In order to make a tentative recommendation for the maximum acceptable daily intake of selenium, relevant data were compiled from the available literature. Normal daily intake of selenium from foods was estimated as about 100 mug, half of which comes from fish and shellfish (in an average adult Japanese). Intake of selenium from other sources was negligible. The amount of selenium excreted in the urine was found to be compatible with the estimated value of the daily oral intake. The range of the margin of safety was then estimated as 10 to 200 times the normal level on the basis of human and animal toxicity data. The variation of dietary selenium intake in the general population is discussed, leading to the conclusion that the consumers of large amounts of fish may ingest as much as 500 mug daily. Consequently, a value of 500 mug is proposed as the tentative maximum acceptable daily intake of selenium for the protection of human health.
Chromosome analysis has been performed on workers from a cadmium plant who were exposed to fumes and dust of cadmium and lead. The 35 workers were classified, according to the type and duration of exposure, into a group (cadmium service) exposed to high levels of lead and cadmium in the absence of zinc (23 people) and a group of rolling-mill workers subjected mostly to zinc but also to lower levels of lead and cadmium (12 people). A higher yield of severe chromosome anomalies (chromatid exchange, disturbance of spiralization, chromosome translocation, ring and dicentric chromosomes) together with a total lower number of structural aberrations was observed in the cadmium workers when compared with the rolling-mill group.
The hexachlorobenzene (HCB) and porphyrin accumulation in the ograns of 18-day-old Wistar rats, whose mothers were fed a diet containing 80 ppm HCB, were studied. Among the organs examined, the highest HCB residue was in the liver larger than kidney larger than or equal to lung larger than brain larger than spleen larger than heart. The porphyrin level in the liver of the HCB-treated. On the contrary, the weights of the kidney, brain, spleen and heart were significantly reduced. Sex did not influence the organ weight except that of the brain. The results suggested that accumulation of HCB in different organs and porphyrin in the liver of suckling Wistar rats was about equal for the males and females.
Absorption of radioactive lead (210Pb) was studied in an intestinal preparation from adult and young rats. Absorption was higher in the jejunal parts than in the duodenum or colon. Moreover, absorption in young rats was greater than in adults. No difference in absorption was found after loading with large amounts of lead. Maintaining the animals on a low calcium diet decreased rather than increased lead absorption.
Rainbow trout (Salmo gairdneri) were exposed to IMOL S-140, a synthetic high-temperature lubricating oil composed of tri-aryl phosphates and, although no sign of acute toxicity was evident, the fish slowly developed symptoms of chronic posioning. Thus, floating food pellets were refused, the activities of glutamic oxalacetic transaminase and lactate dehydrogenase in serum were greatly elevated, and internal fatty tissues became discoloured. Neither serum nor brain cholinesterase activities were inhibited.
Temefos and six of its metabolites were tested for their capacity to inhibit the in vitro activity of brain acetylcholinesterase (AChE) of Fundulus heteroclitus. While temefos was not inhibitory at levels up to 10.7 mM in brain homogenate samples, its metabolites were active within the range of 2 X 10(-4)mM to 1.26 mM in causing a 50% reduction in the enzyme activity. Exposure of F. heteroclitus to temefos under laboratory conditions caused a reduction in AChE activity, which was proportional to the pesticide concentration and the exposure period. Visible symptoms of organophosphate poisoning were apparent only after the AChE inhibition reached 80%. F. heteroclitus and Cyprinidon variegatus exposed to 10 biweekly applications of temefos granules in the field showed no inhibition of brain AChE. However, exposure of F. heteroclitus to biweekly applications (four) of temefos emulsion caused a reduction in the enzyme (50%), but only in the pre-third application samples. A gradual increase in brain AChE occurred both in F. heteroclitus and C. variegatus as the season progressed from April to October.
Reproduction was studied in SWV female mice that had raised one litter and then received either 0.2.5,5,10,15,20 or 25 parts/10(6) dietary dieldrin (n = 18 or 19 per group). Exposure began 4 weeks prior to the second mating and continued until day 28 postpartum (weaning). Fertile males were caged with the females during weeks 5-6 of exposure. Significantly mortality of the females occurred only at 20 and 25 parts/10(6) (89% and 56%, respectively) and all deaths occurred before parturition. Dieldrin did not affect behavioural oestrus. At 10 and 15 parts/10(6), 18% of the bred females did not become pregnant; all animals at lower doses and all survivors at higher doses were fertile. The gestation period was not affected. At 25 parts/10(6), the litter size was decreased by 17% over the control size (13.2 pups). The infertility and reduced fecundity resulted from a lesion(s) preceding implantation. Thus, in a separate experiment, 15 parts/10(6) increased the number of bred females that had no implantation sites 5 days post coitum while 25 parts/10(6) decreased the number of sites per pregnant female. As expected from the original dose-responses for infertility and decreased litter size, the converse effects did not occur. Pre-weaning mortality of all the pups occurred in 31%, 47%, 80% and 100% of the litters at 0,2.5,5, and larger than or equal to parts/10(6), respectively. Within the litters raised at 2.5 and 5 parts/10(6), the pup survival was not different from the controls (75%). Thus, in this strain, litter -oss is dieldrin's most important reproductive effect and it correlated with a dieldrin-induced maternal hepatomegaly. The birth weight of pups in litters that were lost was reduced by 3-13% and pre-death growth was reduced or absent. Pup-killing and pup-neglect were important proximate causes of mortality, but only at doses larger than or equal to 15 parts/10(6).
Japanese quail were maintained on synthetic diets containing 15% corn oil, 15% tallow, and zero fat, and were later exposed at 3.5 degrees C for 21 days. A distinct influence of dietary fat composition upon the adipose tissue triglyceride fatty acid composition was detected, but no change in fatty acid composition was produced with cold exposure. The fatty acid composition of adipose tissue from quail acclimatized to winter temperatures showed no trend towards a greater degree of unsaturation. There was no evidence of a gross selective mobilization of certain fatty acids from the depot lipids. Regional variation in the fatty acid composition of avian fats is discussed with respect to the level of food intake and body temperature.
Rats that swam for 3 h showed a 6-fold increase in serum creatine phosphokinase (SCPK) activity which declined to control values within 7 h after swimming. Of the excess SCPK, 77% was BB isoenzyme; the remainder was mainly MM with traces of MB. Kidney, liver, brain and lung contain mainly BB (50-80%) and only a trace of MB (0-7%). Heart CPK was composed of little BB (8%) and more MB (28%) and MM (64%). Skeletal muscle CPK was almost entirely MM. CPK activity is highest in skeletal muscle, intermediate in heart and brain and lowest in kidney, liver and lung. It is suggested that skeletal muscle and heart are not involved in CPK release in swimming, and kidney, liver and brain may be sites of release.
Mice were given cadmium chloride orally for 18 weeks, after which they were given two subcutaneous injections of cadmium chloride. Cadmium-and zinc-containing proteins were obtained from livers by ultracentrifugation, Sephadex chromatography and isoelectric focusing. Metallothionein with apI of 4.2 at 8 degrees C was separated from other proteins (possibly including other forms of metallothionein) by the isoelectric procedure. The metallothionein with pI = 4.2 had a high E250, reflecting abundant Cd-SH bonds, in accord with amino acid analysis, which gave a cysteine content of 34.6 residues % and showed an absence of aromatic amino acids. These results indicated a very high purity of the form of metallothionein isolated after isoelectric focusing.
Free amino acid composition of brain and kidney of guinea-pig showed significant decrease after repeated exposure of skin to P-P1 DDT. Gamma amino butyric acid of the brain and proline, tyrosine and valine of kidney disappeared completely. The remaining amino acids showed a marked depletion.
The Cd-binding capacity of soluble proteins in 10 tissues of normal rats not excessively exposed to heavy metals was measured by saturation of freshly isolated cytosol with 109CdCl2 in vitro followed by Sephadex G-75 chromatography. The Cd-binding capacity of a 10,000 molecular weight Cd-binding peak (10,000 MW Cd-BP), which had a high affinity for Cd and was probably metallothionein, was the highest in kidney (78nmol Cd/g fresh tissue), followed by testis (63 nmol/g), liver (38 nmol/g) and then by brain (14 nmol/g). The amount of the Cd-BP in these tissues (assuming that it was metallothionein and bound 9 mol Cd/10,000g) was calculated to be 87, 70, 42 and 16 mg/kg fresh tissue in kidney, testis, liver and brain, respectively, or in the order of 10(-5) to 10(-6) mol/kg tissue. A significant amount of the 10,000 MW Cd-BP was also found in small intestine. It was present in rather small amounts in heart and lung, and possibly in spleen and skeletal muscle as well. In contrast, the protein was not detectable by this technique in plasma. The results suggest that metallothionein is a rather ubiquitous, intracellular protein in tissues of normal animals and may have other biological functions, besides its possible fortuitous role in heavy metal detoxification. A 30,000 molecular weight Cd-binding peak (30,000 MW Cd-BP) having a very high affinity Cd, apparently higher than that of the 10,000 MW Cd-BP, was found only in testes, among the 10 tissues examined. Its estimated Cd-binding capacity was 51 nmol Cd/g of testis, slightly less than that of metallothionein in testis. These findings support the hypothesis that the 30,000 MW Cd-BP is a plausible target of Cd in Cd-induced testicular injury, and suggest a basis for the peculiar sensitivity of the rat testis to Cd.
Tissue from a harp seal given methyl mercury at a concentration of 0.25 mg/kg in its diet for 61 days, was highly contaminated with mercury. Over 70% of the mercury in the seal's liver (64.0 p.p.m.) was in the inorganic form indicating a demethylating system in this organ. Most of the mercury in the liver, spleen and kidney of an untreated seal was also in the inorganic form. In contrast, over 75% of the mercury in the adrenals and gonads (14.2 and 13.0 p.p.m., respectively) of the treated seal was methyl mercury. Mercury was not detectable in the gonads and not analyzed in the adrenals of the untreated seal. Biosynthesized (in vitro) cortisol, corticosterone, cortisone, and 11-ketotestosterone were isolated and identified from the adrenal incubations, and delta4-androstene-3,17-dione and testosterone were isolated and identified from ovarian incubations from both untreated and methyl mercury (in vivo) treated seals. The ovaries and adrenals from both seals appeared to be normal under the light microscope. The ovaries from both seals were in the same follicular phase, but in vitro incubations of tissue from these organs indicated that the methyl mercury and treatment caused a marked alteration of steroid biosynthesis in tissue from the treated seal. The altered pattern of steroid biosynthesis was also demonstrated by autoradiography, and it is suggested that this technique could be used as an indicator of incipient contamination by a pollutant.
Plasma FSH and LH levels were examined in female rats reared in the dark at different ages from birth until sexual maturation to investigate whether, and to what extent, external factors such as light, influence gonadotropin levels during development. Control animals were raised in diurnal lighting consisting of 12 hours of light and 12 hours of dark. Light deprivation did not eliminate the characteristic peak of gonadotropins seen in early postnatal development but significantly increased levels of FSH and slightly decreased levels of LH (except for a transient rise at day 12). Constant darkness tended to lower whole body, ovarian and pituitary weights but to increase pineal weight. Whereas the time of eye-opening was the same in control and light-deprived animals, puberty (as judged by vaginal opening and first ovulation) was delayed in animals raised in the dark. The data suggest that environmental light has a mediating action on patterns of gonadotropin release, particularly on FSH, during prepuberal development.
Monosodium L-glutamate (MSG), a commonly used food additive, induces convulsive disorders in rats. A reversible change in the cerebrovascular permeability of plasma proteins occurs during convulsions induced by the intraperitoneal administration of 4.0 g/kg of MSG to the neonatal rat. During MSG-induced seizures, but not before or after, trypan blue dye enters into the brain tissues, whereas no dye penetration occurs in control rats receiving saline. The frequency of the incidence of MSG-induced convulsions is inversely proportional to the age of the animal. It decreases with the age of the rat. By 42 days of age no substantial seizure activity of dye penetration into the brain tissue occurs in MSG-treated rats. Histological examination indicates that seizure activity is not correlated with characteristic periventricular-arcuate area lesions known to be induced in neonates by parenteral MSG administration. No hypothalamic damage was observed in MSG-treated rats older than 10 days of age.
The effect of different combinations of aflatoxin B1, alpha-amanitin and actinomycin-D on the incorporation of orotic acid-6-14C into RNA was investigated using rat liver slices. The results support the view that the mode of action of aflatoxin B1 and alpha-amanitin are similar in some respects, and that aflatoxin B1 and actinomycin-D act according to different mechanisms. Evidence was also obtained about the formation of an active metabolite of aflatoxin B1 in this system.
Fish under abnormal environmental conditions suffer from retarded growth and other physiological dysfunctions related to thyroxine deficiency. In teleosts lacking a definite thyroid gland the kidney plays a very important role in biosynthesis of the thyroidal hormone, in which peroxidase has an indirect action. Effects of some industrial pollutants and factory effluents on fish kidney peroxidase activity were recorded in Ophicephalus punctatus and Clarias batrachus. At concentrations of the pollutants at which 70-100% of the fish survive the exposure, peroxidase activity was greatly inhibited, indicating that even sub-lethal doses of toxicants may cause drastic changes in the physiological systems. The peroxidase activity increased well above the control levels at 5-h and 27-h exposures in some cases, but declined towards the end of the test.
