Erythrocyte Delta-aminolevulinic Acid Dehydratase Research Articles

Experimental manipulation of dietary lead levels in great tit nestlings: limited effects on growth, physiology and survival

We manipulated dietary lead (Pb) levels of nestlings in wild populations of the great tit (Parus major L) to find out if environmentally relevant Pb levels would affect some physiological biomarkers (haematocrit [HT], fecal corticosterone metabolites [CORT], heat shock proteins [HSPs], erythrocyte delta-aminolevulinic acid dehydratase activity [ALAd]), growth (body mass, wing length), phenotype (plumage coloration) or survival of nestlings. The responses to three experimental manipulation (control, low and high: 0, 1 and 4 μg/g body mass/day) are compared with those in a P. major population breeding in the vicinity of a heavy metal source, a copper smelter. Our Pb supplementation was successful in raising the fecal concentrations to the levels found in polluted environments (high: 8.0 μg/g d.w.). Despite relatively high range of exposure levels we found only few effects on growth rates or physiology. The lack of blood ALAd inhibition suggests that the circulating Pb levels were generally below the toxic level despite that marked accumulation of Pb in femur (high: 27.8 μg/g d.w.) was observed. Instead, birds in the metal polluted environment around the smelter showed decreased growth rates, lower HT, higher CORT, less colorful plumage and lower survival probabilities than any of the Pb treated groups. These effects are likely related to decreased food quality/quantity for these insectivorous birds at the smelter site. In general, the responses of nestlings to metal exposure and/or associated resource limitation were not gender specific. One of the stress proteins (HSP60), however, was more strongly induced in Pb exposed males and further studies are needed to explore if this was due to higher accumulation of Pb or higher sensitivity of males. In all, our results emphasize the importance of secondary pollution effects (e.g. via food chain disruption) on reproductive output of birds.

Persistent Increase of Blood Lead Level and Suppression of δ-ALAD Activity in Northern Bobwhite Quail Orally Dosed With Even a Single 2-mm Spent Lead Shot

Birds that display grit ingestion behavior are potentially at risk of lead (Pb) poisoning from mistaken ingestion of spent Pb shot pellets. The majority of available studies designed to assess such risk have used unspent shot pellets rather than field-obtained spent shot, which is oxidized and otherwise changed by weathering. Available studies also often administered more or heavier shot pellets to a bird than it might be expected to ingest. The current study dosed northern bobwhite quail (Colinus virginianus) weighing 194.6 ± 23.1 g (female birds) and 199.3 ± 12.2 g (male birds) with one to three spent no. 9 Pb shot collected from a skeet range, with particular interest in the toxicity that may occur from ingestion of a single 2-mm, 50 mg shot. An 8 week post-dosing clinical observation period was employed, over which feed consumption, body weight, blood Pb levels, and a battery of blood physiological parameters were made. Weight loss occurred in the birds, including male birds dosed with one Pb pellet. Erythrocyte delta aminolevulinic acid dehydratase (δ-ALAD) levels were decreased for the duration of the study across exposures and to levels associated with injury in wild bird populations. Decreased ALAD was particularly severe in female birds dosed with one Pb pellet and was still 92 % decreased at 8 weeks after dosing. Together, these results suggest that inadvertent ingestion of a single no. 9 Pb shot pellet can adversely affect the health of northern bobwhite quail.

Anaemia and abdominal pain due to occupational lead poisoning

We describe a 47-year-old patient with chronic anaemia with basophilic stippling of erythrocytes, recurrent abdominal colics, discoloration of gums, sensitive polyneuropathy to the four limbs, hyperuricaemia, hepatosteatosis with raised transaminases, and a long ignored history of lead exposure in a battery recycling plant. The diagnosis of poisoning was confirmed by high lead levels in the blood and urine, decreased erythrocyte delta-aminolevulinic acid dehydratase (ALA-D), raised erythrocyte zinc protoporphyrin (ZP), and elevated urinary excretion of porphyrins. Chelation with EDTA resulted in increased urinary lead excretion, gradual improvement of the clinical picture, and progressive normalization of lead biomarkers. The case highlights the importance of occupational anamnesis for the diagnosis of lead poisoning, an uncommon condition which may mimic a variety of internal and surgical diseases. Since antiquity, lead has been extensively mined, produced, and utilized in a variety of industrial settings, such as metallurgy, construction, production of plastics, ceramics, paints and pigments. Lead and its compounds are systemic toxicants, and a wide range of adverse health effects (including haematological, gastrointestinal, neuropsychiatric, cardiovascular, renal, endocrine, and reproductive disorders) has been observed in exposed workers. The general population (particularly children) may also be exposed to toxic lead levels due to air, soil, food and water contamination. Thanks to the improvement of workplace hygienic conditions, the pathological picture of occupational lead poisoning (plumbism, saturnism) has gradually become less serious, at least in the most industrialized countries, and has progressively changed into aspecific, subclinical manifestations. We describe here an unusual case (nowadays) of anaemia and recurrent abdominal pain due to lead poisoning from battery recycling.

A biomarker approach to measure biological effects of contaminant exposure in largemouth bass from Lake Conestee, South Carolina, USA

Sediments from Lake Conestee, a former reservoir now filled with pollutant-enriched sediments, located south of Greenville, South Carolina, USA, and other nearby reservoirs were collected and analyzed for lead and polycyclic aromatic hydrocarbons (PAHs). Hepatic ethoxyresorufin-O-deethylase (EROD), glutathione S-transferase (GST), UDP-glucuronosyltransferase (UGT), sulfotransferase (SULT), and erythrocyte delta-aminolevulinic acid dehydratase (ALAD) were measured in largemouth bass (Micropterus salmoides) to characterize biological effects of these contaminants over three seasons. Results showed that total PAH concentrations in Lake Conestee sediments were significantly greater than the control during each season. An average 10-fold induction in EROD activity was observed at Lake Conestee compared with the control over all three seasons, indicating that PAHs present in sediment were bioavailable to fish. Significant gender effects were observed in EROD activity during the spring, in which activity in reproductively active female fish was significantly suppressed compared with the male fish. Sediments from Lake Conestee had elevated lead concentrations, but the lack of ALAD inhibition in bass indicated that lead was not biologically available. Total GST activity, UGT activity, and SULT activity were not significantly induced in fish from any of the affected sites compared with the reference site. Both EROD and UGT activities were highest during the winter, as were sediment PAH concentrations in Lake Conestee, possibly linked to seasonal resuspension events. The biomarkers measured in this study were useful as a first investigation into the biological effects of contaminant exposure, as well as in determining the bioavailability of contaminants in Lake Conestee.

Lead, renal disease and hypertension

Lead, renal disease and hypertension

Inhibition of erythrocyte delta-aminolevulinic acid dehydratase (ALAD) activity in fish from waters affected by lead smelters.

We assessed the effects on fish of lead (Pb) released to streams by smelters located in Trail, BC (Canada), E. Helena, MT, Herculaneum, MO, and Glover, MO. Fish were collected by electrofishing from sites located downstream of smelters and from reference sites. Blood from each fish was analyzed for delta-aminolevulinic acid dehydratase (ALAD) activity and hemoglobin (Hb), and samples of blood, liver, or carcass were analyzed for Pb, zinc (Zn), or both. Fish collected downstream of all four smelters sites had elevated Pb concentrations, decreased ALAD activity, or both relative to their respective reference sites. At E. Helena, fish from the downstream site also had lower Hb concentrations than fish from upstream. Differences among taxa were also apparent. Consistent with previous studies, ALAD activity in catostomids (Pisces: Catostomidae-northern hog sucker, Hypentelium nigricans; river carpsucker, Carpiodes carpio; largescale sucker, Catostomus macrocheilus; and mountain sucker, C. platyrhynchus) seemed more sensitive to Pb-induced ALAD inhibition than the salmonids (Pisces: Salmonidae-rainbow trout, Oncorhynchus mykiss; brook trout, Salvelinus fontinalis) or common carp (Cyprinus carpio). Some of these differences may have resulted from differential accumulation of Zn, which was not measured at all sites. We detected no ALAD activity in channel catfish (Ictalurus punctatus) from either site on the Mississippi River at Herculaneum. MO. Our findings confirmed that Pb is released to aquatic ecosystems by smelters and accumulated by fish, and we documented potentially adverse effects of Pb in fish. We recommend that Zn be measured along with Pb when ALAD activity is used as a biomarker and the collection of at least 10 fish of a species at each site to facilitate statistical analysis.

Prophylactic effect of melatonin on lead-induced inhibition of heme biosynthesis and deterioration of antioxidant systems in male rats.

We studied the protective role of the pineal hormone melatonin on lead-induced suppression of the heme synthesis pathway as a consequence of reduced antioxidant systems in rat. We injected rats intramuscularly with lead acetate (10 mg/kg body weight) daily for 7 days, which significantly abolished heme synthesis as evidenced by decreased blood hemoglobin, liver delta-aminolevulinic acid synthetase, erythrocytic delta-aminolevulinic acid dehydratase, and hepatic iron content. These effects were accompanied with marked elevation of hepatic lipid peroxidation and decreased enzymatic antioxidants such as glutathione reductase, glutathione-S-transferase, superoxide dismutase, and catalase, as well as nonenzymatic antioxidants such as total sulfhydryl groups and glutathione. Furthermore, lead treatment caused hepatic deficiency in copper and zinc accompanied by a significant elevation of lead concentration in both plasma and liver. Daily pretreatment with melatonin (30 mg/kg body weight) intragastrically prevented the suppressive effects of lead on heme-synthesizing enzymes and iron deficiency. In addition, preadministration of melatonin reduced the inhibitory effect of lead on both enzymatic and nonenzymatic antioxidants. This was accompanied by marked normalization of lipid peroxidation and modulation of copper and zinc levels in liver. The action of melatonin on lead-induced changes was attributed to protection of the antioxidant capacity in cells in addition to the ability of melatonin to scavenge free radicals.

Lead poisoning associated with the use of Ayurvedic metal-mineral tonics.

The aim of this study was to confirm the connection between lead poisoning and the use of traditional Ayurvedic metal mineral tonics. 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. 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 micrograms Pb/g; 0.35-29,900 micrograms 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 < 0.001). Chelation therapy was successful in normalization of laboratory findings and clinical recovery. Ayurvedic metal-mineral tonics are again identified as a potential source of high lead. The import of such tonics should be strictly controlled.

Evaluation of lead exposure in workers at a lead-acid battery factory in Korea: with focus on activity of erythrocyte pyrimidine 5'-nucleotidase (P5N).

To evaluate lead exposure among lead-acid battery workers in Korea, to evaluate in more detail the erythrocyte pyrimidine 5'-nucleotidase (P5N) test for lead exposure, and to evaluate the abnormal accumulation of erythrocyte pyrimidine nucleotides in the battery workers. Activity of P5N and other biological variables were examined in 66 exposed workers in a lead-acid battery factory and in 26 non-exposed workers in Korea. At the factory the time-weighted average of 13 (72%) of 18 air samples for lead exceeded 0.05 (range 0.012-0.468) mg/m3. Blood lead concentration (PbB) in 39 of the 66 exposed workers was above 40 micrograms/dl, and the mean (SD) PbB in the exposed group was 45.7 (15.7) micrograms/dl. Compared with the nonexposed group, free erythrocyte protoporphyrin in the exposed group was significantly increased, whereas erythrocyte P5N activity and activity of erythrocyte delta-aminolevulinic acid dehydratase (ALAD) were significantly inhibited. Erythrocyte P5N activity had valid correlation biologically with PbB and with other biological variables, such as ALAD activity. In 28 exposed workers, the concentration of erythrocyte pyrimidine nucleotides (uridine 5'-diphosphate-glucose and cytidine 5'-triphosphate) correlated inversely with P5N activity and positively with PbB. These findings show that the depression of erythrocyte P5N activity by lead exposure results in the accumulation of erythrocyte pyrimidine nucleotides. In general, the standard analysis of PbB performed in laboratories around the world remains the most useful index of recent exposure. The results indicate that the erythrocyte P5N activity test provides supporting evidence of lead exposure and shows the effect of lead on nucleotide metabolism.

Bioavailability of biologically detoxified lead: risks arising from consumption of polluted mussels.

The possible risk for human health arising from consumption of lead-polluted shellfish was suggested by experiments on the bioavailability for mice of a "biologically detoxified" form of the metal. In this work, young mice were fed with a mixed diet including mussels collected in a Pb-polluted area. Metal concentrations in blood, kidney, liver, urine, and feces and the activity of erythrocytic delta-aminolevulinic acid dehydratase were determined after 1, 2, and 4 weeks. Comparisons were made with mice treated with balanced diet, mixed diet including control mussels, and drinking water with lead dissolved as acetate. In mice fed polluted mussels, lead concentrations increased in blood, kidney, and liver, whereas no significant accumulation was observed in urine. Different responses in mice treated with Pb(CH3COO)2 in drinking water are probably due to the diversity of lead chemical form in the two treatments. Our results demonstrate the bioavailability of biologically detoxified lead that can be transferred to a consumer with possible consequences also for human health.

Method for preserving erythrocytic delta-aminolevulinic acid dehydratase activity that facilitates population studies on lead intoxication.

A method preserving the activity of the erythrocytic enzyme delta-aminolevulinic acid dehydratase (EC 4.2.1.24) was developed using a vehicle of 50% aqueous glycerol containing dithiothreitol (80 microM). Whole heparinized blood (0.5 ml) was added to 0.75 ml of this mixture in a cryovial tube (capacity 1.3 ml), mixed well and stored in a freezer at -20 degrees C for 21 days. Statistical comparison of the enzyme activity when freshly assayed and after storage indicated excellent agreement for quantitation of the non-activated enzyme (intraclass correlation coefficient = 0.99) and the activated enzyme (intraclass correlation coefficient = 0.98). This storage method will facilitate future population studies on lead intoxication, particularly those in remote locations.

Erythrocyte ALA-d activity in experimentally lead-poisoned ducks and its change during treatment with disodium calcium EDTA

To determine useful procedures for the diagnosis and prognosis of lead poisoning in waterfowl caused by ingestion of lead pellets, erythrocyte delta-aminolevulinic acid dehydratase ( ALA-d) was investigated in experimentally lead-poisoned ducks. A highly positive correlation was observed between the concentration of blood lead and the ALA-d activity ratio (the ratio of activated:non-activated enzyme activity) in those birds given seven lead pellets (3 mm diameter). The ALA-d activity ratio rapidly increased after the administration of lead pellets, but began to fall immediately after the initiation of disodium calcium ethylenediamine tetra-acetate ( CaEDTA) therapy which resulted in a rapid decrease in the concentration of lead in the blood of these birds. In contrast, the ALA-d activity remained inhibited even after blood lead levels began to decrease following treatment. These results demonstrated that the ALA-d activity ratio is a very useful and sensitive indicator for the diagnosis and evaluation of therapeutic effects after lead poisoning in waterfowl.

A comparison of the effects of inorganic and alkyllead compounds on human erythrocytic δ‐aminolevulinic acid dehydratase (ALAD) activity in vitro

A study comprising two experiments comparing the effects of the alkyllead compounds triethyllead acetate and tetraethyllead as well as an inorganic lead compound (Pb(NO3)2) on human erythrocytic delta-aminolevulinic acid dehydratase activity was undertaken. In Experiment 1, four human blood samples were pre-incubated for 0 min or 60 min with increasing concentrations (0-1000 microM) of triethyllead acetate, tetraethyllead and Pb(NO3)2, and the delta-aminolevulinic acid dehydratase activity was determined. There was no discernible inhibitory effect of tetraethyllead at any concentration, with or without pre-incubation. Pb(NO3)2 showed a distinct effect at an addition concentration of 1 microM, with a substantial inhibition only following pre-incubation. Triethyllead acetate showed no difference in effect with pre-incubation. In the second experiment, the activating effects of zinc chloride (60 microM) and dithiothreitol (20 mM) on delta-aminolevulinic acid dehydratase activity were examined on four human blood samples in the presence of varying concentrations of Pb(NO3)2 (0-50 microM) and triethyllead acetate (0-1000 microM). The addition of zinc chloride alone showed little effect on enzyme activity, while dithiothreitol alone caused a substantial activation of the enzyme at all lead concentrations. The addition of both zinc chloride and dithiothreitol caused an even greater activation of the enzyme. The data indicate that Pb(NO3)2 is a much more potent inhibitor of delta-aminolevulinic acid dehydratase activity than triethyllead acetate (Ki values of 0.77 microM versus 130.37 microM. respectively). The use of delta-aminolevulinic acid dehydratase activity as an indicator of exposure may be questionable in cases of alkyllead exposure. Possible causes for differences in the inhibition of delta-aminolevulinic acid dehydratase by these compounds is also discussed.

Dose-response study of oral 2,3-dimercaptosuccinic acid in children with elevated blood lead concentrations

2,3-Dimercaptosuccinic acid (DMSA) is an orally effective orphan drug that is more specific and has a wider therapeutic index than other currently available drugs used for lead intoxication. Its investigational use in the United States has been limited to the treatment of men with occupational plumbism. Twenty-one children with blood lead concentrations of 31 to 49 micrograms/dl, who also had a positive calcium disodium edetate (CaNa2EDTA) mobilization test result, were hospitalized for 7 days. Fifteen children were randomly assigned to three groups that received either 350, 700, or 1050 mg/m2/day, respectively, of DMSA in three divided doses daily. A fourth group of six children received conventional treatment with 1000 mg/m2/day of intravenously administered CaNa2EDTA in two divided doses daily. The 1050 mg/m2/day dose of DMSA was significantly more effective than lower doses of DMSA or intravenously administered CaNa2EDTA in reducing blood lead levels and restoring erythrocyte delta-aminolevulinic acid dehydratase activity. Intravenously administered CaNa2EDTA significantly increased the urinary excretion of several essential minerals (zinc, copper, iron, and calcium), whereas DMSA did not. The DMSA was well tolerated and appears extremely promising as a drug that will simplify the management of childhood lead poisoning.

Relationship between inhibition of erythrocyte pyrimidine 5'-nucleotidase activity and biological response for porphyrin metabolism in workers occupationally exposed to lead.

A rapid determination of erythrocyte pyrimidine 5'-nucleotidase (P5N) activity in lead workers was carried out using a high-performance liquid chromatograph (HPLC). The P5N activity had a good negative correlation with the concentration of lead in blood (PbB) ranging from 16 to 96 micrograms/dl (r = -0.82, n = 77). Further, the P5N was compared with other biological parameters: erythrocyte delta-aminolevulinic acid dehydratase (ALAD) activity, erythrocyte protoporphyrin (PROTO), urinary delta-aminolevulinic acid (ALA) and urinary coproporphyrin (COPRO). The correlation coefficients between P5N and ALAD, log PROTO, log ALA, and log COPRO were 0.59, -0.72, -0.65, and -0.61, respectively. On the other hand, the normal value of P5N obtained from 72 healthy subjects was 11.9 +/- 2.1 units; mumol uridine/h/g Hb (mean +/- SD), indicating that the lower limit of 95% confidence interval for normal P5N was about 8 units. When P5N was cut off at less than or equal to 8 units in 77 lead workers, the validity (sensitivity + specificity) for PbB greater than or equal to 40 micrograms/dl, PbB greater than or equal to 60 micrograms/dl, erythrocyte PROTO greater than or equal to 150 micrograms/dl RBC, urinary ALA greater than or equal to 6 mg/l, and urinary COPRO greater than or equal to 150 micrograms/l was 1.66, 1.76, 1.57, 1.68, and 1.60, respectively. From these results, it was confirmed that the erythrocyte P5N test is suitable for the biological monitoring of exposure to lead in a wide range, and its activity is useful in predicting the disturbance of porphyrin metabolism induced by lead.

Acute-Subacute Lead Poisoning

A prospective study of an epidemic outbreak of acute lead poisoning characterized by unusual clinical and analytic manifestations was carried out. Its source was traced to lead-contaminated flour. Thirty-two adult patients presented with classic clinical symptoms of saturnism; however, 13 severely poisoned patients simultaneously manifested unusual clinical features such as hemolytic anemia and multiorgan dysfunction. We compared the diagnostic value of the different toxicity markers in 68 of 136 adults exposed to lead. Porphyrin precursors, urine levels of lead, and results from an edetic acid-provocative test gave poor diagnostic information and low correlation values with lead levels in blood. However, erythrocyte delta-aminolevulinic acid dehydratase activity showed a closer correlation with lead levels in blood, although we observed a frequent overlap of results in severe cases. The test for levels of lead in blood was the most reliable, suitable, and simplest test performed, and gave the best correlation with the external dose of lead, the clinical situation, and the toxicologic effects described by 12 different analytic data.

Effect of aluminum on porphyrin metabolism in hemodialyzed patients.

In patients with renal failure and on chronic hemodialysis, serum aluminum, serum delta-aminolevulinic acid, serum porphobilinogen and erythrocyte zinc protoporphyrin (ZPP) are significantly elevated, whereas erythrocyte delta-aminolevulinic acid dehydratase activity (ALAD, values in percent) is significantly reduced. The last two parameters (ZPP and ALAD) are statistically related to serum aluminum concentration (Al-S), but only the correlation between Al-S and ALAD remains statistically significant after standardization for the degree of renal insufficiency (expressed in terms of urea level). This study does not support the hypothesis that the retention of aluminum is responsible for the increase of ZPP in uremic patients on dialysis. The disturbances of porphyrin metabolism found in patients with renal failure and on chronic dialysis are not similar to those observed in porphyria cutanea tarda.

Nitrogen utilization, enzyme activity, glucose intolerance and leukocyte chemotaxis in human experimental zinc depletion

We previously reported significant decreases in plasma, whole blood, urinary, seminal and fecal zinc in six young men consuming a semipurified formula diet providing 0.28 mg zinc and 0.8/kg protein per day for 4-9 weeks. During a one-week baseline period, 15.7 mg of zinc (as ZnSO4) were fed; three of the men were repleted with 6.0, 23.2 or 46.3 mg zinc for 2-5 weeks. Biochemical and functional measures of zinc status other than tissue zinc levels were also monitored. No one parameter appeared to parallel dietary zinc status in all subjects, although significant mean changes were seen in serum and leukocyte alkaline phosphatases. Inconsistent changes were noted in erythrocyte delta-amino levulinic acid dehydratase, plasma alkaline ribonuclease and the serum alkaline phosphatase isoenzymes. Nitrogen balance was unaffected by zinc nutritional status. However, alterations in hair root growth phase and morphology, decreases in lymphocyte counts and in transferrin levels during depletion suggest impairment in protein synthesis. Impaired leukocyte chemotaxis and clinical signs indicative of decreased resistance to infection were also noted.

In vitro study on lead and alcohol interaction and the inhibition of erythrocyte delta-aminolevulinic acid dehydratase in man.

The effect of lead (Pb) and ethanol (EtOH) interaction on the inhibition of erythrocyte delta-aminolevulinic acid dehydratase (ALAD) was investigated in human blood in vitro. Two different doses of ethanol (equivalent to 16.28 mmol of EtOH/l of blood and 108.53 mmol of EtOH/l of blood) and lead (equivalent to 2.17 mumol of Pb/l of blood and 4.34 mumol of Pb/l of blood) were examined separately and in combination. The dose-effect (EtOH-ALAD) relationship for a wide range of ethanol concentrations (0-217.06 mmol of EtOH/l of blood) was also investigated. The results obtained indicate that ethanol by itself does not inhibit ALAD, while lead does it readily. Neither ethanol concentrations significantly altered ALAD activity. The dose-effect (EtOH-ALAD) relationship did not reveal any inhibitory effect of ethanol on ALAD either; however, a weak trend towards increased ALAD activity was found. The effect of ethanol combined with lead indicated no significant difference as compared to the effect of the same dose of lead per se; however, a weak trend towards decreased ALAD activity was found. These findings support the hypothesis that the effect of ethanol on the transient inhibition of ALAD activity in vivo does not occur directly, but possibly through the intermediary action of lead from the body lead pool.

In vivo study on lead and alcohol interaction and the inhibition of erythrocyte delta-aminolevulinic acid dehydratase in man.

The effect on alcohol (EtOH) consumption on the inhibition of erythrocyte delta-amino-levulinic acid dehydratase (ALAD) was investigated in 13 male lead workers and 7 "normal" male subjects. Lead and zinc protoporphyrin in blood and lead, delta-aminolevulinic acid, porphobilinogen and coproporphyrin in 24-h urine specimens were also determined. During 1 h the subjects drank 122.8 (SD 18.65) ml of an almost lead-free brandy, ie, a dose of 11.07 mmol/kg of body weight. This dose resulted in a trend toward a parallel decrease in ALAD activity and an increase in lead in blood (PbB), both of which approached the prealcohol value 24 h after the initial alcohol ingestion. A trend toward increased lead excretion in urine (PbU) was observed on the day of alcohol ingestion, as compared to the preceding and succeeding 24-h urine specimens. However, the observed increase in PbB and PbU cannot be attributed to the small amount of lead ingested through the brandy, ie, 7.09 (SD 1.06) nmol. The characteristic dose-effect relationship between PbB and ALAD (examined prior to and 1, 3, 5, and 24 h after the initial alcohol ingestion) reached the highest correlation coefficient 3 h after the initial alcohol ingestion (p less than 0.001). The data obtained appear to support the hypothesis of a possible role for the body lead pool and the lead-mediated influence of alcohol consumption on ALAD activity in man.