R. L. Zielhuis

Dose-response relationships for inorganic lead. I. Biochemical and haematological responses

SummaryThe author reviewed literature data on the relationship between lead in blood levels (PbB) and various biochemical and haematological responses. PbB levels may be regarded as representative for internal dose. The percentage of subjects with a specified intensity of a specified response in groups of subjects has been calculated in relation to PbB. This Dose-Response (D-R) relationship portrays the increase of biological effects with increasing internal dose, qualitatively and quantitatively, and can be used to evaluate the health significance of Pb exposure in occupational and public health. D-R-curves have been calculated for δ-aminolaevulinic acid dehydratase activity in erythrocytes (ALAD), δ-aminolaevulinic acid excretion in urine (ALAU), protoporphyrin in erythrocytes (PPE), Na+-K+-ATPase activity in erythrocytes and reduced glutathion content of erythrocytes. Various other biochemical and haematological responses are discussed in regard to their relationship with PbB. In a subsequent paper the prevalence of functional effects in relation to PbB will be discussed.

Definitions of monitoring activities and their relevance for the practice of occupational health.

SummaryThe authors discuss the definitions of environmental monitoring (EM), biological monitoring (BM) and health surveillance (HS) as agreed upon by a CEC/NIOSH/OSHA-seminar in 1980. They emphasize the essential differences in underlying principles. They add a fourth definition of biological effect monitoring (BEM). Each method has its own assets and liabilities. Moreover, EM and BM require another decision-making process (situation-centered) then BEM and HS (client-entered) of measures to be taken. When the differences between the four approaches are not taken into account, valid preventive measures may be hampered.

Renal function of chrome-plating workers and welders

SummaryThe influence of occupational exposure to water-soluble chromium (VI) on renal function was examined. In male chrome-plating workers (n = 29), stainless steel welders (n = 45), boilermakers (n = 18) and a control group of workers (n = 71), the level of chromium in the urine (Cr-U), the chromium clearance, and sensitive renal function parameters were determined. The glomerular-function parameters of the chrome-plating workers (Cr-U 1 to 34 μg/g crest) and welders (Cr-U 1 to 62 μg/g creatine) appeared to differ from those of the boilermakers (Cr-U 0.3 to 1.5 μg/g creatine) and controls (Cr-U 0.1 to 2 gg/g creatine). The renal function parameters were not related to chromium concentration in the urine or to chromium clearance.

Work hygienic behaviour as modifier of the lead air-lead blood relation.

SummaryKnowledge of hygienic behaviour at the workplace appears to explain the low correlation between external and internal exposure. Differences in hygienic behaviour explain at least the same magnitude of variation in levels of lead in blood as the level of lead in air. Adding hygienic behaviour to the lead air-lead blood model increases the accuracy of prediction of PbB. In this study, the frequency of putting on/off gloves and the frequency of hand-mouth nose/shunt are the strongest modifiers of the PbA-PbB relation. In general, the actual behaviour of workers exposed to chemical agents may explain the often observed poor or moderate relationships between environmental and biological monitoring parameters of chemical exposure in occupational health studies.

The use of a safety factor in setting health based permissible levels for occupational exposure

SummaryWhen adequate human observations are not or scarcely available, permissible levels for occupational exposure have to be extrapolated from animal experiments. Taking into account experimental conditions, e. g., duration of exposure (⩾ 3 months), animal species, knowledge of no- (adverse-) effect level or minim al-(adverse-) level, presence of data on human observations, the authors worked out a procedure for extrapolation. This procedure should only be applied for systemic non-carcinogenic effects. The proposed procedure is to be regarded as tentative and as suggestion for international discussion.The evaluation starts with a safety factor = 10 for extrapolation from dose/kg b. w. in long-term animal experiments to exposure of adult workers (40 h/wk); this factor corresponds to a safety factor = 3–10 for extrapolation from doses presented as concentrations in air. If long-term experimental exposure is 24 h daily, the safety factor can be lowered to the minimum value of 1. If only short-term exposure studies are available, the safety factor may have to be increased to a maximum of 400.

Smoking habits and levels of lead and cadmium in blood in urban women.

SummaryIn 222 Dutch urban women lead (PbB)- and cadmium (CdB)-levels in blood were measured and related to smoking habits. PbB ranged from 40 ppb to 240 ppb and CdB rangedfrom 0.2 ppb to 4.4 ppb. Smokers had slightly higher PbB-levels and distinctly higher CdB-levels.

Validity of biological tests in epidemiological toxicology

SummaryThe authors emphasize the need to introduce the concept of validity (sensitivity and specificity) of biological test methods in epidemiological toxicology (occupational and public health). Up till now too often relevant information is lost, because the frequency distribution of individual data is not taken into account. The method of calculating parameters of validity is demonstrated. These parameters add relevant information for determining the feasibility of test methods; they provide valuable information not presented by classical statistical treatment of data. Several examples have been worked out to elucidate the approach.

Pleura mesothelioma and exposure to asbestos. A retrospective case-control study in the Netherlands.

SummaryIn 67 cases of pleura mesothelioma and in matched controls (cardiovascular disease) a retrospective in depth interview was carried out. In 72% of cases occupational exposure to asbestos was elucidated, whereas in matched controls only 18% had a positive exposure history. In 60% of cases with positive history there had been a rather intensive exposure, however often intermittent; duration of exposure often was over 10 yr, latent period over 30 yr. In individual cases a short duration of exposure and/or latent period was observed. A relationship with smoking history could not be confirmed. Some unexpected possibilities for occupational exposure were found. All 67 cases were reviewed by a panel of pathologists; in 66% the diagnosis could be confirmed; in the other cases the diagnosis was never fully rejected. It could be shown that histological confirmation of diagnosis is highly dependent on adequate supply of material, at least to be obtained through thoracotomy, pleurectomy, preferably through autopsy. The authors stress the methodological aspects of a restrospective study: absolute underreporting dependent on method of history taking, relative underreporting dependent on method of selection of controls. Prevalences as reported in literature cannot be taken at their face value because of pitfalls in study design.

Biological quality guide for inorganic lead

Summary1.If environmental exposure of the general public to a considerable extent takes place through various routes of entry, quality standards for one source of exposure (e.g. air, food, water) will not protect public health adequately. This is the case for inorganic lead.2.Biologically available lead (lead in blood levels) and parameters of subclinical response may be expected to be feasible for indirect estimation of total environmental exposure; the feasibility has been studied.3.Lead in blood levels (PbB) in target groups of the general population portray the total environmental exposure to Pb for this group. Such groups should include at least 50 subjects, of same sex, similar socio-cultural class, with narrow age range, and preferably at high risk (exposure or susceptibility).4.Neither average levels nor one maximum level, but the distribution of levels in 98% of the target group should be taken as parameter of external exposure.5.The maximum acceptable individual level for adults is PbB=40 Μg Pb/100ml; because of increased uncertainty in regard to pregnancy and developing neonate this level should be lowered to PbB=35 Μg Pb/100 ml.6.Taking into account the maximum acceptable level of 35 Μg Pb/100 ml in 98% of subjects, and the normal variability of PbB levels as occurring in practice, the following distribution of PbB levels is proposed as biological quality guide: 98% ≦35 Μg Pb/100 ml, 90% ≦30 Μg Pb/100 ml, 50% ≦20 Μg Pb/100 ml. PbB levels in women should be corrected to male level on the basis of hematocrite.7.If the general distribution of PbB levels in a target group exceeds the proposed guide, total exposure in the environment studied is too high; action should be undertaken directed at the total environment. If the distribution only exceeds the guide at high PbB levels, a point source of external lead exposure is probable; action should be directed at this source.8.If in the environment total exposure to lead is too high, subsequent studies should determine contribution through various routes and sources: quality standards for air, food, water may have to be imposed; the same applies to emission standards.9.Due attention to errors of measurement of Pb in blood is necessary.10.It is not yet possible to propose a biological quality guide based upon Pb in urine or hair.11.It is not possible to propose a biological quality guide based upon ALAD-activity in erythrocytes, neither on ALA-excretion in urine.12.The proposed biological quality guide for lead in blood could enter governmental regulations, and so become a biological quality standard, if prevention of direct adverse effect on human health is aimed at.

Health risks to female workers in occupational exposure to chemical agents

1 Introduction.- 1.1 Objective.- 1.2 Theoretical Possibilities for Extra Health Risks in Female Workers.- 1.2.1 Differences Between Women and Men Apart from Reproduction.- 1.2.2 Differences Related to the Reproductive System and Reproduction.- 1.3 Sources.- References.- 2 Organic Solvents.- 2.1 Health Risks.- 2.1.1 Different for Women than for Men.- 2.1.2 Reported for Women Only.- 2.1.3 To the Female Reproductive System.- 2.1.3.1 Disturbed Menstruation.- 2.1.3.2 Uterine Cancer.- 2.1.4 To Pregnancy and Offspring.- 2.1.5 Through Lactation.- 2.2 Discussion and Conclusions.- References.- 3 Carbon Disulfide.- 3.1 Health Risks.- 3.1.1 Different for Women than for Men.- 3.1.2 Reported for Women Only.- 3.1.3 To the Female Reproductive System.- 3.1.4 To Pregnancy and Offspring.- 3.1.5 Through Lactation.- 3.2 Discussion and Conclusions.- References.- 4 Pesticides.- 4.1 Cholinesterase Inhibitors (Organophosphates and Carbamates).- 4.1.1 Health Risks.- 4.1.1.1 Different for Women than for Men.- 4.1.1.2 Reported for Women Only.- 4.1.1.3 To the Female Reproductive System.- 4.1.1.4 To Pregnancy and Offspring.- 4.1.2 Discussion and Conclusions.- 4.2 Cyclic Chlorinated Pisticides.- 4.2.1 Health Risks.- 4.2.1.1 Different for Women than for Men.- 4.2.1.2 To the Female Reproductive System.- 4.2.1.3 To Pregnancy and Offspring.- 4.2.1.4 Through Lactation.- 4.2.2 Discussion and Conclusions.- 4.3 Halogenated Aliphatic Pesticides.- 4.4 Miscellaneous Pesticides.- 4.4.1 2,4,5-Trichlorophenoxyacetic Acid (2,4,5-T).- 4.4.2 Organic Mercury Compounds.- 4.4.3 Tetramethylthiuramdisulfide.- 4.4.4. Dinitro-o-cresol.- 4.4.5 Anticoagulants.- 4.4.6 Zineb.- 4.4.7 Nicotine.- References.- 5 Polychlorobiphenyls and Polybromobiphenyls.- 5.1 Polychlorobiphenyls.- 5.1.1 Health Risks.- 5.1.1.1 To the Female Reproductive System.- 5.1.1.2 To Pregnancy and Offspring.- 5.1.1.3 Through Lactation.- 5.1.2 Discussion and Conclusions.- 5.2 Polybromobiphenyls.- References.- 6 Plastic Monomers.- 6.1 Vinyl Chloride.- 6.2 Styrene.- 6.3 Caprolactam.- 6.4 Acrylates.- 6.5 Formaldehyde.- References.- 7 Carbon Monoxide.- 7.1 Health Risks to Pregnancy and Offspring.- 7.2 Discussion and Conclusions.- References.- 8 Metals: General Orientation.- 8.1 Toxicokinetics.- 8.2 Health Risks in the Metal Industry.- 8.3 Conclusions.- 8.4 Metals on Which Little Information Is Available.- 8.4.1 Arsenic.- 8.4.2 Antimony.- 8.4.3 Chromium.- 8.4.4 Copper.- 8.4.5 Manganese.- 8.4.6 Nickel.- 8.4.7 Selenium.- References.- 9 Inorganic Lead.- 9.1 Health Risks.- 9.1.1 Different for Woman than for Men.- 9.1.1.1 To Heme Synthesis and Hematopoiesis.- 9.1.1.2 To the Nervous System.- 9.1.2 Reported for Women Only.- 9.1.3 To the Female Reproductive System.- 9.1.4 To Pregnancy and Offspring.- 9.1.4.1 Placental Transfer.- 9.1.4.2 Birth Weight, Abortion, Congenital Malformation.- 9.1.4.3 Central Nervous System.- 9.1.4.4 Heme Synthesis.- 9.1.5 Through Lactation.- 9.2 Discussion and Conclusions.- References.- 10 Cadmium.- 10.1 Health Risks.- 10.1.1 Different for Women than for Men.- 10.1.2 Reported for Women Only.- 10.1.3 To the Female Reproductive System.- 10.1.4 To Pregnancy and Offspring.- 10.1.5 Through Lactation.- 10.2 Discussion and Conclusions.- References.- 11 Mercury.- 11.1 Metallic Mercury, Mercury Salts, and Long-chain Organic Mercury Compounds.- 11.1.1 Health Risks.- 11.1.1.1 Different for Women than for Men.- 11.1.1.2 Reported for Women Only.- 11.1.1.3 To the Female Reproductive System.- 11.1.1.4 To Pregnancy and Offspring.- 11.1.1.5 Through Lactation.- 11.1.2 Discussion and Conclusions.- 11.2 Short-chain Organic Mercury Compounds.- 11.2.1 Health Risks.- 11.2.2 Discussion and Conclusions.- References.- 12 Operating Room Personnel.- 12.1 Health Risks.- 12.1.1 Different for Women than for Men.- 12.1.1.1 Renal Diseases.- 12.1.1.2 Cancer.- 12.1.2 Reported for Women Only.- 12.1.3 To the Female Reproductive System.- 12.1.4 To Pregnancy and Offspring.- 12.1.4.1 Abortion.- 12.1.4.2 Congenital Malformations.- 12.1.4.3 Lower Birth Weight.- 12.1.4.4 Deviant Sex Ratio.- 12.1.4.5 Perinatal Death.- 12.1.5 Through Lactation.- 12.2 Discussion and Conclusions.- References.- 13 Health Care Personnel.- 13.1 Health Risks.- 13.1.1 Reported for Women Only.- 13.1.1.1 Mutagenicity.- 13.1.1.2 Immunity.- 13.1.1.3 Skin Diseases.- 13.1.2 To Pregnancy and Offspring.- 13.1.2.1 Abortion.- 13.1.2.2 Congenital Malformations.- 13.2 Discussion and Conclusions.- References.- 14 Pharmaceutical Industry.- 14.1 Health Risks.- 14.1.1 Different for Women than for Men.- 14.1.2 To the Female Reproductive System.- 14.1.2.1 Hyperestrogenism.- 14.1.2.2 Menstruation.- 14.1.2.3 Vaginal Diseases.- 14.1.3 To Pregnancy and Offspring.- 14.2 Discussion and Conclusions.- References.- 15 Chemical Industry/Laboratories.- 15.1 Health Risks.- 15.1.1 To the Female Reproductive System.- 15.1.2 To Pregnancy and Offspring.- 15.1.2.1 Abortion.- 15.1.2.2 Congenital Malformations.- 15.1.3 Through Lactation.- 15.2 Discussion and Conclusions.- References.- 16 Rubber Industry.- 16.1 Health Risks.- 16.1.1 Different for Women than for Men.- 16.1.1.1 Thioether Excretion.- 16.1.1.2 Mortality.- 16.1.2 To the Female Reproductive System.- 16.1.3 To Pregnancy and Offspring.- 16.1.4 Through Lactation.- 16.2 Discussion and Conclusions.- References.- 17 Beauticians-Hairdressers.- 17.1 Health Risks.- 17.1.1 Different for Women than for Men, or Studied Mainly in Women.- 17.1.1.1 Mutagenicity.- 17.1.1.2 Cancer.- 17.1.1.3 Impaired Pulmonary Function.- 17.1.1.4 Skin Diseases.- 17.1.2 To the Female Reproductive System, Pregnancy, and Offspring.- 17.2 Discussion and Conclusions.- References.- 18 General Discussion and Conclusions.- 18.1 Limitations of the Review.- 18.1.1 Partial Coverage.- 18.1.2 Data on Exposure.- 18.1.3 Animal Experiments.- 18.1.4 Validity of Studies.- 18.1.5 Uninformative Studies.- 18.2 Specific Conclusions.- 18.3 Overall Conclusions and Recommendations.- References.- 19 Appendix: Recent Data.- 19.1 Reviews.- 19.1.1 Reports, Books.- 19.1.2 Review Papers.- 19.1.3 Papers on Specific Chemicals/Occupations, Human Data.