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The use of iron supplementation for anemia in erythropoietic protoporphyria (EPP) is controversial with both benefit and deterioration reported in single case reports. There is no systematic study to evaluate the benefits or risks of iron supplementation in these patients. We assessed the potential efficacy of oral iron therapy in decreasing erythrocyte protoporphyrin (ePPIX) levels in patients with EPP or X-linked protoporphyria (XLP) and low ferritin in an open-label, single-arm, interventional study. Sixteen patients (≥18years) with EPP or XLP confirmed by biochemical and/or genetic testing, and serum ferritin ≤30ng/mL were enrolled. Baseline testing included iron studies, normal hepatic function, and elevated plasma porphyrins and ePPIX levels. Oral ferrous sulfate 325mg twice daily was administered for 12months. The primary efficacy outcome was the relative difference in total ePPIX level between baseline and 12months after starting treatment with iron. Secondary measures included improvement in serum ferritin, plasma porphyrins, and clinical symptoms. Thirteen patients had EPP (8 females, 5 males) and 3 had XLP (all females) and the mean age of participants was 38.8years (SD 14.5). Ten patients completed all study visits limiting interpretation of results. In EPP patients, a transient increase in ePPIX levels was observed at 3months in 9 of 12 (75%) patients. Iron was discontinued in 2 of these patients after meeting the protocol stopping rule of a 35% increase in ePPIX. Seven patients withdrew before study end. Ferritin levels increased on iron replacement indicating an improvement in iron status. A decrease in ePPIX was seen in both XLP patients who completed the study (relative difference of 0.67 and 0.5 respectively). No substantial changes in ePPIX were seen in EPP patients at the end of the study (n=8; median relative difference: -0.21 (IQR: -0.44, 0.05). The most common side effects of iron treatment were gastrointestinal symptoms. Hepatic function remained normal throughout the study. Our study showed that oral iron therapy repletes iron stores and transiently increases ePPIX in some EPP patients, perhaps due to a transient increase in erythropoiesis, and may decrease ePPIX in XLP patients. Further studies are needed to better define the role of iron repletion in EPP. Trial registration: NCT02979249.

A 27-year-old man bearing an erythropoietic protoporphyria (EPP)-associated ferrochelatase (FECH) mutation was admitted to our hospital for general malaise and marked elevation of the serum levels of hepatobiliary enzymes and bilirubin. Initial treatment with plasma exchange did not reduce the blood protoporphyrin or serum liver enzyme levels, so phlebotomy was started. Surprisingly, weekly phlebotomy normalized the serum levels of liver enzymes, accompanied by a marked reduction in the blood protoporphyrin levels. The clinical course of this case strongly suggests that phlebotomy may be a suitable treatment option for EPP-related hepatopathy.

Background Erythropoietic protoporphyria (EPP) is an inherited disorder leading to an increased concentration of the photoactive protoporphyrin IX (PpIX) in erythrocytes. Upon photoactivation in the dermal blood vessels and release to the skin it causes painful skin symptoms when illuminated depending on PpIX concentration. The present study aimed to investigate if erythrocyte PpIX concentration changes with age in patients with EPP. In addition, we tested gender differences and seasonal variation in erythrocyte PpIX concentration. Methods 53 EPP patients aged 0 to 90 years were included in this retrospective observational study. A total of 751 blood samples were routinely analyzed for erythrocyte PpIX between 2000 and 2020. Trends in erythrocyte protoporphyrin IX concentration depending on age, sex and season were investigated. Results Erythrocyte PpIX levels increased during childhood and youth (median annual increase of 2.7 µmol/L) to reach a stable level in adults though, with a decrease in concentration of about 8% in summer. On average the PpIX level was higher in men (mean of 56 µmol/L, range: 6-139) than women (mean of 38 µmol/L, range: 6-82). Conclusion We hope that our results can contribute to finding a physiological explanation for the changes in erythrocyte PpIX observed throughout the lives of patients with EPP.

BACKGROUNDLaboratory diagnosis of erythropoietic protoporphyria (EPP) requires a marked increase in total erythrocyte protoporphyrin (300–5000 μg/dL erythrocytes, reference interval CONTENTIn studying more than 180 patients with EPP and XLP, the Porphyrias Consortium found that erythrocyte protoporphyrin concentrations for some patients were much higher (4.3- to 46.7-fold) than indicated by previous reports provided by these patients. The discrepant earlier reports, which sometimes caused the diagnosis to be missed initially, were from laboratories that measure protoporphyrin only by hematofluorometry, which is intended primarily to screen for lead poisoning. However, the instrument can calculate results on the basis of assumed hematocrits and reports results as “free” and “zinc” protoporphyrin (with different reference intervals), implying separate measurements of metal-free and zinc protoporphyrin. Such misleading reports impair diagnosis and monitoring of patients with protoporphyria.SUMMARYWe suggest that laboratories should prioritize testing for EPP and XLP, because accurate measurement of erythrocyte total and metal-free protoporphyrin is essential for diagnosis and monitoring of these conditions, but less important for other disorders. Terms and abbreviations used in reporting erythrocyte protoporphyrin results should be accurately defined.

Background Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are inherited cutaneous porphyrias resulting from decreased activity of ferrochelatase and gain-of-function mutations of δ-aminolevulinic acid synthase-2, respectively. Both of these protoporphyrias cause increased protoporphyrin levels that cause photosensitivity and may lead to hepatopathy and further increases in erythrocyte and plasma porphyrin levels. Methods We evaluated erythrocyte protoporphyrin and plasma porphyrin levels in all subjects with EPP (83 subjects) or XLP (9 subjects) without evidence of liver disease tested repeatedly at a single laboratory over 25 years. Results Intersubject variation contributed more than intrasubject variation (78.86% vs 21.14%) to overall variability, and longitudinal variability, estimated by CV, averaged 26%. Erythrocyte total protoporphyrin levels were similar in males and females with EPP (ratio, 0.99; 95% CI, 0.82–1.21; P = 0.96) but were higher in males than females with XLP, although this difference was not statistically significant (ratio, 0.76; 95% CI, 0.43–1.36; P = 0.35). Analysis of 20 subjects from 9 separate families showed significant effects of family compared with effects of individual variation on total variance (50% vs 25%; P < 0.0001). Conclusion Variation of erythrocyte total protoporphyrin up to 25% is expected in patients with protoporphyria, whereas greater increases might raise concern for protoporphyric hepatopathy.

Background Zinc protoporphyrin (ZPP) has been used to screen and manage iron deficiency in individual children, but it has also been recommended to assess population iron status. The diagnostic utility of ZPP used in combination with haemoglobin concentration has not been evaluated in pre-school children. We aimed to a) identify factors associated with ZPP in children aged 12–36 months; b) assess the diagnostic performance and utility of ZPP, either alone or in combination with haemoglobin, to detect iron deficiency. Methods We used baseline data from 338 Kenyan children enrolled in a community-based randomised trial. To identify factors related to ZZP measured in whole blood or erythrocytes, we used bivariate and multiple linear regression analysis. To assess diagnostic performance, we excluded children with elevated plasma concentrations of C-reactive protein or α 1-acid glycoprotein, and with Plasmodium infection, and we analysed receiver operating characteristics (ROC) curves, with iron deficiency defined as plasma ferritin concentration 5.93120) correctly ruled out iron deficiency in 37.4%–53.7% of children screened, depending on the true prevalence, with both specificity and negative predictive value ≥90%. Conclusions In young children, whole blood ZPP and erythrocyte ZPP have added diagnostic value in detecting iron deficiency compared to haemoglobin concentration alone. A single diagnostic score based on haemoglobin concentration and whole blood ZPP can rule out iron deficiency in a substantial proportion of children screened. Trial registration ClinicalTrials.gov NCT02073149 (25 February 2014). Electronic supplementary material The online version of this article (doi:10.1186/s12878-017-0082-z) contains supplementary material, which is available to authorized users.

This study relates tissue concentrations and toxic effects of Pb in Japanese quail (Coturnix japonica) to the dietary exposure of soil-borne Pb associated with mining and smelting. From 0% to 12% contaminated soil, by weight, was added to 5 experimental diets (0.12 to 382 mg Pb/kg, dry wt) and fed to the quail for 6 weeks. Benchmark doses associated with a 50% reduction in delta-aminolevulinic acid dehydratase activity were 0.62 mg Pb/kg in the blood, dry wt, and 27 mg Pb/kg in the diet. Benchmark doses associated with a 20% increase in the concentration of erythrocyte protoporphyrin were 2.7 mg Pb/kg in the blood and 152 mg Pb/kg in the diet. The quail showed no other signs of toxicity (histopathological lesions, alterations in plasma–testosterone concentration, and body and organ weights). The relation of the blood Pb concentration to the soil Pb concentration was linear, with a slope of 0.013 mg Pb/kg of blood (dry wt) divided by mg Pb/kg of diet. We suggest that this slope is potentially useful in ecological risk assessments on birds in the same way that the intake slope factor is an important parameter in risk assessments of children exposed to Pb. The slope may also be used in a tissue-residue approach as an additional line of evidence in ecological risk assessment, supplementary to an estimate of hazard based on dietary toxicity reference values. Integr Environ Assess Manag 2014;10:22–29. © 2013 SETAC

A 53-year-old Texas rancher developed a blistering skin rash that was sensitive to exposure to sunlight. He was referred to hematology with a presumptive diagnosis of porphyria. His peripheral blood counts were within normal limits, and a bone marrow examination revealed erythroid dyspoiesis and ringed sideroblasts. Serum, plasma, and erythrocyte protoporphyrin levels were elevated, the findings of which are consistent with a diagnosis of erythropoietic protoporphyria. This paper discusses the diagnosis and etiology of the porphyrias.

Summary X-linked dominant protoporphyria (XLDPP) was first reported in the genetics literature in 2008. It has a phenotype very similar to erythropoietic protoporphyria (EPP), but is distinguished from EPP by higher concentrations of erythrocyte protoporphyrin (of which a high proportion is zinc-chelated), its apparently higher incidence of liver disease, and an X-linked dominant pattern of inheritance. Dermatologists should understand how XLDPP differs from EPP, in order to advise newly diagnosed patients correctly about the genetic implications and the long-term management strategy. We present a case series of XLDPP to introduce this condition to the dermatology literature.

Day-to-day variations in serum iron, serum iron binding capacity, serum ferritin and erythrocyte protoporphyrin were determined on 2 successive days in 48 patients with anaemia. The correlation coefficients between the paired determinations were 0.86, 0.89, 0.95 and 0.95, and the day-to-day coefficients of variation (in per cent) were 33, 11, 12 and 13 for serum iron, serum iron binding capacity, erythrocyte protoporphyrin and serum ferritin, respectively. Thus, in patients with anaemia, day-to-day variations in serum iron, serum iron binding capacity, erythrocyte protoporphyrin and serum ferritin are at least as high as in healthy controls. The results indicate important limitations in the use, particularly, of serum iron in the clinical investigation of anaemia.

Aims: To investigate the effects of smoking and personal hygienic behaviour on blood lead (BPb) and free erythrocyte protoporphyrin levels (FEP) in lead exposed workers. Methods: Subjects were 105 lead exposed male workers in a battery recycling plant during the years 2000–03. BPb and FEP were measured as part of the ongoing occupational surveillance. Each worker completed a questionnaire for assessment of smoking and four measures of personal hygienic behaviour (glove and mask use, hand and face washing before meals during working hours). Results: Statistically significant decreases in mean BPb and FEP occurred during the three years. The proportion of BPb reduction in the non-smoking workers was significantly higher (mean 24.3%) than in the smoking workers (15.3%). When the workers were classified into three groups (excellent, good, and poor) based on the four personal hygienic behavioural indicators, the greatest decreases of BPb and FEP were observed in the non-smoking workers of the excellent group. Conclusions: The consistent use of protection devices and cleanliness at work appeared to contribute to the lowering of BPb and FEP. Cessation of smoking in the workplace was also of importance.

Se estudió, en 77 puérperas, la relación entre la protoporfirina eritrocitaria (PE), la ferritina sérica (FS), el receptor soluble de transferrina (RsT) y los indicadores hematológicos utilizados en la rutina clínica. En sangre venosa se determinó: Hematocrito (Hto), Hemoglobina (Hb), recuento de glóbulos rojos (GR) y glóbulos blancos (GB) (contador electrónico MEGA); PE (Piomelli); en suero: RsT (ELISA, Orion Diagnostica), FS (ELISA, IMx Ferritina, Abbott) y Proteína C-Reactiva (PCR- Látex, Wiener lab). Se analizaron sensibilidad (S), especificidad (E) y puntos de corte mediante el modelo ROC (Receiver Operating Characteristics), considerando como gold standard el RsT. Los resultados (media ± DE) fueron: Hto (%) 35 ± 5; Hb (g/l) 113 ± 18; GRx10³/mm³ 3 893 ± 489; VCM (fL) 90 ± 6; GB/mm³ 9 543 ± 2.669; PE (µg/dl GR) 46 ± 39; RsT (mg/l) 4.7 ± 2.8; FS (µg/l) 26 ± 31; PCR (Pos/Neg) 72/5. La PE no correlacionó con FS, pero sí con el RsT (r=0.323, p=0.007). La S y E de la FS fueron de 83% y 63%, respectivamente, para un punto de corte de 25 µg/l; para la PE la S fue de 38% y la E de 90% para un punto de corte de 53 µg/dl GR. Estos resultados sugieren que ese punto de corte en el puerperio, permitiría detectar con un bajo costo un mayor porcentaje de mujeres (16% en nuestro estudio) que presentan deficiencia de Fe pese a sus valores normales de hemoglobina.Erythrocyte protoporphyrin (EP), serum ferritin (SF), soluble transferrin receptor (sTfR) and routine hematological laboratory tests were studied in 77 women 24 h post-partum, assisted at Paroissien Hospital (in Buenos Aires Province). Hematocrite (Hct), hemoglobin (Hb), red blood cells (RBC) and white blood cells (WBC) were determined using an electronic counter (Mega); EP by Piomelli’s; SF by ELISA (IMx Ferritina, Abbott); sTfR by ELISA (Orion Diagnostica) and C-Reactive Protein (PCR-Latex, Wiener lab). All determinations were made in fasting blood samples. Statistical analysis (Receiver Operating Characteristics, ROC) were performed using Med Calc software. The soluble transferrin receptor (sTfR) was used as gold standard. Results: (mean ± SD): Hct (%) 35 + 5; Hb (g/l) 113 + 18; RBC x 10³ /mm³ 3 893 + 489; MCV (fL) 90 ± 6; WBC/mm³ 9.543 ± 2.669; EP (µg/dl RBC) 46 + 39; sTfR (mg/l) 4.7 + 2.8; SF(µg/l) 26 + 31; PCR (Pos/Neg) 72/5. EP did not correlate with SF but it did with sTfR (r=0.323, p=0.007). Sensitivity (Se) and specificity (Sp) of SF and EP were, respectively: 83% and 63% for a cut-off point of 25 µg SF/L; 38% and 90% for a cut-off point of 53 µg EPdl RBC. These results suggest that EP might be a useful and cheap indicator to assess maternal Fe nutritional status during the early perinatal period in hospital laboratories, allowing the detection of 16% of women presenting normal Hb values.

Lead-induced mortality appears to have been a major factor in the decline of the California condor (Gymnogyps californianus). We orally dosed turkey vultures (Cathartes aura) with BB-sized lead shot from January 1988 through July 1988 to determine physiologic response (delta-aminolevulinic acid dehydratase inhibition, erythrocyte protoporphyrin levels, anemia), diagnostic tissue lead concentrations (blood, liver, and kidney), and comparative sensitivity of this species. Two turkey vultures died and two became so intoxicated they were euthanized. Overall, responses of measured parameters were comparable to other species exposed to lead although there was considerable individual variation. Survival time (143-211 days), even with the large numbers of shot and constant redosing, was much longer than reported for other species of birds, suggesting considerable tolerance by turkey vultures to the deleterious effects of lead ingestion. Based on these observations, turkey vultures appear to be poor models for assessing the risk of lead poisoning to California condors or predicting their physiologic response.

Background Iron-deficient erythropoiesis results in excess formation of zinc protoporphyrin (ZPP), which can be measured instantly and at low assay cost using portable haematofluorometers. ZPP is used as a screening marker of iron deficiency in individual pregnant women and children, but also to assess population iron status in combination with haemoglobin concentration. We examined associations between ZPP and disorders that are common in Africa. In addition, we assessed the diagnostic utility of ZPP (measured in whole blood and erythrocytes), alone or in combination with haemoglobin concentration, in detecting iron deficiency (plasma ferritin concentration 70 μmol/mol haem) resulted in gross overestimates of the prevalence of iron deficiency. Conclusions Erythrocyte ZPP has limited value to rule out iron deficiency when used for screening in conditions with a low prevalence (e.g., 10%). ZPP is of unreliable diagnostic utility when discriminating between pregnant women with and without iron deficiency. Based on these findings, guidelines on the use of ZPP to assess iron status in individuals or populations of pregnant women need review. Trial registration NCT01308112 (2 March 2011).

Anemia is the most prevalent nutritional problem worldwide due mainly to iron deficiency. Studies of anemia are less common in adolescents than in women and children. We examined anemia prevalence in adolescent Kuwaiti schoolgirls and its association with hemoglobinopathies as well as the most common environmental cause Fe deficiency. A cross-sectional sample of 1051 healthy adolescent schoolgirls was studied. Sample size was based on WHO criteria. Anemia Fe deficiency and hemoglobin (Hb) variations were studied by Hb concentration erythrocyte protoporphyrin (EP) and an HPLC quantitation respectively. Of the subjects sampled 30% were anemic. Mildly elevated EP values were found in 68%. Girls with high EP levels were more likely (P < 0.001) to be anemic than girls with normal EP. Up to 25% of the girls may have had Fe deficiency anemia. Hemoglobinopathies were neither prevalent nor significantly associated with anemia. These data indicate that environmental factors play a significant role in anemia among healthy well-to-do Kuwaiti adolescent girls. (authors)

In August 1997 we performed a follow-up survey of 146 lead-poisoned children from a community near a previously active auto battery recycling smelter in Haina near Santo Domingo, Dominican Republic. Our follow-up survey confirmed a severe incidence of elevated blood lead (BPb) and erythrocyte protoporphyrin/zinc protoporphyrin (EP-ZnPP) levels. The mean BPb level was 32 micrograms/dL and the mean EP-ZnPP level was 128 micrograms/dL. The frequency distribution of BPb showed that only 9% of the children had BPb levels below the currently acceptable 10 micrograms/dL threshold level, 23% had between 10 and 19 micrograms/dL, 40% had between 20 and 39 micrograms/dL, 27% had between 40 and 99 micrograms/dL, and the remainder had > 100 micrograms/dL. These findings are significantly greater than the mean BPb and EP-ZnPP levels of 14 and 35 micrograms/dL, respectively, in a comparison group of 63 children in Barsequillo, 4 miles away. BPb frequency distributions for these groups were < 10 micrograms/dL (42%), 10-19 micrograms/dL (32%), and 20-39 micrograms/dL (16%); in the remaining 10%, BPb levels were between 40 and 99 micrograms/dL. Similarly, the corresponding frequency distribution of EP-ZnPP levels in Haina children were proportional to the severity of lead poisoning and significantly higher than those of the Barsequillo comparison group. This study reveals that at least 28% of Haina children require immediate treatment; of these, 5% with lead levels > 70 micrograms/dL are also at risk for severe neurologic sequelae, and urgent action is imperative. Images Figure 1 Figure 2 Figure 3 Figure 4

In order to examine the prevalence of lead exposure and iron deficiency in Jammu, blood lead (B-Pb) and erythrocyte protoporphyrin (EP-ZnPP) levels were measured in a group of 125 children and compared with B-Pb and EP levels of 46 New Delhi children. The mean B-Pb level of Jammu children was 15 micrograms/dl and ZnPP level 46 micrograms/dl. The frequency distribution of B-Pb in Jammu children according to the 1997 CDC stratification showed that only 33% were below the 10 micrograms/dl "normal" threshold levels and 50.5% were between 10-19 micrograms/dl, an increasing level of concern. The remaining 16.5% were in the medical intervention lead poisoned level between 20-87 micrograms/dl with corresponding EP levels between 29-160 micrograms/dl. The mean B-Pb and ZnPP levels for New Delhi children were 14 micrograms/dl and 55 micrograms/dl respectively. This study on Jammu children shows a modest increase in mean B-Pb and EP levels from those in 1985; the percentage of children with higher levels of B-Pb10 micrograms/dl have significantly increased. Moreover, the continued underlying high prevalence of iron deficiency among these children predisposes them to increased lead absorption from various sources thus aggravating further, the detrimental effects of lead. Therefore, a more extensive screening of all children below 10 years of age and an ongoing B-Pb and EP monitoring and iron supplementation programme for Jammu and New Delhi is essential. An environmental assessment of the sources leading to serious lead intoxication problem in Jammu, a rapidly growing and overpopulated city of the state of Jammu and Kashmir is strongly recommended.

A method is presented to estimate a cutoff for hemoglobin concentration appropriate for estimating the prevalence of iron deficiency anemia in poor Jamaican girls 13-14 y of age. Iron deficiency was determined from a three-variable model of iron status (serum ferritin, erythrocyte protoporphyrin, and mean corpuscular volume). The most appropriate hemoglobin cutoff was considered the one that minimized misclassification of iron deficiency: that yielding the maximum kappa coefficient for correctly classifying iron deficiency between 100 and 120 g/L, at 1-g/L intervals. By using this method, a hemoglobin cutoff of 107 g/L was considered most appropriate. This cutoff and the other indicators were used to estimate prevalence of iron deficiency and iron deficiency anemia in the Jamaican girls: 7.6% and 4.3%, respectively. This approach should be appropriate for determining hemoglobin cutoffs for iron deficiency anemia in other populations.

We describe results of a 3-year study in which 499 paired venous and capillary blood specimens, collected by fingerstick on the same day, were analyzed for lead (BPb) and erythrocyte protoporphyrin (EP). False-positive rates (FPRs) and the proportion of false positives were calculated at four BPb thresholds. At the 100 μg/L threshold, the FPR for all data was 13%, but the proportion of false positives was only 5%. The log ratios of capillary-to-venous BPb data indicate that, with the exception of eight outliers, two subpopulations exist that follow a log-normal distribution. These two subpopulations, the “core” (n = 303) and “shifted” (n = 188) groups, on average generated a positive bias at 100 μg/L BPb of 8.6% and 30.3%, respectively. The log ratios of capillary-to-venous EP data followed a normal distribution, indicating that capillary EP is not statistically different from venous EP.

Ferrochelatase, estimated as zinc chelatase, was measured in the lymphocytes of 30 patients with erythropoietic protoporphyria (EPP), in 35 first- or second-degree relatives of patients with EPP, and in 50 healthy controls. In 30 EPP patients the zinc chelatase level (mean +/- standard deviation, SD) was 0.45 +/- 0.10 nmol of zinc protoporphyrin per hour per milligram of protein, in 14 EPP carriers the zinc chelatase level (mean +/- SD) was 0.42 +/- 0.09 and in 50 healthy controls the zinc chelatase level (mean +/- SD) was 0.84 +/- 0.27. All patients with EPP were also demonstrated to have an elevated protoporphyrin level in their red blood cells: the erythrocyte protoporphyrin levels were as follows EPP patients (mean +/- SD) 1300 +/- 758 nmol protoporphyrin/dl, EPP carriers (mean +/- SD) 60 +/- 24, and healthy controls (mean +/- SD) 50 +/- 25 (P < 0.001 for EPP patients compared to controls and EPP carriers). The families of 12 out of 15 EPP patients were examined with respect to the mode of inheritance of the disorder. Of 35 relatives, 14 were carriers of EPP, as characterized by reduced zinc chelatase activity in lymphocytes and by a normal protoporphyrin level in red blood cells. None of the 14 EPP carriers had presented with clinical symptoms of EPP. The mod of inheritance was autosomal dominant in seven of the 12 examined families, and autosomal recessive in two. In two families only one parent could be investigated, but we nevertheless concluded that the inheritance was autosomal dominant. Inheritance in one EPP family could not be elucidated as both parents showed normal zinc chelatase levels and did not demonstrate abnormal erythrocyte protoporphyrin levels.

Objective: The aim of this study was to confirm the connection between lead poisoning and the use of traditional Ayurvedic metal mineral tonics. Methods: The study group comprised 29 subjects (26 adults and three children) who had previously taken Ayurvedic metal mineral tonics. All subjects were tested for lead absorption by blood lead, erythrocyte delta-aminolevulinic acid dehydratase activity and erythrocyte protoporphyrin. Results: Eighteen samples of Ayurvedic preparations were obtained from 15 subjects and analyzed for lead content. Five adult subjects with established lead poisoning received chelation therapy. In Ayurvedic preparations a wide range of lead content was found (0.9-72, 990 ug Pb/g ; 0.35-29, 900 ug Pb/capsule or tablet). The blood lead, erythrocyte delta-aminolevulinic acid dehydratase and erythrocyte protoporphyrin of the subjects, grouped according to the remedies used, correlated with the lead content in the preparations (p

The dose-response relationship between erythrocyte protoporphyrin (EP) and blood lead (PbB) was investigated among children with different subgroups of iron status. The data bank from Santo Amaro City, Brazil, was taken to study 490 children aged 1-9 years who lived at less than 900 m from a primary lead smelter. Mean PbB was 58.9 +/- 25.3 micrograms/dl and mean EP was 87.1 +/- 68.1 micrograms/dl. At PbB levels lower than 60 micrograms/dl, the dose-response curve for EP versus PbB followed the classical pattern; children with low iron status showing greater EP "response" than those with typical iron status and those with high iron status, after controlling for the effects of age and racial group. Among children with PbBor = 60 micrograms/dl, EP response increased according to the following order: typicallowhigh iron status.

The influence of exposure to lead on the frequency of micronuclei (MN), nuclear buds and nucleoplasmatic bridges was investigated in peripheral blood lymphocytes in 15 male battery-manufacturing workers and 15 controls matched for age and smoking habits. In addition to MN test, blood lead (B-Pb) and cadmium (B-Cd), delta aminolevulinic acid dehydratase (ALAD) activity, erythrocyte protoporphyrin (EP), serum vitamin B12 (S-Vit B12) and folate (S-folate) were determined in all subjects. Lead-exposed subjects had significantly higher MN frequency and B-Pb concentrations than controls. In control smokers we found a significant negative correlation between B-Pb concentration and frequency of nucleoplasmatic bridges, and nuclear division index. In control non-smokers a significant positive correlation was observed only between age and nuclear buds frequency, and between S-folate and B-Pb level. In lead exposed smokers, significant positive correlations between MN frequency and S-Vit B12, S-folate, and nuclear buds frequency were found. A positive correlation in exposed smokers was also found between nuclear buds frequency and S-Vit B12 concentration. A negative correlation was found between ALAD and EP, and B-Pb in exposed smokers. Exposed non-smokers showed significant negative correlation between MN frequency and B-Cd, and ALAD and EP. The results indicate a genotoxicity of lead, pointing to a micronucleus assay as a relevant test for assessing genotoxic effects resulting from occupational exposure. The other indicators did not necessarily follow the results of MN test. Influence of smoking should be further investigated. Copyright Ó John Wiley & Sons, Ltd.