Investigations on neurotoxicity of chemical substances at the workplace

Summary A cross-sectional study was performed in order to investigate the influence of chronic lead-exposure on the peripheral nervous system. We examined 148 male workers of a storage battery manufacturing plant, who had been exposed to lead metal and inorganic lead compounds for 1 to 28 years (mean 11 years). Fifteen workers with non-occupational risks of peripheral neuropathy (former diseases, alcohol abuse, medication) were excluded from the study. The investigation program comprised: case history, physical examination, analyses of blood- and urine-samples and determination of maximal motor, mixed and sensory conduction velocity (NCV) of the ulnar and median nerve of the right forearm. Objectively no worker showed any signs of health effects related to lead exposure. The Biological Monitoring included the determination of (1) Blood-lead level (Pb-B), (2) Free erythrocyte porphyrins (FEP), (3) -Aminolevulinic acid dehydratase (ALA-D) and (4) -Aminolevulinic acid in urine (ALA-U). Further time-weighted-average (TWA)-values of Pb-B were calculated on the basis of several determinations over the period 1975–1981. The following actual (TWA) median values resulted: Pb-B 53 g/dl (54 g/dl), ALA-U 5.6 mg/l (8.4 mg/l), FEP 2.0 mg/l (2.0 mg/l). The Biologischer Arbeitsstoff Toleranz Wert (BAT) of 70 g//dl for Pb-B was exceeded in 15 workers (11%), and of 15 mg/l for ALA-U in 30 cases (23%). In comparison with age-matched controls, the lead workers showed a mild slowing of NCV with mean values between 0.8 and 2.0 m/s. Multiple stepwise regression analyses revealed statistically significant correlations between the four NCV and age as well as Pb-B. There were better correlations by using TWA than actual data of Pb-B. Consideration of the results of the regression analyses, together with an evaluation of the individual neurophysiological status as a function of internal lead exposure, a dose-effect-relationship was found only in the case of Pb-B exceeding 70 g/dl. From our study it is concluded that chronic lead exposure resulting in blood-lead levels of below 70 g/dl is no occupational risk causing a functionally significant slowing of nerve conduction velocities.With Grants from the Deutsche Forschungsgemeinschaft, Bonn (Project no. Va 23/19-1)     

An electroneurographic assessment of subclinical lead neurotoxicity

Summary 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 -ALAU in lead exposed group were 40.03 g/dl, 71 g/l and 4.68 mg/l respectively, which were significantly higher (P < 0.001) than those (7.01 g/dl, 6.0 g/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 bloodlead levels and the neurophysiological measurements except for the median MCV. No correlation was seen between the median MCV and the exposure duration. A reduction in MCVs of median and ulnar nerves and sural SCV was unexpectedly seen in eight lead workers after chelation therapy with CaEDTA, although their mean PbB decreased from 42.08 to 27.92 g/dl. No consistent findings in nerve conduction were found at these exposure levels.     

Relationship of air lead and blood lead for workers at an automobile battery factory

Summary Air lead and blood lead data, recorded over a period of 3 years for 972 employees at an automobile battery factory as part of a lead control program, were summarized and statistically analyzed. The air lead values were measured by mobile area samplers for approximately 2 years and then by personal samplers for approximately 1 year. Blood lead analyses were usually performed once a month for most of the workers.The trend in air lead levels was significantly upward in the 1st year and significantly downward in the 2nd year while the trend in blood lead levels was significantly downward in the 1st year and in the 3rd year. There were no other significant trends.To assess the relationship between air lead and blood lead, data were used whenever an air lead obtained by personal sampler was followed within 1 month by a blood lead on the same worker. The variables age, job tenure, and department identity were included in an analysis of covariance. Only air lead and departments were significant, accounting for 9% and 13% of the variance in blood lead, respectively. From these data 95% confidence limits were calculated for predicting blood leads from given air leads for an individual worker. These were 30–68 g/100 ml at 200 g/m³; 25–62 g/ 100 ml at 100 g/m³, and 22–60 g/100 ml at 50 g/m³.     

Search for anti-laminin antibodies in the serum of workers exposed to cadmium,mercury vapour or lead

Summary Anti-laminin antibodies were sought for in the serum of workers exposed to mercury vapour (Hg, n = 58), lead (Pb, n = 38) or cadmium (Cd, n = 47). Thirty-one workers removed from Cd exposure for an average of eight years were also examined. Compared with control workers matched for age and socio-economic status, the prevalence of circulating anti-laminin antibodies was not increased in workers exposed to Hg (mean duration of exposure: 7.9 years and mean urinary excretion of Hg: 72 g/g creatinine) nor in those exposed to Pb (mean duration of exposure: 10.6 years and mean Pb levels in blood: 535 g/l). In contrast, anti-laminin antibodies were significantly more prevalent in Cd-exposed workers whose urinary Cd exceeded 20 g/g creatinine. This observation was made in both currently exposed workers and in workers removed from Cd exposure (mean duration of exposure: 9.4 and 24.6 years and mean urinary Cd: 7.8 and 13.4 g/g creatinine respectively). These autoantibodies were found in Cd workers with normal renal function as well as in those with increased proteinuria.     

Motor nerve conduction velocity in asymptomatic lead workers

Summary No difference was found between the nerve conduction velocities of the ulnar nerve of 32 lead exposed workers in the mill of a lead-zinc mine, compared to that of a control group of 14 persons. The lead exposure period was 2–37 months (mean: 12.9 months).The blood lead of the exposed group was as an average (± SD): 53 ± 16 g per 100 ml compared to 11 ± 4 g per 100 ml for the control group.Further studies are needed to establish a possible dose-time-response relationship for the possible, subclinical neuropathy found by some investigators.     

An evaluation of the significance of mouth and hand contamination for lead absorption in lead-acid battery workers

Summary The present study was conducted to evaluate the role of ingestion through hand and mouth contamination in the absorption of lead in 25 lead-acid battery workers. Levels of personal exposure to airborne lead ranged from 0.004 to 2.58 mg/m³ [geometric mean 0.098, with 25% of samples exceeding threshold limit values (ACGIH) of 0.15 mg/m³]; the mean (SD) blood lead level was 48.9 (10.8) g/dl. Mean hand lead contents increased 33-fold from preshift levels on Monday mornings (33.5 g/500 ml) to midshift levels on Thursday afternoons (1121 g/500 ml). Mouth lead contents increased 16-fold from 0.021 g/50 ml on Mondays to 0.345 g/50 ml on Thursdays. The typical Malay racial habit of feeding with bare hands and fingers without utensils (closely associated with mouth and hand lead levels on Mondays) explained the bulk of the variance in blood lead levels (40%), with mouth lead on Thursdays (closely associated with poor personal hygiene) explaining a further 10%. Air lead was not a significant explanatory variable. The implementation of a programme of reinforcing handwashing and mouth-rinsing practices resulted in a reduction of the blood lead level by 11.5% 6 months later. These results indicate that parenteral intake from hand and mouth contamination is an important cause of lead absorption in lead-exposed workers.     

Assessment of thyroid,testes, kidney and autonomic nervous system function in lead-exposed workers

Summary The objective of the study was to assess whether moderate occupational exposure to lead may be associated with early changes in potential target organs (thyroid, testes, kidney, autonomic nervous system). Workers exposed to lead in a lead acid battery factory (n = 98; mean blood lead 51 g/dl, range 40–75 g/dl) and 85 control workers were examined. None of the indicators of kidney function (in urine: retinol-binding protein, ₂-microglobulin, albumin,N-acetyl--d-glucosaminidase; in serum: creatinine, ₂-microglobulin), endocrine function (follicle-stimulating hormone, luteinizing hormone, thyroid-stimulating hormone, thyroxine, triiodothyronine) and autonomic nervous system (R-R interval variations on the electrocardiogram) were correlated with lead exposure (blood lead or duration of exposure) or showed significantly different mean values between the exposed group and controls. These results and an assessment of the published data suggest that compliance with the Directive of the Council of the European Communities on lead exposure (health surveillance in workers whose lead in blood exceeds 40 g/dl and removal from exposure when blood lead exceeds 70–80 g/dl) would prevent the occurrence of significant biological changes in the majority of lead-exposed workers.     

Lead in finger bone, whole blood, plasma and urine in lead-smelter workers: extended exposure range

Objectives: To assess the historical exposure and to study the relationships between lead concentrations in whole blood (B-Pb), plasma (P-Pb), urine (U-Pb), finger bone (Bone-Pb) and duration of employment in workers at a secondary lead smelter and to compare the relationships between B-Pb and P-Pb with results from previous studies of populations with a wide range of lead exposure. Methods: In 39 lead workers (29 active, ten retired), recruited from those with the highest exposure at a German secondary lead smelter, levels of B-Pb, P-Pb and U-Pb were determined by inductively coupled plasma mass spectrometry (ICP-MS). Bone-Pb was determined by in vivo X-ray fluorescence (XRF). Results were compared with data from a previous study on 90 workers (71 active, 19 retired) with lower exposure, from a Swedish secondary lead smelter, as well as with previously collected data from 42 active Russian lead workers and 34 Ecuadorian lead-exposed subjects. Results: The median values in the active/retired German lead workers were: age 44/59 years, duration of employment 20/38 years, Bone-Pb 71/150 g/g, B-Pb 500/330 g/l, P-Pb 2.7/1.1 g/l, and U-Pb 25/13 mol/mol creatinine. Bone-Pb increased with duration of employment by 4.2 g/g per year and 1.6 g/g per year in German and Swedish workers, respectively. The median Bone-Pb was three times higher in both active and retired German workers than in Swedish smelter workers with essentially the same age distribution and duration of employment. The linear regression equation between B-Pb and log P-Pb in the combined group of Ecuadorian, German, Russian and Swedish lead-exposed subjects (n=176) was B-Pb=545×log[P-Pb] + 258 (r_s=0.94; P<0.001). Conclusions: The high Bone-Pb values recorded for the German smelters implied a historical lead exposure of considerable magnitude. The long-term high lead exposure also showed up in the B-Pb levels for both active and retired workers, leading to the implementation of necessary industrial safety measures in order to respond to biological threshold limits. The suggested equation describing the relationship between B-Pb and P-Pb in the combined group of subjects with a wide range of lead exposure can be useful in future cross-sectional and longitudinal studies of lead-exposed populations, relating, e.g., lead exposure to adverse health outcomes.     

Psychological performance of workers with blood-lead concentration below the current threshold limit value

Summary The effects of lead exposure on psychological test performance and subjective feelings of well-being were investigated in 40 exposed workers whose PbB levels had never exceeded 60 g/100 ml and in 20 controls matched for sex, age and educational level. The exposed workers were divided into two groups of 20, with recent PbB levels in the range 45–60 g/100 ml or below 35 g/100 ml. The group of workers with the higher PbB levels showed significantly poorer performance and reported more physical symptoms than the other two groups. These differences were unrelated to socio-demographic and personality characteristics. A principal component analysis suggested that the poorer performance was mainly due to an impairment of general functioning and only to some extent to a deterioration in specific functions, such as verbal reasoning and abstraction. Higher lead concentrations were correlated with poorer performance and a higher number of physical complaints. These results indicate that in exposed workers the threshold for impaired performance lies below the blood-lead concentration of 60 g/100 ml, which is the current threshold limit value (TLV).This study was supported by the Consiglio Nazionale delle Ricerche (CNR, Roma), Gruppo Nazionale Scienze del Comportamento (Grant no. 81.00083.04 and no. 82.02117.04)     

Occupational lead exposure and pituitary function

Summary Twenty-five moderately exposed lead workers (mean blood-lead level 1.9 mol/l) had lower plasma levels of follicle stimulating hormone than 25 individually matched controls without occupational lead exposure (blood-lead level 0.2 mol/l). In addition, the ten most heavily exposed individuals had higher levels of thyroid stimulating hormone, and the 14 workers under the age of 40 had decreased plasma levels of luteinizing hormone and serum levels of cortisol, as compared to the controls. All values were within normal reference limits. There was no significant change of the plasma testosterone level. These data indicate a complex effect on the endocrine system by moderate lead exposure, possibly mediated by changes at the hypothalamic-pituitary level. Besides the effect on hormone levels, there was also a decrease in plasma selenium level for the lead exposed workers.     

Effects of lead on red blood cell membrane proteins

Summary The effects of lead on red blood cell (RBC) membrane proteins were studied in two groups of workers with different lead exposure levels: Group 1 (6 subjects employed in a battery plant) with a mean blood lead of 40.1 (SD = 3.7) g/100 ml; Group II(5 workers employed in different industries) with a mean blood lead of 60.6 (SD = 8.0) g/100 ml, compared with a control group with mean blood lead of 15.6 (SD = 9.3) g/100 ml. The analysis of RBC membrane polypeptides was carried out by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and by using a densitometer for percentage measurement of the bands corresponding to protein fractions. The results show a very significant decrease in Band 3 (anion channel) and 4.1 in more exposed workers (Group II) only. The effects of lead on RBC membrane proteins seem to be evident at blood-lead levels higher (> 50 g/100 ml) than those previously reported in literature. These results confirm the effects of lead on membrane proteins, even if the exact mechanism, particularly the influence of proteolysis and the meaning of the interference, still needs to be investigated thoroughly.     

Biologic monitoring of workers exposed to silver

Summary Air-lead levels (PbA) and biological indices were studied in three ceramic factories (185 workers altogether). A difference in the pattern of lead exposure was found in the largest factory (A) and the other two smaller factories (B and C). PbA never exceeded 67 g/m³ in factory A, but reached values as high as 378 g/m³ in factory B. 19% of PbB values were higher than 40 g/100 ml in factory A, 63% in factory B and 35% in factory C. As was expected, a closer analysis of the jobs confirmed a higher exposure level in people directly in contact with lead glazes (glazers and kiln operators). In factories B and C, however, there was also a significant lead uptake in selection and maintenance staff, who worked in areas at some distance from the glazing lines. This may be due in part to pollution spread over all departments, but also to the lack of hygiene and washing facilities whose importance is stressed for effective prevention. Biological monitoring is suggested as being useful for all workers, whatever the lead-air level, bearing in mind the possibility of lead intake orally through soiling.     

External and internal antimony exposure in starter battery production

In the production of lead batteries two antimony compounds occur: in the casting of grids antimony trioxide (Sb₂O₃), and in the formation of lead plates stibine (SbH₃). Seven workers from the gridcasting area and 14 workers from the formation area were examined with regard to the antimony concentration in blood (Sb-B) and urine (Sb-U). Antimony air concentrations (Sb-A) were measured by means of personal air samplers. Urine samples were collected at the end of the working week, at the beginning (U1) and the end (U2) of the shift, and at the beginning of work following a weekend without Sb exposure (U3). At U2 among the casters the median Sb-A exposure was 4.5 (1.18–6.6) g Sb/m³ and among the formation workers, 12.4 (0.6–41.5) g Sb/m³. The exposure in both groups is more than 10 times lower than the present threshold limit values. The median Sb-B concentrations in the preshift samples was 2.6 (0.5–3.4) g Sb/l for the casters and 10.1 (0.5–17.9) g Sb/l for the formation workers. The average Sb-U values (U2) were 3.9 (2.8–5.6) g Sb/g creatinine in the casting area and 15.2 (3.5 23.4) g Sb/g creatinine in the forming area. Our investigation indicates that the two antimony compounds show virtually equal pulmonary absorption and renal elimination. The statistically significant correlations between Sb-A/Sb-B and Sb-A/Sb-U form the basis for proposals regarding appropriate biological exposure limits for occupational antimony exposure.Dedicated in constant gratitude to our highly honoured mentor, Prof. Dr. med. H. Valentin, on the occasion of his 75th birthday     

Biochemical response of male volunteers ingesting inorganic lead for 49 days

Summary Male volunteers (n = 11) ingested lead acetate, starting with 30 30 g Pb/kg daily until PbB had reached 300 ppb; thereafter daily dosage was changed into 20, 10 or 0 g Pb/kg to sustain an intended individual level of PbB = 400 ppb; 10 controls ingested a placebo (single blind); exposure lasted for 49 days. On the average PbB = 350 ppb was reached in 15 days. ALAD activity in blood decreased as soon as PbB increased; it showed a decrease of 45–69% at the end of exposure. FEP increased in 10 exposed subjects after a calculated lag time of 0 – 21 days (in 7 subjects > 5 days) and did not level off during the period of exposure. There was no effect on serum Fe values; there was a small decrease of GSH; ALAU and number of reticulocytes did not change. At PbB < 400 ppb, FEP can be used as a parameter of lead effect. Increase of FEP should be regarded with more caution than inhibition of ALAD. In biological monitoring programs, the combination of PbB and FEP will present a more valid picture of exposure and of response (health risk).     

Fecal lead excretion in young children as related to sources of lead in their environments

Summary Fecal lead excretion (PbF) was studied in young children with elevated lead exposure. PbB was generally 40–70 g/dl. The children's home environments were classified as to lead-base paint hazard and traffic density. There was a significant correlation between paint hazard classification and PbF but not between traffic density and PbF. There also was a correlation of PbB with paint hazard classification. Long-term fecal collections were instituted using 10 children who lived in high hazard homes and three children with low PbB's, whose PbF's were considered normal. Among the children living in high hazard homes, median fecal lead excretion generally was only moderately elevated. Grossly elevated amounts of lead were found only occasionally and only in a few of the children. Movement of two children from a high hazard home to a low hazard home resulted in prompt and substantial reduction in PbF. By contrast, PbB fell only very slowly.This study was supported by a grant from the US National Science Foundation—RANN Program, Grant 77-22186     

Lead in deciduous teeth of children living in a non-ferrous smelter area and a rural area of the FRG

Summary Lead concentrations were measured in the deciduous teeth (incisors) of 302 children living in a lead-smelter area in the FRG (Stolberg, Rheinland) and of 86 children living in a nonpolluted rural area (Gummersbach, Bergisches Land). Blood lead levels were determined in 83 of the children living in the lead smelter area. On average, tooth lead levels of children living in the smelter area (mean: 6.0 g/g; range: 1.49–38.5 g/g) were significantly higher than those of children living in the rural area (mean: 3.9 g/g; range: 1.6–9.4 g/g). Blood lead levels were 6.8–33.8 g/100 ml (mean: 14.3 g/100 ml). Children of lead workers had on average higher tooth lead and blood lead levels than children of people who were not lead-workers. Tooth lead levels increased with increasing duration of residence in the lead-smelter area and with the degree of local environmental pollution by lead, as indicated by the lead content of the atmospheric dust fall-out around the children's homes. The correlation coefficient of tooth lead vs blood lead was 0.47. The intra-individual variability of tooth lead levels was low (r=0.86), and tooth lead levels of brothers and sisters were similar (r=0.75), suggesting that tooth lead may be used as a representative and reliable indicator of long-term lead exposure.This study was carried out at the request and with support of the Ministerium für Arbeit, Gesundheit und Soziales NW, Düsseldorf     

Effect of lead on cardiac parasympathetic function

Summary A cross-sectional survey was performed on 172 male, lead exposed workers to clarify the effects of lead on the cardiac autonomic nervous system expressed as the decrease of R-R interval variation on an electrocardiogram and to obviate the dose-effect relationship between blood-lead level (Pb-B) and the degree of the decrease. For 132 workers who were exposed to lead for more than one year and whose Pb-B levels were relatively stable (Pb-B variation less than 20 g/dl during recent one year), a significant dose-related decrease of R-R interval variation during deep breathing was observed. Age-adjusted R-R interval variation during deep breathing in those whose Pb-B were 30 g/dl or above was significantly decreased compared with those whose Pb-B levels were 20 g/dl or below. This decrease was observed more clearly in younger workers. These results suggest that an effect on autonomic nervous system expressed as decrease of R-R interval variation during deep breathing might be one of the earliest effects of lead exposure.     

High medical consultation rates of lead workers after industrial dispute over lead effects

Summary Medical consultation rates were compared between a group of lead workers (346 males) and two groups of non-lead workers (317 and 329 males) in a newspaper company where a serious industrial dispute took place over health effects of lead three years before this study. The comparison was also made within the group of lead workers. Maximal blood lead concentrations (PbBs) ranged from 0.1 mol/kg to 3.6 mol/kg (74 g/ 100 g) with an average of 1.3 mol/kg in the past three years. Ages averaged 35 years in lead workers, and 34 and 30 years in non-lead workers, the ranges being 19-55 years in all.The consultation rate of lead workers was significantly higher than that of both the non-lead workers (P<0.001), when the number of workers who consulted physicians or dentists once or more for a year per 100 workers (general consultation rate) was compared. Disease-specific consultation rates were also higher in lead workers for seven categories of diseases and injuries such as hypertensive disease and peptic ulcers.When lead workers were divided into three groups by PbB or erythrocytes delta-aminolevulinic acid dehydratase (ALAD) levels, however, no significantly high rate was found in the higher PbB groups nor lower ALAD groups in terms of general and disease-specific consultation rates.It was concluded that the industrial dispute might have been a major cause of the high consultation rate of lead workers.     

Blood lead levels of traffic policemen in Bursa,Turkey

This study was conducted in January 2001, in Bursa, Turkey. Of the 99 traffic policemen who were included in the study, 21 were office workers. Blood lead levels were determined by using an electro-thermal atomic absorption spectrometer (ET-AAS). Average blood lead levels were 9.4 +/- 1.6 micrograms/l and 8.7 +/- 1.7 micrograms/l for policemen working outdoors and indoors, respectively. The difference between the two groups was statistically insignificant (P > 0.05). When policemen less than 15 years on duty were taken into account (n = 48) the difference between the outdoors and indoors working groups was significant (9.3 +/- 1.3 and 8.2 +/- 1.8 micrograms/l, P < 0.05). In order to prevent the negative effects of tetraethyl lead on humans and the environment the use of lead in petrol must be prohibited.     

Free erythrocyte protoporphyrin as an indicator of the biological effect of lead in adult males

Summary The relationship between FEP and the indicators of dose (PbB, PbU, PbU-EDTA) was examined in a group of male subjects who had left lead-exposing jobs more than 12 months previously.In these subjects, FEP and PbB and FEP and PbU were correlated to a distinctly lower degree compared to previous findings in currently exposed subjects, although the correlations were still statistically significant. In the previously exposed subjects the erythrocyte metabolite displayed definitely higher values than those found in currently exposed subjects at the same PbB or PbU levels.A very close correlation was found between FEP and PbU-EDTA, as was found in exposed subjects. The regression curve assumed an identical profile in the two situations. From these results it may be concluded that FEP persists at high levels for a long time after cessation of exposure due to a direct inhibition of heme synthetase caused by lead released from the tissue deposits.It should be noted that FEP proved to be a valid test for predicting the amount of lead storage, even a long time after cessation of exposure.Abbreviations PbB blood lead (g/100 ml) - PbU lead in urine (g/l) - PbU-EDTA amount of chelatable lead excreted with 24 h urine after administration of Ca NA₂ EDTA (1 g intravenously) - FEP free erythrocyte protoporphyrin (g/100 ml RBC) - ALAU urinary delta-aminolevulinic acid (mg/l) - CPU urinary coproporphyrin (g/l)