Effect of combined exposure to silica nanoparticles and cadmium chloride on female zebrafish ovaries

Silica nanoparticles (SiNPs) and cadmium chloride (CdCl₂) are two important environmental pollutants. In previous research, found that SiNPs in zebrafish larvae can amplify the cardiovascular damage caused by cadmium. Whether SiNPs in the ovaries can amplify the adverse effects of cadmium on the zebrafish ovaries is worth studying problem. In this study, sexually mature female zebrafish were used as model organisms and exposed to 1 μmol/L CdCl₂ and/or 25 μg/mL SiNPs for 30 days. The results showed that the structure and function of ovaries in the sole and combined exposure groups changed significantly, resulting in reduced ovarian quality, decreased number of mature oocytes, and the development of malformed offspring. A deep-sequencing analysis showed that organisms’ lipid metabolism and transportation, estrogen metabolism, and response to the maturation, meiosis, and vitellogenin synthesis of oocytes were significantly affected by single exposure or combined exposure. These findings provide further insights into the harm of cooperation of CdCl2 and/or SiNPs to the aquatic ecosystems.     

Neurotransmitter concentrations and binding at dopamine receptors in rats after maternal exposure to 3,4,3',4'-tetrachlorobiphenyl: the role of reduced thyroid hormone concentrations

Polychlorinated biphenyls (PCBs) are environmental contaminants, which accumulate in the food chain and are transferred to the offspring during prenatal development through the placenta and postnatally via breast milk. It is reported that PCBs exert effects on thyroid hormone levels and brain neurotransmitter levels. Both actions may alter neuronal development. The aim of the present study was to investigate, if PCB-induced effects on concentrations of catecholamines and serotonin can be attributed to PCB-induced reductions in thyroid hormone concentrations. In addition, binding to dopamine D(1) and D(2) receptors was examined. Time-mated Wistar rats were treated prenatally with 1 mg 3,4,3',4'-tetrachlorobiphenyl (PCB 77)/kg bodyweight or the vehicle. A third group serving as the positive control received perinatally 5 mg propylthiouracil (PTU)/l drinking water. There were no overt toxic signs in dams or offspring. Thyroid hormone measurements demonstrated effects in dams and offspring up to postnatal day 40. In particular, total T(4) in serum and in the thyroid were decreased in PCB- and PTU-treated dams and offspring. Only PTU exposed rats exhibited significantly increased concentrations of TSH in the serum and pituitary. Measurement of neurotransmitters revealed changes in the PCB-exposed offspring at PND 40, while PTU-treatment was without effect. Dopamine and DOPAC were increased in the medial prefrontal cortex. In adulthood, there were no PCB-related effects on thyroid hormones and neurotransmitters. Binding studies of dopamine D1 and D2 receptors demonstrated that PCB and PTU had no influence on receptor concentration and affinity. Comparison of PCB 77 exposed offspring to PTU exposed offspring demonstrated differential effects on TSH and neurotransmitter levels, the latter result indicating that not all PCB-induced effects on the nervous system can be ascribed to decreases in thyroid hormone concentrations.     

Increased spontaneous motor activity in offspring after maternal cadmium exposure during lactation

Lactating rats were exposed to 0, 5 or 25ppm cadmium as cadmium chloride in the drinking water. A battery of neurobehavioural tests was applied to the male offspring after weaning at 5 weeks until 4 months of age. The mean cadmium levels in exposed pup kidneys ranged from 0.006 to 0.030mg/kg wet weight at weaning, with the corresponding maternal kidney cadmium levels ranging from 4 to 13mg/kg wet weight. Significantly increased activity during the initial 20min of the spontaneous motor activity test was observed in the highest-dose group compared to the control group. The activity outcome was significantly positively correlated with cadmium levels in the pup kidneys. No cadmium-related changes in performance were observed in the Morris water maze, the E-shaped maze or the elevated plus-maze. The results indicate that neurobehavioural effects during development may be a more sensitive parameter for Cd toxicity than renal dysfunction.     

Decreased learning ability and low hippocampus glutamate in offspring rats exposed to fluoride and lead

Fluoride (F) and lead (Pb) are two common environmental pollutants which are linked to the lowered intelligence, especially for children. Glutamate, a major excitatory neurotransmitter in the central nervous system, plays an important role in the process of learning and memory. However, the impact of F and Pb alone or in combination on glutamate metabolism in brain is little known. The present study was conducted to assess the glutamate level and the activities of glutamate metabolism related enzymes including asparate aminotransferase (AST), alanine aminotransferase (ALT) and glutamic acid decarboxylase (GAD) in the hippocampus, as well as learning abilities of offspring rat pups at postnatal week 6, 8, 10 and 12 exposed to F and/or Pb. During lactation, the pups ingested F and/or Pb via the maternal milk, whose mothers were exposed to sodium fluoride (150 mg/L in drinking water) and/or lead acetate (300 mg/L in drinking water) from the day of delivery. After weaning at postnatal day 21, the pups were exposed to the same treatments as their mother. Results showed that the learning abilities and hippocampus glutamate levels were significantly decreased by F and Pb individually and the combined interaction of F and Pb. The activities of AST and ALT in treatment groups were significantly inhibited, while the activities of GAD were increased, especially in rats exposed to both F and Pb together. These findings suggested that alteration of hippocampus glutamate by F and/or Pb may in part reduce learning ability in rats.     

Neuroglial alterations in the zebrafish brain exposed to cadmium chloride

Cadmium is an extremely toxic heavy metal that widely occurs in industrial workplaces with various hazardous effects on brain functions. The cytotoxic effects of cadmium chloride (CdCl₂) on the neuroglial components of the zebrafish brain were analysed by detecting the glial fibrillary acidic protein (GFAP) expression and the mRNA levels of myelin genes mbp, mpz and plp1 in adult specimens exposed to cadmium for 2, 7 and 16 days. A significant decrease in the GFAP protein by Western blotting experiments was observed after 2 days of treatment, reaching 55% after 16 days. No change was observed in the mRNA levels. Using immunohistochemistry, a reduction in GFAP‐positive structures was revealed with a progressive trend in all the brains at 2, 7 and 16 days of treatment. In particular, a considerable reduction in GFAP‐positive fibres, with a different course, was observed in the ventricle areas and at the pial surface and in blood vessels after 16 days. Our experiments also showed a structural and chemical alteration of myelin and upregulation of mpz mRNA levels, the oligodendrocyte gene that is upregulated in experiments of neuronal injury, but not of plp1 and mbp mRNA levels, other myelin structural genes. These data confirm the toxic action of cadmium on the zebrafish brain. This action is time‐dependent and involves the glial cells, key components of the protection and function of nerve cells, hence the basis for many neurological diseases. Copyright © 2016 John Wiley & Sons, Ltd.     

Effect of maternal cadmium exposure on postnatal development and tissue cadmium,copper and zinc concentrations in rats

Administration of 60 ppm cadmium (Cd) in drinking water from the 1^st to the 20^th day of gestation to female rats did not affect the viability, body weight gain, food, and water consumption of offspring. The blood hemoglobin level was reduced in 2-week-old females and males but not in 16-week-old offspring. Hematocrit and serum glucose level were not affected at either age. Cadmium concentration in the intestinal wall was increased in both age groups, with marginal uptake in other organs. A decrease in copper (Cu) concentration was found in the brain of 2-week-old offspring of both sexes and of 16-week-old females. The brain zinc (Zn) concentration was decreased only in 16-week-old animals. The physical and neuromuscular development of offspring before weaning was not impaired by maternal Cd treatment. The alterations in Cu and Zn metabolism were associated with reduced locomotor activity and affected open-field behavior in adult offspring of either sex and with decreased avoidance acquisition in adult female offspring.The results obtained suggest a relationship between the reduced brain Cu and Zn levels and CNS dysfunction in adult offspring of female rats exposed to Cd during gestation.     

Sub-chronic exposure to noise affects locomotor activity and produces anxiogenic and depressive like behavior in rats

Noise is defined as a displeasing and unwanted sound. It is one of the most encountered stressor to which mankind is exposed. Frustration, poor reading, impaired hearing and difficulty in problem solving activities are the common consequences of noise stress. It has been reported to produce atrophy of dendrites and alterations in neurotransmitter levels. Long term exposure to inescapable noise stress induces exhaustion, defeat, annoyance followed by decreased muscle movement, social contacts and mood changes. The present study was aimed to investigate the detrimental effects of noise exposure on behavior of rats and its association with altered neurochemistry. Changes in neurotransmitter levels in different brain regions including hippocampus have been reported following noise exposure and these changes in neurotransmitters levels have also been associated with altered behavior. In the present study, locomotor activity in rats was assessed by open field test (OFT) while anxiety and depressive behavior was monitored by elevated plus maze (EPM) and tail suspension (TST) tests. The results showed that 15 days sub-chronic exposure to noise stress induced anxiety and depression like behavior in male rats. These behavioral deficits observed in the present study suggest that an altered brain serotonergic and dopaminergic activity may be involved in the various psychological disorders following exposure to noise stress.     

Neurobehavioral toxic effects of perinatal oral exposure to aluminum on the developmental motor reflexes, learning, memory and brain neurotransmitters of mice offspring

Aluminum (Al) is a known neurotoxicant and circumstantial evidence has linked this metal with several neurodegenerative disorders like Alzheimer's disease, but no causal relationship has yet been proved. Al-induced behavioral alterations as well as cognitive deficits and rodent brain neurotransmitter level, are well known in adults but the exact mechanism in the offspring of perinatally Al exposed dams is not yet understood properly and needs more attention. In the present study, the perinatal oral exposure of the dams to 300 and 600 mg/kg/day Al (aluminum chloride) resulted in significant and deleterious effects in the offspring inflicting a dose-dependent reduction in postnatal body weight gain, delays in opening of the eyes and appearance of body hair fuzz, and deficits in the sensory motor reflexes of the mice pups during weaning period (from the day of birth to postnatal day 21). During adolescent ages of the male offspring, a significant and dose-dependent deficit was also observed in their locomotor activity at postnatal day 22 (PD 22), learning capability (at PD 25), and cognitive behavior (at PD 30-36). Furthermore, a significant and dose-dependent disturbance in the levels of neurotransmitters like dopamine (DA) and serotonin (5-HT) was also observed in the forebrain region of the offspring at PD 7, PD 14, PD 21, PD 30, and PD 36. Thus, perinatal Al exposure, particularly during pregnancy and lactation period, can affect the in utero developing fetus and postnatal developing sucklings, raising the concerns that during a critical perinatal period of brain development, Al exposure has potential and long lasting neurotoxic hazards and might modify the properties of the dopaminergic system and thus can change the threshold of that system or other related systems at later ages. A reduced use of Al during pregnancy is of crucial importance in preventing Al-induced delayed neurotoxicity in the offspring.     

Plasticity in offspring contaminant tolerance traits: developmental cadmium exposure trumps parental effects

Parental effects are non-genotypic influences on offspring phenotype that occur via parental phenotypes or environments, while developmental plasticity is phenotypic variation that arises during development in response to environmental cues. We evaluated the relative contribution of these two sources of phenotypic variation on offspring toxicant tolerance in Physa pomilia snails exposed to cadmium. We exposed adult snails to 0, 2, or 20 μg/L cadmium for 7 days, then exposed egg masses collected from these adults to 0 or 2 μg/L cadmium in a factorial design (adult cadmium exposure × egg mass cadmium exposure). Starting at 2 days old, we recorded time to death for hatchlings exposed to 150 μg/L cadmium for 72 h at 8 h intervals. Juveniles hatched from cadmium-exposed egg masses displayed higher cadmium tolerance than juveniles from unexposed egg masses. Among juveniles from egg masses not exposed to cadmium, offspring of parents exposed to 20 μg/L cadmium had higher cadmium tolerance than offspring of parents exposed to 0 or 2 μg/L cadmium. Our results show that both parental effects and developmental plasticity can impact offspring toxicant tolerance and point to the potential importance of both processes in understanding how offspring respond to chemical contaminants. When both parents and offspring are exposed to a toxicant, our results showed that the effects of parental exposure on offspring toxicant tolerance may be eclipsed by the effects of offspring exposure during development.     

Post‐partum testosterone administration does not reverse the effects of perinatal exposure to cadmium on rat offspring development

This study investigated the effects of perinatal cadmium exposure on physical and reflexologic development of pup rats. It was examined if the immediate postpartum testosterone administration was able to reverse the toxic effects of the metal. Forty Wistar pregnant rats were divided into three groups: control and 10 and 20 mg kg^?1 per day of cadmium chloride. These dams were treated from gestational days 18 to 21, and until the 7th lactation day. Immediately after birth, half of the offspring from the experimental and control groups received 50 µL of testosterone 0.2% i.p. The maternal body weight gain, food and water consumption were measured during the treatment period. In pups, the body weight, body length, physical landmarks, reflex development and the general activity were assessed. Results showed that: only 20 mg kg^?1 cadmium induced maternal toxicity; pup body weight and body weight gain were reduced in all experimental groups; only the cadmium‐exposed offspring not treated with testosterone treatment showed a reduction in body length and body length gain; cadmium highest dose reduced the anogenital index in pups and delayed physical and reflexes development; and cadmium effects on the offspring, except in body length gain, were not reversed by testosterone. The results indicate that perinatal maternal exposure to cadmium promoted changes in the development of male rat offspring, reprogramming the pup's development. Testosterone administration was not able to reverse the cadmium effects, even on those parameters more directly related to the androgenic system as the testis descent and anogenital distance delays. Copyright © 2009 John Wiley & Sons, Ltd.     

Neurochemical effects in rats following gestational exposure to styrene.

Styrene was evaluated for the reproductive effects of pregnant rats and the neurochemical effects in the offspring of rats exposed during gestation. Pregnant Wistar rats were exposed to 0, 50, or 300 ppm styrene for 6 h/day during days 7 to 21 of gestation. No significant differences in the number of offspring delivered were observed between the exposed and control groups. Body weights at 1 day of age of the offspring whose mothers were exposed to styrene were significantly lower than those of the control group. Although, there were neither statistically significant differences of protein contents nor brain weights among styrene-exposed and their control offsprings of rats, analyses of neurotransmitter studies showed dose-dependent decreases of neuroamines, especially 5-HT (serotonin) and its metabolite 5HIAA (5-hydroxyindoleacetic acid) in the newborn offspring of styrene-exposed rats. The results suggest that gestational exposure to styrene at these concentrations does not produce apparent reproductive toxicity but affects the body weight of pups and causes lowering of the neurotransmitter levels in the brain.     

Brief embryonic cadmium exposure induces a stress response and cell death in the developing olfactory system followed by long-term olfactory deficits in juvenile zebrafish

The toxic effects of cadmium and other metals have been well established. A primary target of these metals is known to be the olfactory system, and fish exposed to a number of different waterborne metals display deficiencies in olfaction. Importantly, exposure over embryonic/larval development periods can cause deficits in chemosensory function in juvenile fish, but the specific cell types affected are unknown. We have previously characterized a transgenic zebrafish strain expressing the green fluorescent protein (eGFP) gene linked to the hsp70 gene promoter, and shown it to be a useful tool for examining cell-specific toxicity in living embryos and larvae. Here we show that the hsp70/eGFP transgene is strongly and specifically upregulated within the olfactory sensory neurons (OSNs) of transgenic zebrafish larvae following a brief 3-h exposure to water-borne cadmium. This molecular response was closely correlated to an endpoint for tissue damage within the olfactory placode, namely cell death. Furthermore, cadmium-induced olfactory cytotoxicity in zebrafish larvae gives rise to more permanent effects. Juvenile zebrafish briefly exposed to cadmium during early larval development display deficits in olfactory-dependent predator avoidance behaviors 4-6 weeks after a return to clean water. Lateral line neuromasts of exposed zebrafish larvae also activate both the endogenous hsp70 gene and the hsp70/eGFP transgene. The data reveal that even a very brief exposure period that gives rise to cell death within the developing olfactory placode results in long-term deficits in olfaction, and that hsp70/eGFP may serve as an effective indicator of sublethal cadmium exposure in sensory cells.     

Effects of prednisolone on behavior and hypothalamic–pituitary–interrenal axis activity in zebrafish

Prednisolone is a synthetic glucocorticoid used clinically for treating allergies, inflammation, and autoimmune diseases. Long-term prednisolone use has been shown to have negative effects on physiology and mood. We aimed to study the pharmacology and toxicology of glucocorticoid-like drugs by investigating behavioral and hypothalamic–pituitary–interrenal (HPI) axis effects in a zebrafish model. Zebrafish embryos 24 h post fertilization were exposed to 25 μM prednisolone. Their behavior was investigated 5 days post fertilization (dpf), and their HPI axis-related activity and related neurotransmitter levels were investigated 3, 4, 5, and 6 dpf. The behavior results showed that exposure to prednisolone resulted in decreased autonomic activity and low sensitivity to light. qRT-PCR and ELISA results showed decreased activity of the HPI axis and increased secretion of dopamine and serotonin after exposure to prednisolone. This study provides us with new insights into understanding the effects of glucocorticoids on the HPI axis.     

Cadmium-induced disturbances in lactating mammary glands of mice

Previous studies in various species have demonstrated that cadmium levels in milk are low and that cadmium is retained in the mammary glands of lactating rodents. The objective of the present study was to examine mammary glands following cadmium exposure during peak lactation. Mice were given 5 microg, 100 microg or 2000 microg cadmium/kg body weight subcutaneously on lactation days 8-10 and mammary glands were dissected on lactation day 11 for histology, quantitative gene expression and mineral analyses. Cadmium exposure induced morphological changes in the lactating mammary gland. A remodelling of the lactating mammary tissue including an increase in fat content, a less active feature of the mammary alveolar epithelial cells and more condensed appearance of the milk alveoli were observed. Although these changes were most prominent in the animals exposed to the highest cadmium dose similar morphological alterations were indicated at the two lower doses. A significant negative dose-response relationship between beta-casein gene expression and exposure of cadmium was demonstrated, while mRNA levels of alpha-lactalbumin were not affected by cadmium treatment. Furthermore, reduced levels of calcium in the mammary glands of the dams exposed to the highest cadmium dose and a positive correlation between calcium and beta-casein were demonstrated. No other differences were detected among the cadmium dose groups in mammary levels of calcium, zinc, iron or copper. In conclusion, our results indicate that cadmium disturbs the function of the lactating mammary gland, which consequently may impair the development of the suckling offspring.     

Effects of low-dose perinatal cadmium exposure on tissue zinc and copper concentrations in neonatal mice and on the reproductive development of female offspring

It has been suggested that the toxic effects of cadmium (Cd) are the result of interactions with essential metals, such as zinc (Zn) and copper (Cu). Previous studies have shown altered Zn and/or Cu levels in the tissues of rodents that drank water supplemented with >50 ppm Cd. To evaluate the effects of lower level Cd exposure on maternal and neonatal Zn and Cu levels and on the reproductive organs of female offspring, mice were exposed to 0, 1 and 10 ppm Cd in the drinking water from conception to 10 days after birth. The Cd concentrations in the brains of the offspring were higher in the exposed group than in the control group at birth. In the kidneys and livers, the Cd concentrations were higher in the Cd-exposed group 10 days after birth. At birth, increased Zn concentrations were observed in the kidneys and livers of the Cd-exposed offspring, although the Cd concentrations in these tissues did not differ between the exposed and non-exposed groups. The hepatic Cu concentrations of the exposed mice tended to be lower than those of the control mice at birth and were significantly lower 10 days after birth. In addition, Cd exposure tended to delay the timing of vaginal opening and perturbed the estrous cycles of the female offspring. These findings suggest that perinatal Cd exposure, even at low levels, affects the Zn and Cu concentrations of neonates and the reproductive functions of female offspring.     

Levels of transaminases, alkaline phosphatase, and protein in tissues of Clarias gariepienus fingerlings exposed to sublethal concentrations of cadmium chloride

The freshwater fish, Clarias gariepienus fingerlings, were exposed to sublethal concentrations (1.7 and 3.4 mg/L) of cadmium chloride for 12 days. Aspartate aminotransferase (AAT), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total protein levels were assayed in the gill, brain, and muscle of the fish at regular intervals of 6 and 12 days. The activities of AAT, ALT, and ALP of the treated fishes increased significantly in all the tissues compared with the control fish. Protein level in all the tissues showed a significant decrease in comparison to unexposed controls throughout the experimental periods. These results revealed that cadmium chloride effects the intermediary metabolism of C. gariepienus fingerlings and that the assayed enzymes can work as good biomarkers of contamination.     

Role of early GnRH administration in sexual behavior disorders of rat pups perinatally exposed to lead

The effects of maternal exposure to lead (Pb) during the perinatal (1% and 0.1% Pb) periods of sexual brain differentiation were studied in adult male offspring. Maternal Pb levels were measured after treatment. Behavioral (open field and sexual behavior), physical (sexual maturation, body and organ weights), and biochemical (testosterone levels and hypothalamic monoamine and respective metabolite levels) data were assessed in perinatally exposed offspring. The effects of gonadrotopin-releasing hormone (GnRH) administration to pups at birth on puberty and sexual behavior were also investigated in offspring postnatally exposed to the metal. Results showed that perinatal administration of the two Pb concentrations did not modify maternal weight gain; 1% Pb exposure reduced offspring body weight during the 7 days of treatment while no changes were observed after 0.1% Pb exposure; neither Pb concentration altered offspring sexual maturation; the higher Pb concentration improved sexual behavior while the 0.1% concentration reduced it; exposure to 0.1% Pb caused decrease in testis weight, an increase in seminal vesicle weight and no changes in plasma testosterone levels; hypothalamic VMA levels were increased compared to the control group; GnRH administration reversed the effects of 0.1% Pb administration on male sexual behavior. These results show that perinatal exposure to Pb had a dose-dependent effect on the sexual behavior of rats and that a decrease in GnRH source in the offspring was probably involved in the reduction of their sexual performance.     

Effects of Ipomoea carnea aqueous fraction intake by dams during pregnancy on the physical and neurobehavioral development of rat offspring

The effects of daily prenatal exposure to 0.0, 0.7, 3.0 and 15.0 mg/kg of the aqueous extract (AQE) of Ipomoea carnea dried leaves on gestational days 5-21 were studied in rat pups and adult offspring. The physical and reflex developmental parameters, open-field, plus-maze, social interaction, forced swimming, catalepsy and stereotyped behaviors, as well as striatal, cortical and hypothalamic monoamine levels (at 140 days of age) were measured. Maternal and offspring body weights were unaffected by exposure to the different doses of the AQE. High postnatal mortality, smaller size at Day 1 of life, reversible hyperflexion of the carpal joints and delay in the opening of both ears and in negative geotaxis were observed in the offspring exposed to the higher dose of AQE. At 60 and 90 days of age, open-field locomotion frequency was quite different between 0.0 and animals treated with 0.7 and 3.0 mg/kg AQE. No changes were observed in the plus-maze, social interaction, forced swimming, catalepsy, stereotyped behavior and central nervous system monoamines concentrations. Dams treated with the higher AQE dose showed severe cytoplasmic vacuolation in liver, kidney, pancreas and thyroid tissues, in contrast to the mild vacuolation observed in the other experimental groups. No alterations were observed in the histopathological study of the offspring of all experimental groups at 140 days of age. During adulthood, behavior was not modified in offspring exposed to the higher dose of AQE as well as no changes occurred in central nervous system neurotransmitters. The present data show that the offspring development alterations were not severe enough to produce behavioral and central monoamine level changes.     

Comparison of the toxicity of inorganic and liver-incorporated cadmium: a 4-wk feeding study in rats

The toxicity of cadmium was examined in rats fed diets containing either tissue-incorporated cadmium or cadmium salt for 4 wk. The test diets contained 30 mg cadmium/kg either as cadmium chloride, or as cadmium incorporated in pigs' livers; the control group was fed a diet containing liver from a pig not treated with cadmium. Over 90% of the cadmium present in the pigs' livers was bound to metallothionein. Analysis of the diet and determination of the food consumption revealed that both cadmium-fed groups were exposed to similar dietary cadmium levels. There was no adverse effect on general health or survival. Feeding cadmium resulted in growth retardation and slightly decreased water intake. Moreover, both cadmium-treated groups showed clear signs of anaemia and increased plasma aspartate and alanine aminotransferase activities. For the group fed cadmium chloride, all of these effects were more pronounced than for the group fed cadmium incorporated in liver. Microscopic examination of the liver and kidneys, however, did not reveal any lesion that could be attributed to the cadmium treatment. After exposure to cadmium the spleen showed decreased extramedullary haematopoiesis, an effect that was also more pronounced after feeding of the cadmium chloride than after feeding liver-incorporated cadmium. The differences in the extent of the toxic effects between the inorganic and the tissue-incorporated cadmium were accompanied by differences in the cadmium concentrations in liver and kidneys: the feeding of cadmium incorporated in pigs' livers resulted in about half the accumulation of cadmium in the rats' livers that took place after intake of a diet containing cadmium chloride. In contrast a much less marked difference in cadmium accumulation was observed in the kidneys. Since humans are usually exposed to tissue-incorporated cadmium these findings deserve further investigation, with special attention to the observed difference in tissue accumulation.