Lowest Effect Level Research Articles

An Evaluation of the Efficacy of Tree Growth Regulators Paclobutrazol, Flurprimidol, Dikegulac, and Uniconazole for Utility Line Clearance

A multi-year field program was conducted in California and Nevada to determine the efficacy of tree growth regulators (TGRs). At 37 sites, trees were trimmed and treated with paclobutrazol, flurprimidol, dikegulac or uniconazole by trunk injection, tree implants, or bark banding. Tree growth was determined over a period of 1-4 years for 12 common West Coast species. Growth was determined by measuring increase in tree height. At most sites that were not compromised during the study, the TGRs had no detectable effect on growth. Inhibition of growth was observed over 4 years at one site with London plane (Platanus acerifolia) trunkinjected with uniconazole, at one site with big leaf maple (Acer macrophyllum) trunk-injected with uniconazole, and over 2 years at one site with Chinese elm {Ulmus parvifoWa) trunkinjected with paclobutrazol or uniconazole. Trunk injections and bark banding of flurprimidol inhibited the growth of blue gum {Eucalyptus globulus) over 2 years at one site. There was a lack of consistency in the effects observed; for example, the growth of London plane was inhibited at only one of eight sites. Possible explanations for the low level of effectiveness and lack of consistency include site variability, tree water relations, and hole spacing. Problems were experienced while conducting this large-scale research effort under field conditions. Factors that contributed to a low level of effectiveness and a lack of consistency need to be addressed to improve the cost-effectiveness of the product formulations evaluated.

Loadings, Dynamics and Response Time of Seven Metals in Hamilton Harbour: Results of a Mass Balance Study

Abstract Steady-state and unsteady-state mass balance models based on the QWASI fugacity/aquivalence model (Mackay 1991; Mackay and Diamond 1989) are used to describe the fate of lead, zinc, copper, cadmium, chromium, arsenic and nickel in Hamilton Harbour. To examine the effect of sediment “hot spots” on chemical dynamics in the harbour, a steady-state model with two sediment segments was developed. Model results indicate that the major contamination sources are land-based; sediments are of secondary importance as a source, and Lake Ontario can play a relatively important role as a diluent in some cases. The correspondence between measured and observed water and sediment concentrations obtained with the steady-state model suggests that average sediment concentrations are supported by present inputs rather than historical loadings. We suggest that a 20% annual loading reduction can decrease the average sediment concentrations of Zn, Cr and Cu to below the “severe effect level” of the provincial sediment quality guidelines in 2 to 6 years. The “lowest effect level” can be achieved within 10 years for As and Ni, and more than 20 years for the remaining chemicals at this loading rate. The results of the two-sediment model are illustrative since input values are uncertain, but are consistent with our understanding of harbour dynamics: the central zone accumulates more chemical and is slower to loose chemical, whereas chemical is lost from the nearshore sediment more rapidly.

Immunotoxicity of the pyrethroid insecticides deltametrin and α-cypermetrin

The synthetic pyrethroids deltametrin and α-cypermetrin were studied for effects on the immune system in 28-day studies in F344 male rats. Sixteen rats per group were dosed with either deltametrin 0, 1, 5, or 10 mg/kg body wt./day or α-cypermetrin 0, 4, 8, or 12 mg/kg body wt./day in soy bean oil by gavage. Haematology, bone marrow cell counts, tests for natural killer (NK) cell activity and mitogen response (Con A and STM) as well as quantitation of lymphocyte subpopulations were performed. Spleen cells from immunized animals (six animals/group) were tested for antibody production (SRBC-PFC). Volumes of lymphoid compartments of mesenteric lymph nodes and thymus were estimated using stereological methods. In the deltametrin study an effect was found in the groups receiving 5 or 10 mg/kg body wt. The effects were: increased weight of mesenterial lymph nodes, decreased thymus weight in immunized animals and an increase in numbers of SRBC-PFC and splenic NK cell activity. An effect on relative adrenal weight was seen in the 10 mg/kg body wt. group. No severe effects on the immune system was found. The lowest effect level of α-cypermetrin was 12 mg/kg body wt./day based on increased relative adrenal weight.

Trace metal composition and speciation in street sediment: Sault Ste. Marie, Canada

Street sediment collected in Sault Ste. Marie, Ontario was examined for trace element composition (As, Cd, Cr, Cu, Fe, Pb, Hg, Ni and Zn) and the metal partitioning to various sediment properties was determined by sequential extraction. Total Ni, Cu, Zn and Pb concentrations exceeded the lowest effect levels specified in the Ontario Provincial Sediment Quality Guidelines for Metals (Environment Ontario, 1992) and derived from bioassay studies. According to these Guidelines, the disposal of such sediment has to be guided by environmental considerations. A significant fraction of these metals was extractable in 0.5 N HCl over a 12-hour period and considered as potentially bioavailable. The major accumulative phases of toxic metals in this sediment are exchangeable, carbonate, Fe/Mn oxides and organic matter but the relative importance of each phase varied for individual metals. Approximately 20% of the total extractable Cd is found in each of these four fractions. Pb, Zn and Mn are predominantly bound to carbonates, Fe/Mn oxides and organic matter. Cu shows a high affinity for organic matter and to a lesser extent for carbonates. Elevated levels of Cd, Pb, Cu, Zn, Mn and Cr in the exchangeable and/or soluble phase suggest that sediment associated metals, mobilised from streets in Sault Ste. Marie during runoff and snowmelt, would adversely impact water quality in the receiving waters. However, large fractions of the total metal load are associated with coarser particles which are unlikely to be transported through the drainage system into receiving waters.

Severn Sound Sediment Chemistry and Bioassessment, 1988–1990

Abstract Fine-grained sediment in the embayments of Severn Sound contains metals that exceed the Ontario Ministry of the Environment's lowest effect level, the level at which some disturbance of the sediment dwelling community can be expected. Sediment in Penetang Bay has concentrations of Cr that are above the provincial Severe Effect Level, the level at which a compound is expected to be detrimental to the majority of benthic species. Nevertheless, chronic sediment bioassays resulted in little measurable sublethal toxicity. Based on evidence from weak acid extraction of metals from sediment, the lack of toxicity may be due to the limited bioavailability of metals. The potential for metals to enter the food web was suggested by metal bioaccumulation observed for test species. Chromium and Ni concentrations in mayflies were significantly correlated with total Cr and Ni in sediment, and Zn and Cu tissue concentrations were not correlated with total metals in sediment. In general, the bioaccumulation of Cd, Cr, Cu, Ni and Pb by test species was more strongly correlated with extractable metals and with metals in the <63 µm size fraction than with total metals in bulk sediment, demonstrating that the total sediment pool of metals was not biologically available. Remedial actions for sediment in Severn Sound should focus on source control and natural sediment recovery, given the lack of sublethal chronic toxicity. Confirmation that active sources are not present and an ability to predict the natural recovery period for marginally contaminated regions would assist in fully restoring the sound.

Combination therapy with 5-fluorouracil and L-canavanine

L-Canavanine (CAV) is a potent L-arginine antagonist, produced by legumes such as the jack bean, Canavalia ensiformis. CAV is cytotoxic to MIA PaCa-2 human pancreatic cancer cells. We sought to determine whether CAV's efficacy as an anticancer agent might be increased in combination with 5-fluorouracil (5-FU), a pyrimidine antimetabolite with activity against solid tumors. Using optimal conditions for the expression of CAV's cytotoxicity against MIA PaCa-2 cells, CAV was more cytotoxic to the cells than 5-FU. The combination of both drugs at a fixed molar ratio of 1:1 exhibited synergistic effects in the cells as determined by combination index analysis. The combination of 5-FU:CAV was tested at a ratio of 5:1 and exhibited antagonism at lower effect levels, additivity at 50% effect levels and slight synergism at higher effect levels. A 10:1 combination of both drugs (5-FU:CAV) exhibited antagonistic effects at all levels. When the drugs were combined at a molar ratio of 20:1, increased antagonism was observed. When CAV (1.0 or 2.0 g/kg daily) and/or 5-FU (35 mg/kg daily) was administered to colonic tumor-bearing rats for five consecutive days, the antitumor activity of the drug combination was significantly greater than the combined effects of either drug alone. However, the body weight loss experienced by CAV-treated rats was increased in those rats exposed to a combination of both drugs. These studies using different tumors provide in vitro and in vivo evidence that combination therapy offers a viable means of improving CAV's intrinsic efficacy while decreasing the concentration of 5-FU required to produce the same cytotoxic effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Connection between low energy effective Hamiltonians and energy level statistics.

We study the level statistics of a non-integrable one dimensional interacting fermionic system characterized by the GOE distribution. We calculate numerically on a finite size system the level spacing distribution $P(s)$ and the Dyson-Mehta $\Delta_3$ correlation. We observe that its low energy spectrum follows rather the Poisson distribution, characteristic of an integrable system, consistent with the fact that the low energy excitations of this system are described by the Luttinger model. We propose this Random Matrix Theory analysis as a probe for the existence and integrability of low energy effective Hamiltonians for strongly correlated systems.

Are interspecies comparisons in the toxicity of centrally acting drugs valid without brain concentrations? A commentary

Many pharmacological and toxicological studies of centrally acting drugs are undertaken in animals at doses expressed in mg.kg −1, and the results extrapolated to the clinical dose in man. Safety margins based on such no or lowest effect levels may have little relevance since they do not take into account differences in the kinetics and metabolism of the compounds. These deviations are accentuated when extremely high doses are used, and saturation of metabolism occurs.

Incorporation of pharmacokinetics in noncancer risk assessment: example with chloropentafluorobenzene.

Noncancer risk assessment traditionally relies on applied dose measures, such as concentration in inhaled air or in drinking water, to characterize no-effect levels or low-effect levels in animal experiments. Safety factors are then incorporated to address the uncertainties associated with extrapolating across species, dose levels, and routes of exposure, as well as to account for the potential impact of variability of human response. A risk assessment for chloropentafluorobenzene (CPFB) was performed in which a physiologically based pharmacokinetic model was employed to calculate an internal measure of effective tissue dose appropriate to each toxic endpoint. The model accurately describes the kinetics of CPFB in both rodents and primates. The model calculations of internal dose at the no-effect and low-effect levels in animals were compared with those calculated for potential human exposure scenarios. These calculations were then used in place of default interspecies and route-to-route safety factors to determine safe human exposure conditions. Estimates of the impact of model parameter uncertainty, as estimated by a Monte Carlo technique, also were incorporated into the assessment. The approach used for CPFB is recommended as a general methodology for noncancer risk assessment whenever the necessary pharmacokinetic data can be obtained.

Preparing yourself for an international assignment

A s more U.S. companies expand their business overseas, the need to send employees on international assignments will increase. Many companies use overseas assignments as a means to assess which individuals should be promoted to top-level positions. Unfortunately, up to 40 percent of expatriate managers terminate their assignments early, costing their companies between $50,000 and $150,000 and derailing their careers. Moreover, 50 percent of those who do not terminate their assignments early function at a low level of effectiveness. Why do so many expatriates fail? Primarily because they neglect to prepare for such assignments. Despite the high failure rates and associated costs, most companies do not train managers for international assignments. So what can a manager do to prepare for an overseas assignment? This article contains practical suggestions for designing a personal training program.

Aggressive Children and Effective Communication

Testing a component of a theoretical model which postulates that low levels of communication effectiveness accompany the social and affective problems presented by aggressive children, the study compared the communication skills of a group of aggressive (n = 49) and nonaggressive (n = 49) elementary school children (selected on the basis of teacher ratings) in a structured and cooperative communication task. Based on direct observational measures of communication effectiveness and aggression, and on teacher, peer, and self-rating measures of peer rejection and depressive symptoms, results showed that (a) aggressive children exhibited less effective communication skills and more disruptive communication skills than nonaggressive peers; (b) aggressive children experienced higher levels of peer rejection and depressive symptoms than nonaggressive peers; and (c) group differences in communication effectiveness could not be accounted for by differences in observed aggression and remained significant, even after controlling for differences in peer status and affective functioning. These findings highlight the role that ineffective communication may play in the development and maintenance of aggression and have important theoretical and applied implications, which are briefly discussed. © 1994 Wiley-Liss, Inc.

Neurodevelopmental toxicity in vitro: Primary cell culture models for screening and risk assessment

Robust models for the evaluation of developmental toxicity are briefly reviewed with emphasis on embryonic brain and retina cells in vitro. Organ slice and aggregate cultures under constant gyratory movement as well as high cell density monolayer (“micromass”) cultures are considered as robust models. An in vitro model using high cell density monolayer and re-aggregated cells isolated from embryonic chick brain (ED 6) is presented. Cell development and differentiation of the astrocytes and nerve cells are monitored by marker proteins and cytotoxicity was quantified by neutral red uptake and protein content. Four human teratogens, six possible human teratogens and six unlikely human teratogens were tested in brain and retina cells for their cytotoxic and morphologic effect. All 16 substances were classified correctly except the neurotoxicants MPTP and MPP+, both of which are strong dopaminergic toxicants in vitro as well as in humans and are therefore proposed to be classified as human neuroteratogens. Preliminary data on the lowest effect levels of four potential neurotoxicants (cadmium chloride, Ara-C, Phenytoin, MPTP) in chick brain aggregate cultures correlate suprisingly well with known toxic human plasma levels. Further validation has to be undertaken to confirm these promising results. A battery of such robust in vitro models is proposed that could cover neurodevelopmental toxicity of drugs and chemicals for screening and risk assessment purposes.

Film Cooling on a Gas Turbine Rotor Blade

The film cooling effectiveness on a low-speed stationary cascade and the rotating blade has been measured by using a heat-mass transfer analogy. The film cooling effectiveness on the suction surface of the rotating blade fits well with that on the stationary blade, but a low level of effectiveness appears on the pressure surface of the rotating blade. In this paper, typical film cooling data will be presented and film cooling on a rotating blade is discussed.

Heavy Metals and Toxic Organic Contaminants in Effluents, Water, and Sediments of the Bay of Quinte, Lake Ontario

In 1988, water and sediment samples were collected from 10 point sources, 4 tributaries and 15 in-bay locations in the Bay of Quinte, Lake Ontario. These were analyzed for trace contaminants (inorganic and organic). Point source sampling showed that Domtar Wood Preserving at Trenton was a major contributor of chlorinated phenols; several sewage treatment plants were significant sources of heavy metals, but tributary metal loadings were generally higher than sewage treatment plant loadings. In the Bay of Quinte water, Provincial Water Quality Objectives (PWQO) were exceeded only on a small portion of samples for copper, cadmium, iron, zinc, and phenols; indeed, most samples showed undetectable amounts of arsenic, cadmium, mercury, nickel, and lead. Metal levels in Bay of Quinte water were, however, greater than those in open Lake Ontario. While the levels of heavy metals in sediments were generally found to exceed the low effect level of Ministry sediment quality guidelines, they were toward the low end of the range of values observed in Lake Ontario depositional zones, and less than those in Hamilton Harbour. Detectable levels of many PAHs were found in the sediments, with the highest concentrations at the mouth of the Trent and Moira rivers. Other organic contaminants were seldom, if ever, found in the sediments. Levels of PAHs were lower than those in Hamilton Harbour and the Detroit River.

Mercury and monomethylmercury: present and future concerns.

Global atmospheric changes carry the potential to disrupt the normal cycling of mercury and its compounds. Acid rain may increase methylmercury levels in freshwater fish. Global warming and increased ultraviolet radiation may affect the global budget of methylmercury, including its formation and degradation in both biotic and abiotic environments. In this article we review current knowledge on mercury and monomethylmercury with regard to their environmental fate and the potential for human health effects. Recent findings indicate that atmospheric Hg deposition readily accounts for the total mass of Hg in fish, water, and sediment of Little Rock Lake, a representative temperate seepage lake in north-central Wisconsin. It is strikingly evident that modest increases in atmospheric Hg loading could lead directly to elevated levels in the fish stock. It is doubtful, given the experimental limitations in many recent studies, that the temporal pattern for Hg emissions, for background atmospheric Hg concentrations, and for changes in Hg depositional fluxes has been identified. Thus, the present and future questions of whether the environmental impact is of local, regional, or hemispheric significance remain. Contemporary investigations must address these important questions. Human exposure to methylmercury in the United States is probably increasing due to increased consumption of fish and fish products. A recent epidemiological investigation indicates high susceptibility to brain damage during prenatal exposures to Hg. An important objective for future investigation is to establish the lowest effect level for human exposure to methylmercury.

Mercury and Monomethylmercury: Present and Future Concerns

Global atmospheric changes carry the potential to disrupt the normal cycling of mercury and its compounds. Acid rain may increase methylmercury levels in freshwater fish. Global warming and increased ultraviolet radiation may affect the global budget of methylmercury, including its formation and degradation in both biotic and abiotic environments. In this article we review current knowledge on mercury and monomethylmercury with regard to their environmental fate and the potential for human health effects. Recent findings indicate that atmospheric Hg deposition readily accounts for the total mass of Hg in fish, water, and sediment of Little Rock Lake, a representative temperate seepage lake in north-central Wisconsin. It is strikingly evident that modest increases in atmospheric Hg loading could lead directly to elevated levels in the fish stock. It is doubtful, given the experimental limitations in many recent studies, that the temporal pattern for Hg emissions, for background atmospheric Hg concentrations, and for changes in Hg depositional fluxes has been identified. Thus, the present and future questions of whether the environmental impact is of local, regional, or hemispheric significance remain. Contemporary investigations must address these important questions. Human exposure to methylmercury in the United States is probably increasing due to increased consumption of fish and fish products. A recent epidemiological investigation indicates high susceptibility to brain damage during prenatal exposures to Hg. An important objective for future investigation is to establish the lowest effect level for human exposure to methylmercury.

Embryotoxicity and teratogenicity study in rats dosed epicutaneously with dimethylformamide (DMF)

The reproductive effect of N,N-dimethylformamide (DMF) administered epicutaneously to rats was examined. The rats were dosed on gestation days 6-15 or on gestation days 1-20 at dose levels of up to 2 ml DMF kg-1 body weight. Body weight, weight gain and pregnancy rate were reduced in those rats receiving 2 ml DMF kg-1 body weight per day on days 6-15. A reduction in the number of live fetuses and in fetal weight, as well as an increase in postimplantation loss, were also observed at this dose level. Similar but more pronounced effects were observed in rats dosed on days 1-20 with 2 ml DMF kg-1 body weight. The lowest effect level was 1 ml DMF kg-1 body weight. No other dose-related effects were found in this study.

The toxicity and bioaccumulation of selenate, selenite and seleno-L-methionine in the cyanobacteriumAnabaena flos-aquae

A laboratory investigation was conducted to study the toxicity and bioaccumulation of seleno-L-methionine, selenate and selenite in the cyanobacterium Anabaena flos-aquae. The first sub-lethal effects of seleno-L-methionine, selenite and selenate occurred at 0.1, 3.0, and 3.0 mg/L, respectively with a decrease in chlorophyll a concentration (P less than 0.0001). Selenium bioconcentration factors (BCF) were in the order of seleno-L-methionine, selenite, and selenate. Significant decreases in intracellular selenium concentration were observed at both the no effect (NOEL) and low effect levels (LOEL) at each oxidation state tested in the given experiment (p less than 0.0001). Mechanisms for the assimilation, toxicity and regulation of selenium are presented.

Direct Estimation of Latent Time for Radiation Injury in Late-responding Normal Tissues: Gut, Lung, and Spinal Cord

Mixture models are proposed for simultaneous analysis of the latency and fractionation characteristics of radiation injury in late-responding normal tissues. The method is an extension of the direct analysis for quantal response data. Conceptually, the application of the mixture model is based on the biological observation that over a wide range of doses a proportion of the irradiated subjects will never express damage. Mixture models allow the time of occurrence to be utilized in the analysis. Furthermore, this type of model takes time-censored observations into account in a natural way and provides an adequate framework for modelling and analysis of effect-dependent latency. Mixture models with complete and incomplete repair are applied to dose-incidence data for four late endpoints in rodents: death from radiation-induced pneumonitis, leg paralysis after spinal-cord irradiation, and radiation-induced rectal stenosis and anal discharge. Radiation-induced pneumonitis had an effect-dependent latency. The modelling of this phenomenon correlates well with the results of histologic studies. Interestingly, the ratio of hazard rates was not constant for this endpoint. The dominating feature in the latency of radiation injury to the spinal cord was a strong dependency on dose per fraction. After correction for this effect a tendency towards a longer latent time for lower effect levels was observed. For the rectal complications, there was no difference between latency with radiation only vs. radiation combined with cis-platin.

The development of a protocol to assess reproductive effects of toxicants in the rat

The determination that a chemical poses a reproductive risk to man typically relies upon fertility studies using rodents. However, fertility in rodents is often difficult to disrupt and more sensitive indicators of reproductive function should be included in the risk assessment process. The present discussion compares the sensitivity of fertility to other endpoints following exposure to known reproductive toxicants. In our studies rats were dosed from weaning through puberty, gestation, and lactation. The reproductive function of the male, the female, and the offspring was assessed. The effects of methoxychlor, carbendazim (MBC), dibutyl phthalate (DBP), and lindane are discussed and compared to fertility. For each compound a ratio (SR = sensitivity ratio) of the lowest effect level (LEL) for infertility or reduced fecundity to the LEL for the most sensitive physiologic endpoint was calculated. The SR should be large when a compound produces effects over a wide range of doses, but should equal unity when the dose-response curve is very steep. For methoxychlor, which blocked implantation, pubertal landmarks and estrous cyclicity provided rapid and sensitive indicators of the subsequent reproductive failure. The SR = 8 (100/12) for methoxychlor using data from females. In contrast, DBP and MBC directed altered testicular function, and for these compounds, sperm and testicular measures provided sensitive indicators of toxicity. The SR for MBC was 2 (100/50), while DBP had a SR of 1 (500/500). In the lindane study, fertility was not reduced but most of the pups (F1) died shortly after birth. The SR for lindane is equal to 0.5 (10/20). At 20 mg/kg the treated females were larger and their estrous cycles were erratic. The data from these studies indicate that no single endpoint will consistently be the most sensitive indicator of reproductive toxicity. Studies must include a number of well validated endpoints that provide a comprehensive assessment of the entire reproductive system of the male and female.