Frank M. Kendall

Acute and subchronic toxicity studies of rats exposed to vapors of methyl mercaptan and other reduced‐sulfur compounds

Acute inhalation experiments were conducted to determine 24-h LC50 values for adult Sprague-Dawley rats of both sexes exposed to vapors of methyl mercaptan and other reduced-S compounds for 4 h periods. Using calculated gas concentrations, the following LC50 value for each gas and combination was determined: metyhl mercaptan, 675 ppm; dimethyl sulfide, 40,250 ppm; dimethyl disulfide, 805 ppm; hydrogen sulfide, 444 ppm; and an equimolar mixture of methyl mercaptan, dimethyl sulfide, and dimethyl disulfide, 550 ppm. The effects of body and tissue weights, gross metabolic performance, O2 consumption, systolic blood pressure, various blood parameters, and intestinal transit time associated with 3-mo exposures of young adult male rats to chemically verified concentrations of 2, 17, and 57 ppm methyl mercaptan vapor are summarized in this report. No mortality was experienced by any group. Histopathological findings were essentially nil except for microscopic suggestions of liver damage. The most readily apparent phenomenon was the decrease in body weight. Average values of terminal body weights for all exposed groups were lower than that for the sham control group. This difference was significant in the 57 ppm group and followed a statistically significant dose-related trend.

Experimental and clinical aspects of gastrocolic reflexes

It is doubtful whether any hypothesis which has so far been advanced to explain the relation between the ingestion of food and defecation in normal man and in lower animals is adequate. The literature pertaining to this subject matter has, in recent years, become so voluminous that all of the experimental evidence in favor of the various views cannot be reviewed here but rather an attempt has been made to point out certain lines of evidence which, to the authors, appear to be the most outstanding. The earliest description of a mass emptying response of the large bowel was that which was radiographically observed by Walter Cannon (1) in 1902. His observations were made in cats which had been fed test meals subsequent to the administration of opaque enemas. MacEwen (2) in 1904 supplied the first published human data on mass colonic emptying after ingestion of a meal in patients with cecal fistulas. In 1909, Holzknecht (3) provided radiographic evidence of mass peristalsis as he observed a wave of contraction passing down the colon subsequent to the disappearance of interhaustral folds. A year earlier, Hertz (4) similarly observed that colonic contents tended to travel further during the dinner hour than in any other defined period during the day. Hertz also deserves the credit for designating this propulsive response as a gastrocolic reflex. In later experiments, Hertz and Newton (5) noted again in humans that when the propulsive movement occurred, the colonic contents of a distended section near the hepatic flexure

Chronic biological effects of methyl methacrylate vapor: I. Body and tissue weights, blood chemistries, and intestinal transit in the rat☆

Abstract The effects upon body and tissue weights, various blood parameters, and intestinal transit time associated with chronic exposures of rats to monomeric methyl methacrylate (MMA) vapor concentrations are summarized in this report. The most remarkable and readily apparent phenomenon was the obvious lack of body fat in the group which had been exposed for 3 months to an MMA vapor concentration of 116 ppm in air. It was determined that rats which have received a daily 8-hour exposure to 116 ppm of MMA vapor for 6 months have significantly lower adiposity, as measured by the popliteal fat pad, than those of a similar group which have received sham exposures. It was also determined that protracted exposures to MMA vapor in this concentration were associated with a significant decrease in intestinal transit performance.

Chronic biological effects of methyl methacrylate vapor: III. Histopathology, blood chemistries, and hepatic and ciliary function in the rat☆

Abstract Inhalation experiments were conducted by exposing rats, mice, and frogs to methyl methacrylate (MMA) monomer vapor in air. Rats were exposed for periods of up to 6 months to near threshold limit value (TLV) concentrations and for a shorter period to approximately ten times the TLV. Blood chemistries were unremarkable. Histopathological findings were essentially nil except for microscopic indications of damage to the tracheal mucosa, supported by scanning electron microscopy (SEM) observations that the cilia and microvilli characteristic of these epithelial cells were absent. A reduction in oropharyngeal transport efficiency was shown when frogs were exposed to 400 ppm of MMA vapor. The sodium pentobarbital detoxification function of mouse liver may be altered consequent to exposures to 160 hr to both 100 and 400 ppm of MMA vapor. It is concluded that, at the TLV, cellular responses may be manifested regardless of whether gross systemic effects are seen.

The differential action of somatostatin on the motor effector system of the canine gastrointestinal tract

Abstract Considerable attention has recently been devoted to the effects of somatostatin on the secretory activities of the digestive system. The opposite is true for the effects of somatostatin on the motor activities of the digestive tract. One of the papers that forms the basis for linking somatostatin with possible digestive system muscle function is the work of Creutzfeldt et al. 1 In this study, somatostatin inhibited gallbladder contraction stimulated by an infusion of exogenous cholecystokinin-pancreozymin in man. In animal experimentation, the somatostatin effect on gallbladder contraction was confirmed in the pig 2 and in the dog. 3 Only a few published abstracts have alluded to the possibility that this substance might influence the motor activities of the gastrointestinal tract. 4–6 In preliminary experiments, spontaneous gastric antral contractions were not modified by somatostatin. 4 On the other hand, somatostatin had a distinct motor effect on the duodenum of the nembutalized dog. 4 Unfortunately, no explanation for this difference in responsiveness was advanced. Therefore, the purposes of these studies were to determine the natures and the mechanisms of action of the effects of somatostatin on the canine stomach, intestines, and extrahepatic biliary system.

Chronic biological effects of methyl methacrylate vapor. II. Body and tissue weights, blood chemistries, and gross metabolic performance in the rat.

Abstract Chronic exposures of mature male Sprague-Dawley rats to near threshold-limit value (TLV) concentrations of methyl methacrylate (MMA) monomer vapor were conducted in order to assess the effects of such exposures on gross metabolic performance. There was no significant effect on food or water intake or water excretion. Average fecal excretion during the exposure portion of the week tended to be higher in the exposed than in sham-exposed rats. These differences were absent for average values obtained on weekends. Final mean body, adrenal, epididymal fat pad, and popliteal fat pad weights were not significantly different.

Gastrointestinal Hormones and the Quantitation of Spontaneous Duodenal Motor Activity

This is a survey of the results of recent investigations on gastrointestinal (GI) peptide hormones. In addition to the classical GI hormones (secretin, gastrin, and cholecystokinin-pancreozymin (CCK-PZ)), there are at least nine other peptides whose structures and GI effects are known. These include vasoactive intestinal polypeptide (VIP), gastric inhibitory polypeptide (GIP), motilin, pancreatic polypeptide (PP), substance P, neurotensin, somatostatin, enkephalins, and a bombesin-like gastrin-releasing peptide. It is now obvious that the traditional distinctions between hormones, neurotransmitters, and paracrines are rapidly becoming obsolete, as the actions and interactions of these substances within the complex motor system of the GI tract are gradually revealed. The study of perturbed states and toxic effects on the motor function of the small intestine is complicated by the integration of the activity of the small intestine with the activities of the body as a whole. A contemporary approach for evaluating intestinal contractile activity is described that uses computer assistance to measure the intercontractile interval (ICI). This technique may prove useful in assessing the effects of toxicological agents on spontaneous intestinal motor activity in vitro when the agents are delivered to the target sites by physiological mechanisms, in contrast to adding them to the tissue bath.

Subacute inhalation toxicity testing with iodoform vapor

Subacute inhalation experiments were conducted to determine the LC50 value for adult Sprague-Dawley rats exposed to iodoform vapor. Each dose consisted of 5 males and 5 females that were together for a 7-h exposure or sham exposure and then separated for observation over the subsequent 24-h period. The rats were deprived of food and water during actual exposure or sham exposure. Exposures were conducted in a custom-designed 75-l glass chamber. Vapor concentrations were verified in samples taken from the exposure chamber. Under the conditions of the experiments the 7-h LC50 was found to be 183 ppm. The second objective of these experiments was to determine the toxic effect of iodoform vapor on rats exposed for 7 h/d for 7 consecutive days. Three groups of 5 young adult male and 5 female rats were used. One group served as a sham control and the other groups were exposed to 1 and 14 ppm iodoform vapor. No significant differences were noted in food and water intake, urine and feces output, and intestinal transit performance in either exposed group. No remarkable changes were noted in SMA 12/60 blood values for either exposed group. The only histopathological manifestation noted was the presence of mineralized deposits in the medullary renal tubules of some of the rats from the 14-ppm group.

Short-Term Inhalation Toxicity Testing with Aerosolized Aluminum Chlorhydrate

Short-term exposures of adult male and female Sprague-Dawley rats to aerosolized aluminum chlorhydrate in a silicone-ethanol vehicle were conducted to assess the effects of such exposures upon body and tissue weights, various blood constituents, tissue aluminum concentrations, and appropriate histopathology. Rats were exposed 4 hours/day 5 days/week (excluding weekends) for 22 days to concentrations of 0.34 ± 0.22 μg/L and 2.50 ± 0.37 μg/L of solubilized aluminum chlorhydrate as determined by atomic absorption spectroscopy. The mass medium aerodynamic diameter (MMAD) for the low-dose group was 1.57 ± 0.45 μm. The mean MMAD for the high-dose exposure was 4.28 ± 0.93 μm. No mortality was experienced by any group. Final mean body and most tissue wet weights were not significantly different from sham control values. No remarkable changes were noted in SMA 12/60 blood values for either exposed group. Mean aluminum concentrations of lungs, liver, gastric mucosa, or parathyroids from the high-dose group were not significantly different than mean values for the same organs obtained from a sham exposed group of rats. There were no remarkable histopathological observations.

Gastrointestinal motor activity following exposure to a high-frequency electric field.

Nachweis, dass die Exposition von männlichen Sprague-Dawley-Ratten im hochfrequenten elektrischen Feld zu Veränderungen der gastro-intestinalen Motilität führt.