Research management in the Great Lakes and St. Lawrence River basins: challenges and opportunities.

Research management in the Great Lakes and St. Lawrence River basins is both challenging and filled with opportunities. From the perspective of public health practice, research management is more than just research managers managing discrete programs; it requires everyone involved in the process to become active participants, including researchers, communities, potential interest groups, policymakers, and other stakeholders. Agencies, organizations, and individuals responsible for managing research and resources in the Great Lakes and St. Lawrence River basins are facing problems of decreased research funding, data gaps, and research quality. Managers of research and resources in the basins face many challenges as they address these problems. They are challenged with strengthening the link between research and management in the face of decreasing resources and increasing expectations of results and findings while extending those results and findings to public health practice. A number of actions and activities have been proposed that can lead to better management of constrained programs, pooled resources, partnerships, targeted priorities, and improved effectiveness. With guidance and assistance from the International Joint Commission (IJC), research managers in the Great Lakes and St. Lawrence River basins who have initiated and maintained traditional research programs based on sound science are now adopting different and innovative management strategies. The research community must be proactive in articulating the role of science in bridging the gaps in knowledge between public health practice and regulatory programs. Supported by a firm foundation of credible science, critical assessment, and public service, basin research managers are recognizing the need to move outside the comfort zone and extend to areas previously unwelcomed or uncomfortable.

The health Canada Great Lakes multigeneration study--summary and regulatory considerations.

The Health Canada Multigeneration Study was initiated to determine the consequences in rodents consuming diets containing Lake Ontario (LO) or Lake Huron (LH) chinook salmon over successive generations. Following lyophilization, the contaminant levels in the salmon used in the formulation of the diets for this study exceeded a number of tolerances or guidelines established for contaminants in commercial fish and seafood products (PCBs, dioxin, mirex, chlordanes, mercury). Consumption of the fish diets by rats of two consecutive generations resulted in a variety of effects that can be described as adaptive responses or of limited biological significance. The two exceptions to this were (1) the suggestion of modification of working and reference memory in males of the high-dose groups 20% fish diets, which may have been related to decreases noted in neurotransmitters in several brain regions in these rats; and (2) an effect on thymus weights noted in the high-dose first generation (F1) reversibility study animals and an overall effect on T-helper/inducer lymphocyte subset numbers in the second generation (F2) male rats fed the LH diets compared to the LO diets. Relatively minor effects were observed in the rats consuming the 5% fish diets from either Great Lakes location (LH-5, LH-5), although their fish intake was approximately 16-fold greater on a daily basis than the average angler consuming Great Lakes sport fish (compared to a 60-fold greater intake in the 20% diet groups: LH-20, LO-20). Based on these study results with rats it would appear that for the average consumer of Great Lakes sports fish, the risk presented by the complex mixture of contaminants in chinook salmon collected from these two locations in the Great Lakes basin could be considered minimal, especially if sport fish consumption advisories are followed.

Uranyl nitrate: 28-day and 91-day toxicity studies in the Sprague-Dawley rat.

Although uranium (U) is a classic experimental nephrotoxin, there are few data on its potential long-term chemical toxicity. These studies were undertaken to derive a no-observed-adverse-effect level (NOAEL) in male and female Sprague-Dawley rats following 91-day exposure to uranium (as uranyl nitrate hexahydrate, UN) in drinking water. Following a 28-day range-finding study, five groups of 15 male and 15 female weanling rats were exposed for 91 days to UN in drinking water (0.96, 4.8, 24, 120, or 600 mg UN/L). A control group was given tap water (< 0.001 mg U/L). Daily clinical observations were recorded. Following the study, animals were euthanized and exsanguinated, and multiple hematological and biochemical parameters were determined. Necropsies were conducted, and multiple tissues were sampled for histopathological examination. The hematological and biochemical parameters were not affected in a significant exposure-related manner. Although there were qualitative and slight quantitative differences between males and females, histopathological lesions were observed in the kidney and liver, in both males and females, in all groups including the lowest exposure groups. Renal lesions of tubules (apical nuclear displacement and vesiculation, cytoplasmic vacuolation, and dilation), glomeruli (capsular sclerosis), and interstitium (reticulin sclerosis and lymphoid cuffing) were observed in the lowest exposure groups. A NOAEL was not achieved in this study, since adverse renal lesions were seen in the lowest exposed groups. A lowest-observed-adverse-effect level of 0.96 mg UN/L drinking water can be reported for both the male and the female rats (average dose equivalent 0.06 and 0.09 mg U/kg body wt/day, respectively).

Uranyl nitrate: 91-day toxicity studies in the New Zealand white rabbit.

These studies were undertaken to derive a lowest-observed-adverse-effect level (LOAEL) in the New Zealand White rabbit following a 91-day exposure to uranium (U, as uranyl nitrate hexahydrate, UN) in drinking water. Males were exposed for 91 days to UN in their drinking water (0.96, 4.8, 24, 120, or 600 mg UN/L). Subsequently, females were similarly exposed for 91 days (4.8, 24, or 600 mg UN/L). Control groups were given tap water (< 0.001 mg U/L). Regular observations were recorded, and urine was collected periodically. Four males showed evidence of Pasteurella multocida infection and were excluded from the study. Following the study, all animals were euthanized, and multiple hematological and biochemical parameters were determined. Necropsies were conducted, and histopathological examination was performed. The hematological and biochemical parameters were not affected in a significant exposure-related manner. Dose-dependent differences consisted of histopathological changes limited primarily to kidney. Changes in renal tubules were characteristic of uranium toxicity. Based on changes in the tubular nuclei, the 91-day LOAEL for males in this study is 0.96 mg UN/L drinking water. The females drank 65% more water than the males, yet appeared to be less affected by the exposure regimen, although they also developed significant tubular nuclear changes in their lowest exposure group, deriving a LOAEL of 4.8 mg UN/L. Tissue uranium residue studies suggested that pharmacokinetic parameters for the males and females differ, possibly accounting for the difference in observed sensitivity to UN. An adverse effect of P. multocida infection cannot be excluded.

Uranyl nitrate: 91-day exposure and recovery studies in the male New Zealand white rabbit.

This study was undertaken to examine the reversibility of renal injury in the male New Zealand White rabbit subsequent to a 91-day exposure to uranyl nitrate (UN) in drinking water, followed by various recovery periods. Specific pathogen-free (SPF) animals were exposed for 91 days to UN in their drinking water (24 or 600 mg UN/L). Control groups were given municipal tap water (< 0.001 mg U/L). Regular clinical observations were recorded, and urine was collected periodically. Recovery periods between the last UN exposure and termination were 0, 8, 14, 45, or 91 days. Following the study, all animals were anesthetized and terminated by exsanguination, and multiple hematological and biochemical parameters were determined. Necropsies were conducted, and histopathological examination was performed. Exposure-related histopathological changes were observed only at much higher doses than in our previous male rabbit study where non-SPF-free animals had been used. Minor increases in kidney to body weight ratios were observed in the high-dose groups following exposure and early recovery. Renal tubular injury with degenerative nuclear changes, cytoplasmic vacuolation, and tubular dilation was seen in the high-dose group, without consistent resolution even after 91 days recovery. Animals ingested approximately 33% more uranium per day in this study than did males in a comparable dose group in the previous study, yet their kidney tissue uranium residues were 30% lower. These results suggest that SPF rabbits are less sensitive to uranyl injury than the non-SPF animals. The lowest-observed-adverse-effect level is estimated to lie at or below 24 mg UN/L.

Absorption and retention of uranium from drinking water by rats and rabbits.

Uranium in the form of uranyl nitrate hexahydrate was administered in drinking water to Sprague-Dawley rats for periods of 28 and 91 d and New Zealand White rabbits for 91 d. The animals consumed food and water ad libitum. Subgroups of rabbits were followed for recovery periods of up to 91 d; 24-h collections of urine and feces were performed for some of the rabbits at various times during the exposure and recovery periods. At the end of the experiment, all animals were sacrificed and femur and kidney samples were analyzed for uranium residues. The results show that both rats and rabbits absorb about 0.06% of ingested uranium in the gastrointestinal (GI) tract. The distribution and retention of uranium in the skeleton and kidneys of rats are comparable to parameters reported for humans. The retention half-time in rabbit bone is substantially longer than for humans. The implications of extrapolating from animal data to effects on humans are discussed.

Subchronic oral toxicity of triethyl lead in the male weanling rat. Clinical, biochemical, hematological, and histopathological effects.

This study was designed to ascertain the effects of low level exposure of triethyl lead (3EL) to the male weanling rat. Groups of 20 animals were administered by gavage 3EL at 0.05, 0.10, 0.20, 0.50, and 1.00 mg/kg body wt for 91 days, 5 days/week. Lead acetate (PbHOAC) at 200 mg/kg body wt/day was given as a positive control. Weight gain was reduced in those animals receiving 1.0 3EL. Spleen and kidney weights were elevated in the PbHOAC group. Residues of 3EL and its metabolites diethyl lead (2EL) and lead (Pb) accumulated in a dose-dependent manner in blood, liver, kidney, and brain; 3EL accumulated preferentially in the liver while inorganic lead accumulated in the kidney. Dose-dependent changes occurred in serum calcium which was decreased and in phosphorus which was elevated for all dose groups. Serum cholesterol was elevated in the three highest 3EL groups as was alkaline phosphatase. LDH was lowered in the PbHOAC-treated group but microsomal aniline hydroxylase was elevated. Hematological changes consisted of elevated platelet counts in the 1.0 3EL group and decreased mean corpuscular hemoglobin content and mean corpuscular volume in the PbHOAC-treated group. Treatment related histopathological changes were seen in thyroid, liver, kidney, and bone marrow. Based on these data a no observed adverse effect level for 3EL was set at 0.10 mg/kg/body wt.

Total organically-bound chlorine and bromine in Lake Ontario herring gull eggs, 1977, by instrumental neutron activation and chromatographic methods.

In order to determine the extent to which organically-bound chlorine in Herring Gull eggs from Lake Ontario can be accounted for by gas chromatographic analysis, comparison was made with values obtained for total chlorine using instrumental neutron activation analysis (INAA). Total chlorine and bromine (mg/kg fresh weight of egg) was determined by INAA on crude extract (Cl, 65 +/- 35; Br, 1.03 +/- 1.00), Florisil-chromatography treated extracts (Cl, 46 +/- 10; Br, 0.93 +/- 0.82) and H2SO4-treated extracts (Cl, 43 +/- 11; Br, 0.44 +/- 0.22) of eggs collected from seven colonies around Lake Ontario in 1977. Levels of chlorine were also determined by gas chromatography using the Hall electrolytic conductivity detector (51 +/- 11 mg/kg) and estimated by conversion of levels of individual residues determined by electron-capture gas chromatography (61 +/- 12 mg/kg). The agreement between the various determinations indicated that PCBs, DDE, mirex and photomirex accounted for most of the organically-bound chlorine. Two colonies had total chlorine levels in crude extracts 2--4 times higher than could be accounted for by know compounds. The "excess" chlorine was removed by H2SO4-treatment or Florisil clean-up. The same two samples had abnormally high bromine levels, possibly indicating the presence of compounds formed during aqueous chlorination processes.