Os Exposure Research Articles

The Effect of Combined Exposure of Fusarium Mycotoxins on Lipid Peroxidation, Antioxidant Defense, Fatty Acid Profile, and Histopathology in Laying Hens' Liver.

Fumonisin B1, T-2 toxin, and deoxynivalenol are frequently detected in feed materials. The mycotoxins induce free radical formation and, thereby, lipid peroxidation. The effects of mycotoxin exposure at the EU recommended limit (T-2/HT-2 toxin: 0.25 mg/kg; DON = 3AcDON/15-AScDON: 5 mg/kg; fumonisin B1: 20 mg/kg) and double dose (T-2/HT-2 toxin: 0.5 mg/kg, DON/3-AcDON/15-AcDON: 10 mg, and FB1: 40 mg/kg feed) were investigated during short-term (3 days) per os exposure in the liver of laying hens. On day 1 higher while on day 3 lower MDA concentrations were found in the low-dose group compared to the control. Fatty acid composition also changed: the proportion of monounsaturated fatty acids increased (p < 0.05) and the proportion of polyunsaturated fatty acids decreased by day 3. These alterations resulted in a decrease in the index of unsaturation and average fatty acid chain length. Histopathological alterations suggested that the incidence and severity of liver lesions were higher in the mycotoxin-treated laying hens, and the symptoms correlated with the fatty acid profile of total phospholipids. Overall, the findings revealed that mycotoxin exposure, even at the EU-recommended limits, induced lipid peroxidation in the liver, which led to changes in fatty acid composition, matched with tissue damage.

Investigating conspecific CsRV1 transmission in Callinectes sapidus

A reo-like virus, CsRV1, is found in blue crabs, Callinectes sapidus, from every North American location assessed, including Chesapeake Bay and the Atlantic and Gulf coasts, USA and associated with blue crabs in softshell production. CsRV1-associated crab mortality is prevalent in captive crabs, but it is still unknown how CsRV1 is transmitted. The purpose of this study was to examine the role that conspecific predation or scavenging may play in per os transmission in single exposure and repeated exposure experiments. For viruses without cell culture propagation, repeated exposure experiments have the challenge of presenting the virus consistently during the experiment and across time replicates. In a single-exposure experiment, none of the crabs fed muscle tissue of crabs carrying intense infections of CsRV1 developed CsRV1 infections. In a repeated-exposure trial, using infected muscle tissue prepared in alginate blocks, CsRV1 was detected in 11% of the crabs fed infected tissue but was not significantly different from the control group fed alginate lacking CsRV1. For repeated per os exposure experiments, the study demonstrated the utility of using alginate to present the same homogenous sample of virus, both injected and per os, over time for oral challenge experiments. Conspecific predation and scavenging could be a transmission route, but future work into this and other possible routes of transmission for CsRV1 is important to better understand the role this virus plays in wild crab populations and the soft-shell crab industry.

Efficacy and safety exposure-response relationships of apalutamide in patients with metastatic castration-sensitive prostate cancer: results from the phase 3 TITAN study.

Apalutamide plus androgen-deprivation therapy (ADT) has been approved for treatment of patients with metastatic castration-sensitive prostate cancer (mCSPC) based on data from phase 3 TITAN study. This analysis was conducted to describe pharmacokinetics of apalutamide and N-desmethyl-apalutamide and explore relationships between apalutamide exposure and selected clinical efficacy and safety observations. 1052 patients were randomized to apalutamide + ADT (n = 525) or placebo + ADT (n = 527). A previously developed population pharmacokinetic model was applied. Cox regression analysis investigated the relationships between apalutamide exposure and overall survival (OS; n = 1004) and radiographic progression-free survival (rPFS; n = 1003). Logistic regression analysis assessed the relationships between apalutamide exposure and selected clinically relevant adverse events (n = 1051). Apalutamide + ADT treatment was efficacious in extending rPFS and OS versus placebo + ADT. Within a relatively narrow apalutamide exposure range (coefficient of variation: 22%), no statistical association was detected between rPFS, OS and apalutamide exposure quartiles. Incidence of skin rash and pruritus increased significantly with increasing apalutamide exposure. Differences in apalutamide exposure were not associated with clinically relevant differences in rPFS or OS in patients with mCSPC. Patients with increased apalutamide exposure are more likely to develop skin rash and pruritus. Dose reductions may improve these adverse events, based on an individual risk-benefit approach.

123P Clinical and environment factors impacting malignant pleural mesothelioma prognosis

While previous studies have investigated prognostic variables in malignant pleural mesothelioma, there continues to be imprecisions with models aimed to inform prognosis. Thus, we decided to investigate the association between OS, smoking or asbestos exposure, neutrophil to lymphocyte ratio (NLR), and change in tumor thickness (TT) following neoadjuvant therapy.

Transcriptional analyses of acute per os exposure and co-exposure of 4-vinylcyclohexene and methylmercury-contaminated diet in adults of Drosophila melanogaster

Continuous exposure to low levels of toxic substances can be associated with delayed physical disturbances, which can be preceded by changes in enzyme activities and gene expression. Thus, understanding changes in the transcriptional profile could help in recognition of early molecular events involved in the toxicity mechanism of toxicants. Vinylcyclohexene (VCH) and methylmercury (MeHg+) are xenobiotics, which do not present a completely elucidated mechanism of toxicity. Metabolites of both compounds have some overlapping chemical properties that involve moderate to high affinity for thiol and selenol groups. In this work, we characterized by deep-sequencing transcriptomic approach the effects of VCH and MeHg+ on the mRNA transcriptional profile of adults fruit flies (Drosophila melanogaster) after individual and concomitant exposure to VCH and MeHg+. The flies were separated into four groups: control, VCH, MeHg+, and VCH + MeHg+. After individual exposure, VCH deregulated 38 genes (of which the majority was up-regulated), whereas MeHg+ altered 26 genes (i.e., 14 down-regulated). VCH and MeHg+ co-exposure changed 72 genes with a high number of genes down-regulated. Together, the results suggest that although the compounds could have some similar protein targets (e.g., sulfhydryl-containing proteins), the transcriptional profile after individual exposures and co-exposure were completely different.

EXPERIMENTAL INFECTIONS OF MILKY HEMOLYMPH DISEASE IN SPINY LOBSTER Panulirus homarus

Milky hemolymph disease of spiny lobster (MHD-SL) is categorized as the most destructive disease in farming spiny lobster. Therefore, it is required to investigate the routes of milky disease infection in spiny lobster as a basic knowledge in order to prevent milky disease transmission. The aim of the present study was to perform an experimental infection of milky disease in spiny lobster Panulirus homarus. Experimental infection of milky disease was carried out by several modes of infection which were injection, immersion and per os exposure. Injection of each 0.2 mL undiluted and diluted hemolymph from the diseased lobster resulted in a cumulative mortality of 100% at 15 days post-infection (dpi), and 75% at 16 dpi, respectively. Experimental infection through water immersion caused in a cumulative mortality of 50% at 7 dpi. In contrast, no mortality was observed in per os exposure as well as in control groups. Results of this experimental study provided evidence for horizontal transmission of MHD-SL among P. homarus. Histopathological analysis exhibited that there were masses of Rickettsia-like bacteria (RLB) in the connective tissues of the gill, hepatopancreas, gonad, midgut, and muscle tissues of the affected lobsters. Mass of RLB was not only found in the moribund lobsters but also in the surviving lobsters with milky hemolymph appearance.

Effect of zearalenone on circulating testosterone concentration, testicular and epididymal morphology and epididymal sperm characteristics in wild boars

This study investigated the effect of exposure to zearalenone (ZEN) and its metabolites on the characteristics of epididymal spermatozoa, testicular and epididymal biometry and histology, and the concentration of testosterone in blood plasma in male wild boars. The study was performed during more than one year on 18 clinically healthy male wild boars with initial and final body weight, of 39 ± 4 kg and 59 ± 3 kg, respectively. The animals were divided into two experimental groups (group I and group II) and one control group (group C) comprising 6 boars per group. Group I animals were administered per os pure zearalenone (ZEN) at 150 μg/kg BW for 7 consecutive days every two months, while group II animals received a dose of 50 μg/kg BW/day via feed that was naturally contaminated with ZEN. These male wild boars were exposed to ZEN over a period of 1 year. Control animals were fed a placebo. Testicles with epididymides of the boars were collected on the last day of the experiment within 3 min after slaughter. Blood samples were collected from each of the male wild boars. Testes and epididymides were measured and sampled for histological examination. Epididymides were dissected and epididymal spermatozoa were harvested. The spermatozoa were diluted with swine-specific BTS extender and stored at 17°C for 144 h. Sperm motility was analyzed with CASA, and other parameters including viability, acrosome integrity, DNA fragmentation index, lipid peroxidation and apoptosis were assessed with flow cytometry. In these wild boars, per os exposure to natural sources of ZEN or a combination of ZEN and its metabolites changed the testicular interstitium and led to modification of some epididymal sperm parameters. The interstitial glands in testes of experimental group I were markedly reduced and hyperemic with evident blood stasis in small capillaries. Also in group I were single degenerating seminiferous tubules. In both groups I and II, immediately after dilution of spermatozoa with BTS remarkable decreases in motility rate as well as in progressive motility and the subpopulation of cells with rapid movement were noted compared with the control group (P < 0.05). But unexpectedly, after 24 h incubation of boar semen in the BTS diluent, these sperm properties improved and were not significantly different from the control group. Thus, exposure to ZEN has no lasting but only a temporary, reversible effect on wild boar sperm motility. There was no influence of exposure to ZEN and its metabolites on the integrity of membranes, intensity of lipid peroxidation and apoptosis or on sperm chromatin structure. This study is the first using these direct measures of sperm motility and integrity to show a redundant adverse effect of ZEN exposure on wild boar sperm characteristics. There were no effects of exposure to ZEN and its metabolites on body weight, testicular and epididymal biometry, gonadosomatic index and the concentration of testosterone in blood plasma in the male wild boars.

Zearalenone and its metabolites in the tissues of female wild boars exposed per os to mycotoxins

The study was performed on 18 clinically healthy female wild boars with initial body weight of 35 ± 2 kg. The animals were divided into two experimental groups (group I and group II) and one control group (group C) of 6 female wild boars per group. Group I animals were administered per os pure zearalenone (ZEN) at 150 μg/kg BW every two months for 7 subsequent days, whereas group II animals received feed naturally contaminated with ZEN at 50 μg/kg BW/day. Female wild boars were exposed to ZEN over a period of 1 year. Control group animals were fed a placebo. Tissue samples (dorsal muscles, left lobe of liver, left kidney, spleen, apical part of the cardiac muscle, cranial lobe of lung, left ovary, central part of the left horn of the uterus) were collected on the last day of the experiment within 3 min after slaughter. In group I, the highest ZEN levels were noted in the spleen (19.813 ng/g), cardiac muscle (18.105 ng/g) and kidneys (14.555 ng/g). In group II, the highest concentrations of ZEN were observed in muscle tissue (12.033 ng/g), uterus (10.821 ng/g) and kidneys (10.463 ng/g). The highest values of the carry-over factor were noted in the same tissues. In the examined female wild boars, per os exposure to natural sources of the parent substance or a combination of ZEN and its metabolites led to different concentrations of ZEN in the analyzed tissues. Zearalenone concentrations were compatible with CF values in both experimental groups.

Enhancement of the Musca domestica hytrosavirus infection with orally delivered reducing agents

House flies (Musca domestica L.) throughout the world are infected with the salivary gland hypertrophy virus MdSGHV (Hytrosaviridae). Although the primary route of infection is thought to be via ingestion, flies that are old enough to feed normally are resistant to infection per os, suggesting that the peritrophic matrix (PM) is a barrier to virus transmission. Histological examination of the peritrophic matrix of healthy flies revealed a multilaminate structure produced by midgut cells located near the proventriculus. SEM revealed the PM to form a confluent sheet surrounding the food bolus with pores/openings less than 10nm in diameter. TEM revealed the PM to be multilayered, varying in width from 350 to 900nm, and generally thinner in male than in female flies. When flies were fed on the reducing agents dithiothetriol (DTT) or tris (2-caboxyethyl)phosphine hydrochloride (TCEP) for 48h before per os exposure to the virus, infection rates increased 10- to 20-fold compared with flies that did not receive the reducing agent treatments. PM’s from flies treated with DTT and TCEP displayed varying degrees of disruption, particularly in the outer layer, and lacked the electron-dense inner layer facing the ectoperitrophic space. Both drugs were somewhat toxic to the flies, resulting in>40% mortality at doses greater than 10mM (DTT) or 5mM (TCEP). DTT increased male fly susceptibility (55.1% infected) more than that of females (7.8%), whereas TCEP increased susceptibility of females (42.9%) more than that of males (26.2%). The cause for the sex differences in response to oral exposure the reducing agents is unclear. Exposing flies to food treated with virus and the reducing agents at the same time, rather than pretreating flies with the drugs, had no effect on susceptibility to the virus. Presumably, the reducing agent disrupted the enveloped virus and acted as a viricidal agent. In summary, it is proposed that the reducing agents influence integrity of the PM barrier and increase the susceptibility of flies to infection by MdSGHV.

692P - Influence of Primary Pancreatic Tumor Location on Efficacy and Treatment Exposure in the Mpact Trial of Nab-Paclitaxel (Nab-P) Plus Gemcitabine (Gem) Vs Gem Alone for Patients with Metastatic Pancreatic Cancer (Mpc)

ABSTRACT Aim: The prognosis of pancreatic cancer may be influenced by the primary tumor location within the pancreas. In the phase III MPACT trial, nab-P + Gem demonstrated superior efficacy vs Gem alone as first-line treatment for MPC (median overall survival [OS]: 8.5 vs 6.7 mo; hazard ratio [HR] 0.72; P Methods: Previously untreated pts (N = 861) with MPC and baseline bilirubin ≤ upper limit of normal were randomized 1:1 to receive nab-P 125 mg/m2 + Gem 1000 mg/m2 on d 1, 8, and 15 of each 28-d cycle or Gem 1000 mg/m2 weekly for 7 wk followed by 1 wk of rest (cycle 1) and then d 1, 8, and 15 of each 28-d cycle (cycle ≥ 2). In this analysis, OS, PFS, and treatment exposure were analyzed according to primary tumor location. Results: nab-P + Gem demonstrated superior survival vs Gem alone, independent of the primary tumor location (Table). Tumor location did not appear to be associated with any differences in treatment exposure. The median cumulative dose of nab-P was 1500 mg/m2 vs 1375 mg/m2 in pts who had primary tumors in the head vs tail or body. The most common grade ≥ 3 adverse events in pts with pancreatic head tumors for nab-P + Gem vs Gem (neutropenia [35% vs 26%], peripheral neuropathy [21% vs 1%], and fatigue [18% vs 9%]) were similar to those in the intent-to-treat (ITT) population. Efficacy by Primary Tumor Location Efficacya nab-P + Gem Gem HR P Value Head n (%) 191 (44) 180 (42) - Median OS, mo 9.3 6.5 0.59 Median PFS, mo 5.5 3.7 0.53 Other n (%) 237 (55) 246 (57) - Median OS, mo 8.1 6.9 0.80 0.033 Median PFS, mo 5.4 3.7 0.74 0.013 a PFS by independent assessment. Conclusions: nab-P + Gem demonstrated superior efficacy vs Gem alone. This effect remained clinically and statistically significant regardless of the primary tumor location. These findings are consistent with previous efficacy findings in the ITT population from MPACT. No new safety signals were observed. Disclosure: W.W. Ma: has received research funding and honoraria from Celgene; M. Stahl: I am an advisor to Celgene and receive honoraria; B. Lu: is an employee of Celgene and owns stock; D. Penenberg: Owns stock in Celgene and is a Celgene employee; D. D Von Hoff: is a consultant/advisor to Celgene and has received honoraria from them. He also received research funding from TGen Clinical Research. All other authors have declared no conflicts of interest.

Streptococcosis in farmed Litopenaeus vannamei: a new emerging bacterial disease of penaeid shrimp

Presumptive systemic streptococcal infections were detected histologically in farmed Litopenaeus vannamei juveniles submitted from a Latin American country and the bacteria isolated. Characterization work demonstrated that the Gram-positive cocci form chains, grow aerobically and anaerobically, are oxidase- and catalase-negative, non-hemolytic, non-motile, Lancefield Group B positive and PCR positive when amplified with a universal streptococcal primer set. Differing Streptococcus identifications were obtained using API 20 Strep and Biolog systems, the former identifying the isolate as S. uberis and the latter as S. parauberis. Injection of specific pathogen-free (SPF) L. vannamei with the bacteria resulted in 100% mortality by 3 d post-injection with successful recovery of the agent from moribund test shrimp hemolymph samples. The recovered isolate was used in per os and waterborne exposure studies of SPF L. vannamei with mortalities ranging from 40 to 100% and 80 to 100%, respectively. Histologic analysis of 5 to 8 moribund shrimp from each exposure method demonstrated that all contained a severe bacteremia characterized by numerous free cocci within the hemolymph and aggregates of vacuolated hemocytes with notable intravacuolar cocci. This unique lesion type was most pronounced within the lymphoid organ and considered pathodiagnostic for this disease. Experimentally induced lesions were identical to those in naturally infected farmed shrimp and the Streptococcus sp. responsible was re-isolated, fulfilling Koch's postulates. Five freeze/thaw cycles of 10 experimentally infected shrimp were performed over a 2 mo period and the bacteria successfully cultured from all shrimp at each interval. These collective findings describe the first reported case of streptococcosis in marine penaeid shrimp in the Western Hemisphere and indicate that the agent may be disseminated via live or frozen infected shrimp.

Experimental infection of Pacific white shrimp Litopenaeus vannamei with Necrotizing Hepto-pancreatitis (NHP) bacterium by per os exposure

Necrotizing Hepatopancreatitis Bacterium (NHPB), which causes Necrotizing Hepatopancreatitis, was successfully transmitted in individually isolated Kona stock Litopenaeus vannamei through per os exposure. Animals (140) were individually exposed orally to a 0.05 g piece of an NHPB-infected hepatopancreas and 120 control animals were each exposed to a 0.05 g piece of NHPB-negative hepatopancreas. Shrimp were maintained in Sterilite containers with approximately 41 of artificial seawater at 30 per thousand salinity and 30 degrees C for 60 d. Mortality of infected shrimp was observed from Day 16 to Day 51 post-exposure. Infected animals sustained reduced feeding activity and displayed empty guts. Some infected animals developed a pale hepatopancreas noticeable through the carapace. Survival probabilities fit a Weibull distribution and parametric survival analysis revealed lowered survival due to NHPB infection. Median survival time of NHPB-infected animals was 34.5 d. After correcting for background daily mortality in the controls, mean acute daily mortality of NHPB was estimated at 0.09, a value much lower than that estimated for other diseases in Kona stock L. vannamei such as White Spot Syndrome Virus (0.40) and Taura Syndrome Virus (0.30). A chronic, or carrier, state was not demonstrated in NHPB epizootics because all NHPB-positive animals experienced mortality and no animals surviving to 60 d post-exposure were diagnosed NHPB-positive through PCR or histology.

Loma salmonae -associated xenoma onset and clearance in rainbow trout, Oncorhynchus mykiss (Walbaum): comparisons of per os and cohabitation exposure using survival analysis

Survival analysis techniques were used to compare experimental exposure methods of Loma salmonae (Microspora) in rainbow trout (RBT) by measuring xenoma onset and clearance time. Twenty-eight naive RBT were exposed per os (fed L. salmonae spores) and 28 RBT were exposed by cohabitation with 28 L. salmonae-infected RBT. Exposed fish were examined once every week (7 days) post exposure (PE). For xenoma onset, the median survival time, the time to first appearance of branchial xenomas, was 6 weeks PE for both per os and cohabitation exposure. For xenoma clearance, the median survival time, the time to total clearance of branchial xenomas, was 10 weeks for per os exposure and 12 weeks for cohabitation exposure. There was a significant difference between the survival curves of per os fish compared with cohabited fish for both xenoma onset and xenoma clearance. The incidence rate of xenoma development was greater for per os exposure (0.1745 cases per fish-week) compared with cohabitation exposure (0.1342 cases per fish-week). Similarly, the rate of xenoma clearance was greater for per os exposure (0.1028 cases per fish-week) compared with cohabitation exposure (0.0885 cases per fish-week). Differences between exposure methods were attributed to differences in the frequency and duration of exposure to spores. Survival analysis was useful for examining the onset and clearance of L. salmonae and may have applications for understanding disease dynamics in aquaculture.

Experimental infection of Penaeus vannamei by a rickettsia-like bacterium (RLB) originating from P. monodon.

A rickettsia-like bacterium (RLB), which caused severe mortalities of commercially farmed Penaeus monodon in the southwest region of Madagascar, was investigated to determine whether the organism would produce the same disease in P. vannamei. Two series of bioassays were performed to determine whether this RLB could be transmitted to P. vannamei through injection and per os exposure. The first series of challenge bioassays used frozen, RLB-infected P. monodon tissue from Madagascar as the inoculum and feed for the injection, and per os bioassays with specific pathogen free (SPF) P. vannamei. In the second series of bioassays, frozen RLB-infected P. vannamei tissue derived from the first series of injection bioassays was used as the inoculum to challenge by injection and per os SPF P. vannamei. Disease status was determined through standard histological techniques and by in situ hybridization assays with a digoxigenin-labeled probe specific for this RLB. The results indicated that P. vannamei did develop the RLB infection when injected with either RLB infected P. monodon or P. vannamei tissue homogenates. This contrasts with results from the per os exposure to the RLB in which the disease could not be reproduced.

Effects of monensin dose and treatment time on xenoma reduction in microsporidial gill disease in rainbow trout, Oncorhynchus mykiss (Walbaum)

AbstractThe objectives of the study were (1) to determine an acceptable dose of dietary monensin against microsporidial gill disease (MGD) of salmon caused by Loma salmonae and (2) to determine the life stage of L. salmonae at which the action of monensin was most effective at reducing clinical disease. Rainbow trout (RBT) were fed monensin diets at concentrations of 0, 10, 100, 1000 and 5000 ppm starting 1 week before per os exposure to L. salmonae infected gill material. Lethal sampling occurred at weeks 6, 7, 8 and 9 post‐exposure (PE). The acceptable dose of dietary monensin was determined to be 1000 ppm because it was the lowest concentration that produced a significant and constant reduction in xenoma formation. RBT were fed monensin at 1000 ppm beginning at 0, 1, 2 and 3 weeks before exposure and at 1, 2 and 3 weeks after exposure and continuing until week 9 PE. Fish in which treatment was initiated at the time of exposure or 1 week before, showed the greatest reduction in xenoma production when compared with the untreated RBT.

A Laboratory Challenge Method for Estimating Taura Syndrome Virus Resistance in Selected Lines of Pacific White Shrimp Litopenaeus vannamei

AbstractAmong the strategies being developed to improve survival and harvest yields in the farming of Pacific white shrimp Litopenneus vannumei is breeding domesticated family lines and the selection for further development of those lines that demonstrate resistance to Taura syndrome virus (TSV) challenge in the laboratory. A standardized laboratory challenge method for measuring TSV resistance by per os exposure to the virus, relative to a reference stock of L. vannamei, was developed and used to screen a total of 176 family lines provided by five different companies over a period of several months. All challenged shrimp were exposed to TSV per os by feeding minced TSV‐positive shrimp carcasses at ∼10% of the shrimp biomass once per day for three consecutive days. Studies were carried out for a minimum of 14 d from the first day (day 0) of exposure to TSV. The survival rates obtained following TSV challenge of the selected L. vannamei families ranged from 0% to 100%, with a mean of 31%. The reference line of L. vannamei (“Kona line”) gave survival rates of 0% to 37% with a mean of 13%. The results of the present study demonstrate that the use of a relatively simple laboratory challenge procedure provides a mechanism to evaluate and compare resistance to TSV among selected L. vannamei families and to predict the performance of selected stocks in farm environments where TSV is enzootic.

Biomonitoring of a worker population exposed to low antimony trioxide levels

Antimony trioxide (Sb 2O 3) is used as a flame retardant in the textile industry. We carried out a study in a factory for the evaluation of antimony (Sb) occupational exposure and urinary levels in workers exposed to Sb 2O 3. Urinary levels and airborne Sb 2O 3 personal exposure values were very low when compared to international occupational standards (500 μg/m 3, as Sb). The range of forty-two personal exposures was 0.01–0.55 μg Sb/m 3, while twenty-four area samplings ranged from < 0.01 μg Sb/m 3 to 1.45 μg Sb/m 3. The mean urinary Sb levels at the beginning (n = 39) and end of the shift (n = 39) were 0.31 ± 0.25 μg/L and 0.35 ± 0.29 μg/L respectively, without any significant statistical difference. When the workers were divided into two subgroups according to “higher” and “lower” exposure levels, a statistical difference (P < 0.001) was observed between the mean Sb urinary levels of the two subgroups during the workweek, both at the beginning and end of the shift. A statistical difference was also observed between the above mentioned subgroups and the controls (n = 15). No correlation was found between personal Sb 2O 3 exposure and the difference in urinary Sb levels at the beginning and end of the workshift on the day the flame retardant was utilized. This lack of correlation could be due to low airborne Sb 2O 3 levels and Sb dietary intake, estimated as 3 μg/day in UK, but not yet fully investigated in Italy. Any accidental occupational Sb per os exposure however low, could further enhance the lack of correlation.

Modes of transmission of Loma salmonae (Microsporidia).

Loma salmonae (Putz, Hoffman and Dunbar, 1965) Morrison and Sprague, 1981 (Microsporidia) causes prominent gill disease in pen-reared chinook salmon Oncorhynchus tshawytscha in the Pacific Northwest. Transmission of the parasite was examined by exposing Pacific salmon Oncorhynchus spp. to infectious spores by various routes: per os, intraperitoneal, intramuscular, and intravascular injection, by cohabitation with infected fish, and by placement of spores directly on the gill. All exposure methods led to infections except placement of spores on the gill. Putative sporoplasms were visible in epithelial cells of the alimentary canal within 24 h of per os exposure. L. salmonae may initially infect alimentary epithelial cells and then migrate into the lamina propia to access the blood stream. Positive results obtained by intravascular injection suggest that autoinfection from spores of ruptured xenomas in the endothelium may also occur. The cohabitation experiment demonstrates that fish may become infected by spores released from live fish.

Toxicity of an Anthraquinone Violet Dye Mixture Following Inhalation Exposure, Intratracheal Instillation, or Gavage

Toxicity of an Anthraquinone Violet Dye Mixture Following Inhalation Exposure, Intratracheal Instillation, or Gavage. Jaskot, R. H., and Costa, D. L. (1994). Fundam. Appl. Toxicol. 22, 103-112.Anthraquinone dyes are utilized by the military in colored-smoke grenades. During production, workers in munitions plants may be exposed to fugitive emissions of these dyes or mixtures thereof. The effects of a prototype violet dye mixture (VDM) consisting of Disperse Red 11 (DR11), [1,4-diamino-2-methoxy-anthraquinone] and Disperse Blue 3 (DB3) [1-methylamino-4-hydroxyethylamino-anthraquinone] on F344 male and female rats have been investigated. Acute 1-day inhalation exposures (6 hr) to VDM were conducted at 1000, 300, 100, 70, 40, and 10 mg/m3, with an additional exposure to 40 mg/m3 6 hr/day for 5 days; 4.22 ± 2.1 μm (MMAD ± δg). Lung burdens of dye, general histopathology, and/or liver function were evaluated at 0, 3, and 7 days postexposure. Unexpected lethality due to severe liver damage was observed with acute exposures of ⩾300 mg/m3 and in the 5-day 40 mg/m3 exposures. Centrilobular degeneration and necrosis of liver cells was concentration-dependent with inhalation of VDM ⩾40 mg/m3. In addition, nasal olfactory epithelium exhibited degeneration and necrosis with acute exposures ⩾10 mg/m3. Lung instillations at 250, 500, and 1000 μg of the VDM revealed no lung or liver toxicity. Because per os exposure due to preening was suspected as a major exposure route, a gavage study with the VDM and its two component dyes DR11 and DB3 (800 mg/kg) was undertaken. One day following gavage with DR11 or DB3, serum enzymes indicative of liver toxicity (LDH, SGPT, SDH, and ICDH) were slightly elevated (1-6× control). However, rats gavaged with VDM had serum enzyme levels 10-100× control by Day 1 after gavage, indicating acute liver toxicity. Activities of liver enzymes involved in xenobiotic and glutathione metabolism were also acutely affected. All of the dyes caused various degrees of induction of glucose-6-phosphate dehydrogenase, glutathione reductase, glutathione peroxidase, and nonprotein sulfhydryls. The enzymes involved in xenobiotic metabolism (glutathione S-transferase, NADPH cytochrome-c reductase, and P450) were also elevated by the two component dyes, in contrast to their significant depression with VDM treatment. The similarity between the liver and olfactory epithelium effects of these compounds and the lack of pulmonary tissue effects is not fully understood, but the interaction of the individual dyes as VDM emphasizes the need to assess chemicals such as the anthraquinones as their likely-to-be-encountered mixtures.

Response of nuclear polyhedrosis virus-resistant Spodoptera frugiperda larvae to other pathogens and to chemical insecticides

Selection in the laboratory for Spodoptera frugiperda (Sf) resistant to nuclear polyhedrosis virus (NPV) affected the susceptibility of the insect to certain other mortality agents, including a chemical insecticide. Median lethal concentrations (LC 50s) and associated statistics were compared for several mortality agents between colonies of NPV-resistant and -susceptible (control) insects. Compared to the susceptible insects, the NPV-resistant insects were cross-resistant to the S. frugiperda granulosis virus and to the Autographa californica NPV based on nonoverlap of 95% fiducial limits of the LC 50s. The NPV-resistant insects were significantly more susceptible to methyl parathion than the control insects. The two colonies of S. frugiperda did not differ significantly in their response to Bacillus thuringiensis, Varimorpha necatrix, or carbaryl. The cross-resistance experiments were based on per os exposure of the insects to the pathogens and insecticides; the susceptibility of the resistant and control insects did not differ significantly when the Sf NPV was injected into the hemocoel or when methyl parathion was applied topically.