Efficacy of two pyrethroid insecticides applied as barrier treatments for managing mosquito (Diptera: Culicidae) populations in suburban residential properties.

Increased threat of mosquito-borne disease coupled with decreased tolerance of nuisance mosquitoes has opened a market for pest management professionals to offer mosquito control services for homeowners. A pest management professional applied bifenthrin (0.08%) and lambda-cyhalothrin (0.1%) at their maximum label concentrations as barrier treatments. We tested treatments residual efficacy in reducing adult mosquito populations and compared these chemicals against a water control at 24 residential properties (eight replications by three treatments). Mosquito populations were measured on each property by using five methods: CO2-baited Centers for Disease Control (CDC) light traps (without a light), human landing rates, CDC gravid traps, ovitraps, and sweep nets. Populations were monitored weekly for 2 wk before treatment and 8 wk posttreatment. Additionally, to confirm residual efficacy of each insecticide, a randomly treated leaf underwent a no-choice bioassay with laboratory-reared Aedes albopictus (Skuse). Trap collections were dominantly Aedes albopictus and Culex pipiens L. Both insecticidal treatments significantly reduced Aedes spp. lambda-Cyhalothrin- and bifenthrin-treated sites had 89.5 and 85.1% fewer Ae. albopictus bites than the untreated control, respectively. Ae. albopictus bioassay results showed significant residual efficacy for both insecticides up to 6 wk posttreatment. There were no significant differences between properties treated with the two insecticides. In contrast, Culex spp. were not reduced by either insecticidal treatment. Our study indicated that barrier sprays applied to low-lying vegetation do not properly target adult daytime resting sites for Culex mosquitoes but that they can reduce Aedes mosquitoes. Perhaps by treating upper tree canopies Culex spp. abundance may be reduced.

Acoustic indicators for mapping infestation probabilities of soil invertebrates.

Acoustic and traditional excavation methods were used in consecutive summers to conduct two geospatial surveys of distributions of white grubs and other soil invertebrates in two forage fields. Indicator variables were constructed from listener- and computer-based assessments of sounds detected at each recording site and then applied in geostatistical analysis, contingency analysis, and spatial analysis of distance indices (SADIE) of soil invertebrate distributions. Significant relationships were identified between the acoustic indicators and the counts of sound-producing soil invertebrates in a majority of the geostatistical and contingency analyses. Significant clusterings and overall spatial associations were identified also in most of the SADIE analyses. In addition, significant local spatial associations were identified between acoustic indicators and counts of sound-producing soil invertebrates that could be of potential value in selection of specific sites as targets for treatment or for untreated reserves in integrated pest management programs. An example is presented of the relative efficiency of acoustic surveys for targeting of white grub treatments.

Life history and natural enemy associations of calico scale (Homoptera: Coccidae) in Kentucky.

Seasonal phenology of calico scale, Eulecanium cerasorum (Cockerell), was monitored for 3 yr on various deciduous tree species in central Kentucky. Infestations were found on 16 host species in six plant families. Calico scale is a univoltine parthenogenic species that overwinters as second instars on bark. Nymphs molted to adult females around mid-April and began producing eggs in late April. Mean fecundity ranged from 3,728 to 4,654 eggs per female, depending on host plant species. Date of first crawler hatch in 2001-2003 ranged from 21 to 26 May, corresponding to a mean accumulation of 818 +/- 2 Celsius degree-days (DDC), calculated from 1 January and a base of 4.4 degrees C. This value predicted crawler hatch within 2 d in Lexington, KY, in 2004. Crawler dispersal lasted 2 to 3 wk. Upon hatching, crawlers move to leaves where they feed during summer. Crawlers primarily settled on the abaxial side of leaves and their within-leaf distribution varied between different tree species. Settled crawlers molted in mid-July and second instars remained on leaves until late September through mid-October, when they returned to bark to overwinter. On hackberry, Celtis occidentalis L., they were concentrated toward the basal end of shoots, primarily because leaf flush continued beyond the end of the crawler dispersal period. Crawler distribution did not differ between upper and lower canopy zones. Fourteen species of parasitoids and a coccinellid beetle were reared from individual scales. Monitoring with sticky traps in tree canopies confirmed that targeting crawlers with insecticides during late May or June would not coincide with peak flight activity of the scale's primary parasitoids.

Role of stereochemistry in N-(3,5-dichlorophenyl)-2-hydroxysuccinamic acid (2-NDHSA) nephrotoxicity.

The nephrotoxicity induced by the agricultural fungicide N-(3,5-dichlorophenyl)succinimide (NDPS) is mediated through oxidative metabolites of NDPS. Oxidation of the succinimide ring in NDPS yields the nephrotoxic metabolites N-(3,5-dichlorophenyl)-2-hydroxysuccinimide (NDHS) and its hydrolysis product N-(3,5-dichlorophenyl)-2-hydroxysuccinamic acid (2-NDHSA). The oxidation of NDPS on the succinimide ring also introduces an asymmetric carbon atom into these NDPS metabolites, so that R- and S- enantiomers of NDHS and 2-NDHSA are possible. The purpose of this study was to begin to explore the importance of the stereochemical orientation at the asymmetric carbon atom for the nephrotoxicity induced by NDPS metabolites. Male Fischer 344 rats were administered a single intraperitoneal (ip) injection of R-(+)- or S-(-)-2-NDHSA (0.05, 0.1 or 2.0 mmol/kg) or vehicle, and renal function was monitored for 48 h. R-2-NDHSA (0.1 mmol/kg) administration had little effect on renal function. R-2-NDHSA (0.2 mmol/kg) treatment induced mild diuresis on day 1, increased proteinuria, and a small increase in blood urea nitrogen (BUN) concentration, but no change in kidney weight or glucosuria. S-2-NDHSA (0.1 mmol/kg) induced marked nephrotoxicity as evidenced by diuresis on both post-treatment days, increased proteinuria, glucosuria, and increased kidney weight and BUN concentration. No evidence of hepatotoxicity was obtained in any treated group. Thus, the S-isomer of 2-NDHSA is a more potent nephrotoxicant than the R-isomer, and stereochemistry may play a role in NDPS metabolite-induced nephrotoxicity.

First direct structural comparison of complexes of the same metal fragment to ketenes in both C,C- and C,O-bonding modes.

Using a series of Ir(I) and Rh(I) ketene complexes, conclusions about the structure and bonding of complexes of the fundamentally important ketene ligand class are reached. In a unique comparison of X-ray structures of the same metal fragment to ketenes in both the eta(2)-(C,C) and the eta(2)-(C,O) binding mode, the Ir-Cl bond distances in complexes of trans-Cl(Ir)[P(i-Pr)(3)](2) to phenylketene [4, eta(2)-(C,C)] and diphenylketene [2a, eta(2)-(C,O)] are 2.371(3) and 2.285(2) A, respectively. This would be consistent with greater trans influence of a ketene ligand bound to a metal through its C=C bond than one connected by its C=O bond. Back-bonding of Ir(I) and Rh(I) to diphenylketene was assessed using trans-Cl(M)[P(i-Pr)(3)](2)[eta(2)-(C,O)-diphenylketene] (2a and 2d). Most bond lengths and angles are identical, but slightly greater back-bonding by Ir(I) is suggested by the somewhat greater deformation of the ketene C=C=O system [C-C-O angles are 136.6(4) and 138.9(4) in the Ir and Rh cases 2a and 2d, respectively]. Syntheses of new labeled ketenes Ph(2)C=(13)C=O and Ph(2)C=C=(18)O and their Ir(I) and Rh(I) complexes are reported, along with the generation of an Ir(I) complex of PhCH=(13)C=O. The effects of isotopic substitution on infrared absorption data for ketene complexes are presented for the first time. Preliminary normal coordinate mode analysis allowed definitive assignment of absorptions ascribed to the C-O stretching frequencies of coordinated ketenes, which are near the absorptions for aromatic ring systems commonly found as substituents on ketenes. For free diphenylketene and four of its complexes and a phenylketene complex characterized by X-ray diffraction, the magnitude of the (13)C-(13)C coupling between the two ketene carbons is correlated to carbon-carbon bond distance.

Oviposition site and food preference of the green June beetle (Coleoptera: Scarabaeidae).

Relative preferences of green June beetle, Cotinis nitida (L.), adults and grubs for different organic fertilizers were determined in field and laboratory choice experiments. Six organic fertilizer treatments (low rate of broiler litter, high rate of broiler litter, cow manure, hay, Milorganite, or no fertilizer [the control]) were applied to sandy-loam soil and exposed to adults in 2.7 by 3.7 by 2.4-m screen cages. More eggs and larvae were found in pots treated with broiler litter (43%), cow manure (23%), and hay (30%) than in pots treated with Milorganite (4%) or no fertilizer (0%). Orientation preferences of third-instar grubs were tested in Y-tube and satellite olfactometers. Of the five treatments (broiler litter, cow manure, hay, Milorganite, and a blank control), preference was greatest for broiler litter and cow manure, but all organic fertilizer treatments were generally preferred over the blank control. These experiments suggest that use of organic fertilizers may result in higher densities of green June beetle grubs both by attracting the ovipositing females, and by acting as a food attractant for the mobile larvae.

Body composition and energy balance: lack of effect of short-term hormone replacement in postmenopausal women.

Postmenopausal women (PMW) commonly believe that hormone replacement (HR) leads to weight gain, and fear of weight gain and/or an actual increase in weight is one of the principle reasons evoked for the discontinuation of HR. However, the potential effects of physiologic HR on body composition have yet to be separated from the effects of lifestyle or aging. Therefore, we examined the effect of short-term hormone replacement and age on alterations in weight, body composition, and energy balance. A prospective study of 28 healthy PMW aged 45 to 55 years (younger PMW, studies completed n = 18) and 70 to 80 years (older PMW, studies completed n = 15) was conducted. The last menstrual period was more than 12 months previously. The women had a body mass index (BMI) less than 30 kg/m(2) and were taking no medication. Subjects were studied at baseline, after 1 month of transdermal estrogen (Estraderm, 50 microg/day) administration (E2), followed by a further month of transdermal estrogen with progesterone (100 mg per vagina twice daily) for the final 7 days (E2 + P). Anthropometric measurements and energy assessments were performed at each visit. Physiologic HR was achieved in each subject, and there was no difference between levels achieved in older and younger women. Resting energy expenditure and activity level were positively correlated with fat-free mass (P <.0001), while energy intake was not. Resting energy expenditure was lower in older compared with younger PMW when adjusted for fat-free mass (P <.005). Energy intake was also lower in the older PMW when corrected for fat-free mass (P <.0001); as was activity level (P <.05). There was no effect of hormonal treatment on any of the parameters measured. Changes in weight from baseline for E2 (0.37 +/- 0.25 and 0.61 +/- 0.27 kg in younger and older) and E2 + P (0.11 +/- 0.38 and 0.28 +/- 0.31 kg) were not statistically significant. In addition, there was no difference in BMI, fat mass, fat-free mass, total body water, or waist-to-hip ratio (WHR) between groups or with hormonal treatment. In conclusion, short-term transdermal HR is not associated with significant changes in weight or other anthropometric measures in younger or older PMW. These studies confirm the decrease in energy expenditure that occurs with aging, but indicates that there is no effect of HR on resting energy expenditure.

Mapping of soil insect infestations sampled by excavation and acoustic methods.

Geostatistical analysis was used to map traditionally and acoustically sampled populations of soil invertebrates at two different times in a hayfield at Grove Hill, AL, and once in an Auburn, AL, hayfield. The distributions of nearly all the soil invertebrates and their sounds were nonrandom in all three mapping studies. The maps constructed by excavation and acoustic sampling methods were compared by correlating the estimated (kriged) soil invertebrate counts with the estimated (kriged) counts of sounds per minute (pulse rate). Acoustic and traditional estimates were positively correlated in the Auburn study. Kriged estimates for green June beetle grub counts overlapped significantly with kriged estimates of sound pulse rate (R2 = 0.47). Overlap with sound pulse rates increased slightly when other soil organisms were counted along with green June beetle grubs: estimates of sound pulse rates were significantly correlated with counts of all white grubs (R2 = 0.50), all white grubs with earthworms (R2 = 0.52), all white grubs with earthworms and earwigs (R2 = 0.59), and total invertebrates (R2 = 0.59). The correlation between acoustic and traditional estimates was not significant at Grove Hill in either year, possibly because of a lack of experience in signal analysis or because the soil invertebrates may not have generated enough sounds to be detected above the background noise levels. These results suggest that acoustic technology is a promising tool for detecting insect pests in soil, but that further study and additional analysis are needed to improve interpretation of acoustic data obtained in the field.

Assessment of macronutrient and micronutrient intake in women with anorexia nervosa.

OBJECTIVE: The purpose of this study is to evaluate the accuracy of diet history compared to observed food intake in the nutritional assessment of women with anorexia nervosa (AN) and healthy age-matched controls. METHOD: One-month diet history was compared to 1-day observed food intake in 30 women with AN and 28 control subjects. RESULTS: Reported intake by diet history was similar to observed intake for macronutrient composition and fat intake for patients with AN. Reported energy intake was higher than observed intake (1,602 +/- 200 kcal vs. 1,289 +/- 150 kcal, p <.05), but was in agreement with predicted energy expenditure by the Harris-Benedict equation (1,594 +/- 18 kcal, p =.97) in patients with AN. Micronutrient intake by diet history was highly correlated with observed intake in patients with AN. More than one half of the patients with AN failed to meet the recommended dietary allowance (RDA) for vitamin D, calcium, folate, vitamin B12, zinc, magnesium, and copper when assessed by diet history. In contrast to patients with AN, diet history did not correlate with observed intake of energy, macronutrients, or most micronutrients among the controls. DISCUSSION: Diet history is an accurate tool to assess fat intake and macronutrient composition in patients with AN and demonstrates significant micronutrient deficiencies in this population. The agreement between total energy intake and predicted energy expenditure supports the overall utility of the diet history in the nutritional assessment of patients with AN.

Synthesis and structures of heterocyclic azidogallanes [(CH3)ClGaN3]4 and [(CH3)BrGaN3]3 en route to [(CH3)HGaN3]x: an inorganic precursor to GaN.

The synthesis of [(CH3)ClGaN3]4 (1) with a heterocyclic cyclooctane-like structure and [(CH3)BrGaN3]3 (2) with a trimeric structure has been demonstrated. X-ray structural determinations reveal that 1 and 2 consist of Ga4N4 eight-membered rings and Ga3N3 six-membered rings, respectively, in which the Ga atoms are bridged by the alpha nitrogens of the azide groups. [(CH3)ClGaN3]4 crystallizes in the tetragonal space group P42(1)c with a = 11.017(4) A, c = 8.699(7) A, and Z = 8. [(CH3)BrGaN3]3 crystallizes in the triclinic space group P1 with a = 8.1080(10) A, b = 9.9390(13) A, c = 10.4439(13) A, alpha = 86.069(3) degrees, beta = 86.771(3) degrees, gamma = 80.829(2) degrees, and Z = 6. The reaction of 1 and 2 with LiGaH4 yields [(CH3)HGaN3]x, which is a new low-temperature source of GaN.

Studies of the synthesis and thermochemistry of coordinatively unsaturated chelate complexes (eta 5-C5Me5)IrL2 (L2 = TsNCH2CH2NTs, TsNCH2CO2, CO2CO2).

A comparative synthetic, structural, and thermochemical study on a series of chelate complexes containing the fragment (eta 5-C5Me5)Ir [(eta 5-C5Me5)Ir(TsNCH2CH2NTs) (1), (eta 5-C5Me5)Ir(TsNCH2CO2) (2), (eta 5-C5Me5)Ir(CO2CO2) (3)] was performed to clarify the roles of carboxylato and sulfonamido ligands. Whereas 1 and 2 are monomeric in solution and in the solid state, 3 appears to exist as an oligomer or polymer, (3)n, which can be broken up by addition of a ligand L such as a phosphine, CO, or 2-methoxypyridine to form (eta 5-C5Me5)Ir(L)(CO2CO2) (6). The synthesis of (3)n from [(eta 5-C5Me5)IrCl(mu-Cl)]2 required the use of silver oxalate in CH3CN, but if other solvents were used, the bridging oxalato complex (eta 5-C5Me5)IrCl(mu-eta 2-eta 2-C2O4)ClIr(eta 5-C5Me5) (7) was obtained and identified by X-ray diffraction. Enthalpies for reaction of THF-soluble monomers 1 and 2 with PMe3 were determined to be -28.7(0.5) and -28.5(0.4) kcal mol-1, respectively. The oligomerization behavior of 3 may be a result of reduced sigma- or pi-donation of carboxylato ligands compared to N-tosylamido ligands, because the values for nu CO in oxalato and bissulfonamido complexes 6-CO and (eta 5-C5Me5)Ir(CO)(TsNCH2CH2NTs) (4-CO) were 2064 and 2042 cm-1, respectively.

Nephrotoxic potential of N-(3,5-dichloro-4-fluorophenyl)succinimide in Fischer 344 rats: comparison with N-(3,4,5-trichlorophenyl)succinimide.

Numerous structure-nephrotoxicity relationship studies from our laboratory have demonstrated that N-(3,5-dichlorophenyl)succinimide (NDPS) is one of the most potent nephrotoxicants among the N-arylsuccinimides. The purpose of this study was to extend our previous structure-nephrotoxicity relationship studies by examining the effect of addition of a fluoro verses a chloro group at the 4-phenyl position in NDPS. Male Fischer 344 rats (four rats/group) received a single intraperitoneal (i.p.) injection of N-(3,5-dichloro-4-fluorophenyl)succinimide (NDCFPS) or N-(3,4,5-trichlorophenyl)succinimide (NTCPS)(0.4 or 0.8 mmol/kg) or vehicle, and renal function monitored at 24 and 48 h. NDCFPS did not induce significant nephrotoxicity at either dose tested. In contrast, NTCPS (0.4 or 0.8 mmol/kg) induced marked nephrotoxicity characterized by diuresis, increased proteinuria, glucosuria, elevated kidney weight and increased blood urea nitrogen (BUN) concentration. NTCPS also induced marked proximal tubular necrosis at both doses tested. Neither NDCFPS nor NTCPS induced hepatotoxicity at either dose tested. The results of these experiments indicate that addition of a fluoro group at the 4-position on the phenyl ring of NDPS produces a nonnephrotoxicant NDPS derivative (NDCFPS), while addition of a chloro group at this site produces an NDPS derivative with similar nephrotoxic potential to NDPS. The mechanism for this differential effect between 4-halophenyl substitution is unclear, but may result from increased hydrolysis of the succinimide ring and/or increased clearance of N-arylsuccinimide metabolites when a fluoro group is added to the 4-position of the phenyl ring.

Report on a protocol for the active management of labor.

The authors review a protocol for the active management of labor, first developed by Kieran O'Driscoll, MB, and colleagues at the National Maternity Hospital in Dublin, Ireland, in 1969. This protocol is based on the principle that every pregnant woman would deliver within 12 hours of being admitted to the hospital. Although this approach to labor management has successfully reduced the number of cesarean sections performed in Dublin, Ireland, it has failed to do so in the United States, where active labor management has come under considerable criticism.

Couvelaire uterus.

Uteroplacental apoplexy is a rare but nonfatal complication of severe forms of placental abruption. It occurs when vascular damage within the placenta causes hemorrhaging that progresses to and infiltrates the wall of the uterus. It is a syndrome that can only be diagnosed by direct visualization or biopsy (or both). For this reason, its occurrence is perhaps underreported and underestimated in the literature. The subject of this report is a 24-year-old pregnant woman who had a placental abruption an in whom classic uteroplacental apoplexy was diagnosed at the time of her cesarean section.

Hydatidiform mole.

Hydatidiform mole is a gestational trophoblastic disease that arises from fetal rather than maternal tissue and can become metastatic. Most signs and symptoms occur late in the first trimester and are often confused with symptoms of a normal pregnancy and, thus, are often disregarded. The two most important diagnostic tools to detect this disease are the ultrasound and the quantitative beta-human chorionic gonadotropin assay. Treatment includes dilation and evacuation of the uterus and strict follow-up of quantitative beta-human chorionic gonadotropin levels. It is also important that the patient be placed on a reliable form of birth control during her follow-up period.

Nephrotoxic potential of 2-amino-5-chlorophenol and 4-amino-3-chlorophenol in Fischer 344 rats: comparisons with 2- and 4-chloroaniline and 2- and 4-aminophenol.

Nephrotoxicity occurs following intraperitoneal (i.p.) administration of 2-chloroaniline or 4-chloroaniline hydrochloride to Fischer 344 rats, but the nephrotoxicant chemical species and mechanism of nephrotoxicity are unknown. The purpose of this study was to evaluate the in vivo and in vitro nephrotoxic potential of 2-amino-5-chlorophenol and 4-amino-3-chlorophenol, metabolites of 4-chloroaniline and 2-chloroaniline. A comparison was also made between the nephrotoxic potential of the aminochlorophenols and the corresponding aminophenols to examine the effect of adding a chloride group on the nephrotoxic potential of the animophenols. Male Fischer 344 rats (4/group) were given an i.p. injection of a chloroaniline or aminochlorophenol hydrochloride (1.5 mmol/kg), and aminophenol (1.0 or 1.5 mmol/kg), or vehicle, and renal function monitored at 24 and 48 h. Both aminochlorophenols induced smaller and fewer renal effects that the parent chloroanilenes in vivo. Also, 4-aminophenol was markedly more potent as a nephrotoxicant that 4-amino-3-chlorophenol, while 2-aminophenol and 2-amino-5-chlorophenol induced only mild change in renal function. In vitro, the phenolic compounds reduce p-aminohippurate accumulation by renal cortical slices at bath concentrations of 0.01 mM, while a bath concentration of 0.50 mM or greater was required for the chloroanilines. However, all compounds reduced tetraethylammonium accumulation at bath concentrations of 0.1-0.5 mM or greater. These results indicate that extrarenally-produced aminochlorophenol metabolites do not contribute to the mechanism of chloroaniline nephrotoxicity. Also, the reduced nephrotoxic potential of 4-amino-3-chlorophenol compared to 4-aminophenol could result from an altered ability of the aminochlorophenol to redox cycle or form conjugates.

Acute renal and hepatic effects induced by 3-haloanilines in the Fischer 344 rat.

Haloanilines are commonly used as chemical intermediates in the manufacture of a wide range of products. The purpose of this study was to examine the in vivo nephrotoxic and hepatotoxic potentials of the 3-haloanilines. The in vitro effects of the 3-haloanilines on renal function were also examined. In the in vivo experiments, male Fischer 344 rats (four rats/group) were administered a single intraperitoneal (i.p.) injection of an aniline hydrochloride (1.0 or 1.25 mmol kg-1) or vehicle. Renal and hepatic function were monitored at 24 and/or 48 h post-treatment. None of the 3-haloanilines were potent nephrotoxicants at either dose level. The greatest effects on renal function were observed following administration of 3-chloroaniline at a dose of 1.25 mmol kg-1 (oliguria, glucosuria, hematuria, decreased p-aminohippurate accumulation by renal cortical slices and increased blood urea nitrogen concentration). 3-Chloroaniline also was the only aniline compound to increase plasma ALT/GPT activity at 48 h. In the in vitro experiments, the ability of an aniline (10(-5) - 10(-3) M) to decrease organic ion accumulation in renal cortical slices from untreated rats was examined. The decreasing order of in vitro nephrotoxic potential was 3-iodoaniline > 3-bromoaniline > 3-chloroaniline > aniline > 3-fluoroaniline. These results indicate that the 3-haloanilines are not potent nephrotoxicants or hepatotoxicants at sublethal doses. In addition, the reasons why the 3-haloanilines have different orders of nephrotoxic potential in vivo and in vitro are not clear at this time.

Successful re-treatment with taxol after major hypersensitivity reactions.

PURPOSE: To describe the successful re-treatment of eight patients who had major hypersensitivity reactions (HSRs) to taxol and to suggest a regimen for re-treating patients who develop major HSRs. PATIENTS AND METHODS: The treatment courses of eight patients who developed major HSRs and were rechallenged with taxol were reviewed. Patients in this report represent all patients who are known to have been rechallenged with taxol after major HSRs. RESULTS: The most common approach used to rechallenge patients consisted of premedication with multiple high doses of corticosteroids and H1- and H2-histamine antagonists followed by the initiation of the taxol infusion at a reduced rate. All patients who experienced major HSRs were rechallenged successfully. After the rechallenge, these patients received 32 additional courses of taxol without HSRs. CONCLUSION: Re-treatment with taxol after major HSRs is feasible using multiple high doses of corticosteroids and antihistamine premedications and a reduced taxol infusion rate under close supervision. This approach may represent a valid alternative to the termination of taxol; however, a prospective evaluation is required to determine the true efficacy of this approach.

Renal and hepatic toxicity of monochloroacetanilides in the Fischer 344 rat.

Chlorinated anilines are widely used chemical intermediates which have been shown to be nephrotoxicants and hepatotoxicants. A major metabolic pathway for the chloroanilines is via acetylation of the amino group to form chlorocetanilides. The purpose of this study was to examine the hepato- and nephrotoxic potential of the three monochloroacetanilides to determine if N-acetylation is an important biotransformation step for activation or detoxification of the chloroanilines in organ-directed toxicity. In one set of experiments, male Fischer 344 rats (4 rats/group) were injected intraperitoneally (i.p.) with a chloroacetanilide (CAA) (0.5, 1.0 or 1.5 mmol/kg) or vehicle and renal function monitored for 24 or 48 h. Liver function and tissue morphology also were determined at 24 or 48 h. None of the CAA were marked nephrotoxicants at doses of 0.5 or 1.0 mmol/kg. However, 4-CAA (1.5 mmol/kg) induced an increase in blood urea nitrogen concentration and kidney weight at 24 h and 3-CAA (1.5 mmol/kg) was lethal within 24 h. The decreasing order of in vivo nephrotoxic potential was found to be 4-CAA > or = 3-CAA > 2-CAA. Based on the elevation of ALT/GPT activity at 48 h, the order of hepatotoxic potential was found to be 4-CAA > 3-CAA, 2-CAA. In a second set of experiments, the in vitro effect of the chloroacetanilides on organic ion transport by renal cortical slices was examined. Both 3- and 4-CAA decreased organic ion accumulation at bath concentrations of 10(-5) M or greater, while 2-CAA had no effect at concentrations up to 10(-3) M. These results demonstrate that the order of nephrotoxic and hepatotoxic potential among the chloroacetanilide isomers is different than among the chloroanilines and that the chloroacetanilides were generally less potent as hepatotoxicants or nephrotoxicants than the corresponding chloroaniline. In addition, N-acetylation appears to be a detoxification rather than a bioactivation step in chloroaniline-induced liver or kidney injury.

Acute renal and hepatic toxicity of 2-haloanilines in Fischer 344 rats.

Aniline and its halogenated derivatives are widely used as chemical intermediates. The purpose of this study was to determine the hepatotoxic and nephrotoxic potential of the 2-haloanilines. Male Fischer 344 rats (n > or = 4) were injected (i.p.) with 1.0 or 1.25 mmol/kg of: aniline (A), 2-fluoroaniline (2-FA), 2-chloroaniline (2-ClA), 2-bromoaniline (2-BrA), 2-iodoaniline (2-IA) or vehicle (0.9% saline, 2.5 ml/kg). All compounds were injected as hydrochloride salts. Renal and hepatic function was monitored 24 h after treatment. All of the 2-haloanilines induced oliguria, diminished kidney weight, tubular casts and decreased renal cortical slice accumulation of organic anions. Blood urea nitrogen (BUN) levels were increased (P < 0.05) by treatment with 1.0 or 1.25 mmol/kg of 2-FA, 2-ClA or 2-BrA. Hepatic alterations were also observed and characterized by elevated plasma ALT/GPT activity and altered morphology in the centrilobular region. The nephrotoxic and hepatotoxic potentials were similar among the 2-haloanilines but aniline was less toxic than its 2-halo derivatives. These results demonstrated that halogen substitution at the 2-position of aniline increased hepatic and renal toxicity. However, the severity of toxicity was not influenced by the nature of the halogen substituent.