Studies on erythrocyte pyrimidine 5′-nucleotidase (P5N) test and its evaluation in workers occupationally exposed to lead

Summary An erythrocyte pyrimidine 5-nucleotidase (P5N) test was performed for 171 workers occupationally exposed to lead. Erythrocyte P5N activity was markedly inhibited by exposure to lead. Among several biological indicators (erythrocyte P5N, -aminolevulinic acid dehydratase (ALAD), protoporphyrin (PROTO), urinary -aminolevulinic acid (ALA), coproporphyrin (COPRO)), the P5N activity had the highest correlation with the concentration of lead in blood (r = – 0.77). A significant inhibition of erythrocyte P5N was found in groups of lead workers with blood-lead levels of more than 10 to 19 g/dl. This P5N inhibition started before any changes occurred in urinary ALA and COPRO. A 45 to 50% inhibition of P5N corresponded to the blood-lead value (50 g/dl) of the BEI recommended by ACGIH. In some lead workers, erythrocyte nucleotides (mainly CTP and UTP) were determined. The data indicated that a marked accumulation of these nucleotides had occurred, and their levels correlated negatively with P5N activity and positively with blood lead.     

Erythrocyte pyrimidine 5′-nucleotidase activity in workers exposed to lead,mercury or cadmium

Summary The erythrocyte pyrimidine 5-nucleotidase activity (P5N) was measured in workers exposed to lead, cadmium or inorganic mercury and the effect of lead on this enzyme activity was compared with that on the classical biological parameters (ALAD, ZPP, ALAU), reflecting the interference of this metal with the heme biosynthesis pathway. P5N is inhibited by lead but not by cadmium and mercury. The correlation coefficient between log P5N and lead in blood (PbB) amount to 0.79 (n = 278; PbB ranging from 4.9 to 73.5 g/100 ml). The response of P5N to lead closely parallels that of ALAD.     

Response of free erythrocyte porphyrin and urinary δ -aminolevulinic acid in men and women moderately exposed to lead

Summary The responses of various biological parameters of the haem biosynthesis pathway in a group of adult male and female workers moderately exposed to inorganic lead have been compared. The identical range of blood lead levels in both groups indicates a similar degree of exposure. Women, however, exhibit a larger increase in free erythrocyte porphyrin (FEP) and in urinary -aminolevulinic acid (ALA-U) than men.The earlier response in women is probably not due to a relative degree of anaemia (menstrual blood loss) as compared to men, since there is no significant correlation between haemoglobin (Hb) and FEP or ALA-U, and consequently standardization for the same Hb-content does not modify the independent effect of lead on the FEP and ALA-U responses. A greater susceptibility to Pb of the haem biosynthesis pathway in women has therefore been confirmed by the results of the present epidemiological survey among workers of both sexes.A preliminary and limited survey on children (11 to 12 years old) of schools situated at less than 1 km from a Pb-processing plant revealed increased FEP and blood lead concentrations and demonstrated that like women children exhibit an earlier biological response to Pb-B than adult men.     

Perceived odor and irritation of isopropanol: a comparison between naïve controls and occupationally exposed workers

OBJECTIVES: To assess sensory irritation levels from isopropanol (IPA) unconfounded by subjective evaluations of odor for comparison against the recommended exposure limits (400 ppm threshold limit value (TLV); American Conference of Governmental Industrial Hygienists). METHOD: The lateralization method was used to assess intra-nasal irritation thresholds for IPA, while odor detection thresholds were also measured. Thresholds for 1-butanol and phenyl ethyl alcohol (PEA) were obtained as positive and negative irritant controls. To compare potency and hedonic characteristics, subjects provided subjective ratings of odor, irritation and annoyance intensity for three concentrations of each chemical. Workers occupationally exposed to IPA ( n=26) were compared with previously unexposed controls ( n=26). RESULTS: The (geometric) mean odor detection threshold for IPA was slightly higher among exposed workers than controls (39 ppm vs. 11 ppm). Lateralization thresholds measuring intra-nasal irritation were elevated when compared with controls (6,083 ppm in exposed workers vs. 3,361 ppm in na?ve controls), with a significantly higher proportion of phlebotomists being unable to lateralize the maximum concentration regarded as safe, than controls. Calculations of the 6th percentile for lateralization thresholds revealed that 95% of the sample did not experience sensory irritation below 512 ppm. Thus, while odor detection thresholds were well below the current recommended exposure limits, the irritation thresholds were well above these values. The odor, irritation and annoyance from IPA was perceived, on average, as between weak and almost strong, from lowest to highest concentration. CONCLUSIONS: The results indicate that current exposure guidelines would be adequately protective of the acute adverse effect of nasal sensory irritation, as operationally defined by the intra-nasal lateralization threshold. Exposures to higher concentrations should perhaps be evaluated on the basis of existing knowledge about systemic, rather than local (e.g., irritation), toxic effects. IPA appears to be a weak sensory irritant and occupational exposure to IPA appears to elicit small changes in sensitivity that do not generalize to other odorants (e.g., PEA and 1-butanol) and are likely to be reversible.     

Improvement in the GC–MS method for determining urinary toluene-diamine and its application to the biological monitoring of workers exposed to toluene-diisocyanate

Objectives: To develop a simple and sensitive GC–MS method for determining toluene-diamine (TDA) in urine and to apply the method for biological monitoring of workers exposed to toluene-diisocyanate (TDI). Methods: After acid hydrolysis of 0.1 ml of urine, diluted tenfold with water, for 1.5 h, the free TDA formed was extracted with dichloromethane, and the heptafluorobutyric anhydride derivative was determined by GC–MS. We applied the method to the biological monitoring of 18 workers who were using an 80:20 mixture of 2,4-TDI and 2,6-TDI. Results: 2,6-TDA and 2,4-TDA were simply determined in 7 min by GC–MS. TDA levels in post-shift urine were well correlated with personal exposure levels of TDI. The correlation was improved by correction with creatinine or specific gravity in the 2,6-isomer, but not in the 2,4-isomer because of low exposure levels. From the correlation equation, the 2,6-TDA level (corrected with creatinine), corresponding to the TDI level of 5 ppb, was calculated to be 31.6 g/g Cre. TDAs in pre-shift urine also correlated significantly with the personal exposure levels of TDIs, although the slope of the correlations for pre-shift samples was 60%–70% of those for post-shift samples. The correlation between 2,4-TDA and 2,6-TDA levels was significant, although the levels of the 2,4-isomer were less than one-tenth of the 2,6-isomers in both air (personal exposure) and urine. Conclusion: The present method is simple and practicable and can be useful for biological monitoring of TDI workers.     

Blood toluene as a biological index of environmental toluene exposure in the “normal” population and in occupationally exposed workers immediately after exposure and 16 hours later

Blood toluene was measured in a group of 100 workers occupationally exposed to a mean 8-h environmental toluene concentration of 128 g/l (34 ppm), and in a group of 269 normal subjects without occupational exposure to toluene. The mean blood toluene of the workers at the end of the shift and the following morning, after 16 h, was 457 and 38 g/l, respectively. The normal subjects had a blood toluene level of 1.1 g/l. On the basis of the highly significant correlation between blood toluene and occupational exposure, it can be calculated that environmental toluene exposure of 188 and 377 g/l (50 and 100 ppm) gives end-of-shift blood toluene levels of 690 and 1390 g/l, respectively. The corresponding blood toluene levels on the following morning are 50 and 100 /l, respectively.     

UrinaryN-acetyl-β-d-glucosaminidase and β-aminoisobutyric acid in workers occupationally exposed to metals such as chromium,nickel, and iron

Summary To examine the relationships between the urinary excretion ofN-acetyl--d-glucosaminidase (NAG) and -aminoisobutyric acid (AIBA) as a metabolite of thymine, and exposure to chromium, nickel, and iron, we determined these parameters in 58 workers engaged in the cutting and grinding of stainless steel or iron-steel plates. A significant increase in urinary NAG activity or urinary AIBA excretion was found in some of these workers. However, we could not find a significant positive correlation between the urinary excretion of NAG or AIBA and the urinary concentration of chromium, nickel, or iron as an indicator of internal dose.     

The effect of different warming methods on sensory nerve conduction velocity in shipyard workers occupationally exposed to hand–arm vibration

OBJECTIVES: Segmental sensory nerve conduction velocity (SNCV) was measured from the wrists to the hands and digits in a population of 134 (126 men and 8 women) vibration-exposed shipyard workers following systemic warming using a bicycle ergometer. Results were compared to earlier nerve conduction tests, identical in execution, except that the warming process was segmental and cutaneous. The study was designed to investigate whether SNCVs, which were selectively slow in the fingers after segmental cutaneous (skin surface) warming, would be affected differently by systemic warming. METHODS: Wrist-palm, palm-proximal digit, and digital sensory nerve segments were assessed antidromically by stimulating at the wrist with recording electrodes placed distally. The same subjects were cutaneously warmed in 2001 to >/=31 degrees C and were systemically warmed 28 months later in 2004 by ramped sustained exercise to 100 W for 12 min. Skin temperatures were measured by traditional thermistry and by infrared thermal images taken over the hand and wrist surfaces. RESULTS: When systemic warming was compared to segmental cutaneous warming, SNCVs were increased by 15.1% in the third digit and 20.4% in the fifth digit of the dominant hand. Respective increases in the non-dominant hand were 11.0% and 19.4%. A strong association between increased surface skin temperature and faster SNCV, which had been observed after segmental cutaneous warming, was largely eliminated for both digit and palmar anatomic segments after systemic warming. Significant differences in SNCV between vibration-exposed and non-exposed workers, which had been observed after segmental cutaneous warming, were eliminated after systemic warming. Systemic warming had only a small effect on the wrist-palm (transcarpal) segmental SNCVs. CONCLUSIONS: Reduced SNCV in the digits was observed in vibration-exposed and non-exposed workers. Substituting exercise-induced systemic warming for segmental cutaneous warming significantly increased SNCV in the digits and appeared to reduce differences in SNCV between vibration-exposed and non-exposed workers. These findings persisted despite a substantial time interval between tests, during which the subjects continued to work. There may be more general implications for diagnosing clinical conditions in industrial workers, such as the carpal tunnel syndrome and the hand-arm vibration syndrome.     

Relationships between three indicators of lead exposure in workers: Blood lead, δ-aminolevulinic acid and free Erythrocyte Protoporphyrin

Summary Whole blood lead (Pb-B), urinary -aminolevulinic acid (ALA-U) and free erythrocyte protoporphyrin (FEP) were measured in three groups of workers (n = 196) with different degrees of exposure to lead, and one group of men with no previous exposure to the metal (n = 48). Inter-group comparison showed a correlation of r = 0.73 between Pb-B and log of ALA-U, and r = 0.91 between Pb-B and log of FEP. ALA-U and FEP values rose sharply after Pb-B values reached 450–500 g/1.     

Ocular fundus photography of workers exposed to carbon disulfide — A comparative epidemiological study between Japan and Finland

Summary Using color fundus photography, the occurrence of retinopathy was studied in Japanese and Finnish viscose rayon workers and unexposed control subjects. Interobserver error was avoided by strict method control. Retinopathy (microaneurysms/small dot hemorrhages) was detected in 103 of 419 Japanese exposed (24.6%) and in 7 of 188 Finnish exposed subjects (3.79% (P < 0.05). The respective prevalences for the unexposed subjects were 3.8% and 2.6%. The retinopathy due to carbon disulfide, retinopathia sulfocarbonica, seen in Japanese viscose rayon workers did not occur in Finnish workers.     

Biological monitoring of workers exposed to 4,4′-methylenediphenyl diisocyanate (MDI) in 19 French polyurethane industries

OBJECTIVES: To study the range of urinary levels of 4,4'-methylenedianiline (MDA), a metabolite of methylenediphenyl diisocyanate (MDI), across factories in the polyurethane industries and to evaluate the validity of this biomarker to assess MDI occupational exposure. METHODS: Workers exposed to MDI, as well as non-occupationally exposed subjects, were studied and pre- and post-shift urine samples were collected from 169 workers of 19 French factories and 120 controls. Details on work activities and practices were collected by a questionnaire and workers were classified into three job categories. The identification and quantification of the total urinary MDA were performed by high-performance liquid chromatography with electrochemical detection (HPLC/EC). RESULTS: For all the factories, MDA was detectable in 73% of the post-shift urine samples. These post-shift values, in the range of <0.10 (detection limit)-23.60 microg/l, were significantly higher than those of the pre-shift samples. Urinary MDA levels in the control group were in the range of < 0.10-0.80 microg/l. The degree of automation of the mixing operation (polyols and MDI) appears as a determinant in the extent of exposure levels. The highest amounts of MDA in urine were found in the spraying or hot processes. The excretion levels of the workers directly exposed to the hardener containing the MDI monomer were significantly higher than those of the other workers. In addition, skin exposure to MDI monomer or to polyurethane resin during the curing step were always associated with significant MDA levels in urine. CONCLUSIONS: Total MDA in post-shift urine samples is a reliable biomarker to assess occupational exposure to MDI in various industrial applications and to help factories to improve their manufacturing processes and working practices. A biological guiding value not exceeding 7 microg/l (5 microg/g creatinine) could be proposed in France.     

Cancer mortality in workers exposed to dieldrin and aldrin: over 50 years of follow up

Objective  Dieldrin and aldrin, pesticides widely used until the 1970s, have been under suspicion of being carcinogenic. In this study, overall and cause-specific mortality was assessed in a cohort of 570 employees occupationally exposed to the pesticides dieldrin and aldrin to investigate the long-term health effects, in particular carcinogenic effects. Methods  All of the employees worked in the production plants between January 1954 and January 1970 and were followed for cause-specific mortality until 30 April 2006. Based on dieldrin levels in blood samples taken from 343 workers during the exposure period, the total intake of dieldrin was estimated for each individual subjects in the cohort. The estimated total intake ranged from 11 to 7,755 mg of dieldrin, with an average of 737 mg. Results  Two hundred and twenty-six workers had died before 30 April 2006 compared with an expected number of 327.3, giving a standardized mortality ratio (SMR) of 69.0 (95% confidence interval (CI): 60.3–78.7). Overall cancer mortality was also significantly lower than expected (SMR: 76.4, 95% CI: 60.8–94.9). Also, none of the specific cancer sites showed a significant excess mortality and no association between exposure level and cancer mortality was found. Conclusion  The results from this study support findings from other epidemiological and recent animal studies concluding that dieldrin and aldrin are not likely human carcinogens.     

Synthesis and aldose reductase inhibition activity of spiro-[9H-fluoren-9,4′-imidazolidine]-2′,5′-dione derivatives

A series of substituted spiro-[9H-fluoren-9,4′-imidazolidine]-2′,5′-diones was prepared by Bucherer—Berg condensation followed by various modifications of a carboxylic functional group. The compounds obtained were examined for their abilities to inhibit the enzyme aldose reductase both in vitro and in vivo.High potency in inhibiting the semi-purified calf lens enzyme in vitro was observed for several of the tested compounds. Two of the compounds have been found to be very effective in reducing sorbitol accumulation in the lenses and sciatic nerves of rats treated with streptozotocin. Substitution on positions 1 or 2 of the fluorene ring led to inactive compounds, whereas substitution on positions 3 or 4 enhanced inhibitory activity with respect to the unsubstituted spirofluorohydantoin 50. These observations are discussed in light of the previously published structural requirements of the allosteric binding site of the enzyme aldose reductase.     

Exposure to lead and cadmium of children living in different areas of North-West Germany: results of biological monitoring studies 1982–1986

Summary Between 1982 and 1986 several surveys were carried out to determine the levels of lead and cadmium in blood, urine, and shed deciduous teeth (incisors only) of children living in rural, suburban, urban, and industrial areas of North-West Germany. Blood lead (PbB) and blood cadmium (CdB) were measured in about 4000 children. In rural, suburban and urban areas the median PbB levels vary between 5.5 and 7 g/dl, with 98th percentiles varying between 10 and 13 g/dl. The median CdB levels are between 0.1 and 0.2 g/dl, with 95th percentiles between 0.3 and 0.4 g/l. Children from urban areas have significantly higher PbB levels than children from rural and suburban areas. Regarding CdB no differences could be detected. Children living in areas around lead and zinc smelters, particularly those living very close to the smelters, have substantially increased PbB and CdB levels. Children from lead worker families also have substantially increased PbB and CdB levels. The lead levels in shed milk teeth (PbT) were determined in about 3000 children. In rural, suburban and urban areas the median PbT levels are between 2 and 3 g/g, with 95th percentiles between 4 and 7 g/g. Children from urban areas have significantly higher PbT levels than children from rural and suburban areas. The highest PbT levels (on a group basis) are in children from nonferrous smelter areas. The median levels of lead in urine (PbU) are between 6 and 10 g/g creatinine, with 95th percentiles between 20 and 30 g/g creatinine. Children from polluted areas have higher PbU levels than children from less polluted areas. The median levels of cadmium in urine (CdU) are in the order of 0.1 g/g creatinine, with 95th percentiles being in the range of 0.5 and 1.0 g/g creatinine. Girls have higher CdU levels than boys. There are no differences between groups of children from different areas. Children from lead worker families have higher PbU and CdU levels than otherwise comparable children. The results of the present studies indicate a further decrease of PbB in children from North-West Germany since the CEC blood lead campaigns carried out in 1979 and 1981. The decrease of lead exposure also seems to be reflected by a decrease of tooth lead levels.The studies presented in this communication were supported by the Ministry of Work, Health and Social Affairs and the Ministry of Environment and Agriculture of Nordrhein-West-falen, FRG     

4,4′-Methylenedianiline in hydrolysed serum and urine from a worker exposed to thermal degradation products of methylene diphenyl diisocyanate elastomers

A 45-year-old mechanic employed in blowing hot air (350°–600°C) onto the surface of a polyurethane methylene diphenyl diisocyanate (MDI) conveyer belt developed dyspnoea, rhinoconjunctivitis and fever. The illness was suggestive of an MDI-associated illness, compatible with both immediate hypersensitivity and a complement-mediated immune-complex reaction. In his serum there were specific IgG and IgE antibodies against MDI and other isocyanates, and high values of circulating immune complexes. The patient's blood and urine samples were analysed for the presence of 4,4-methylenedianiline (MDA) in hydrolysed urine and plasma. MDA was derivatized to amides using pentafluoropropionic acid anhydride (PFPA). Gas chromatography-mass spectrometry determinations were made monitoring the (M-20; M = molecular mass) fragments from the MDA-PFPA and the [²H₂]MDA-PFPA derivative. The first urine sample was obtained 22 h and the last sample 114 h after start of exposure. The urine concentrations of MDA were corrected for creatinine. The half-time of MDA was 70–80 h. The first serum sample was obtained 19 h and the last sample 1967 days after the start of exposure. The half-time was 21 days, which suggests the presence of MDI/MDA plasma protein adducts in the exposed worker.     

Scientific Uncertainty as a Moderator of the Relationship between Descriptive Norm and Intentions to Engage in Cancer Risk–Reducing Behaviors

Little research has focused on what precedes the processing of health messages to predict recall of information and whether age matters in this regard. To address this gap, this study investigates the relationship between attention and recall among younger (<65 years) and older (≥65 years) adults. Using eye tracking, we exposed participants to a webpage consisting of text-only information, text with cognitive illustrations, or text with affective illustrations. When attention to text increased, older adults recalled more information, whereas younger adults did not. However, younger adults paid more attention to cognitive illustrations than older adults and recalled more information. These results reveal conditions under which health messages are effectively recalled by younger and older adults.     

Immunodeficiency and lymphocyte ecto-5′-nucleotidase activity in the elderly: A comparison of the effect of a trace mineral supplement (1 USRDA) with high zinc (6.7 X USRDA)

The effect of administering a total mineral supplement (TMS) or 100 mg of elemental zinc alone on immune function was studies in 17 normal subjects, aged 66–85. Subjects were given either TMS containing 1 USRDA of zinc, copper, iron, and manganese or 100 mg of elemental zinc alone as zinc sulfate (ZnSO₄). Administration of either supplement led to a slight increase in peripheral blood lymphocytes and improved maturation of B-lymphocytes to antibody-producing cells in culture of peripherla blood mononuclear cells. Ecto-5′-nucleotidase, a zinc obligate enzyme of lymphocyte cell membranes, increased when TMS was administered daily but failed to increase when ZnSO₄ was administered. Serum zinc levels increased in all subjects receiving the ZnSO₄. Only those subjects with low initial serum zinc levels had higher serum zinc levels after 3 months on the TMS. These studies indicate that dietary supplementation with a TMS (1 USRDA) can improve certain in vitro parameters of immune competence in the aged, avoiding the deleterious effects possible with excessive intake.     

Correlation between work process-related exposure to polycyclic aromatic hydrocarbons and urinary levels of α-naphthol, β-naphthylamine and 1-hydroxypyrene in iron foundry workers

Summary In two Danish iron foundries the concentration of polycyclic aromatic hydrocarbons (PAH) in 24 personal air samples of workers employed in selected processes, i.e. melters, melted iron transporters, casters, machine molders, hand molders, shake-out workers and finishing workers, were measured and correlated to levels of 1-hydroxypyrene, -naphthol and -naphthylamine in the urine of exposed workers. The highest total airborne PAH concentrations (sum of 15 selected PAH compounds: 9.6–11.2 g/m³) were associated with casting, machine molding, and shake-out. The highest concentrations of the sum of six selected airborne carcinogenic PAH compounds were found for melting, casting and machine and hand molding. As seen in other working environments involving low-level PAH exposure, the content of naphthalene was high, in general exceeding 85% of the total content of PAH compounds. The present study demonstrates that 1-hydroxypyrene is a useful and direct biomarker of low-dose occupational exposure to PAH compounds. Molding and casting had the highest pyrene levels in iron foundries. Furthermore, the data shows that levels of -naphthylamine in urine are significantly elevated in iron foundry workers. Hand molders, finishing workers and truck drivers tended to have the highest levels. Concerning -naphthol the highest concentrations were measured in urine from casters and shake-out workers. With regard to epidemiologic studies demonstrating that molders and casters have a higher risk of lung cancer, the present study suggests that the elevated risk may be due to exposure to carcinogenic PAH compounds in iron foundries, particularly in some high-risk work processes, e.g. casting and molding. In addition, the present study suggests that biological monitoring of 1-hydroxypyrene and -naphthylamine may be used to estimate the individual exposure, which seems to be correlated with exposure during individual work processes.