10 workers, N-methylvaline levels were significantly lower, but still increased.

Conclusions: The present study is to our knowledge the first to report increased N-methylvaline levels after occupational exposure to dimethyl sulphate. As ambient monitoring values in the plant could not explain this exposure, skin contact was considered to be the main route of uptake for this substance. Dimethyl sulphate may therefore represent an occupational problem that has been generally underestimated in the past.

     

Toxicity of explosives and related compounds to the luminescent bacterium Vibrio fischeri NRRL-B-11177

Aqueous samples containing various explosives, their reduced metabolites, as well as related compounds were subjected to the luminescent bacterium Vibrio fischeri NRRL-B-11177 to determine their ecotoxicological potential. As the most important parameter, the EC₅₀ values of 24 test compounds were calculated. The EC₅₀ value means the concentration of a chemical compound that is needed to reduce bacterial luminescence by 50%. According to the widely accepted classification scheme of Strupp et al. (1990) and in consideration of an incubation period of 30 min (Deutsche Einheits verfahren zur Wasser-, Abwasser-, und Schlammuntersuchung-Testverfahren mit Wasserorganismen; Gruppe L; DIN 38412, L34; DEV 1991) TNT, 26DNT, 2A6NT, 4A2NT, 34DNT, TNB, TNBA, TETRYL and HEXYL must be classified in the category very toxic to aquatic organisms; 2A46DNT, 4A26DNT, 24DA6NT, 24DNT, 2A4NT, RDX, HMX and PETN must be classified in the category toxic to aquatic organisms; and 26DA4NT, TAT, TNPh, 26DAT, 24DAT, HMT and NQ can be classified in the category less toxic to aquatic organisms. EC₅₀ values after 30, 60, and 90 min of incubation of the test compounds are presented and discussed. For many of the compounds tested in this study, there are no, or only a few, toxicological data in the literature available.Abbreviations TNT 2,4,6-trinitrotoluene - 2A46DNT 2-amino-4,6-dinitrotoluene - 4A26DNT 4-amino-2,6-dinitrotoluene - 24DA6NT 2,4-diamino-6-nitrotoluene - 26DA4NT 2,6-diamino-4-nitrotoluene - TAT 2,4,6-triaminotoluene - TNBA 2,4,6-trinitrobenzoic acid - TNPh 2,4,6-trinitrophenol; picric acid - TNB 2,4,6-trinitrobenzene - 26DNT 2,6-dinitrotoluene - 2A6NT 2-amino-6-nitrotoluene - 26DAT 2,6-diaminotoluene - 24DNT 2,4-dinitrotoluene - 2A4NT 2-amino-4-nitrotoluene - 4A2NT 4-amino-2-nitrotoluene - 24DAT 2,4-diaminotoluene - 34DNT 3,4-dinitrotoluene - RDX hexogen; cyclo-1,3,5-trimethylene-2,4,6-trinitramine - HMX octogen;cyclo-1,3,5,7-tetramethylene-2,4,6,8-tetranitramine - HMT hexamethylenetetramine - PETN pentaerythritol tetranitrate - NQ nitroguanidine - TETRYL 2,4,6-trinitrophenyl-N-methylnitramine - HEXYL 2,2,4,4,6,6-hexanitrodiphenylamine     

Biomonitoring results and cytogenetic markers among harbour workers with potential exposure to river silt aerosols

Background: Workers on dredgers and lighters on rivers are potentially exposed to a variety of substances.

Aims: To determine the internal load of heavy metals and arsenic as well as levels of cytogenetic markers in workers exposed to river silt aerosols.

Methods: One hundred exposed workers were examined up to eight times within three years. Additionally, 100 control workers were studied once. Blood samples were analysed for lead, mercury, and cadmium. Additionally, micronuclei frequency and sister chromatid exchange (SCE) rates were determined. Urinary samples were analysed for cadmium, mercury, nickel, chromium, and arsenic. Information on potential confounders, such as smoking habits and consumption of fish were assessed.

Results: Apart from some increased concentrations of mercury in blood (maximum 14.6 µg/l) and arsenic in urine (maximum 356.5 µg/l) all measurements were within reference values. None of the exposure and effect markers were found to be significantly increased in exposed workers compared to non-exposed controls. In multiple linear regression models, mercury levels in blood as well as the concentration of arsenic in urine were strongly related to fish consumption. Cadmium levels in blood as well as urinary cadmium concentrations were strongly related to smoking habits. After adjusting for smoking habits, SCE rates were associated with cadmium levels in blood.

Conclusion: Increased exposure levels or enhanced levels of cytogenetic markers were not found in workers exposed to river silt aerosols. However, cadmium exposure in blood was related to SCE frequency.

     

Effects of chronic 2,4,6,-trinitrotoluene, 2,4-dinitrotoluene, and 2,6-dinitrotoluene exposure on developing bullfrog (Rana catesbeiana) tadpoles

Chronic aqueous exposures were conducted using bullfrog (Rana catesbeiana) tadpoles (8 d old) exposed to TNT (0-4 mg/L), 2,4-DNT (0-4 mg/L), and 2,6-DNT (0-8 mg/L) for 90 d. Survival of tadpoles examined using Cox proportional hazard models was reduced at all concentrations tested. Percent of abnormal swimming and other morphological abnormalities after sublethal exposure to TNT, 2,4-DNT, and 2,6-DNT at 2 mg/L were also evaluated. The effects of TNT, 2,4-DNT, and 2,6-DNT on wet body mass, snout vent length (SVL), and developmental stage of surviving tadpoles were examined. Only 2,4-DNT did not have a significant effect on body mass or SVL, but all three compounds tested had significant effects on survival. Long-term continuous exposure to these compounds at concentrations of 0.25 mg/L could lead to significant changes in growth and survival of larval amphibians.     

Toxicological characterization of 2,4,6-trinitrotoluene, its transformation products, and two nitramine explosives

The soil and groundwater of former ordnance plants and their dumping sites have often been highly contaminated with the explosive 2,4,6-trinitrotoluene (2,4,6-TNT) leading to a potential hazard for humans and the environment. Further hazards can arise from metabolites of transformation, by-products of the manufacturing process, or incomplete combustion. This work examines the toxicity of polar nitro compounds relative to their parent compound 2,4,6-TNT using four different ecotoxicological bioassays (algae growth inhibition test, daphnids immobilization test, luminescence inhibition test, and cell growth inhibition test), three genotoxicological assays (umu test, NM2009 test, and SOS Chromotest), and the Ames fluctuation test for detection of mutagenicity. For this study, substances typical for certain steps of degradation/transformation of 2,4,6-TNT were chosen for investigation. This work determines that the parent compounds 2,4,6-TNT and 1,3,5-trinitrobenzene are the most toxic substances followed by 3,5-dinitrophenol, 3,5-dinitroaniline and 4-amino-2-nitrotoluene. Less toxic are the direct degradation products of 2,4,6-TNT like 2,4-dinitrotoluene, 2,6-dinitrotoluene, 2-amino-4,6-dinitrotoluene, and 4-amino-2,6-dinitrotoluene. A weak toxic potential was observed for 2,4,6-trinitrobenzoic acid, 2,4-diamino-6-nitrotoluene, 2,4-dinitrotoluene-5-sulfonic acid, and 2,6-diamino-4-nitrotoluene. Octahydro-l,3,5,7-tetranitro-l,3,5,7-tetrazocine and hexahydro-1,3,5-trinitro-l,3,5-triazine show no hint of acute toxicity. Based on the results of this study, we recommend expanding future monitoring programs of not only the parent substances but also potential metabolites based on conditions at the contaminated sites and to use bioassays as tools for estimating the toxicological potential directly by testing environmental samples. Site-specific protocols should be developed. If hazardous substances are found in relevant concentrations, action should be taken to prevent potential risks for humans and the environment. Analyses can then be used to prioritise reliable estimates of risk.     

Chrysotile and tremolite asbestos fibres in the lungs and parietal pleura of Corsican goats

Methods: Ten goats from areas with asbestos outcrops and two from other areas were slaughtered. Fibre content of lung and parietal pleural samples was determined by analytical transmission electron microscopy.

Results: Both chrysotile and tremolite fibres were detected. In the exposed goats, the geometric mean concentrations of asbestos fibres longer than 1 µm were 0.27 x 10⁶ fibres/g dry lung tissue and 1.8 x 10⁶ fibres/g dry pleural tissue. Asbestos fibres were not detected in the lungs of the two control goats. Chrysotile fibres shorter than 5 µm were predominant in the parietal pleura. Tremolite fibres accounted for 78% and 86% of the fibres longer than 5 µm in lung and parietal pleural samples, respectively.

Conclusions: Environmental exposure in northeast Corsica results in detectable chrysotile and tremolite fibre loads in the lung and parietal pleura of adult goats. Tremolite fibres of dimensions with a high carcinogenic potency are detected in the parietal pleura.

     

Evaluation of exposure to benzene vapour during the loading of petrol

Sherwood, R. J. (1972).Brit. J. industr. Med.,29, 65-69. Evaluation of exposure to benzene vapour during loading of petrol. The exposure of three workers to benzene vapour has been determined by personal air sampling, and has been related to their intake (assessed by sampling exhaled breath), and to their metabolism of benzene (evaluated from the concentration of phenol in urine.) The results obtained agree in general with those already published in the literature and with a preliminary experimental exposure undertaken as part of the development of techniques.

The two loaders who handled the loading arms were exposed to mean concentrations of 1·6 and 2·5 p.p.m. over the 5-hour period of loading. The probability of their exposure to concentrations greater than 25 p.p.m. was about 0·1 and 1%. The weigher working between the tracks was exposed to a mean concentration of 20 p.p.m. over the same period and had a total exposure of 114 p.p.m.-hour. Samples of exhaled breath taken at the end of work showed 0·14 and 0·18 p.p.m. benzene for the loaders and 0·84 p.p.m. for the weigher. The following morning the latter showed 0·19 p.p.m. Urine samples taken from the loaders at the end of work contained 12 and 25 mg/l total phenol and for the weigher 83 mg/l. The following morning the phenol was not above natural levels in the loaders' urine, and was 38 mg/l in a sample from the weigher.

It is suggested that any or all of the methods developed for this study could be used in conjunction with appropriate clinical studies to provide a more quantitative basis for determining the hazard of occupational exposure to benzene.

     

Can salivary lead be used for biological monitoring of lead exposed individuals?

Aim: To explore the use of salivary lead (SPb) as an alternative.

Methods: BPb and SPb levels were measured in a group of 82 lead exposed adults.

Results: The mean BPb of the workers was 26.6 µg/dl (SD 8.6, range 10–48) and the mean SPb level 0.77 µg/dl, or 3% of the BPb level. As the SPb distribution was skewed, logarithmic transformation was performed to normalise the distribution. A bivariate scattergram of BPb and logSPb (r = 0.41, p = 0.00) had a line of best fit expressed as BPb = 29.7 + 8.95logSPb. The relation of logSPb and BPb was stronger among non-smokers (r = 0.42) compared to smokers (r = 0.3); and among those without a medical condition (r = 0.44). Multiple linear regression analysis (fitting smoking and medical condition into the model) yielded an R of 0.54, and an adjusted R² of 0.26.

Conclusion: The study findings do not support the use of SPb for biomonitoring at BPb levels ranging from 10 to 50 µg/dl.

     

Urinary mercury concentrations associated with dental restorations in adult women aged 16-49 years: United States, 1999-2000

Background: Mercury amalgam dental restorations have been used by dentists since the mid 19th century and issues on safety continue to be periodically debated within the scientific and public health communities. Previous studies have reported a positive association between urine mercury levels and the number of dental amalgams, but this relation has never been described in a nationally representative sample in the United States.

Aims and Methods: Using household interview, dietary interview, dental examination, and laboratory data from the 1999–2000 National Health and Nutrition Examination Survey (NHANES), the association between mercury concentrations and dental restorations was examined in US women of reproductive age.

Results: In women of childbearing age, approximately 13% of all posterior dental surfaces were restored with amalgams and the average urinary mercury level in women was low (1.34 µg/l). It is estimated that an increase of 1.8 µg/l in the log transformed values for mercury in urine would occur for each 10 dental surfaces restored with amalgam.

Conclusions: Although the findings do not address the important issues of adverse health effects at low thresholds of mercury exposure, they do provide important reference data that should contribute significantly to the ongoing scientific and public health policy debate on the use of dental amalgams in the USA.

     

Effects of subchronic exposure to 2,6-dinitrotoluene in the northern bobwhite (Colinus virginianus)

Explosives and their breakdown products are commonly found in soils at U.S. military installations. Many areas where these compounds are found represent useful habitat for ground-foraging birds. Because these birds likely are exposed to such compounds, we evaluated the oral toxicity of 2,6-dinitrotoluene (DNT) in a representative ground-foraging species of management concern. Adult male and female northern bobwhite (Colinus virginianus) were exposed to either 0, 5, 10, 40, or 60 mg/kg/d via gavage for 60 d (subchronic) following determination of the median acute lethal dose (320 mg/kg). Circulating levels of red blood cells and hemoglobin were significantly decreased in a dose-dependent manner; however, levels remained within normal ranges. Plasma concentrations of total protein, albumin, globulin, aspartate aminotransferase, and potassium, sodium, and chlorine ions were significantly decreased, and circulating levels of uric acid were significantly increased. Decreased body weight, enlarged gallbladders, edematous gastrointestinal tracts, pale kidneys, pale and fibrous livers, and loose stools were consistent observations. The effects found in the clinical chemistries taken together with histopathological abnormalities observed in sections of hepatic and renal tissue suggest that the liver and kidneys are major targets for 2,6-DNT. Oral exposures to 2,6-DNT appear to affect northern bobwhite in a manner similar to that of the other main DNT isomer, 2,4-DNT, but in more subtle ways, adversely affecting the gastrointestinal system and leading to diarrhea and, ultimately, emaciation. The lowest-observed-adverse-effect level is 40 mg/ kg/d based on hematological measures, and the no-observed-adverse-effect level is 10 mg/kg/d based on the absence of results indicative of adverse effects.     

Metallic mercury induced tremor in rabbits and mercury content of the central nervous system

Fukuda, K. (1971).Brit. J. industr. Med.,28, 308-311. Metallic mercury induced tremor in rabbits and mercury content of the central nervous system. Tremor induced by metallic mercury was experimentally produced in rabbits by intermittent exposure to mercury vapour (average concentration of 4·0 mg/m³ for 6 hr/day on 4 days/week for 13 successive weeks). Two of six male rabbits exposed developed fine tremor and clonus in the fore- and hind-legs after 13 weeks' exposure. Electromyographic records showed typical grouped voltages accompanying the clonus (amplitude 0·3 to 1·0 mV, duration 20 to 30 ms, frequency 14 to 15 per second).

Activation analysis of the central nervous system showed mercury levels ranging from 0·8 to 3·9 μg/g wet tissue. The concentration in the cerebellum, the tegmentum, and the thalamus was significantly higher than in the remaining structures. The relationship between the tremor and the mercury content of the central nervous system is discussed and a positive causal relationship is suggested.

     

Copper and zinc levels in peripheral nerve tissues of rats with experimental carbon-disulphide neuropathy

Lukáš, E., Kotas, P., and Obrusník, I., (1974).British Journal of Industrial Medicine,31, 288-291. Copper and zinc levels in peripheral nerve tissues of rats with experimental carbon-disulphide neuropathy. By means of neutron activation analysis the levels of zinc and copper in peripheral nerve tissue of two groups of rats with carbon-disulphide neuropathy were estimated. The neuropathy (diagnosed electromyographically) was evoked by inhalation of 3·6 mg CS₂/litre of air (variant 1) or 2·4 mg CS₂/litre of air (variant 2).

Stationary Zn levels were found in control and exposed animals in both of the experimental variants, while the copper levels increased very significantly from 4·2 ± 0·3 ppm to 9·9 ± 1·7 ppm in experimantal variant 1 and from 2·4 ± 0·3 ppm to 5·6 ± 0·6 ppm in variant 2.

The experiments suggest that changes in metal metabolism of peripheral nerve tissue deserve attention as one of the possible pathological links in the development of carbon-disulphide intoxication.