Substrate-mediated toxicity of deltamethrin residues to beneficial invertebrates: Estimation of toxicity factors to aid risk assessment

Laboratory bioassays were carried out to determine the toxicity of residues of the synthetic pyrethroid insecticide, deltamethrin ((S)--cyano-3-phenoxybenzyl (1R)-cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropanecarboxylate) to a range of beneficial invertebrates exposed to treated wheat foliage, sandy loam soil, and glass surfaces. The test invertebrates represented a range of predators and a parasitoid that inhabit the foliage and grounds layers of temperate cereal crops, i.e., Pterostichus melanarius (Illiger), Nebria brevicollis (F.), Demetrias atricapillus (L.) and Bembidion obtusum (Serville) (Coleoptera: Carabidae), Tachyporus hypnorum (F.) (Coleoptera: Staphylinidae), Coccinella septempunctata (L.) (Coleoptera: Coccinellidae) adults (A) and larvae (L), Episyrphus balteatus (Degeer) (Diptera: Syrphidae), and Aphidius rhopalosiphi (De Stefani-Perez) (Hymenoptera: Braconidae). In 2 h flag leaf exposure bioassays, the LD₅₀ values varied from 0.4 g ai/ha to >50 g ai/ha. The susceptibility ranking, from most to least susceptible, was C. septempunctata (L) > T. hypnorum > C. septempunctata (A) > E. balteatus > A. rhopalosiphi > D. atricapillus. On soil, the LD₅₀ values were 52.8 g ai/ha for T. hypnorum and 97.8 g ai/ha for C. septempunctata (A) after 2 h exposure. This period of exposure was, however, found to be of insufficient duration to separate the susceptibilities of the other test species adequately, and therefore 72 h exposure bioassays were also carried out. The 72 h LD₅₀ values varied between 4.2 g ai/ha and 267 g ai/ha. The susceptibility ranking, from most to least susceptible, was T. hypnorum > B. obtusum > C. septempunctata (A) > P. melanarius > N. brevicollis > D. atricapillus. In 2 h glass bioassays the LD₅₀ range was 1.2 g ai/ha to >37 g ai/ha and the susceptibility ranking was T. hypnorum > C. septempunctata (A) > N. brevicollis, and D. atricapillus. Residual toxicities in the different 2 h exposure bioassays were compared for T. hypnorum and C. septempunctata (A) by iterating sequences of lethal dose ratios between LD₁₀ and LD₉₀ from the dose-response statistics for each respective pair of substrates. The mean ratios were termed toxicity factors (Tf). Tf values comparing glass and flag leaf assays, were 0.98 and 1.23, respectively for T. hypnorum and C. septempunctata (A), indicating that the toxicity of fresh deltamethrin residues to both species was similar on these surfaces. Tf values comparing either glass or flag leaf and soil were however in the range of 50–60 for T. hypnorum and C. septempunctata (A), indicating much lower effects on soil. Estimates of the bioavailable half-life on leaf and soil, obtained from in situ bioassays, indicated that effects in the field may vary two- to threefold as a result of differences in the duration of toxicity on these substrates. Overall, T. hypnorum could be at more than 150 times greater risk on leaf compared to soil surfaces. The potential for extrapolating laboratory toxicity data to the field is discussed.     

Exposure of urban applicators to carbaryl

Thirty-eight urban volunteers from the Lincoln and Omaha, Nebraska areas were monitored for carbaryl exposure during the summer of 1979. All volunteers were involved in the application of carbaryl incidental to their employment or leisure activities. The investigators made no attempt to affect the method of carbaryl application. The mean rates of carbaryl exposure were 3.85 and 0.26g cm^–2 hr^–1, respectively, for the outside of the clothing and the skin beneath the clothing; clothing apparently provided an effective barrier to carbaryl penetration. The rate of carbaryl exposure to the hands of applicators was 2.36 and 24.96g cm^–1 hr^–1, respectively, for applicators with and without gloves. The maximum dermal exposure recorded in this study was 2.86 mg kg^–1 hr^–1 which is significantly less than the stimated dermal LD₅₀ value for carbaryl (4000 mg kg^–1). The maximum air concentration of carbaryl was 0.28g L^–1, far less than the Threshold Limit Value of 5g L^–1. Only a small mean decrease was found in the applicators serum (–1.01%) or erythrocyte (–1.39%) acetylcholinesterase activity. Although some applicators had decreases in either serum or erythrocyte acetylcholinesterase activity greater than 20%, an equal number had increases of the same magnitude. The mean total carbaryl exposure to the applicators, expressed as a percent of toxic dose per hr, was 0.01%, with a maximum estimated exposure of 0.08%.Published with the permission of the Director of the Nebraska Agric. Exp. Sta. as Journal Article No. 6001. This research was funded as Grant No. 85-288-042-01 & 02 from the North Central Regional Pesticide Impact Assessment Program, USDA/SEA-CR.     

A dose-effect relationship for the effect of deltamethrin on a linyphiid spider population in winter wheat

The relationship between application rate and effect of deltamethrin (Decis^®) on a linyphiid spider population was studied in relation to ambient physical factors. A field experiment using five application rates and a control was conducted in winter wheat plots. The aim was to determine application rates that allowed for determination of negative as well as positive effects of physical factors on arthropod toxicity using pitfall traps. Several physical variables were measured in the crop canopy and deltamethrin deposition was determined at ground level. The use of Before-After-Control-Impact design (BACI) time series analysis for characterization of instantaneous pesticide effects and velocity of recovery, relative to the application rate sprayed was evaluated.An initial reduction in spider catches ranging from 58% to 85% percent for sprayed concentrations of 0.25 to 4 g active ingredient per hectare (ai ha^–1) was observed, followed by exponential recovery with a half-life time of 2.8 days for all treatments. The effects observed in this study were relatively mild compared to other field-experiments. It was concluded that an application rate near 0.25 g ai ha^–1 deltamethrin (i.e., one twentieth of the recommended rate) would be sufficient to study the relationship between physical factors and the effects of deltamethrin. BACI time series analysis was shown to be a useful technique for characterizing short-term pesticide effects.     

Toxicity of iodine,iodide, and iodate to Daphnia magna and rainbow trout (Oncorhynchus mykiss)

The acute toxicity (96-h LC₅₀) of aqueous stable iodine species (I^–, IO ₃ ^– , I₂) to rainbow trout and Daphnia magna were measured at three individual concentrations of hardness, total organic carbon, and chloride. Rainbow trout were most sensitive to I₂ (LC₅₀0.53 mg/L), and much less sensitive to IO ₃ ^– (LC₅₀220 mg/L) or I^– (LC₅₀860 mg/L). Daphnia magna were equally sensitive to I₂ (LC₅₀0.16 mg/L) and I^– (LC₅₀0.17 mg/L), but were less sensitive to IO ₃ ^– (LC₅₀10.3 mg/L). The external and internal radiological dose imparted by equivalent molar quantities of radioactive ¹²⁵I, ¹²⁹I, and ¹³¹I were calculated for both the Daphnia and trout using the LC₅₀ values obtained from a standard water treatment. As expected, the dose from ¹²⁵I and ¹³¹I would exceed the expected lethal dose rate long before a chemically toxic level is reached. In contrast, a molar concentration of ¹²⁹I likely to cause death by chemical toxicity would impart a radiological dose less than that expected to be lethal. Thus, for short-lived aquatic organisms, risks due to chemical toxicity of ¹²⁹I may exceed risks due to its radioactive emissions.     

Hydrolysis and photolysis of hexachlorocyclopentadiene

The radioactivity on adding ¹⁴C-Hexachlorocyclopentadiene (Hex) to water (7 7gmg/L) decreased by 18% on Day 2 and by 31 to 55% by Day 42. On Day 42, the radioactivity remaining in water consisted of apolar (petroleum ether-extractable), polar (ethyl acetate-extractable), and hydrophilic hydrolysis products with Hex amounting to only 8% of the total radioactivity. The time for Hex to reach 50, 10, and 5% of its initial concentration was estimated to be about 4, 27, and 40 days, respectively. The hydrolysis rate constant compared to 4×10³ hr^–1 as reported in literature. The apolar radioactivity (25% of total) consisted of Hex and a major product as judged by gas chromatography (GC). The polar products resolved into 10 and hydrophilics into 14 different compounds as examined by thinlayer chromatography.The photolysis of Hex in acetone occurred very rapidly (t_1/2=<1 day) with no trace of Hex after 15 days. Most of these products were more polar than Hex as examined by GC. These products on thin-layer chromatography (TLC) separated into two major zones. Further TLC of each of these zones showed products of one zone to resemble those of aqueous hydrolysis. The other zone represented apolar products which resolved into three peaks by HPLC, the major one of these appeared to have an empirical formula of C₆Cl₇O (m/e=408) as analyzed by GCMS.The 8-h photolysis products' mixture had an LT₅₀ to goldfish Carassius auratus of 22 h compared to 15 h for Hex. The 96-h LT₅₀ value of the 15-day photolysis products' mixture was 2,300 compared with 119 g/L for Hex. Thus, Hex in water as well as on exposure to light breaks down to less toxic products.     

Environmental impact of mosquito pesticides: Toxicity and anticholinesterase activity of chlorpyrifos to fish in a salt marsh habitat

Chlorpyrifos was tested for its influence on thein vitro andin vivo brain acetylcholinesterase (AChE) activity ofFundulus heteroclitus under laboratory as well as field conditions. The concentration required for a 50% reduction in the mvitro enzyme activity (I₅₀) was 7.2 × 10^–2 mM for the parent compound and 4.1 × 10^–6 mM for its oxygen analog. A 96-hr exposure of live fish to 1.0g/L chlorpyrifos resulted in a maximum AChE inhibition of 24%. At a concentration of 2.1g/L or higher, a 100% enzyme inhibition was observed after a 24-hr exposure period, followed by varying degrees of recovery during the next 24 hr. A second peak of AChE inhibition, proportional to the concentration of the insecticide, was observed 72 hr after the initial exposure and this was followed by a second phase of recovery during the next 24 hr. In spite of an initial 100% AChE inhibition at test concentrations of 2.1g/L and above, the fish mortality was less at lower concentration of the insecticide than at the higher levels. The 96-hr TL₅₀ and TL₅ (tolerance limit for 50% and 5% fish survival) of chlorpyrifos forF. heteroclitus were 4.7g/L and 12.2g/L, respectively. The LT₅₀ (lethal time in which 50% of the fish died) at a concentration of 5.6g/L was 49.5 hr.Fish exposed to 4 successive field applications of chlorpyrifos granules showed AChE inhibition ranging from 56 to 100% and the insecticide effect was cumulative in nature. By 24 hr after the second application, 18.6% of the treatment fish had died; live fish collected at this time showed a 96% depression of AChE activity. AChE inhibition was still evident (62%) in fish 69 days after the final application of chlorpyrifos.Paper of the Journal Series, New Jersey Agricultural Experiment Station, Rutgers-The State University of New Jersey, New Brunswick, New Jersey 08903, USA. Supported by a grant from N. J. State Mosquito Commission.     

Na+, K+-ATPase,glutathione, and hydroxyl free radicals in cadmium chloride-induced testicular toxicity in mice

Cadmium chloride (CdCl₂)-induced biochemical changes were characterized in male, CD-1 mouse testes. CdCl₂ inhibited the testes microsomal Na^–, K^–-ATPase activity in vitro and in vivo. The inhibitory range was 30–50 m and the concentration for half maximal inhibition (IC50 value) was 90 m over 5 min preincubation. CdCl₂ (2mg/kg/day, s.c.) for 2 days significantly inhibited testes Na^–, K^–-ATPase (near 90% inhibition). The content of testicular GSH and the ratio of reduced glutathione (GSH)/GSSG (oxidized glutathione) decreased in CdCl₂-treated groups. Using salicylate as a trapping agent and high pressure liquid chromatography with electrochemical detection (LCED), we measured the OH production in vivo. 2,5-dihydroxybenzoic acid (2,5-DHBA) and 2,3-dihydroxybenzoic acid (2,3-DHBA) as indices of hydroxyl free radical formation significantly increased after 5 days CdCl₂ exposure. Pretreatment with vitamin E (20 mg/kg, s.i.d., i.m., 7d) protected CdCl₂-induced increase in OH generation in testes. From this study, it was demonstrated that CdCl₂ induced testicular toxicity could possibly be mediated by a significant increase in hydroxyl free radical formation and a reduction in GSH content and Na^–, K^–-ATPase activity. Vitamin E seems to prevent the CdCl₂ induced increase in hydroxyl free radical generation.     

Bioconcentration of 5,5′,6 -trichlorobiphenyl and pentachlorophenol in the midge,Chironomus riparius,as measured by a pharmacokinetic model

A two compartment pharmacokinetic model was developed which describes the uptake and elimination of 5,5,6-trichlorobiphenyl (TCB) and pentachlorophenol (PCP) in the midge, Chironomus riparius. C. riparius were exposed to nominal TCB (2 g L^–1) and PCP (9 g L^–1) concentrations during a 16 h static uptake phase. Depuration was determined over approximately 45 h using a flowthrough system without feeding. The uptake clearance (P) was 330±61 ml g^–1 midge h^–1 for TCB and 55±4 ml g^–1 midge h^–1 for PCP, while measured bioconcentration factors (BCF) were 35,900 and 458 for TCB and PCP, respectively. Overall, the clearance-volume-based pharmacokinetic model predicted BCF values that were consistent with published values as well as with BCF values obtained from the octanol-water partition coefficient (K_OW).     

Quantitative structure-toxicity relationships and volume fraction analyses for selected esters

The acute toxicity of aliphatic and aromatic mono and diesters in two eucaryotic organisms was compared. The test systems were the static 2-d Tetrahymena pyriformis 50% population growth impairment (IGC ₅₀ ^–1 ) assay, and the flow-through 4-d Pimephales promelas 50% mortality (LC ₅₀ ^–1 ) assay. In ciliates, esters act via the nonpolar narcosis mechanism of toxic action. This was indicated by: the high quality 1-octanol/water partition coefficient (log K_ow) dependent quantitative structure-activity relationship (QSAR), log IGC ₅₀ ^–1 =0.79 (log K_ow)–1.93, n=15, r²=0.945, s=0.22, f=222.37 Pr>f=0.0001); volume fraction (V_f) (0.8e-02); and a coefficient (0.3) which are not different from other nonpolar narcotics. In vivo hydrolysis in Tetrahymena appears to be insignificant. However, in fish, presumably because of more active esterases, in vivo hydrolysis is significant and leads to greater toxicity of esters than observed for nonpolar narcotics. Moreover, it leads to a unique high quality QSAR, log LC ₅₀ ^–1 =0.64 (log K_ow)–0.64, n=14, r²=0.945, s=0.22, f=207.08, Pr>f=0.0001). Due to in vivo hydrolysis, a nonreducing concentration gradient is formed between water and fish. Therefore, the fish take up more toxicant as compared to a situation that leads to thermodynamic equilibrium. Additional information about the mechanism of ester toxicity in fish was gained by applying corrections for hydrolysis in volume fraction analyses. The corrected V_f (0.6e-02) is very close to the one found for nonpolar narcotics (0.7e-02). These analyses suggest that esters which hydrolyze to an acid and aliphatic alcohol act as nonpolar narcotics. Moreover, the mechanism of toxic action of esters that yield a phenol upon hydrolysis is mixed and represents polar and nonpolar narcoses.     

Chlorflurenol-methyl in soil: Degradation,leaching, and effects on microbiological processes

Tests were conducted with the synthetic growth regulator chlorflurenol-methyl to investigate its rate of degradation in soil, leaching behavior, and possible side-effects on the soil microflora and on soil physiological processes. With two sandy soils (C_t=1.0 and 2.58%) which were treated with 11.35 mg kg^–1 chlorflurenol-methyl (-2.8 kg a.i. ha^–1), over 90% of the compound disappeared within 4 to 8 days. The degradation products were 2-chloro-9-hydroxyfluorene-9-carboxylic acid and 2-chlorofluorenone, which undergo further decomposition. In leaching tests with three sandy soils (C_t =0.69, 1.0 and 2.58%), chlorflurenol-methyl was not washed from the soil; however, with one soil (0.69% C), very small residues were observed in the effluent identified as 2-chlorofluorenone. In sideeffects experiments with a parabrown (C_t=1.26%) and a chernozem soil (C_t=2.3%), which were treated with 1 and 10 mg kg^–1 chlorflurenolmethyl, no persistent inhibition of anaerobic or aerobic nitrogen fixation (C₂H₂-reduction) was detected. Ammonification, nitrification, and mineralization of soluble starch were also not influenced. The mineralization of cellulose in compost soil (C_t=13.59%) was temporarily delayed; however, this delay was later compensated for by a higher mineralization rate. The colonization density of fungi on soil particles and the numbers of bacteria, actinomycetes, and fungi were not negatively influenced. Chlorflurenol-methyl does not significantly influence these microbiological processes and populations in the soil.     

Experimental human exposure to carbon disulfide

Summary Six human volunteers were exposed to 10 and 20 ppm carbon disulfide at rest and to 3 and 10 ppm carbon disulfide under a 50 W level of physical exercise during four consecutive periods of 50 min. At the start of the experiments, at the end of the exposure periods and during the post-exposure period, urine was sampled and the concentration of 2-thiothiazolidine-4-carboxylic acid (TTCA) was determined. It was established that only a small percentage, ranging from 0.7 to 2.2% of the absorbed carbon sulfide was transformed into TTCA. The excretion rate of TTCA (mol TTCA h^–1) was found to be the best parameter in evaluating the respiratory uptake of carbon disulfide over a range of 37.9 to 163.3 mg CS₂ compared to the urinary concentration of TTCA (mole TTCA ml^–1) or the creatinine corrected concentration of TTCA (mmol TTCA mol^–1 creatinine). The total amount of TTCA (mol TTCA) excreted proved to be independent of the urinary flow (ml h^–1), the estimates of the individual fatty tissue content and the urinary pH. No correlation was found between the respiratory uptake of carbon disulfide (mg CS₂) and the excretion rate of TTCA within each exposure condition of 3, 10 or 20 ppm carbon disulfide, respectively.     

Copper/Metal Ratios in the Gills of Rainbow Trout (Oncorhynchus mykiss) Provide Evidence of Copper Exposure Under Conditions of Mixed-Metal Exposure

Previous work has suggested that the ratio of copper residues to zinc in the gills of rainbow trout may indicate short-term exposure to increased levels of waterborne copper. However, the effect of exposure to a combination of increased copper and zinc concentrates in the water column was unknown. We exposed rainbow trout to 8 ± 2 g L^–1, 40 ± 2 g L^–1 and 90 ± 9 g L^–1 of waterborne copper and 21 ± 3 g L^–1, 129 ± 40 g L^–1, and 202 ± 40 g L^–1 of waterborne zinc in a 2-factor experiments and gill copper and zinc residues were examined. Other gill parameters analyzed included the concentrations of calcium, magnesium, sodium, and potassium, liver copper and zinc concentrations and plasma copper, calcium, sodium, and potassium are also reported here. Copper residues in the gill filaments were significantly higher in the highest level of copper exposure (high Cu, 4.06 g g^–1; low Cu 2.41 g g^–1; 0 Cu 2.01 g g^–1; P = 0.001), whereas no differences were seen in zinc concentrations at any treatment level. Gill sodium and plasma calcium concentrations were also decreased at the highest waterborne copper concentrations. Although copper–zinc ratios in the gills were significantly different between the highest and lowest copper treatments (P = 0.002, F = 6.59), copper–sodium and copper–magnesium ratios were more sensitive to waterborne copper exposure (P = 0.001, F = 17.91 and P = 0.002, F = 15.45, respectively). These copper–metal ratios may be better indicators of copper loading in the water column.     

High tolerance of lampreys to Kepone® toxicity

Larval sea lampreys (Petromyzon marinus) were exposed to the organochlorine insecticide Kepone^® in freshwater solution in a continuous flow diluter system at 12 and 20°C. At 12°, the 36-hr LC50, 96-hr LC50, and incipient lethal concentrations were 1,100, 444 and 145 g Kepone/ L, respectively, while at 20°, the 96-hr LC50 was 414 g/L. These are the highest LC50 values for Kepone ever reported for a fish species. Rates at which larval lampreys accumulate and clear Kepone were measured at 12°C. The depuration rate constant (K_d: 0.13–0.46 per day) was the highest ever reported in a fish species, so rapid elimination may contribute to the exceptional ability of lampreys to survive acute Kepone poisoning. The uptake rate constant (K_u) was 450–650 per day, and the bioconcentration factor averaged about 1900. The most likely source of high tolerance of lampreys to Kepone is an ability to withstand high tissue levels: Lampreys survived body burdens of 500–600 g Kepone/g, exceeding all other known vertebrates. Technical difficulties associated with the use of Kepone solutions are discussed, such as precipitation and loss from solution through apparent volatilization.     

Organ-Specific Toxicokinetics and Dose–Response of Arsenic in Tilapia <Emphasis Type="Italic">Oreochromis mossambicus</Emphasis>

We appraised organ-specific toxicokinetics and dose responses of arsenic burdens in tilapia Oreochromis mossambicus. We kinetically linked an Area-under-the-curve (AUC)–based acute toxicity model and a pharmacodynamic model to derive dose–response relationships between equilibrium organ-specific arsenic concentrations and mortality effects. The AUC-based acute toxicity model was also used to derive organ-specific internal effect concentration (IEC)–time-response relationships, which can also be applied to predict a time–mortality profile. We conducted a 7-day exposure experiment to obtain toxicokinetic parameters, whereas the AUC-based acute toxicity model was verified with LC₅₀(t) data obtained from a 7-day acute toxicity bioassay. Our results demonstrated that 96-hour LC₅₀ and incipient LC₅₀ for tilapia exposed to arsenic are 28.68 (95% confidence interval to 24.92 to 32.44) and 25.55 mg L^–1, respectively. Dose–response relationships followed the Hill equation, which could be expressed as organ-specific bioconcentration factors and incipient LC₅₀. Organ-specific dose-response relationships showed that muscle, gill, and liver have a relatively steep sigmoid dose-response profile in that IEC₅₀ were 26.6, 62.5, and 78.5 g g^–1 dry wt (dw), respectively. Organ-specific arsenic internal lethal burdens were the highest in the gill and the lowest in the muscle in waterborne-exposed tilapia. The IEC and target-organ concentrations derived in this study can be used in site-specific risk assessment.     

Effect of mercury on unidirectional sodium and calcium influx inAsellus aquaticus

The effect of mercuric chloride (HgCl₂) and monomethyl mercury chloride (CH₃HgCl) on unidirectional²²Na and⁴⁵Ca influx were measured in the freshwater isopodAsellus aquaticus. Flux measurements involved short-term (20 min) exposure to²²Na or⁴⁵Ca following 2 h pre-exposure to Hg. Experiments were conducted at two different Na and Ca concentrations, 0.025 mmol L^–1 and 0.25 mmol L^–1.HgCl₂ and CH₃HgCl inhibited Na influx at both Na concentrations although Na influx at 0.25 mmol L^– was always higher. This reflected the uptake kinetics of the Na pump which was determined to be saturable with a k_max values of 32 mol Na g^–1 h^–1 and a Km value of 0.8 mmol L^–1. CH₃HgCl generally resulted in relatively greater inhibition of Na influx. At 0.025 mmol NaL^–1 all CH₃HgCl concentrations tested were inhibitory to Na influx, i.e., the lowest observed effect concentration (LOEC) was <0.04 mol L^–1.Ca influx was inhibited by HgCl₂ at all concentrations tested (LOEC <0.04). The degree of inhibition was unaffected by Ca concentration, which was seen as evidence for non-competitive inhibition. However, CH₃HgCl, which inhibited Ca influx from 0.025 mmol Ca L^–1 by >68% at molar Hg concentrations 1 mol L^–1 showed no significant inhibitory affect at 0.25 mmol Ca L^–1. Elimination of CH₃HgCl inhibition at the higher Ca concentration suggests competition in this case, possibly at the level of access to the Ca pump.Contribution No. 2230 of the Center for Environmental and Estuarine Studies, The University of Maryland System.     

Effectiveness of glyphosate and imazamox on the control of the invasive cordgrass Spartina densiflora

The south-American cordgrass, Spartina densiflora, has become the dominant plant species on recent tidal marsh restorations in the Doñana National Park (SW Spain). We examined the effect of different doses of glyphosate (720–7200 g a.i. ha⁻¹) and imazamox (20–68 g a.i. ha⁻¹) on growth and photosynthetic apparatus of S. densiflora. Imazamox had no effect on neither on growth nor photosynthetic apparatus of S. densiflora. On the contrary, glyphosate inhibited photochemical efficiency of photosynthesis from day one. Net photosynthetic rate, stomatal conductance and photosynthetic pigments and the number of new tillers were reduced. Glyphosate at high doses (ca. 7200 g a.i. ha⁻¹) could be an appropriate method of control, since it has a negative effect over the photosynthetic apparatus and growth of S. densiflora. Furthermore, glyphosate and its main metabolite, AMPA, were not extracted from the soil, since they were retained by the very high iron and aluminum oxide content of this soil.     

Photo-induced toxicity of anthracene to the green alga,Selenastrum capricornutum

The photo-induced toxicity of the polycyclic aromatic hydrocarbon (PAH), anthracene, to the green alga, Selenastrum capricornutum, was characterized. The dose-response relationships among anthracene concentration, ultraviolet (UV) radiation intensity, and algal growth rate and ¹⁴C-bicarbonate incorporation were determined. The 22 h EC₅₀ for specific growth rate was inversely related to UV-A radiation intensity and ranged from 37.4 to 3.9 g/L anthracene. For ¹⁴C-bicarbonate incorporation on a volume basis (primary production), the 24 h EC₅₀ ranged from 24.0 to 3.3 g/L anthracene depending on the UV-A intensity. The incorporation of ¹⁴C-bicarbonate on a per cell basis (cellular photosynthesis) was more resistant than cell growth or primary production. The threshold for photo-induced toxicity of anthracene was 1.5–3 g/L anthracene, however, no UV-A radiation threshold was evident for many of the measurements of toxicity studied. Algae appeared to be slightly more resistant to photo-induced toxicity of anthracene than fishes and invertebrates. An environmental hazard assessment suggests that some aquatic systems are sufficiently contaminated by PAH that a hazard to natural algal communities due to photo-induced toxicity of PAH may be present.     

Cardiorespiratory and thermal effects of wearing gas protective clothing

Summary Six healthy men aged 25 to 37 walked on a treadmill at work levels of 21 and 41% of their for 25 to 30 min wearing gas protective clothing (GPC) consisting of an impermeable suit with a self-contained breathing apparatus (total weight 25 kg) or shorts (control tests, CT) in a temperate environment (t _a 24.3°C ± 1.0°C, rh 30–50%). When the GPC was worn at 21 and 41% , the most prominent increases, compared with the CT, were noted in the heart rate ( ± SE, 120 ± 5 vs 76 ± 3 beats min^–1 and 171 ± 5 vs 103 ± 3 beats min^–1), mean skin temperature (36.1 ± 0.2 vs 31.3° C ± 0.1°C and 36.9 ± 0.3 vs 30.9°C ± 0.4°C) and sweat rate (473 ± 51 vs 70 ± 23 g m^–2 h^–1 and 766 ± 81 vs 135 ± 18 g m^–2 h^–1) indicating a high cardiovascular and thermoregulatory strain, which was not decreased by ventilating the suit with an air flow of 281 min^–1 at 41% . The ventilation, oxygen consumption and production of carbon dioxide increased in relation to the extra weight of the GPC, partly dependent on the dynamic work level. It was concluded that the increase in the physiological load caused by the GPC was so high that the work-rest regimens, workers' level of physical fitness, cardiovascular health and heat tolerance should be considered whenever gas protective clothing is used.     

A single-dose and 3-month clinical—pharmacokinetic study with a new combination oral contraceptive

The study was performed in 14 young women. The combination oral contraceptive contained 75 g gestodene (GSD) and 20 g ethinyl estradiol (EE₂) per dosage unit. The volunteers received a single dose on day 21 of a treatment-free precycle (PCd21) and, after a washout period of 7 days, used the preparation in a 21 d/7 d schedule for three months. Daily drug serum level profiles were taken on PCd21 and on days 1 and 21 of treatment cycles 1 and 3. In addition, trough drug serum levels were followed every other day during treatment cycles 1 and 3. Serum levels of GSD, EE₂, CBG, SHBG and testosterone (T) were determined by means of specifically developed or commercially available RIAs. Pharmacokinetic evaluation was carried out with TOPFIT and parameters were evaluated for differences with thet-test. Main target variables wereC _max,t _max and AUC for EE₂, GSD and unbound GSD on day 21, cycle 3 vs. PCd21.EE₂ pharmacokinetics were in agreement with a dose of 20 g/unit. Single-doseC _max of 65 pg/ml and AUC of 612 pg h ml^–1 increased by 40–60% during treatment cycles as a result of accumulation. EE₂ induced basal SHBG (102 nmol/L) and CBG (42 g/ml) serum levels to about 220 nmol/L and 87 g/ml, respectively, at the end of treatment cycles 1 and 3.Serum T levels dropped to 50% of baseline levels during treatment cycles and free T concentrations were reduced by 60–70%. GSD pharmacokinetics at the end of treatment cycles 1 and 3 were different from single-dose pharmacokinetics. Single-doseC _max of 3.5 ng/ml and AUC_{0–24 h} of 22 ng h ml^–1 increased to steady-state levels of 8–8.7 ng/ml and 90–106 ng h ml^–1, respectively. The increase in GSD levels under treatment is the result of two parallel processes, i.e. accumulation and enlargement of the specific binding compartment. This was shown by protein-binding experiments, demonstrating an increase in specific (SHBG) binding from 69% to 80% and a reduction in the free fraction of GSD by 40% during treatment.The results of GSD and EE₂ pharmacokinetics obtained in the present study confirm previous results with Femodene, when the reduction in the EE₂ dose by 10 g/d is taken into account.

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Resumen Este estudio se realizó con 14 mujeres jóvenes. La combinación de anticonceptivos orales contenía 75 g de gestodén (GDS) y 20 g de etinil estradiol (EE₂) por unidad de dosificación. Las voluntarias recibieron una sola dosis en el vigésimo primer día de un preciclo sin tratamiento (PCd21) y, después de un período de interrupción de siete días — utilizaron la preparación al séptimo día de un programa de 21 días durante tres meses. Se obtuvieron perfiles diarios del nivel sérico de los fármacos en el PCd21 y en los días 1 y 21 de los ciclos del primer y tercer ciclo de tratamiento. Además, se realizó el seguimiento de los niveles séricos mínimos de los fármacos cada dos días durante el primer y tercer ciclo de tratamiento. Los niveles séricos de GSD, EE₂, CBG, SHBG y testosterona (T) se determinaron mediante RIA específicamente desarrollados o comercialmente disponibles. La evaluación farmacocinética se realizó con TOPFIT y se evaluaron las diferencias de los parámetros con el test-t. Las principales variables a determinar fueronC _máx,t _máx y AUC para EE₂, GSD y GSD no ligado al vigésimo primer día del tercer ciclo en comparación con PCd21.La farmacocinética de EE₂ guardaba conformidad con una dosis de 20 g/unidad. LaC _máx de dosis única de 65 pg/ml y AUC de 612 pg h ml^–1 aumentó en un 40–60% durante los ciclos de tratamiento debido a la acumulación. EE₂ indujo niveles séricos de SHBG basal (102 nmol/l) y CBG (42 g/ml) de aproximadamente 220 nmol/l y 87 g/ml, respectivamente, al final del primer y tercer ciclo de tratamiento.Los niveles séricos de T se redujeron al 50% de los niveles de línea de referencia durante los ciclos de tratamiento y las concentraciones de T libre se redujeron en un 60–70%. La farmacocinética del GSD al concluir el primer y tercer ciclo de tratamiento fue diferente de la correspondiente a la dosis única. LaC _máx de dosis única de 3,5 ng/ml y AUC_0–24h de 22 ng h ml^–1 aumentó a niveles de estado estable de 8–8,7 ng/ml y 90–106 ng h ml^–1, respectivamente. El aumento de los niveles de GSD con el tratamiento se debe a dos procesos paralelos, es decir, acumulación y ampliación del compartimiento específico de ligazón. Esto se demostró mediante experimentos de ligazón de proteínas, que señalaron un aumento de la ligazón específica (SHBG) del 69% al 80% y una reducción de la fracción libre de GSD en un 40% durante el tratamiento.Los resultados de la farmacocinética de GSD y EE₂ obtenidos en el presente estudio confirman resultados anteriores con Femodene, al tenerse en cuenta la reducción de la dosis de EE₂ en 10 g/d.

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Resumé Cette étude a été réalisée sur 14 jeunes femmes. Le contraceptif oral combiné contenait 75 g de gestodène (GSD) et 20 g d'éthinyl oestradiol (EE₂) par dose unitaire. Les volontaires ont reçu une dose unique au vingt et unième jour du cycle préliminaire sans traitement (CPj21) et — après une période de 7 jours de sevrage — elles ont absorbé la préparation selon une posologie de 2lj/7j pendant trois mois. Les profils journaliers du taux sérique du produit ont été établis au jour CPj21 et aux jours 1 et 21 des cycles de traitement 1 et 3. En outre, on a suivi tous les deux jours, durant les cycles 1 et 3 du traitment, les taux sériques inférieurs du produit. On a déterminé, selon des méthodes de RIA spécifiquement mises au point ou commercialement disponibles, les taux sériques de GSD, EE₂, CBG, SHBG et testostérone (T). L'évaluation pharmacocinétique a été exécutée à l'aide du TOPFIT et les paramètres ont été évalués en vue de déterminer les différences avec les résultats du test-t. Les principales variables ciblées étaient lesC _max,t _max et ASC pour l'éthinyl oestradiol, GSD et GSD non lié, au jour 21 du cycle 3 par rapport au CPj21.La pharmacocinétique de l'EE₂ correspondait à une dose de 20 g/unité. LeC _max d'une dose unique de 65 pg/ml et l'ASC de 612 pg h ml^–1 augmentaient de 40 à 60% durant les cycles de traitement par suite d'accumulation. L'EE₂ induisait des taux sériques de SHBG de base (102 nmol/l) et de CBG (42 g/ml) d'environ 220 nmol/l et 87 l/ml respectivement à la fin des premier et troisième cycles.Les taux sériques de T tombaient à 50% des niveaux de base durant les cycles de traitement et les concentrations de T libre étaient réduites de 60 à 70%. La pharmacocinétique du GSD à la fin des cycles de traitement 1 et 3 était différente de celle d'une dose unique. LesC _max d'une dose unique de 3,5 ng/ml et l'ASC_0–24h de 22 ng h ml^–1 augmentaient jusqu'à des niveaux stables de -8,7 ng/ml et 90–106 ng h ml^–1 respectivement. La hausse des taux de GSD durant le traitement résulte de deux processus parallèles: accumulation et élargissement du compartiment spécifiquement liant. Ce fait est démontré par des expériences de liaison des protéines, lesquelles indiquent une liaison spécifique accrue (SHBG), passant de 69 à 80% et une réduction de la fraction libre de GSD de 40% au cours du traitement.Les résultats de la pharmacocinétique du GSD et de l'EE₂ obtenus dans la présente étude confirment ceux obtenus précédemment avec le Femodene, lorsque la réduction de 10 g/j de la dose de EE₂ est prise en compte.

     

Cadmium Alters the Biotransformation of Carcinogenic Aromatic Amines by Arylamine N-Acetyltransferase Xenobiotic-Metabolizing Enzymes: Molecular,Cellular, and in Vivo Studies

Background

Cadmium (Cd) is a carcinogenic heavy metal of environmental concern. Exposure to both Cd and carcinogenic organic compounds, such as polycyclic aromatic hydrocarbons or aromatic amines (AAs), is a common environmental problem. Human arylamine N-acetyltransferases (NATs) are xenobiotic-metabolizing enzymes that play a key role in the biotransformation of AA carcinogens. Changes in NAT activity have long been associated with variations in susceptibility to different cancers in relation with exposure to certain AAs.

Objective

We explored the possible interactions between Cd and the NAT-dependent biotransformation of carcinogenic AAs.

Methods

We exposed purified enzymes, lung epithelial cells, and mouse models to Cd and subsequently analyzed NAT-dependent metabolism of AAs.

Results

We found that Cd, at biologically relevant concentrations, impairs the NAT-dependent acetylation of carcinogenic AAs such as 2-aminofluorene (2-AF) in lung epithelial cells. NAT activity was strongly impaired in the tissues of mice exposed to Cd. Accordingly, mice exposed to Cd and 2-AF displayed altered in vivo toxicokinetics with a significant decrease (~ 50%) in acetylated 2-AF in plasma. We found that human NAT1 was rapidly and irreversibly inhibited by Cd [median inhibitory concentration (IC₅₀) ≈ 55 nM; rate inhibition constant (k_inact) = 5 × 10⁴ M⁻¹ · sec⁻¹], with results of acetyl coenzyme A (acetyl-CoA) protection assays indicating that Cd-mediated inhibition was due to the reaction of metal with the active-site cysteine residue of the enzyme. We found similar results for human NAT2, although this isoform was less sensitive to inactivation (IC₅₀ ≈ 1 μM; k_inact = 1 × 10⁴ M⁻¹ · sec⁻¹).

Conclusions

Our data suggest that Cd can alter the metabolism of carcinogenic AAs through the impairment of the NAT-dependent pathway, which may have important toxicological consequences.