Summary
Data on 394 simultaneous measurements of blood lead (PbB) and biological indicators of effect are considered with regard to dose-effect and dose-response relationships, as well as the association between the biological indicators of effect themselves. The indicators are delta-aminolevulinic acid dehydratase (ALAD) and zinc-protoporphyrin (ZPP) in blood, delta-amino-levulinic acid (ALAU) and coproporphyrin (CPU) in 24-h urine specimens. The specimens were taken from periodically controlled male workers “moderately” to “excessively” exposed to inorganic lead. In addition, data are presented on the spontaneous recovery of biological indicators in 14 male workers examined immediately after, approximately 4.5 months and 10 months after cessation of lead exposure. Highly significant (P<0.001) correlations were found between all of the indicators examined, with the following order of agreement with regard to PbB: ALAD>ZPP>ALAU>CPU. Comparative advantages of ALAD in typical (variable) occupational exposure conditions were found to include: (a) the highest sensitivity at both low and relatively high lead exposure levels, (b) better reflection of biologically active lead as opposed to PbB (particularly compared to ALAU and CPU), (c) higher specificity compared to other indicators of lead effect, and (d) generally higher reliability with regard to both biologically and methodologically induced variations. The data obtained undoubtedly demonstrate that urinary indicators ALAU and CPU are not sensitive enough for the recommended health-based occupational exposure limit, as defined by relatively low PbB concentration (WHO 1980). Despite possible theoretical considerations resulting in recommendations for ZPP and ALAU but excluding ALAD (WHO 1980), practical implications seem to be far more in favour of ALAD, which permits a maximal safety margin in preventing “adverse” effects in the entire work population because of its sensitivity and absence of time-lag with regard to lead exposure.
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Alessio L, Castoldi MR, Odone P, Franchini I (1980) Behaviour of indicators of dose and effect after cessation of occupational exposure to lead. In: Holmstedt B, Lauwerys R, Mercier M, Roberfroid M (eds) Mechanisms of toxicity and hazard evaluation. Elsevier/NorthHolland, Amsterdam New York Oxford, pp 357–361
Baloh WR (1974) Laboratory diagnosis of increased lead absorption. Arch Environ Health 28:198–208
Beritić T, Prpić-Majić D, Karačić V, Telišman S (1977) ALAD/EP ratio as a measure of lead toxicity. J Occup Med 19:551–557
Beritić T, Telišman S, Karačić V, Prpić-Majić D, Keršanc A, Pongračić J (1978a) Blood lead in clinical lead poisoning. 19th International Congress on Occupational Health, Dubrovnik 1978, Abstracts, p 38
Beritić T, Markićević A, Telišman S, Karačić V, Pongračić J, Keršanc A (1978b) Delta-aminolevulinic acid and coproporphyrin in urine in the delayed action of lead. 19th International Congress on Occupational Health, Dubrovnik 1978, Abstracts, p 37
Berlin A, Schaller KH (1974) European standardized method for the determination of 6aminolevulinic acid dehydratase activity in blood. Z Klin Chem Klin Biochem 12:389–390
Blumberg WE, Eisinger J, Lamola AA, Zuckerman DM (1977) Zinc protoporphyrin level in blood determined by a portable hematofluorometer. A screening device for lead poisoning. J Lab Clin Med 89:712–723
Davis JR, Andelman SL (1967) Urinary delta-aminolevulinic acid levels in lead poisoning. A modified method for the rapid determination of urinary delta-aminolevulinic acid using disposable ion-exchange chromatography columns. Arch Environ Health 15:53–59
Fernandez FJ (1975) Micromethod for lead determination in whole blood by atomic absorption, with use of the graphite furnace. Clin Chem 21:558–561
Grandjean P, Lintrup J (1978) Erythrocyte Zn-protoporphyrin as an indicator of lead exposure. Scand J Clin Lab Invest 38:669–675
Hernberg S (1976) Biochemical, subclinical and clinical responses to lead and their relation to different exposure levels, as indicated by the concentration of lead in blood. In: Nordberg GF (ed) Effects and dose-response relationships of toxic metals. Elsevier, Amsterdam Oxford New York, pp 404–415
Karačić V, Prpić-Majić D, Telišman S (1980) The relationship between zinc protoporphyrin (ZPP) and “free” erythrocyte protoporphyrin (FEP) in lead-exposed individuals. Int Arch Occup Environ Health 47:165–177
Krasner N, Moore MR, Thompson GG, McIntosh W, Goldberg A (1974) Depression of erythrocyte aminolevulinic acid dehydratase activity in alcoholics. Clin Sci Mol Med 46:415–418
Lamola AA, Yamane T (1974) Zinc protoporphyrin in the erythrocytes of patients with lead intoxication and iron deficiency anemia. Science 186:936–938
Lamola AA, Piomelli S, Poh-Fitzpatrick MB, Yamane T, Harber LC (1975) Erythropoietic protoporphyria and lead intoxication: the molecular basis for the difference in cutaneous photosensitivity. II. Different binding of erythrocyte protoporphyrin to hemoglobin. J Clin Invest 56:1528–1535
MacMahon B, Pugh TF (1970) Epidemiology; principles and methods. Validity. Little Brown, Boston, pp 261–265
Moore MR, Beattie AD, Thompson GG, Goldberg A (1970) Depression of δ-aminolevulinic acid dehydratase activity by ethanol in man and rat. Clin Sci 40:81–88
Nordberg GF (ed) (1976) Effects and dose-response relationships of toxic metals. A consensus report from an international meeting organized by the Subcommittee on the Toxicology of Metals of the Permanent Commission and International Association on Occupational Health, Tokyo 1974, by Task Group on Metal Toxicity. Elsevier, Amsterdam Oxford New York, pp 1–111
Piomelli S (1977) Free erythrocyte porphyrins in the detection of undue absorption of Pb and of Fe deficiency. Clin Chem 23:264–269
Prpić-Majić D, Telišman S, Kežić S (1981) Lead and alcohol interaction in occupational lead exposure. 20th International Congress on Occupational Health, Cairo 1981, Abstracts, p 152
Sakurai H, Sugita M, Tsuchiya K (1974) Biological response and subjective symptoms in low level lead exposure. Arch Environ Health 29:157–163
Telišman S (1979) General aspects of biological monitoring and relative validity of biological indicators for occupational and environmental exposure to inorganic lead. Arh Hig Rada Toksikol 30:49–70
Telišman S, Prpić-Majić D (1979) The relative applicability of PbB, ALAD and EP in the assessment of external exposure and health effect of inorganic lead. Proceedings International Conference Management & Control of Heavy Metals in the Environment, London 1979, CEP Consultants Ltd, Edinburgh, pp 62–65
Telišman S, Karačić V, Meczner J, Prpić-Majić D (1980) Interference of inadequate oxygenation in hematofluorometer zinc-protoporphyrin readings. In: Holmstedt B, Lauwerys R, Mercier M, Roberfroid M (eds) Mechanisms of toxicity and hazard evaluation. Elsevier/North-Holland, Amsterdam New York Oxford, pp 591–594
Tsuchiya K, Sugita M, Sakurai H (1979) Dose-response relationships at different exposure levels—necessity of reevaluation in establishing no-effect levels. Arh Hig Rada Toksikol [Suppl] 30:123–132
Valciukas JA, Lilis R, Eisinger J, Blumberg WE, Fischbein A, Selikoff IJ (1978) Behavioural indicators of lead neurotoxicity: Results of a clinical field survey. Int Arch Occup Environ Health 41:217–236
Weber K, Valić F (1957) Die Fluorometrie im Dienste der medizinischen Chemie. Arh Hig Rada Toksikol 8:39–60
WHO (1977) Environmental health criteria. 3. Lead. World Health Organization, Geneva, pp 1–160
WHO (1980) Recommended health-based limits in occupational exposure to heavy metals. 3. Inorganic lead. World Health Organization, Geneva, pp 36–80
Zielhuis RL, Verberk MM (1974) Validity of biological tests in epidemiological toxicology. Int Arch Arbeitsmed 3:167–190
Zielhuis RL (1977) Second international workshop permissible levels for occupational exposure to inorganic lead. Int Arch Occup Environ Health 39:59–72
Zielhuis RL (1978) Biological monitoring. Guest lecture given at the 26th Nordic symposium on industrial hygiene, Helsinki, October 1977. Scand J Work Environ Health 4:1–18
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Telišman, S., Keršanc, A. & Prpić-Majić, D. The relevance of arguments for excluding ALAD from the recommended biological limit values in occupational exposure to inorganic lead (WHO 1980). Int. Arch Occup Environ Heath 50, 397–412 (1982). https://doi.org/10.1007/BF00377836
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DOI: https://doi.org/10.1007/BF00377836