RESUMEN
Catastrophic ecological regime shifts may be announced in advance by statistical early warning signals such as slowing return rates from perturbation and rising variance. The theoretical background for these indicators is rich, but real-world tests are rare, especially for whole ecosystems. We tested the hypothesis that these statistics would be early warning signals for an experimentally induced regime shift in an aquatic food web. We gradually added top predators to a lake over 3 years to destabilize its food web. An adjacent lake was monitored simultaneously as a reference ecosystem. Warning signals of a regime shift were evident in the manipulated lake during reorganization of the food web more than a year before the food web transition was complete, corroborating theory for leading indicators of ecological regime shifts.
Asunto(s)
Ecosistema , Peces , Cadena Alimentaria , Agua Dulce , Fitoplancton , Zooplancton , Animales , Lubina , Biomasa , Clorofila/análisis , Agua Dulce/química , Modelos Biológicos , Dinámicas no Lineales , Dinámica PoblacionalRESUMEN
2-Ethylhexanol (2EH) is a weak nongenotoxic hepatic peroxisome proliferator in the rat. It is a high-volume chemical intermediate in the preparation of the plasticizers bis-(2-ethylhexyl) adipate (DEHA), bis-(2-ethylhexyl) phthalate (DEHP), and tris-(2-ethylhexyl) phosphate (TEHP), which are weak hepatocellular tumorigens in female mice. In consequence, the oncogenic potential of 2EH was evaluated in male (M) and female (F) rats and mice (50 animals/sex/group). Oral gavage doses of 2EH in 0.005% aqueous Cremophor EL (polyoxyl-35 castor oil) were given five times a week to rats: 0 (water), 0 (vehicle), 50, 150, and 500 mg/kg for 24 months, and to mice: 0 (water), 0 (vehicle), 50, 200, and 750 mg/kg for 18 months. Statistical comparisons of data were made between vehicle controls and treatment groups. There were no differences of biological significance between data from vehicle and water control groups. In rats, there were no dose-related changes at 50 mg/kg. There was reduced body weight gain at 150 mg/kg (M, 16; F, 12%) and 500 mg/kg (M, 33; F, 31%) and an increased incidence of lethargy and unkemptness. There were dose-related increases in relative liver, stomach, brain, kidney, and testis weights at sacrifice. Female rat mortality was markedly increased at 500 mg/kg. There was marked aspiration-induced bronchopneumonia in rats at 500 mg/kg; hematologic, gross, and microscopic changes, including tumors, were otherwise comparable among all rat groups. In mice at 50 and 200 mg/kg there were no dose-related changes and essentially no time-dependent or time-independent adverse trends in liver tumor incidence at the 5% significance level. At 750 mg/kg mouse body weight gain was reduced (M, 26; F, 24%), and mortality increased (M and F, 30%) versus vehicle controls. At 750 mg/kg there was a slight increase in nonneoplastic focal hyperplasia in the forestomach of mice (M 5/50, F 4/50) versus vehicle controls (M 1/50, F 1/50). There were increases in mouse relative liver (F, 21%) and stomach (M, 13%; F, 19%) weights at 750 mg/kg. There was a 12% incidence of hepatic basophilic foci and an 18% incidence of hepatocellular carcinomas in male mice at 750 mg/kg, not statistically significant compared with either control by Fisher's exact test. There was a 12% incidence of hepatic basophilic foci and a 10% incidence of hepatocellular carcinomas in female mice at 750 mg/kg, statistically significant (p < 0.05) compared with vehicle but not with water controls by Fisher's exact test. There were no metastases. Time-dependent and -independent statistical analyses showed an adverse trend in the incidence of hepatocellular carcinomas in male and female mice, correlated with toxicity (expressed as mortality) at 750 mg/kg. The time-adjusted incidence of hepatocellular carcinomas in male mice (18.8%) was within the historical normal range at the testing facility (0-22%), but that in females (13.1%) lay outside the normal range (0-2%). Under the conditions of these studies 2EH was not oncogenic in rats, but there were weak adverse trends in hepatocellular carcinoma incidence in mice at high dose levels which may have been associated with toxicity. The major effects of chronic dosing were mortality in female rats at 500 mg/kg and in male and female mice at 750 mg/kg, accompanied by reductions in body weight gain in rats at 150 and 500 mg/kg and in mice at 750 mg/kg. Direct comparison of any tumorogenic effects of 2EH given alone to female mice with those due to 2EH formed in vivo from DEHA, DEHP, or TEHP is limited by the high mortality caused by 2ER in female mice at equivalent doses of 2EH. While 2EH may be a contributing factor in the hepatocellular carcinogenesis in female mice associated with the chronic administration of DEHA and DEHP, it is unlikely to be the entire proximate carcinogen.
Asunto(s)
Carcinógenos/toxicidad , Hexanoles/toxicidad , Animales , Conducta Animal/efectos de los fármacos , Recuento de Células Sanguíneas/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Pruebas de Carcinogenicidad , Carcinógenos/administración & dosificación , Ingestión de Alimentos/efectos de los fármacos , Femenino , Hexanoles/administración & dosificación , Intubación Gastrointestinal , Masculino , Ratones , Ratones Endogámicos , Tamaño de los Órganos/efectos de los fármacos , Vehículos Farmacéuticos , Ratas , Ratas Endogámicas F344RESUMEN
Data on the subchronic toxicity of 2-ethylhexanol (2EH) were required to establish the dose vehicle and dose levels for oncogenicity studies. In preliminary studies 2EH was given subacutely (11 days) to male and female Fischer 344 rats and B6C3F1 mice as an aqueous emulsion by oral gavage (0, 100, 330, 1000, and 1500 mg/kg/day). Clinical observations were made, body weights, food consumption, clinical chemistries, hematologies, and selected organ weights were measured, and gross and micropathologies were performed. Target organs were the central nervous system, liver, forestomach, spleen, thymus, and kidney in rats and the central nervous system, liver, and forestomach in mice. 2EH was then administered by oral gavage to male and female F344 rats and B6C3F1 mice as an aqueous emulsion (0, 25, 125, 250, and 500 mg/kg/day) for 13 weeks. At 500 mg/kg/day in the rat there was reduced body weight gain (6% male, 7% female), increased relative liver (29% male, 15% female), kidney (16% male, 6% female), stomach (11% male, 16% female), and testes (6%) weights, and moderate gross and microscopic changes in the liver and forestomach. There were no behavioral effects or effects on the spleen or thymus. A no-effect level for target organ effects in the rat was 125 mg of 2EH/kg/day. At 500 mg of 2EH/kg/day in the mouse the only effects were increased relative stomach weights in males (13%) and a low incidence of gross and microscopic findings in the forestomach (male and female) and liver (female). A no-effect level for target organ effects in the mouse was 125 mg of 2EH/kg/day. 2EH was a peroxisome proliferator in the rat but not in the mouse at subchronic dose levels of 500 mg/kg/day. Dose levels in oncogenicity studies were set at 50 mg/kg/day for the absence of treatment-related effects in rats and mice, and 500 and 750 mg/kg/day, respectively, in rats and mice as high doses producing minimal toxicity without altering the life span.
Asunto(s)
Hexanoles/toxicidad , Plastificantes/toxicidad , Administración Oral , Animales , Peso Corporal/efectos de los fármacos , Química Clínica , Femenino , Hexanoles/administración & dosificación , Hígado/efectos de los fármacos , Hígado/enzimología , Masculino , Ratones , Microcuerpos/efectos de los fármacos , Tamaño de los Órganos/efectos de los fármacos , Palmitoil Coenzima A/efectos de los fármacos , Palmitoil Coenzima A/metabolismo , Plastificantes/administración & dosificación , Ratas , Ratas Endogámicas F344 , Pruebas de Toxicidad , Transaminasas/sangre , Transaminasas/efectos de los fármacosRESUMEN
Undiluted 2-ethylhexanol (2-EH) was administered by occluded dermal application for 6 hr per day on Gestation Days 6 through 15 to pregnant Fischer 344 rats, in range-finding (R) and main (M) studies. The dermal route is considered to be the most relevant for human exposure. Treatment levels were (R) 0.0, 0.5, 1.0, 2.0, and 3.0 ml/kg/day (equivalent to 0, 420, 840, 1680, and 2520 mg/kg/day) and (M) 0.0, 0.3, 1.0, and 3.0 ml/kg/day (equivalent to 0, 252, 840, and 2520 mg/kg/day). Controls (0.0 ml/kg/day, sham controls) received deionized water at 3.0 ml/kg/day. Dermal-positive control groups received undiluted 2-methoxyethanol (2-ME) at (R) 0.5 and 1.5 ml/kg/day and (M) 1.0 ml/kg/day as a reference compound in a similar regimen. An oral reference compound, valproic acid, was administered by gavage in the range-finding study on Gestation Days 6 through 15 at 400 mg/kg/day. The range-finding study employed an untreated (naive) control group. Numbers of plug-positive females per group were (R) 8 and (M) 25. Maternal weight gain was reduced for 2-EH at 1680 (R) and 2520 (R and M studies) mg/kg/day. Exfoliation and encrustation were seen at the application site in both studies at 840, 1680, and 2520 mg/kg. Maternal liver, kidney, thymus, spleen, adrenal, and uterine weights, and gestational and fetal parameters were unaffected by treatment with 2-EH. There were no treatment-related increases in the incidence of individual or pooled external, visceral, and skeletal malformations or variations following the application of 2-EH. The NOAELs for the maternal toxicity of 2-EH were 252 mg/kg/day based on skin irritation and 840 mg/kg/day based on systemic toxicity. The developmental toxicity NOAEL was at least 2520 mg/kg/day, with no teratogenicity. Administration of 2-ME at 840 mg/kg/day resulted in reduced maternal weight gain and food consumption, increased postimplantation loss, reduced numbers of live fetuses per litter, and reduced fetal body weights per litter. The incidence of fetal malformations and variations was increased. Oral administration of VPA produced maternal toxicity, developmental toxicity, and teratogenicity. The Fischer 344 rat is thus susceptible to known rodent teratogens by both the dermal and oral routes. It is concluded that 2-EH is not developmentally toxic by the dermal route in the Fischer 344 rat at and below treatment levels which produce maternal toxicity.
Asunto(s)
Hexanoles/toxicidad , Plastificantes/toxicidad , Teratógenos/toxicidad , Administración Cutánea , Animales , Peso Corporal/efectos de los fármacos , Anomalías Congénitas , Relación Dosis-Respuesta a Droga , Glicoles de Etileno/toxicidad , Femenino , Hexanoles/administración & dosificación , Tamaño de los Órganos/efectos de los fármacos , Embarazo , Ratas , Ratas Endogámicas F344 , Ácido Valproico/toxicidadRESUMEN
Parameters of a phosphorus cycling model were estimated for two configurations of a lake ecosystem. The piscivore-dominated configuration had one more trophic level than the planktivore-dominated configuration. We derived four main conclusions from analysis of the model. (1) Results support the argument of DeAngelis et al. that turnover rate of a limiting nutrient is directly related to ecosystem resilience. (2) Results support the hypothesis of Pimm and Lawton that longer food chains are less resilient. (3) Inputs of phosphorus to the pelagic system derived from inshore feeding by fishes were a large flux, which is comparable to inputs from physical-chemical fluxes. (4) Algal (seston) standing crops, unlike all other compartments, were less sensitive to phosphorus inputs in the piscivore-dominated system. Consistent with the trophic cascade hypothesis, the piscivore-dominated system had higher herbivore standing crops and lower algal standing crops than the planktivore-dominated system. Changes in trophic structure that derive from trophic cascades can be viewed as changes in the phosphorus cycle driven by fishes.
RESUMEN
The results of these studies demonstrate that Tri(2-ethylhexyl)trimellitate (TOTM) produces the sam spectrum of morphological and biochemical changes in the rat liver as di(2-ethylhexyl)phthalate (DEHP). TOTM, however, was much less potent in its action, with a dietary level of 2.0%, causing less peroxisome proliferation and enzyme induction than 0.67% DEHP. Also, these studies show that the level of peroxisome induction in rats given TOTM is less than in those receiving a metabolically equivalent dose of 2-ethylhexanol (2-EH). Furthermore, on a molar basis, effects were lower than with DEHP. A "monoester effect" of the kind attributed to MEHP, a metabolite of DEHP, was not seen with TOTM.
Asunto(s)
Hexanoles/toxicidad , Microcuerpos/efectos de los fármacos , Plastificantes/toxicidad , Animales , Benzoatos/toxicidad , Dietilhexil Ftalato/toxicidad , Relación Dosis-Respuesta a Droga , Femenino , Hígado/efectos de los fármacos , Masculino , Ratas , Ratas Endogámicas F344 , Factores SexualesRESUMEN
We performed whole-lake manipulations of fish populations to test the hypothesis that higher trophic levels regulate zooplankton and phytoplankton community structure, biomass, and primary productivity. The study involved three lakes and spanned 2 yr. Results demonstrated hierarchical control of primary production by abiotic factors and a trophic cascade involving fish predation. In Paul Lake, the reference lake, productivity varied from year to year, illustrating the effects of climatic factors and the natural dynamics of unmanipulated food web interactions. In Tuesday Lake, piscivore addition and planktivore reduction caused an increase in zooplankton biomass, a compositional shift from a copepod/rotifer assemblage to a cladoceran assemblage, a reduction in algal biomass, and a continuous reduction in primary productivity. In Peter Lake, piscivore reduction and planktivore addition decreased zooplanktivory, because potential planktivores remained in littoral refugia to escape from remaining piscivores. Both zooplankton biomass and the dominance of large cladocerans increased. Algal biomass and primary production increased because of increased concentrations of gelatinous colonial green algae. Food web effects and abiotic factors were equally potent regulators of primary production in these experiments. Some of the unexplained variance in primary productivity of the world's lakes may be attributed to variability in fish populations and its effects on lower trophic levels.
RESUMEN
Di-(2-ethylhexyl)phthalate (DEHP) and its two major metabolites, mono-(2-ethylhexyl)phthalate (MEHP) and 2-ethylhexanol (EH), were tested for genetic activity in both the Salmonella/mammalian microsome mutagenicity (Ames) assay and the L5178Y TK+/- mouse lymphoma cell mutagenicity assay. All chemicals were tested in both the presence and absence of Aroclor-induced liver microsomes prepared from male Sprague-Dawley rats. Dose levels for both assays were selected from preliminary toxicity studies for each chemical. Neither DEHP, MEHP, nor EH exhibited any significant mutagenic activity in strains TA-98, TA-100, TA-1535, TA-1537, and TA-1538 in the Ames test or when tested in the L5178Y TK+/- mouse lymphoma cell mutagenicity assay.
Asunto(s)
Dietilhexil Ftalato/toxicidad , Hexanoles/toxicidad , Leucemia L5178/genética , Leucemia Experimental/genética , Mutágenos , Mutación , Ácidos Ftálicos/toxicidad , Animales , Biotransformación , Dietilhexil Ftalato/análogos & derivados , Ratones , Microsomas Hepáticos/metabolismo , Pruebas de Mutagenicidad , Plastificantes , Salmonella typhimurium/efectos de los fármacos , Relación Estructura-ActividadRESUMEN
Di-(2-ethylhexyl)phthalate (DEHP) and its two major metabolites, mono-(2-ethylhexyl)phthalate (MEHP) and 2-ethylhexanol (EH), were evaluated for their ability to induce chromosomal damage in male Fischer 344 rats after oral administration. Dose levels, the highest of which represents one-tenth of the five-day LD50, were based on a preliminary five-day dose-finding study for each test material. The dose levels selected were 5.0, 1.7, and 0.5 ml/kg/day for DEHP; 0.14, 0.05 and 0.01 ml/kg/day for MEHP; and 0.21, 0.07 and 0.02 ml/kg/day for EH. All test materials and vehicle control (corn oil) were administered by gavage for five consecutive days. A triethylenemelamine (TEM)-positive control group received a single intraperitoneal injection of 0.5 mg/kg TEM one day prior to sacrifice. Of the 50 metaphase bone marrow cells examined from each animal, no significant increase in chromatid and chromosome breaks or structural rearrangements were noted for DEHP, MEHP, and EH. In addition, the mitotic index, determined from 100 cells per animal, was unaffected by DEHP, MEHP, or EH. The results of this investigation indicate that DEHP, MEHP, and EH, at these dose levels, did not induce detectable chromosomal aberrations after oral administration.
Asunto(s)
Dietilhexil Ftalato/toxicidad , Hexanoles/toxicidad , Mutágenos , Ácidos Ftálicos/toxicidad , Animales , Dietilhexil Ftalato/análogos & derivados , Masculino , Mitosis/efectos de los fármacos , Ratas , Ratas Endogámicas F344RESUMEN
The structural similarity between antileukemic alkaloid coralyne and the carcinogenic and antineoplastic hydrocarbon 7, 12-dimethylbenz[a]anthracene, as well as the similarity between the antileukemic alkaloid nitidine and the carcinogenic hydrocarbon 5-methylchrysene, prompted a mutagenicity evaluation of coralyne sulfoacetate, nitidine chloride, the 8-ethyl homolog of coralyne, nitidine methosulfate, and the tetramethoxy analog of nitidine by the Ames method against the histidine-auxotroph strains of Salmonella typhimurium TA-1537, TA-1538, TA-98, and TA-100; 7,12-dimethylbenz[a]anthracene was used as a reference standard. The mutagenicity of these antileukemic compounds was either completely eliminated or drastically reduced, but the mutagenic response was generally high for 7,12-dimethylbenz[a]anthracene. The results suggest that the presence of a quaternary nitrogen atom and alkoxy groups could be important in alleviating the mutagenicity of the parent mutagenic and carcinogenic hydrocarbons.