In vivo neutron activation analysis of organ cadmium burdens

In vivo neutron activation measurements of liver and kidney cadmium have been mae in 77 exposed workers and 101 referents. Cadmium levels were higher in exposed workers than in referents; both in liver, 25.7 cf. 0.6 μg/g, and kidney, 17.9 cf. 2.7 mg. The 19 referents who never smoked had lower mean organ cadmium burdens than the other referents, the difference achieving statistical significance in the kidney,p<.01. Cigaret smoking was estimated to increase cadmium body burden by 370-140 μg/pack year. These referent cadmium levels are similar to, although slightly below, previous in vivo and autopsy data.

     

Dietary Exposure to Lead and Cadmium in Sweden

Abstract

A duplicate diet study on male and female pensioners in 1970–71 showed mean daily dietary lead intakes of 30 μg and 19 μg respectively. The corresponding cadmium intakes were 10.5μg and 12.9 μg. Analysis of duplicate diets collected during seven consecutive 24-hour periods from 15 women in Stockholm in 1988 showed a mean daily lead intake of 26 μg (range 13–40 μg). The corresponding cadmium intake was 8.5μg (range 5.7–14 μg). Analysis of faeces samples corresponding to the duplicate diets showed similar lead and cadmium contents (mean lead content 24 μg day^?1, range 10–41 μg day^?1; mean cadmium content 8.9 μg day^?1 range 5.5–12 μg day^?1). The median lead and cadmium concentrations in human milk collected in Uppsala were 2 μg kg^?1 and 0.1 mg kg^?1 respectively. The median weekly intakes of lead and cadmium by the breast-fed infants were calculated to be 2 μg kg^?1 body weight and 0.1 μg kg^?1 body weight. Analysis of seven daily diets, together representing the weekly diet of an adult Swedish male, showed a mean lead content of 26 μg (range 15–45 μg), and a mean cadmium content of 10 μg (range 7–15 μg). The mean daily intakes of lead and cadmium found by analysing market baskets prepared in 1987 were 17μg and 12μg respectively. Calculations based on food balance sheet data and levels of lead and cadmium in individual foods showed mean daily intakes of 30 μg lead and 14 μg cadmium per person.     

Dietary Exposure to Lead and Cadmium in Yugoslavia

Abstract

Lead exposure still represents a matter of health concern especially in Yugoslavia. To assess the exposure of normal urban population to lead and cadmium through food, a preliminary monitoring was performed on a small group of urban population. Lead, cadmium and some essential elements (calcium, zinc, iron, copper and manganese) were analysed in collected duplicate diet samples and compared to similar population in Sweden. We found that dietary exposure to lead and cadmium is similar to other countries although Yugoslav urban population is exposed to much higher concentrations of lead in air than in cities of developed countries, due to high lead in gasoline. However, daily intake of some essential elements was significantly lower.

Also populations living around lead smelters in various parts of Yugoslavia are still exposed to elevated environmental lead and cadmium levels. To assess the exposure of the population living in this area, a cumulative long-term exposure to lead was determined by measuring lead in deciduous teeth. Concentrations of lead and cadmium in vegetables, soil and meals from the same region were also analysed. Values obtained for lead and cadmium in food products grown in exposed and control area were found to be related to respective concentrations of these elements in soil as well as to the distance from the smelter. Meals prepared in this region show the same trend, revealing very high intake particularly of lead.

The influence of nutritional factors, i.e. dietary calcium on lead metabolism, was also studied. Blood lead concentration was determined in two groups of peasant women living in two regions with different dietary calcium intake. Lower blood lead values were found in the higher dietary calcium intake region.     

The uptake of lead,zinc, cadmium,and copper by the pulmonate mollusc,Helix aspersa muller,and its relevance to the monitoring of heavy metal contamination of the environment

Summary The occurrence of lead, zinc, cadmium, and copper in individuals of Helix aspersa from two sites of varying degrees of contamination was studied. Zinc, cadmium, and copper were shown to increase in a linear fashion with animal weight. The rate of uptake for zinc and cadmium in particular was significantly greater at the more contaminated site. Statistical analysis of the data, using correlation and regression techniques provided information on apparent intermetallic effects.It is concluded that because metal uptake and body weight show a positive linear relationship only the use of animals of similar weight and/or size can be used for monitoring purposes. Even then, different patterns of uptake into different organs and interactions between metal uptakes are such as to seriously question the use of Helix, and other molluscs, for monitoring purposes unless specific organs from comparably sized and/or aged animals are used.     

Comparison of the toxicity and distribution of cadmium and lead in plant cells

Summary. The toxicity of heavy metals (Cd, Zn, and Pb) was assessed by in vivo observations of their effect on cytoplasmic streaming in Allium cepa L. bulb scale epidermal cells. On the basis of our results, the order of toxicity of the studied cations is Zn < Pb ≪ Cd. The difference in toxicity between cadmium and lead was found to be very large. When cytoplasmic streaming was assessed, this difference was threefold. When the total content of cadmium and lead (determined by inductively coupled plasma mass spectrometry) was the criterion, the difference in toxicity was 15-fold. Fractionation of the tissue and enzymatic digestion of the cells revealed that the largest proportion of cadmium was located in the cell walls (56%), whereas almost all of the lead (97.6%) was accumulated in an insoluble form. The speciation of water-soluble Pb and Cd fractions is discussed on the basis of analysis by capillary zone electrophoresis interfaced with inductively coupled plasma mass spectrometry of water extracts from epidermal cells. Lead and cadmium appeared to be bound mainly to salts, which explains their toxicity. Cadmium was complexed (detoxified) by organic acids, while thiols were the metal-complexing species for lead. Histidine formed complexes with both cadmium and lead. Ultrastructural analyses showed that lead was encapsulated in small vesicles in the cytoplasm. Fluorescence studies of the endoplasmic reticulum (ER) revealed that it underwent extensive fragmentation under the influence of lead, with numerous ER vesicles appearing in the cells. In other words, the lead deposits in the cytoplasm were contained in vesicles arising from fragmentation of the ER. These observations indicate that epidermal cells have a rapid and effective mechanism for detoxifying lead involving the ER, and this may be one of the mechanisms accounting for the lower toxicity of lead in comparison with cadmium. The suitability of Allium cepa bulb scale epidermal cells for use in ecotoxicological studies is also discussed. Step-by-step directions for this test are given. Correspondence and reprints: Department of Ecotoxicology, Institute of Experimental Plant Biology, Faculty of Biology, University of Warsaw, Miecznikowa 1, 02-096 Warsaw, Poland.     

Effect of heavy metals (Cu,Cd and Pb) on aspartate and alanine aminotransferase in Ruditapes philippinarum (Mollusca: Bivalvia)

The accumulation of cadmium, copper and lead and their effects on aspartate and alanine aminotransferases in digestive gland, gills, foot and soft body in the clam Ruditapes philippinarum were examined. The animals were exposed to different concentrations: Cd (200–600 μg·l⁻¹), Pb (350–700 μg·l⁻¹) and Cu (10–20 μg·l⁻¹) for 7 days. The highest concentrations were found in digestive gland for cadmium and copper, and in gills for lead, and the lowest values were observed in the foot. Aspartate aminotransferase activity (AST), in general, was not inhibited by cadmium, lead or copper during the exposure. Only in clams exposed to cadmium (600 μg·l⁻¹, 7 days) and copper (20 μg·l⁻¹, 5 days) were observed significant differences (P<0.05) in foot and gills, respectively, with respect to control. In the case of alanine aminotransferase activity (ALT), significant differences were observed for cadmium and lead in treated animals with respect to control. With regard to copper, a decrease in ALT was observed in gills and foot exposed to 20 μg·l⁻¹. A significant correlation (P<0.05) was observed between ALT and metal accumulation for cadmium, copper and lead in gills. In the case of soft body, only cadmium and lead showed a significant correlation. In summary, R. philippinarum can be considered a bioindicator species for cadmium and lead accumulation and ALT could be useful as biomarker of sublethal stress for these metals in soft tissues and gills. Only gills can be considered an adequate target tissue for copper.     

Association Among Sources Exposure of Cadmium in the Adult Non-smoking General Population of Tehran

Acute and chronic exposure to cadmium can cause numerous health effects including poisoning, as well as, bone, liver, and kidney diseases. Cadmium competes with iron absorption in blood and can induce anemia. Cadmium body burden can be measured through urine and blood samples. Urine reflects chronic and blood indicates recent and cumulative exposures to cadmium. Dietary is considered as the main source of exposure to cadmium in non-smoking general population. The study was conducted to determine cadmium level in blood, urine, and in diet of 120 non-smoking adults in Tehran. Dietary components and consumption pattern of participants estimated by a food frequency questionnaire. Next, the correlation investigated between them. Moreover, serum ferritin measured as a marker of iron storage in blood to determine its association with cadmium. The prediction of cadmium fate in the body is determined by toxicokinetic models. This study tried to evaluate one of these models’ validity which is developed to predict urinary cadmium from dietary. Afterwards, the predicted urinary compared with the measured urinary cadmium. The correlation coefficient between dietary and blood cadmium equaled 0.66 which was statically significant, but the correlation between dietary and urinary cadmium was minimal and not statically significant (p > 0.05). An inverse and negative correlation was found between serum ferritin and blood cadmium. The mean predicted urinary cadmium calculated by the model was 2.5-fold higher than the measured value in the total population. Results of the present study revealed that blood cadmium reflected mainly acute exposure. There was no correlation between chronic and acute exposures to cadmium. The low serum ferritin level increased cadmium amount in blood. Moreover, the mean predicted urinary cadmium by the model was greater than the measured value. It can because of characteristics of populations and type of dietary exposure. Thus, it is suggested that the model coefficients are determined in each society based on their characteristics.

     

Biomonitoring of Lead and Cadmium in the Hair and Fingernails of Elderly Korean Subjects

Lead and cadmium are toxic to humans at excessive levels, and monitoring the human body burden of these metals is important in preventing adverse health effects. In this study, we assessed the exposure to lead and cadmium among an elderly population 60 years of age or older. Based on data from 115 participants, we found that the geometric mean lead concentrations in hair and fingernails were 1.11 μg/g [95% confidence interval (CI) 0.78–1.58] and 1.11 μg/g (95% CI 0.81–1.51), respectively. The lead concentrations in hair and fingernails were significantly related to cigarette smoking. The geometric mean cadmium concentrations in hair and fingernails were 52.6 ng/g (95% CI 42.0–65.9) and 40.1 ng/g (95% CI 29.9–53.9), respectively. Cadmium concentrations in hair were significantly related to body mass index and cigarette smoking, whereas higher fingernail cadmium concentrations were related to alcohol drinking. Correlations between hair and fingernail concentrations of lead and of cadmium were slightly positive. Our findings suggest that the body burden of lead and cadmium varies according to demographic factors, and hair and fingernails could be used differentially as a biological medium for metal exposure.     

Body Fat Percentage and Hemoglobin Levels Are Related to Blood Lead, Cadmium, and Mercury Concentrations in a Korean Adult Population (KNHANES 2008–2010)

Body stores of lead, cadmium, and mercury are determined by the levels in the circulation, and their levels in blood may be related to hemoglobin levels and their absorption by soft tissue and bone. We investigated the association of body fat percentage, hemoglobin levels, and nutrient intakes with the blood concentrations of lead, cadmium, and mercury in a Korean adult population. This study was based on data from the 2008–2010 Korean National Health and Nutritional Examination Survey (n?=?4,522, aged ≥20 years), which examined nutritional, biochemical, and health-related parameters. A multiple regression analysis after controlling for covariates of age, body mass index, residence area, education level, smoking and drinking status, and bone mineral density for men, with menopausal status added for women in addition to covariates for men indicated that blood lead and mercury levels were negatively associated with body fat percentage only in men, and blood lead, cadmium, and mercury levels were positively related to hemoglobin levels in both genders. Additionally, blood lead levels were negatively associated with fat and carbohydrate intake in both men and women but blood mercury levels were only in men, but not women. Sodium intake was a positive predictor of blood lead levels in both genders but was a positive predictor of blood cadmium levels only in men. In conclusion, body fat percentage and hemoglobin levels need to be recognized as confounding factors when considering blood levels of lead, cadmium and mercury as biomarkers for their exposure. Fat, carbohydrates and sodium intakes are also associated with heavy metal levels in the circulation.     

Cumulative Title Index

Abstract

Metal fractionation is a powerful tool for studying the mobility, bioavailability and toxicity of metals in sediments and soils. A seven-step sequential extraction technique was used to determine the potential mobility of selected heavy metals (Fe, Mn, Zn, Cu, Pb, Cd and Ni) in the sediments of Lake Naivasha. Results indicate that residual fraction was the most important phase for the elements Fe, Mn, Cu and Zn. However, Pb and Cd are highly enriched in the non-residual phases. Nickel on the other hand was distributed evenly between the non-residual and the residual fractions.

The total concentrations of the heavy metals suggested a decreasing order of iron ?> manganese ? zinc > nickel > copper ? lead > cadmium. However, the detailed sequential extraction data indicated an order of release or mobility of cadmium > lead ? nickel ? zinc > manganese > copper > iron. The high percentage of Cd and Pb in the mobile fractions suggests high bioavailability of these two elements in the study area and maybe a pointer to anthropogenic input of the two elements in the study area.     

Determination of Human Exposure to Lead and Cadmium: A WHO/UNEP Pilot Study

Abstract

In Stockholm, methods for measuring exposure to lead and cadmium from air, food and beverages were studied in 1988 in a group of 15 non-smoking women, as part of the WHO/UNEP HEAL programme. Airborne particles in the breathing zone air (24-hour samples), duplicate diets (24-hour samples), and faeces (all the stools produced) were collected during 7 consecutive days. Blood was sampled before and immediately after the study period. The results confirmed the need for personal monitoring in the assessment of human exposure to lead and cadmium via air and food. There is need for suitable equipment for 24-hour personal air monitoring. On average, dietary lead (26 μg day^?1, SD 7.9) contributed more than 80% of the total lead uptake, while dietary cadmium (8.5 μg day^?1 SD 2.1) contributed about 99% of the total cadmium uptake. Occasionally consumed foodstuffs with high levels of lead or cadmium seemed to be responsible for a large part of the total weekly intake of lead and cadmium. Fecal lead and cadmium were found to be useful indicators of the total amounts of these metals ingested. Due to the large day-to-day variation observed in the dietary intake of lead and cadmium, the sampling period for duplicate diets and faeces should be at least 5–6 days.     

Variables affecting body burdens of lead,zinc and cadmium in a roadside population of the snailCepaea hortensis Müller

Summary Application of multiple regression analysis to the lead, zinc and cadmium contents of 985Cepaea hortensis collected from a suburban roadside site over two years showed that body weight, age and daylength were the major factors affecting soft tissue body burdens. Other highly significant influences were physiological changes at the juvenile-adult transition, vapour pressure deficit for the two days before sampling, and mean rainfall for the ten days before. Together these factors accounted for 69%, 79% and 87% of the total variance in lead, zinc and cadmium body burdens respectively. Unexplained variance was provisionally ascribed to individual differences in recent diet and digestive activity. The digestive gland contined the majority of the total body burden of each metal and played an important role in lead and zinc elimination. Whereas levels of lead inC. hortensis fluctuated rapidly, zinc was exchanged more slowly, perhaps by active regulation, and cadmium was effectively immobile, accumulating progressively with age. The implications of these results to the predators of land snails, and to terrestrial monitoring programmes, are discussed.     

Concentration of Thyrotropic Hormone in Persons Occupationally Exposed to Lead,Cadmium and Arsenic

Thyroid hormones are essential for body homeostasis. The scientific literature contains restricted proofs for effects of environmental chemical factors on thyroid function. The present study aimed at evaluating the relationship between toxicological parameters and concentration of thyrotropic hormone in persons occupationally exposed to lead, cadmium and arsenic. The studies were conducted on 102 consecutive workers occupationally exposed to lead, cadmium and arsenic (mean age 45.08 ± 9.87 years). The estimated parameters characterizing occupational exposure to metals included blood cadmium concentration (Cd-B), blood lead concentration (Pb-B), blood zinc protoporphyrin concentration (ZnPP) and urine arsenic concentration (As-U). Thyroid function was evaluated using the parameter employed in screening studies, the blood thyrotropic hormone concentration (TSH). No differences were disclosed in mean values of toxicological parameters between the subgroup of persons occupationally exposed to lead, cadmium and arsenic with TSH in and out of the accepted normal values. Logistic regression demonstrated that higher blood total bilirubin concentrations (ORu = 4.101; p = 0.025) and higher Cd-B (ORu = 1.532; p = 0.027) represented independent risk factors of abnormal values of TSH in this group. In conclusion, in the group of workers exposed to lead, cadmium and arsenic, higher blood cadmium concentration seems to augment the risk of abnormal hormonal thyroid function.     

湖北省双孢蘑菇子实体中重金属铅镉含量及来源分析

双孢蘑菇Agaricus bisporus子实体中重金属铅、镉含量分析结果表明,铅、镉的背景值含量分别为0.636mg/kg和0.127mg/kg,样品中铅含量的范围为0.087－2.40mg/kg,镉含量的范围为0.038－0.301mg/kg。在两种不同栽培模式下,子实体中铅含量均有显著差异,但镉的含量并无显著差异。相关性分析表明,子实体中铅来源于覆土而与培养料无关,而镉的来源与栽培方式有关,覆土和培养料中的镉含量均影响子实体中的镉含量。     

Biological monitoring,by in vivo XRF measurements,of occupational exposure to lead,cadmium, and mercury

In vivo X-ray fluorescence (XRF) techniques were used for biological monitoring of lead, cadmium, and mercury. Lead accumulates in bone, the level of which may thus be used for monitoring of exposure. However, there was no close association between lead levels in bone and exposure time, partly because of differences in exposure patterns and partly, probably, because of variations in the toxicokinetics of lead. There are at least two separate bone lead compartments. The average over-all half-time is probably 5–10 yr. The finger bone level may be an index of the lead status of the total skeleton. In lead workers, the mobilization of bone lead causes an “internal” lead exposure and affects the blood lead level considerably. In cadmium workers, in vivo XRF is a sensitive and risk-free method for assessment of accumulation in kidney cortex, the critical tissue as to toxic effects; workers displayed increased levels. However, there was no clear association with duration and intensity of exposure, cadmium levels in urine, or microglobulinuria. Determinations of kidney cadmium may add important information on the state of accumulation and, thus, risk of kidney damage. Workers exposed to elemental mercury vapor, as well as fishermen exposed to methyl mercury, had mercury levels in bone below the detection limit of the XRF method.     

Metal interactions within and between tissues of nestling rooks Corvus frugilegus

We analyzed interactions of concentrations of 11 essential and nonessential elements, including toxic metals within and between internal organs (liver, kidney and lung), muscles and bones of nestling rooks Corvus frugilegus with acute cadmium contamination and elevated level of lead. The number of statistically significant (P ≤ 0.05) metal-metal relationships (positive/negative) within particular tissues was the highest in the kidney (7/6), following in the bone (9/2), liver (6/4), lung (5/2) and muscle (5/2). We found eight significant interactions of lead with other metals, and only two of cadmium (only with lead and cobalt, which probably mirrored a greater ability of lead (than in the case of cadmium) to functional and kinetic interaction with other metals, and/or inhibiting effect of lead or cadmium in co-accumulation. Furthermore, a positive relationship between concentration of cadmium and lead in the kidney could hint at the key importance of this organ in detoxification of both toxic metals. Analyses of relationships of individual metals between examined tissues show only positive results in the case of copper (n = 8), following potassium (n = 3), zinc and iron (in both cases n = 2) and a single ones for calcium and magnesium. We concluded that the lack of significant relationships of individual toxic metals (cadmium or lead) between analyzed tissues could result from high levels of these metals, which destroyed detoxifying capacity of kidney, and ultimately enabled a rapid bioaccumulation of these inorganic contaminations in all tissues of examined nestlings. An explanation of concentration of toxic metals in tissues of animals, especially in the case of their high level, require an identification of the actual level of essential elements associated with physiological status of organism.     

Antioxidant enzyme activity and lipid peroxidation in liver of female rats co-exposed to lead and cadmium: Effects of vitamin E and Mn2+

The oxidative status of liver of female rats exposed to lead acetate and cadmium acetate either alone or in combination at a dose of 0.05?mg/kg body wt intraperitoneally for 15 days was studied. After the administration of lead alone, the activity of superoxide dismutase (SOD) decreased in liver, whereas no changes were observed in catalase (CAT) activity, and glutathione (GSH) and thiobarbituric acid (TBARS) levels. Cadmium exposure and combined exposure to lead and cadmium led to decrease in GSH content and increased TBARS levels. Moreover, animals exposed to either cadmium alone or in combination with lead showed a decrease in SOD activity and an increase in CAT activity. The in vitro experiments showed that vitamin E failed to restore the antioxidant enzyme activities in metal treated postmitochondrial supernatant fraction of liver. But Mn²⁺ ions protected the mitochondria from lipid peroxidation and could completely restore Mn-superoxide dismutase (Mn-SOD) activity following metal intoxication. The results of this study indicate that despite the ability of lead and cadmium to induce oxidative stress the effect in liver is not intensified by combined exposure to both lead and cadmium. The observed changes in various oxidative stress parameters in the liver of rats co-exposed to lead and cadmium may result from an independent effect of lead and /cadmium and also from their interaction such as changes in metal accumulation and content of essential elements like Cu, Zn and Fe. These results suggest that when lead and cadmium are present together in similar concentrations, cadmium mediates major effects due to its more reactive nature.     

Lead,Cadmium and Zinc in Hair Samples: Relationship with Dietary Habits and Urban Environment

This study was performed in order to analyze the relationships between hair zinc, lead, and cadmium with the kind of diet consumed (by recall of the diet consumed the previous 14 days), living area (urban or rural), tobacco smoking, and body mass index (BMI) among 419 individuals of the Canary Archipelago. Median values and interquartile range were 43 μg/g (18.50–132.50) for zinc, 4.09 μg/g (2.19–8.38) for lead, and 0.128 μg/g (0.05–0.30) for cadmium. We observed that hair zinc was markedly elevated among those consuming fish more frequently and, to a lesser amount, among those who consumed meat frequently, among those living in urban areas, and among those with BMI over 25 kg/m², keeping a significant relationship with BMI. Hair lead was also higher among fish consumers, showed a trend to higher values among inhabitants of urban areas, and was lower among obese individuals. Hair cadmium was higher among those who consumed less vegetables and fruits. By multivariate analysis, introducing the variables meat, fish, and vegetable consumption, urban/rural; sex; age; and BMI values, we observed that fish consumption (beta?=?0.15) was the only variable independently associated to higher zinc levels; fish consumption (beta?=?0.15) and meat consumption (beta?=?0.17) were related to high cadmium levels, whereas meat consumption was significantly associated to higher hair lead levels (beta?=?0.15). Therefore, we conclude that hair zinc, cadmium, and lead seem to depend more heavily on dietary habits than on tobacco consumption or living in rural or urban areas.     

Arabidopsis arenosa (Brassicaceae) from a lead–zinc waste heap in southern Poland – a plant with high tolerance to heavy metals

The morphological traits and tolerance to heavy metals (zinc, cadmium and lead) of two populations of Arabidopsis arenosa (Brassicaceae) were compared. One population was from a zinc–lead waste heap in Bolesław near Olkusz (southern Poland), the other one from the Kampinoski National Park (central Poland). Biometric measurements were done in the field and repeated after cultivation under controlled conditions (garden soil, phytotron chamber). Significant heritable morphological differences between the two populations were found. The plants from the waste-heap are smaller in comparison with the reference population, and their leaves are narrower, thicker with fewer trichomes, indicating. genetic adaptation to xerothermic conditions. The level of tolerance to heavy metals (zinc, cadmium, and lead) was compared by the root test. Very high tolerance to the three metals tested was found in the waste-heap population. Its tolerance exceeded that of four other predominant plant species populations growing on the same waste heap that had previously been tested in our laboratory. We consider the waste-heap population of A. arenosa to be a very suitable ecotype for the study of heavy metal tolerance mechanisms in plants. Responsible Editor: SE: Henk Schat.     

Effect of low level exposure of lead and cadmium on hepatic estradiol metabolism in female rats

Toxic effect of metal cations on female reproduction and gonadal functions was studied. Adult synchronized female rats were treated intraperitoneally with lead acetate and cadmium acetate separately and in combination (0.025, 0.05 and 0.1 mg/kg body wt) for 15 days. The metabolizing enzymes (17beta-hydroxy steroid oxidoreductase and UDP glucoronyl transferase) activities decreased with increasing dose showing significant change compared to control. Also, significant decrease in cytochrome P450 (CYP450) content was found after the treatment. Displacement of zinc bound to metallothionein was more in cadmium treated rats compared to other groups. In all these parameters, treatment in combination of lead and cadmium showed intermediate results indicating some kind of competition between the two metals. But the histological studies showed that combined treatment caused more cytotoxic effect than cadmium and lead alone. These results indicated that metal cations tested did have a direct inhibitory effect on metabolizing enzyme activities.