Patterns, trends, and toxicological significance of chlorinated hydrocarbon and mercury contaminants in bald eagle eggs from the Pacific coast of Canada, 1990-1994

Bald eagle (Haliaeetus leucocephalus) eggs were collected during incubation, 1990-1992, from 16 nests near three bleached-kraft pulp mills, from six nests in the Fraser River estuary and from seven nests at a reference site on the Pacific coast of Canada. Polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) were present in all eggs in a qualitatively similar pattern among sites. Mean concentrations of 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD) were significantly higher in eggs collected from near three kraft pulp mill sites in the Strait of Georgia (44, 45, 84 ng/kg) than from the reference area in Johnstone Strait (15 ng/kg). There were few differences among sites in mean organochlorine pesticide levels, indicating the diffuse distribution of those chemicals and the domination of atmospheric inputs. Mean concentrations of total polychlorinated biphenyls (PCBs) were highest in eggs from the Strait of Georgia (4.86 mg/kg) and the PCB congener pattern was significantly different between that area and both the lower Fraser valley and Johnstone Strait. Mean mercury concentrations, which were mainly methyl-mercury, were significantly higher in eggs collected from the lower Fraser Valley (0.258 mg/kg) and Johnstone Strait (0.294 mg/kg) compared to the Strait of Georgia (0.188 mg/kg). Individual and regional variation in concentrations of organochlorine pesticides, PCBs and mercury in eagle eggs were thought to be influenced mainly by dietary differences. Toxicologically, in 1990, mean TCDD-toxic equivalents (TEQs) in bald eagle eggs were about two-fold greater than a lowest-observed-effect level, suggested elsewhere for this species, of 210 ng/kg TEQs. In the Strait of Georgia, PCCDs and PCDFs made a greater contribution to TEQs than non-ortho and mono-ortho PCBs, whereas the reverse was true for eggs outside the strait. Mean eggshell thickness was less than the pre-1947 value at all sites, although there was no significant relationship between eggshell thickness and DDE concentrations. Levels of other organochlorine pesticides and mercury were below those considered to be toxic.     

Mercury in alligators (Alligator mississippiensis) in the southeastern United States

Mercury methylation may be enhanced in wetlands and humic-rich, blackwater systems that crocodiles and alligators typically inhabit. Given their high trophic level and long life-spans, crocodilians could accumulate significant burdens of Hg. Our objectives were to survey Hg concentrations in alligators from several areas in the southeastern United States to test their utility as sentinels of Hg contamination, to examine relationships among Hg concentrations in various tissues and to look for any differences in tissue Hg concentrations among locations. We measured total Hg concentrations in alligators collected in the Florida Everglades (n = 18), the Okefenokee National Wildlife Refuge, Georgia (n = 9), the Savannah River Site (SRS), South Carolina (n = 49) and various locations in central Florida (n = 21), sampling tissues including blood, brain, liver, kidney, muscle, bone, fat, spleen, claws and dermal scutes. Alligators from the Everglades were mostly juvenile, but Hg concentrations in tissues were high (means: liver 41.0, kidney 36.4, muscle 5.6 mg Hg/kg dry wt.). Concentrations in alligators from other locations in Florida were lower (means: liver 14.6, kidney 12.6, muscle 1.8 mg Hg/kg dry wt.), although they tended to be larger adults. Alligators from the Okefenokee were smallest and had the lowest Hg concentrations (means: liver 4.3, kidney 4.8, muscle 0.8 mg Hg/kg dry wt.). SRS alligators had the greatest size range and intermediate Hg levels (means: liver 14.9, muscle 4.8 mg Hg/kg dry wt.). At some locations, alligator length was correlated with Hg concentrations in some internal organs. However, at three of the four locations, muscle Hg was not related to length. Tissue Hg concentrations were correlated at most locations however, claw or dermal scute Hg explained less than 74% of the variation of Hg in muscle or organs, suggesting readily-obtained tissues, such as scutes or claws, have limited value for non-destructive screening of Hg in alligator populations.     

Overview and regional and temporal differences of heavy metals in Arctic whales and ringed seals in the Canadian Arctic

Concentrations of mercury, cadmium, and other heavy metals in tissues of belugas (Delphinapterus leucas), narwhal (Monodon monoceros) and ringed seals (Phoca hispida) from across the Canadian Arctic are reported. Published and new information is used to provide an overview of metals in tissues of these animals, to delineate the existence of a spatial trend of mercury and cadmium in belugas and ringed seals, and to show a temporal trend is superimposed on the geochemical trend. Mercury concentrations in tissues of Arctic whales and ringed seals were high relative to the Canadian guideline of 0.5 micrograms/g wet wt., for mercury in fish, except in the skin of belugas (0.59-0.78 micrograms/g wet wt.) and flesh of ringed seals (0.39-0.41 micrograms/g wet wt.). In the flesh of belugas (0.94-1.34 micrograms/g wet wt.), and in the liver of ringed seals, tissues that are also consumed by Native people in the Arctic (8.34-27.5 micrograms/g wet wt.), the guideline value was significantly exceeded. Mean lead concentrations in tissues of belugas, narwhal and ringed seals were generally low (0.002-0.028 micrograms/g wet wt.), except in tissues of belugas in the St. Lawrence River (0.10-0.15 micrograms/g wet wt.). The concentration of zinc in the skin of whales was two to three times higher than in other tissues. The concentration of cadmium in organs was highest in narwhal. There was a positive correlation between mercury and selenium in the liver of all three species. The concentration of mercury in tissues of belugas and ringed seals was higher in the western than the eastern Arctic. This was attributed to different natural background concentrations in the western and eastern Arctic of Canada dictated by different geological formations in the two regions. Cadmium concentrations in tissues of belugas and ringed seals were higher in the eastern than the western Arctic. Zinc and copper in some tissues of belugas and ringed seals were also higher in the eastern than the western Arctic. Mercury in the liver of belugas was found to have increased in the western and eastern Arctic over 10-12 years. Mercury in the liver of ringed seals in the western Arctic and narwhal in the eastern Arctic showed similar increases. In recently collected belugas, the rate of accumulation of mercury in the liver was approximately twice that in belugas collected 10-12 years ago. In ringed seals, the rate was three times higher in recent samples compared to 15-20 years ago. There was no temporal change in cadmium levels in tissues of belugas, ringed seals or narwhal.     

Decline in PCB levels in otters (Lutra lutra)

A decline in total PCB levels in tissues of otters (Lutra lutra) from England and Wales, averaging 8% per year over the period 1983-1992, is reported. Mean PCB levels are now unlikely to pose a threat to otter populations.     

Pharmacokinetics of ceftiofur and metabolites after single intravenous and intramuscular administration and multiple intramuscular administrations of ceftiofur sodium to dairy goats

Twelve (12) lactating dairy goats (46-71 kg body wt at study initiation) were divided into four treatment groups and dosed with ceftiofur sodium at 1.1 mg ceftiofur free acid equivalents (CFAE)/kg or 2.2 CFAE/kg using a complete two route (intravenous, i.v.; intramuscular, i.m.), two-period crossover design, with a 2-week washout between injections. After another 2-week washout period, the goats were dosed with ceftiofur sodium i.m. for 5 consecutive days at either 1.1 or 2.2 mg CFAE/kg. The goats from the 2.2 mg/kg multiple dose group were dried off and the i.v. kinetic study repeated. After all injections, blood samples were obtained serially for determination of combined serum concentrations of ceftiofur and metabolites. After intravenous doses of 1.1 and 2.2 mg/kg, the harmonic means of the terminal phase half-lives were 171.8 and 233 min, respectively, for lactating does. The harmonic mean of the terminal phase half-life after an i.v. dose of 2.2 mg/kg in non-lactating does was 254 min. The AUC0-infinity was significantly less and the clearance significantly greater during lactation. After i.m. doses of 1.1 and 2.2 mg/kg, the harmonic mean terminal phase half-lives were 163 and 156 min, respectively. The i.m. bioavailability of ceftiofur sodium in goats was 100%, and the AUC0-infinity was dose-proportional from 1.1-2.2 mg CFAE/kg body weight. After five daily i.m. doses of ceftiofur sodium at either 1.1 or 2.2 mg CFAE, there was minimal accumulation of drug in serum as assessed by Cmax, and serum concentrations were dose-proportional after the multiple dosing regimen.     

Further observations on the anatomy of the ulnar nerve at the wrist

The mercury content of various parts of single fruit-bodies of the Yellow Bolete Boletus edulis (n = 26), the Field-Mushroom Agaricus campester (n = 23) and of Agaricus silvicola (n = 17) was determined by flameless atomic absorption spectroscopy. In each species the lowest mercury content was found in the stem (x = 1,96--3,21 mg/kg dry wt.), whereas the caps contained significantly more mercury (x = 4,19--6,97 mg/kg dry wt.). The highest mercury content was found in the gills and tubes (x = 4,85--8,77 mg/kg dry wt.), which contained significantly more mercury then the flesh of the caps (x = 3,11--5,60 mg/kg dry wt.). Young mushrooms seemed to contain more mercury then older ones.     

Some pharmacodynamic and biochemical aspects of cefamandole

The pharmacodynamic and nephrotoxic effects of cefamandole were investigated. Cefamandole at concentrations of 512 and 1024 micrograms/ml bath caused complete relaxation in isolated guinea pig ileum and rabbit duodenum, respectively. Concentrations of 2048 and 4096 micrograms cefamandole/ml bath caused marked stimulation in force and frequency of rat uterine muscle in all stages of sex cycle. Cefamandole in all tested concentrations did not induce any response on isolated guinea pig tracheal chain or isolated rabbit aortic strip. Cefamandole in concentrations of 256 to 1024 micrograms/ml bath as well as 256 and 512 micrograms/ml cannula produced marked inhibition on isolated guinea pig auricles and rabbit heart, respectively. The effect of graded increased concentrations on isolated frog gastrocnemius muscle, frog rectus abdominis muscle and rat phrenic nerve hemidiaphragm was recorded. Cefamandole in a dose of 53.2 mg/kg b. wt. in anaesthetized dogs caused very marked hypotensive effects and decrease in rate of respiration. Single intramuscular injection of cefamandole in a therapeutic (23.3 mg/kg b. wt.) and double therapeutic (46.6 mg/kg.b. wt.) doses in rabbits had no effect on electrocardiographic parameters among a period of 8 hours after injection. Effects of cefamandole on serum and urine concentrations of creatinine, urea, sodium, potassium, calcium, glucose and protein as well as clearance tests were investigated in rats.     

Systemic autoimmunity due to mercury vapor exposure in genetically susceptible mice: dose-response studies

Six groups of genetically mercury-susceptible female SJL/N (H-2s) mice were exposed to mercury vapor at a concentration of 0.3-1.0 mg Hg/m3 air for 0.5-19 hr/day 5 days a week for 10 weeks. The absorbed doses were calculated to be between 75 and 2365 micrograms Hg/week/kg body wt (micrograms Hg/week/kg). The correlation between the dose and the concentration of Hg in kidney, spleen, and thymus was highly significant (p < 0.0001; Spearman's rank correlation test). The lowest observed adverse effect level (LOAEL) for serum IgG antinucleolar antibodies (ANoA) was 170 micrograms Hg/week/kg, corresponding to a renal mercury concentration of 4.0 +/- 0.76 micrograms Hg/g wet wt. The correlation between the absorbed dose and the ANoA titer was highly significant (p < 0.0001; Spearman's rank correlation test), and all mice were ANoA-positive at a dose of 480 micrograms Hg/week/kg. High-titer ANoA targeted the nucleolar 34-kDa protein fibrillarin. The LOAEL for B-cell stimulation, measured as an increase in serum IgG2a and IgG1 concentrations, was 360 micrograms Hg/week/kg, but the increase was fivefold higher and also included IgE at a dose of 690 and 2365 micrograms Hg/week/kg. The serum Ig concentrations peaked after 2-4 weeks and then slowly declined but, except for IgE, remained significantly increased during the entire exposure time. Glomerular, mesangial IgG immune complex (IC) deposits, accompanied by systemic vessel wall IC deposits, were first detected at a dose of 480 micrograms Hg/week/kg. The mesangium also showed increased titers of IgM IC deposits and complement factor C3c. The correlation between the absorbed dose, and the individual titer of IgG, IgM, and C3c, was highly significant (p < 0.0001; Spearman's rank correlation test). In conclusion, mercury vapor efficiently induced an autoimmune syndrome in genetically susceptible mice, and the LOAEL for the adverse effects varied in the order ANoA < B-cell stimulation < IC deposits. Comparing the body burden of mercury in mice at the LOAEL for autoantibodies with the body burden in populations of occupationally exposed humans suggests that the safety margin may be narrow for genetically susceptible individuals.     

湖南省磷肥中重金属含量及形态特征

对湖南省现有磷肥生产企业磷肥生产原料和产品进行采样,并按《肥料中砷、镉、铅、铬、汞生态指标》（GB/T 23349-2009）对重金属进行污染指数评价,结果表明:普通过磷酸钙中砷、铬、铅、镉、汞平均含量分别为26.78 mg/kg、18.86 mg/kg、18.51 mg/kg、1.55 mg/kg、1.27 mg/kg.钙镁磷肥中铬、铅、砷、镉、汞平均含量分别为798.39 mg/kg、9.78 mg/kg、6.31 mg/kg、0.67 mg/kg、0.11 mg/kg.绝大部分磷肥产品中砷、镉、铅、铬、汞均未超标.过磷酸钙产品中铅、镉、砷、铬的来源主要为磷矿,汞的来源主要为硫酸;钙镁磷肥产品中铅、镉、汞、砷、铬的来源主要为磷矿.在酸性条件下,磷肥中的镉对农产品安全具有潜在风险.      

An examination of spatial variation in mercury concentrations in otter (Lutra canadensis) in south-central Ontario

Hair samples were collected from otter (Lutra canadensis) trapped in several parts of south-central Ontario, Canada. The concentrations of total Hg in hair were compared with methyl mercury concentrations in liver tissues from the same individuals to determine if hair is a suitable monitoring tissue. Hg in the two tissues was significantly correlated. Hair was used to monitor Hg in 51 individuals from four townships. The concentrations of total Hg in hair ranged from 4 to 20 micrograms/g. No significant variation among the four sample regions existed. Generally the highest concentrations were found in the youngest members of the population. Some possible explanations for the observations are presented.     

Physical map of the Clostridium difficile chromosome

The present study was designed to investigate the effect of mercuric chloride administration on copper, zinc, and iron concentrations in the liver, kidney, lung, heart, spleen, and muscle of rats. The results showed that after dose and time exposure to mercuric chloride, the concentration of mercury in the six tissues was significantly elevated. Data showed that there were no interaction between mercury and tissue iron. There was a considerable elevation of the content of copper in the kidney and liver. The most significant changes in the copper concentration took place in the kidneys. About a twofold increase in the copper content of the kidney was noted after exposure to mercuric chloride (3 mg and 5 mg/kg). Only slight elevations in the copper content occurred in the liver especially in high dose and longer exposure time. In the remaining organs, the copper content was not changed significantly (p > 0.05). The most significant changes in the zinc concentration took place in liver, kidney, lung and heart (5 mg/kg). Marked changes in kidney zinc concentrations were observed at any of the specified doses. Zinc concentrations were significantly increased in kidney of rats sacrificed 9-48 h after s.c. injection of HgCl2 (5 mg/kg); in liver obtained from rats at 18, 24 or 48 h after injection; and in lung after 24 or 48 h of treatment. The heart and spleen zinc concentrations were elevated at 24 and 48 h after injection of HgCl2 (5 mg/kg), respectively. The results of this study implicate that effects on copper and zinc concentrations of the target tissues of mercury may play an important role in the pathogenesis of acute mercuric chloride intoxication.     

Postnatal changes in size and actomyosin content of rabbit gastric myocytes

Maximal tension generated by gastric muscle is three to four times greater in weanlings than in newborn rabbits. To determine if this functional maturation is accompanied by structural changes, we compared length-tension relationships, myocyte number and size, and actomyosin content in muscle from the gastric body of newborn (1 day) and weanling (12 weeks) rabbits. Passive tension at optimal length (Lo) was six times greater in circular smooth muscle strips from weanling rabbits than from newborn rabbits. Active tension at Lo in weanling rabbits was three times greater than in newborn rabbits. For morphometry, muscle cross-sections stretched to Lo in the circular axis were photographed with electron microscopy (5300x). Cell number/unit area was counted in circular muscle layers from newborns and weanlings. Cross-sectional area of each cell was measured by computerized planimetry. There were 2.5 times more cells per unit area in newborn than in weanling tissue, P < 0.001. However, the mean cell area in newborns (5.4 +/- 4.6 microns2) was less than that in weanlings (13.5 +/- 11.7 microns2). Consequently, the muscle cells occupied similar total areas in newborns and weanlings. We measured actin and myosin heavy chain in full-thickness muscle homogenates using SDS gel electrophoresis and densitometric scanning. Actin and myosin concentrations were lower in newborns (9.6 +/- 1.3 micrograms g-1 wet weight and 5.6 +/- 0.7 micrograms g-1 wet wt, respectively) than in weanlings (17.7 +/- 3.0 micrograms g-1 wet wt and 8.2 +/- 1.6 micrograms g-1 wet wt respectively), each P < 0.01. The proportion of myosin heavy chain isozymes did not change with age. We conclude that there are postnatal increases in cell size and the quantity of actin and myosin in rabbit gastric muscle. The increase in quantity of contractile protein may be in part responsible for age-dependent increases in maximal tension.     

A randomized study comparing retroperitoneal drainage with no drainage after lymphadenectomy in gynecologic malignancies

Drug-nutrient interactions affecting chromium were investigated in this study. Rats were injected with indomethacin to reduce endogenous prostaglandin synthesis and dosed with prostaglandin analogues or prostacyclin. Effects on absorption, tissue distribution and urinary excretion of 51Cr from 51CrCl3 were evaluated using a 2 x 4 factorial experimental design. Forty-eight adult male rats were food deprived for 12 h and then injected intraperitoneally with indomethacin (5 mg/kg body wt) or placebo. Thirty minutes later, rats were intubated and dosed with one of four treatments: a prostaglandin E1 analogue (misoprostol) at 50 microg/kg body wt; a prostaglandin E2 analogue (16,16-dimethylprostaglandin E2) at 7.5 microg/kg body wt; prostacyclin at 20 microg/kg body wt; or control (7.64 mmol/L Tween-80 suspended in 0.15 mol/L NaCl containing 0.48 mol/L ethanol). Immediately after intubation, rats were dosed with 3.7 mBq of 51CrCl3 by micropipette. Blood was collected from the tail at intervals after 51Cr dosing. Six hours after dosing, 51Cr rats were exsanguinated by cardiac puncture. Indomethacin, an inhibitor of prostaglandin synthesis, significantly increased (P < 0.05) 51Cr in blood at all time periods tested except at 15 min. In tissues, indomethacin significantly increased 51Cr retention. Urinary 51Cr excretion at 6 h was higher (P < 0.05) in indomethacin-pretreated rats than in control rats. Administration of indomethacin, which blocks prostaglandin synthesis, enhanced 51Cr absorption, whereas dosing with 16,16-dimethylprostaglandin E2 decreased 51Cr absorption.     

Mercury in human hair and relation to fish consumption in Bangladesh

Human scalp hair mercury concentrations were determined in 219 hair samples from male individuals from different regions of Bangladesh. Total hair mercury concentrations were very low with a mean value of 0.44 +/- 0.19 micrograms Hg/g (range 0.02-0.95) for a moderately elevated fish consumption averaging 2.1 kg/month (range 1.4-2.6). A highly significant positive correlation (r = 0.88, P < 0.001) was found between fish consumption and hair mercury concentration. Neither age, region nor occupation had any influence on the hair mercury content. Our results in agreement with literature values, are described by equation (X = 183Y + 0.16) linking calculated daily methylmercury intake (X, mg) and hair total mercury level (Y, micrograms/g). Low concentrations in hair were linked to extremely low levels of daily mercury intake, the determining factor being remarkably low mercury levels in Bangladesh fish.     

Structure-activity relationships of cysteine esters and their effects on thiol levels in rat lung in vitro

Pretreatment with cysteine esters increases cysteine (CySH) levels in rat lung and protects against the lethal effects of inhaled perfluoroisobutene in vivo. There are marked differences in the duration of protection achieved with different cysteine esters. In this study we have compared the uptake and metabolism of CySH, N-acetyl cysteine (NAc), cysteine esters and cystine esters in vitro using rat lung and liver homogenates and lung slices. Liver homogenates metabolized CySH and cysteine esters faster than lung homogenates. The half life (T1/2) of CySH in lung was 58.8 +/- 17.3 min and in liver was 14.0 +/- 1.6 min (mean +/- SEM). T1/2 of the esters in lung ranged between 6.5 and 12.1 min and in liver between 1.9 and 5.3 min. Cysteine tertiary butyl ester, which does not protect in vivo, was not hydrolysed to CySH by lung or liver homogenates. All esters increased and prolonged intracellular CySH concentrations in lung slices to a much greater extent than CySH itself. NAc did not raise intracellular CySH above that of the controls and no NAc appeared within the slice. After CySH incubation intracellular CySH was 0.9 +/- 0.1 nmol/mg wet wt at 10 min whereas after incubation with the esters it ranged between 2.60 and 3.65 nmol/mg wet wt. Cysteine cyclohexyl ester prolonged the increase of CySH the longest and cysteine methyl ester the shortest. CySH levels with cysteine cyclohexyl ester were 2.74 +/- 0.15 and 4.13 +/- 0.37 nmol/mg wet wt at 10 and 60 min, respectively, whereas with cysteine methyl ester, CySH levels were 2.60 +/- 0.5 and 1.25 +/- 0.08 nmol/mg wet wt at similar times. Cystine esters increased intracellular concentrations of both cystine and CySH. CySH concentrations ranged between 2.92 and 3.19 nmol/mg wet wt and cystine between 1.39 and 1.47 nmol/mg wet wt at 60 min. The elevation and duration of CySH in lung slices is well correlated with the duration of protection against perfluoroisobutene achieved in vivo.     

Decreased basal, noninsulin-stimulated glucose uptake and metabolism by skeletal soleus muscle isolated from obese-hyperglycemic (ob/ob) mice

Insulin resistance of diaphragms of ob/ob mice has been repeatedly demonstrated previously both in vitro and in vivo. In the present study, transport and metabolism of glucose with and without insulin stimulation were compared in a skeletal muscle more likely than diaphragm or heart to be representative of the overall striated muscle mass, i.e. isolated soleus muscle. Compared with soleus muscle from lean controls, unstimulated lactate release in the presence of exogenous glucose was depressed from 16.2 to 12.3 nmol/60 min per mg wet wt in soleus from ob/ob mutants; glycolysis was decreased from 6.6 to 3.7 and [14C]glucose oxidation to 14CO2 from 0.90 to 0.33 nmol glucose/60 min per mg wet wt. Uptake of 2-deoxyglucose (2-DOG), both with and without insulin, was very much less for soleus from ob/ob than from lean mice, at 2-DOG concentrations ranging from 0.1 to 10 mM, and in mice of 6-15 wk. When 2-DOG concentration was 1 mM, its basal uptake was 0.53 nmol/30 min per mg wet wt for soleus of ob/ob as against 0.96 for soleus of lean mice. The absolute increment due to 1 mU/ml insulin was 0.49 in muscle of ob/ob as against 1.21 in that of lean mice. When the resistance to insulin action was decreased by pretreatment in vivo by either streptozotocin injection or fasting, the decreased basal 2-DOG uptake of subsequently isolated soleus muscle was not improved. Inhibition of endogenous oxidation of fatty acids by 2-bromostearate, while greatly increasing 14CO2 production from [14C]glucose, did not affect basal [5-3H]glucose metabolism or 2-DOG uptake. It is suggested that transport and/or phosphorylation of glucose under basal, unstimulated conditions are depressed in soleus muscle of ob/ob mice, whether or not resistance to insulin and hyperinsulinemia are also present. Although the origin of the decreased basal glucose uptake remains unknown it might be related to a similar decrease in basal glucose uptake by ventromedial hypothalamic cells, an event presumably resulting in a tendency to hyperphagia. Decreased basal glucose uptake by soleus muscle of ob/ob mice might explain the hyperglycemia, and hence partly the hyperinsulinemia and excessive fat deposition of those animals.     

Varying mercury exposure with varying food source in a James Bay Cree community

James Bay Quebec Crees are exposed to methylmercury (MM) through fish consumption. Hair mercury concentrations were measured in women of child-bearing age and men and women 40 years of age and above in a small Cree community of James Bay (with traditionally low exposure to MM) before and after fishing expeditions to inland lakes where fish were contaminated with methylmercury. Median hair mercury concentrations in persons 40 years and above increased from 4.1 mg/kg to 9.9 mg/kg and the highest value from 17.4 to 47.2 mg/kg. A similar increase was seen after a second fishing expedition where the median hair concentration increased from 3.4 mg/kg to 7.2 mg/kg and the highest value from 17.7 to 49.9 mg/kg. Populations with traditionally low exposure to MM can become highly exposed with changes in sources or quantities of fish consumed.     

Molecular and biochemical characterization of the protein template controlling biosynthesis of the lipopeptide lichenysin

To assess the duration of immunosuppression in FK506-dosed pigs, an undiluted whole blood assay was established to measure reactivities of T cells in their physiological milieu. PMA and ionomycin were shown to induce IL-2 production in swine blood. The IC50 of FK506 in inhibiting IL-2 production in whole blood and isolated PBMC stimulated with PMA and ionomycin measured 1.2 and 0.04 nM, respectively. These data underscore the influence of red blood cells and plasma proteins on drug potency. IL-2 levels were determined in blood drawn immediately before and 1, 24, 48, and 72 h after iv dosing. For pigs dosed with 0.05 mg/kg, 50% recovery of IL-2 production was observed at 16 h and 100% at 35 h after dosing. For pigs dosed with 0.15 mg/kg, 50% recovery was observed at 38 h and 100% at 72 h. Blood concentrations of FK506 at 50 and 100% recovery of IL-2 production measured 10.8 and 2.2 nM for pigs dosed with 0.05 mg/kg and 6.1 and 1.1 nM for pigs dosed with 0.15 mg/kg, respectively. These concentrations are severalfold higher than predicted from the IC50 of FK506 for inhibiting IL-2 production in the whole blood assay. These data suggest that the true potency of FK506 in blood after dosing is influenced by additional factors, which could include plasma protein binding, the presence of active or interfering metabolites, serum interfering factors, and sequestration of drug in blood cells. Our results demonstrate the utility of an undiluted whole blood assay for assessing the duration of immunosuppression in drug-dosed animals and emphasize the importance of assessing drug potency in the whole blood environment ex vivo.     

Lactational exposure and neonatal kinetics of methylmercury and inorganic mercury in mice

The concentration of mercury in milk and the distribution pattern in the sucking pup was followed over time after administration of a single iv injection of 0.5 mg/kg body wt of 203Hg-labeled methylmercuric chloride or mercuric chloride to lactating mice on Day 10 of lactation. Mercury concentrations in milk of the dams and in whole body, blood, plasma, GI-tract, liver, kidneys, and brain of the offspring were followed up to 11 days after dosing (until lactational Day 21). Following the inorganic mercury dose to the dams, most of the mercury in milk was delivered to the pups during the first 24 h, but the maximum mercury concentration in plasma and tissues of pups was not reached until 7 days after dosing, indicating a prolonged absorption of inorganic mercury in the sucking pup. Pups of dams given methylmercury were exposed to a much lower and constant mercury concentration in milk. The estimated accumulated mercury dose via milk per pup of dams given methylmercury was less than half of that estimated after the inorganic mercury dose. When the accumulated dose via milk from methylmercury-exposed dams was compared to the amount of mercury in pup's carcass (whole body minus GI-tract including content), it was revealed that almost all mercury delivered via milk was absorbed, and that the suckling pups had a very low elimination of mercury until lactational Day 17. Lactational exposure following a maternal methylmercury or inorganic mercury dose resulted in almost similar mercury concentrations in liver, kidneys, and plasma of the suckling, but higher concentrations in brain (as most 14 times) and also twice as high mercury body burden in the methylmercury group. Thus, differences in kinetics indicate that lactational exposure of methylmercury is a greater hazard for the breast-fed infant than inorganic mercury.     

Intracellular responses from cells of the medulla of the fly, Calliphora erythrocephala

[14C] Methyl mercury was administered by three different routes: intravascular (iv) injection, ingestion, and absorption from the ambient water. After iv administration (0.1 mg/kg) [14C] methyl mercury was rapidly removed from the plasma, followed by slow loss from the hepatopancreas and a strikingly persistent increase in the amount of radioactivity in the tail muscle. Most (80-90%) of the radioactivity in the hepatopancreas was shown by TLC methods to be the parent compound, and approximately 10% of this persisted for 6 days after injection. The half-life in this organ was found to be 21 days. One month after iv treatment with methyl mercury, the only organs that contained more than 0.1 ppm of this xenobiotic were egg masses, male gonads, heart, brain, intestine, and tail muscle. The half-lives for disappearance from sexual organs were greater than 1 month. After ingestion of [14C] methyl mercury (0.1 mg/kg) in food the hepatopancreas contained most of the administered dose at 6 days (68%), while the stomach (10%), tail muscle (8%), and carcass (15%) contained less. A unique distribution pattern emerged 6 days after exposure to [14C] methyl mercury-containing ambient water (0.1 ppm). The tail muscle contained most (50%) of the absorbed dose, whereas the hepatopancreas and carcass contained only 23 and 10%, respectively. In view of the small molecular size and high lipid solubility of methyl mercury and the lipophilic properties of the chitin-protein exoskeleton of the lobster, it is likely that significant uptake directly from the water as well as storage of absorbed methyl mercury occurred in the tail region. Residue analysis on untreated lobsters indicated that the egg masses contained the largest amount of methyl mercury (0.1 ppm). The hepatopancreas and carcass (muscle) levels were less than 0.05 ppm.