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Skin sensitization testing in guinea pigs, using methods such as the Buchler, maximization and split adjuvant, requires wrapping the animals torso to secure the test patch to the skin. Potential health effects of wrapping other than temporary stress, are generally not considered. The repeated wrapping procedure typically used in epicutaneous skin sensitization testing can result in the development of hepatic necrosis, confirming observations made following a single wrapping during acute irritation screening.

Aims: The purpose of this study was to evaluate the effects of altered environmental conditions on the persistence of Francisella tularensis bacteria and Venezuelan equine encephalitis virus (VEEV), on two material types., Methods and Results: Francisella tularensis (F.t.) and VEEV were inoculated (c. 1 × 10 8 colony-forming units or PFU), dried onto porous and nonporous fomites (glass and paper), and exposed to combinations of altered environmental conditions ranging from 22 to 60°C and 30 to 75% relative humidity (RH). Viability of test organism was assessed after contact times ranging from 30 min to 10 days. Inactivation rates of F.t. and VEEV increased as both temperature and/or RH were increased. Greater efficacy was observed for paper as compared to glass for both test organisms., Conclusions: The use of elevated temperature and RH increased rate of inactivation for both organisms and greater than six log reduction was accomplished in as little as 6 h by elevating temperature to approximately 60°C., Significance and Impact of the Study: These results provide information for inactivation of nonspore-forming select agents using elevated temperature and humidity which may aid incident commanders following a biological contamination incident by providing alternative methods for remediation., (© 2019 The Society for Applied Microbiology.)

Tri-n-butyl phosphate (TBP), an industrial chemical, was administered in the diet at concentrations of 0, 150, 1000 or 3500 ppm to groups of 50 male and 50 female CD-1 mice for 18 months. Survival, clinical signs and hematology parameters were unaffected by treatment at any concentration. Initial weight losses and significant decreases in body weight gain occurred in males and females receiving the high dose (3500 ppm) of TBP in diet. A significant dose-related increase in absolute and relative liver weights was seen in male and female mice which received the two highest dietary concentrations of TBP (1000 and 3500 ppm). The incidence of hepatocellular adenomas was significantly increased in male mice treated with 3500 ppm TBP in diet. No other tumors were associated with TBP administration in this study. The NOEL for chronic toxicity was 150 ppm, or 28.9 mg/kg/day for females and 24.1 mg/kg/day for males. Although rats treated chronically with TBP have exhibited urinary bladder hyperplasia and urinary bladder papillomas and transitional cell carcinomas, no urinary bladder alterations attributed to TBP administration occurred in this study.

Tri-n-butyl phosphate (TBP, CAS No. 126-73-8), an industrial chemical, was administered in the diet at concentrations of 0, 200, 700 and 3000 ppm to groups of 50 male and 50 female Sprague-Dawley rats for 2 years. Body weights and food consumption were measured weekly for the first 13 weeks and monthly thereafter. Hematology was performed at 12, 18 and 24 months; urinalyses were performed at 3 weeks and 3, 6, 12 and 18 months. All surviving animals were euthanized after 24 months of treatment. Macroscopic postmortem examinations were performed on all animals; complete histopathological evaluation was performed on control and high dose animals; target organs were examined in all dose groups. Significant decreases in body weight gain occurred in males and females receiving the 3000 ppm concentration and a slight decrease in weight gain occurred in females receiving the 700 ppm concentration. The only clinical sign attributed to TBP was an increased incidence of red discoloration of the urine in some high-dose males. Survival, hematology and urinalysis parameters were unaffected by treatment at any concentration. A dose-related increase in the incidence and severity of urinary bladder hyperplasia and the incidence of urinary bladder papillomas was evident in male and female rats receiving the 700 and 3000 ppm concentrations. Transitional cell carcinomas were present in six of 49 males and two of 50 females and a squamous cell carcinoma was present in one of 49 males in the group which received 3000 ppm. The oncogenic effects showed a clear threshold of 700 ppm in the diet. The NOEL (no observable effect level) for chronic toxicity was 200 ppm. Mean intake of TBP was 9 and 12 mg/kg/day for males and females, respectively, receiving 200 ppm; 33 and 42 mg/kg/day for males and females, respectively, receiving 700 ppm, and 143 and 182 mg/kg/day for males and females, respectively, receiving 3000 ppm. TBP was negative in genotoxicity tests, suggesting that the tumors are induced by nongenotoxic mechanisms.

Historically, a direct and irreversible genotoxic reaction of a xenobiotic with DNA has been considered to be a universal and obligatory initiating event in the etiology of neoplasia, and it was assumed therefore that (1) there was no threshold other than zero exposure for cancer initiation, and (2) like radiation, exposure was additive over a lifetime. Human exposure to xenobiotics causing neoplasia in laboratory rodents has been regulated in many countries on that basis. In the last decade evidence has accumulated indicating that some neoplasia in laboratory rodents may not be caused by a direct and irreversible interaction of xenobiotics with DNA. In addition, it has been found that some neoplasia caused in laboratory rodents by xenobiotics may not be relevant for biochemical/physiological reasons. This has raised the question whether human exposure to these xenobiotics should be regulated by the no-threshold philosophy used for direct-acting genotoxic xenobiotics or whether they can be regulated by the threshold philosophy used for classical xenobiotic-induced toxic effects. In a bioassay carried out by the National Cancer Institute and published in 1979, toxaphene was found to cause an increase in the occurrence of two spontaneously occurring tumors in laboratory rodents that since have been found to have both genotoxic and nongenotoxic etiologies in laboratory rodents. Experiments described in this paper are part of a program to help elucidate whether the increased incidence of these two neoplasms in laboratory rodents could have had a nongenotoxic origin, and thus whether toxaphene could be regulated by a threshold approach. Forty male rats were orally intubated with 100 mg/kg/day technical grade toxaphene in corn oil for 3 days. The dose was reduced to 75 mg/ kg/day on Day 4 due to toxicity. This lower dose was administered daily for 25 days. Another group of 40 male rats was orally gavaged daily with equivalent volumes of corn oil. After 0, 7, 14, and 28 doses, 10 test and 10 vehicle control animals were sacrificed for gross and histopathological examination of thyroid, parathyroid, and pituitary glands. Weights of these endocrine organs, body weights, and brain weights were determined. Prior to sacrifice, a blood sample was obtained from each animal for preparation of serum for analyses of thyroid stimulating hormone (TSH), thyroxine (T4), thyroid hormone (T3), and reverse T3 (rT3). Thyroid glands were evaluated microscopically for follicular cell hypertrophy, hyperplasia, and colloid storage. There were significant time-related increases in serum TSH in the test animals after 7, 14, and 28 doses of toxaphene. The serum levels of T3, T4, rT3, and corrected T3 (CrT3) in the test group were not significantly different from controls at each interval. Thyroid gland weights and thyroid to brain weight ratios were not significantly (p > 0.05) increased in the test group at each sacrifice interval. Pituitary weight, brain weight, and the ratios of these organ weights to body weights were similar in the test and control groups at each sacrifice interval. Thyroid follicular cell hypertrophy and intrafollicular hyperplasia increased and thyroid follicular cell colloid stores decreased with duration of treatment with toxaphene. The hormonal and histopathologic changes seen in the test group were consistent with increased excretion of T3 and/or T4 resulting from cytochrome P450 enzyme induction in the liver. This mechanism for thyroid neoplasia is not known to occur in humans.

Mongolian gerbils fed diets containing lead acetate maintained body weight comparable to gerbils fed the same diet without added lead. Intranuclear lead inclusion bodies in epithelial cells of the proximal convoluted tubules of the kidney were first observed at 4 weeks, and increased in number to about 50 per high power field at 12 weeks. At this time, a corticomedullary area of empty-appearing tubules was prominent. Transmission electron microscopy confirmed the increase in number and size of nuclear lead inclusion over the 12-week period. Cytoplasmic changes observed in proximal tubule cells containing lead inclusions were considered indicative of acute lethal injury. Distinct cytoplasmic fibrillar structures, first apparent at 8 weeks, were present in some proximal tubular lining cells and strongly resembled newly formed intranuclear lead inclusions. After 12 weeks, the total amount of lead present in the gerbil kidney was four to six times greater than that in rat kidney as determined by atomic absorption spectrophotometry. A hypothesis has been formulated that relates the more efficient nephron of the gerbil kidney to the rapid and extensive development of intranuclear inclusion bodies and the greater accumulation of total lead.

Cis-diamminedichloroplatinum [cis-DDP; NSC-119875] and four analogs (NSC-241240, NSC-271674, NSC-263158, and NSC-268252) were evaluated for their acute nephrotoxic potential in male F344 rats following iv administration. Indices of nephrotoxicity included blood urea nitrogen, serum creatinine, kidney weights, and microscopic examination. Results indicated that renal function, organ weights, and histology are important criteria for assessing the nephrotoxic potential of cis-DDP analogs, although alterations in these parameters may have been influenced by severe body weight loss. cis-DDP appeared to be the most nephrotoxic compound studied, and NSC-241240 demonstrated minimal renal damage. Ranking of compounds in order of their nephrotoxic potential (most to least) was cis-DDP, NSC-263158, NSC-268252, NSC-271674, and NSC-241240.

A two-generation bioassay on sodium saccharin (NaS), involving 2500 second-generation male rats, was designed to determine the dose response for urinary bladder tumours in male rats and to evaluate other changes possibly related to the occurrence of the tumours. Six treatment groups (125-700 rats/group) were fed dietary levels of NaS ranging from 1.0 to 7.5%. To evaluate the role of in utero exposure, two additional groups were exposed to NaS either only during gestation via dams fed diet containing 5.0% NaS or for a single generation beginning at birth. In the latter group, the nursing dams were placed on an NaS diet immediately after giving birth and their offspring were weaned onto diets containing 5.0% NaS. A third additional group, included to evaluate the specificity of NaS and the role of excess sodium in the occurrence of urinary bladder tumours, was fed diet containing sodium hippurate (NaH) for two generations--5.0% NaH to the first generation and to the second until 8 wk old, and subsequently 3.0% because of unexpected toxicity. A clear dose response for urinary bladder tumours was observed in the second-generation NaS-treated male rats. The steep slope of the dose-response curve indicated a rapid decline in tumour incidence with decreasing dose. The 1.0% dietary level (fed to 700 rats) was considered to be a no-effect level for bladder tumours. The only other treatment-related pathological changes were an increase in urinary bladder weight in rats fed greater than or equal to 3.0% and an increase in mineralization of the kidneys with greater than or equal to 1.0%. Several physiological effects were seen in the NaS-treated groups showing an increase in bladder tumours (i.e. those fed greater than or equal to 3.0%). Some changes, e.g. depressed growth and increased water consumption, were indicative of a general disturbance of these rats, but analysis of body-weight, food-consumption, compound-consumption and water-consumption data revealed no correlations within any dose group between these quantitative data and the occurrence of bladder tumours. Other changes indicative of the compromised situations of the rats fed high dietary levels of NaS were anaemia in weanling rats fed 5.0 or 7.5% and a reduction in litter size at dietary levels greater than or equal to 3.0%. Changes in urine volume and urine osmolality were highly correlated with the occurrence of the urinary bladder tumours.(ABSTRACT TRUNCATED AT 400 WORDS)

Earlier statements to the contrary, the present study demonstrates the presence of a cell surface coat (glycocalyx) on the luminal plasma membrane of the superficial transitional epithelial cells lining the urinary bladder of male Buffalo rats. This coat was demonstrated with ruthenium red, an electron dense stain, which revealed a surface layer, 60-80 A thick, separated from the outer leaflet of the plasma membrane by an electron lucent layer, approximately 30 A thick. The structure of the glycocalyx was not affected by 12 weeks of treatment with dibutylnitrosamine, a known bladder carcinogen.

Eleven Rhesus monkeys received injections of intravenous methamphetamine hydrochloride (Desoxyn) and/or intra-arterial 60% iothalamate meglumine (Conray) according to a schedule previously reported to produce marked radiological and pathological changes in the cerebral vasculature of the Rhesus monkey. While radiological changes consistent with impaired cerebral circulation were observed, they could not be correlated directly with the administration of intravenous methamphetamine because of the trauma and variability of the technique utilized. Moreover, significant pathological changes could not be found in animals given intravenous methamphetamine alone, intra-arterial iothalamate meglumine alone, or both drugs together. This was true for both drug naive and drug experienced monkeys. These results suggest: (1) radiological changes consistent with decreased cerebral blood flow are not necessarily pathognomonic for reported morphological lesions, and (2) further investigation is required to determine the specific factors necessary to cause the previously reported changes.

This paper reports the use of zonal ultracentrifuge techniques to conduct biophysical studies of rhinoviruses grown with WI-38 cells. Good clean-out of infectivity from rhinovirus harvests was obtained with the continuous-flow B-V and B-IX rotors. Use of the B-V rotor resulted in the successful concentration of rhinovirus infectivity and antigenicity. Additional purification was achieved by the combined use of continuous-flow centrifugation and isopycnic banding procedures. Two particle sizes were found to be associated with the virus-infected cell harvests. The infectious 22-nm particle banded in density ranges of 1.38 to 1.40 g/cm(3) in CsCl and 1.26 to 1.27 g/cm(3) in potassium citrate. The 8.0 nm capsomere was composed of 2.0 nm subunits and banded with a density of protein at 1.28 g/cm(3) in CsCl. Equivalent sedimentation coefficients of 155 or 185, depending on particle density in sucrose, were calculated from rate zonal experiments by use of the B-IV zonal rotor.

Proteus infection in the rat produces an acute bacterial pneumonia which resolves without necrosis or significant organization within 2 weeks. Ultrastructural changes included widespread damage to type 2 cells and endothelial cells and rapid proliferation of the alveolar epithelial cells, which were the predominant site of labeling with tritiated thymidine. Histochemical staining for lysosomal enzymes showed an initial reduction in type 2 cell reactivity. The majority of proliferating epithelial cells were also unreactive until the normal pattern of staining and morphology returned at 8 to 12 days after infection. The acute inflammatory exudate was reactive, but there was only minimal to moderate staining in the subsequent clusters of alveolar macrophages. These data suggest that resolution with the preservation of the normal architecture of the peripheral airspaces may be correlated with superficial injury and limited reactivity for digestive enzymes.

The distribution of carbonic anhydrase in the exocrine pancreas of the rat has been examined during the first 3 weeks after duct ligation. The normal pattern of positive reaction in ducts, centroacinar cells and capillaries changed, by the end of the first week, to one in which all the cells in the dilated ducts showed the enzyme. This situation persisted through the third week. By electron microscopy, the enzyme was found on the apical membranes of ductular, centroacinar and acinar cells, as well as on the surface membranes of the modified cells seen at 1 week. The significance of these findings with respect to function and cell origin is discussed.