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.

Species difference in GI motor response to somatostatin.

Acute experiments were performed on overnight fasted chloralose-urethan anesthetized dogs, cats, rabbits, and rats. Under these conditions, somatostatin practically abolished gastric contractions and decreased GI tonus in all species examined. The canine duodenum, jejunum, and ileum exhibited only a contractile response to somatostatin, whereas motor activities of the small intestines of the cat, rabbit, and rat were inhibited. In all instances and at all dosages, both the inhibitory and excitatory effects showed suggestions of tachyphylaxis. The data also indicate that excitatory or inhibitory effects were not dependent on the presence of long arc pathways. It is concluded that somatostatin exerts a direct stimulatory effect on the canine small intestine that is mediated by the muscularis mucosa.

Metabolic performance and GI function in magnesium-deficient rats.

A quantitative evaluation of the mass balance and GI motor effects of dietary magnesium deficiency in the adult male Sprague-Dawley rat is described. Seventy-seven animals were used. Both sham control and experimental groups were maintained on a commercial stock laboratory diet ad libitum for 30 days, after which the experimental rats were switched for 30 days to magnesium-deficient diet ad libitum, containing a magnesium concentration of 16.2 ppm. Ten rats were used to determine the acetylcholine responsiveness of duodenal muscle segments in vitro. In all cases, the segments from the deficient rats were hyperresponsive to a fixed acetylcholine dose. Forty-six rats were used to determine the average intestinal transit rate, which increased significantly in 30-day magnesium-deficient rats. A final series employed 21 rats who were housed in individual metabolic cages. After 5 days on the deficient diet, the average daily fecal pellet counts and fecal weights were significantly reduced. It is concluded that chronic magnesium deficiency is associated with altered GI motor function in the adult male rat.

Evidence of reflexive beta adrenergic motor stimulation in the canine stomach and small intestine.

Studies in our laboratory have confirmed the previous observations that adequate electrical stimulation of either the left or right central vagus nerves in the dog after bilateral vagectomy produces relaxation of the stomach and small intestine. On the other hand, central vagal stimuli delivered to dogs that were either chronically reserpinized or were premedicated with the alpha adrenolytic phenoxybenzamine resulted in increased segmenting activity of these two organs. These excitatory responses were abolished by bilateral section of the sympathetic chains and could be reproduced by electrically stimulating the chains. The excitatory effects of either central vagal stimulation, peripheral sympathetic stimulation or intravenous isoproterenol administration could be abolished by dichloroisoproterenol. It was also determined that isoproterenol produced a tonic contraction of the separated muscularis mucosa which was distinguishable from a relaxation of the muscularis externa. It is suggested that a sympathetic pathway exists which is excitatory to the stomach and small intestine and that these excitatory effects are mediated by beta adrenergic neurotransmitters. The results further suggests that the beta excitatory reflex response is mediated by the muscularis mucosa as the target effector system.

A cilia-bearing cell system in the intrahepatic bile ductules of the rat.

A scanning electron microscopic investigation of the luminal surface of the intrahepatic bile ducts of the rat has been performed using tissue prepared by critical point drying. Results of these studies have demonstrated that intrahepatic bile ducts of the rat are composed of cells, the luminal surface of which contains either microvilli or numerous long cilia. It was suggested that these cilia play an important role in tissue function, particularly in the propulsion of hepatic bile.

The occlusive competence of the duodenal orifice of the canine pancreatic duct.

Observations by scanning electron microscopy indicate that the mucosa of the terminal part of the major pancreatic duct of the dog is organized into numerous, highly convoluted folds. The individual mucosal cells are tall, columnar and studded with numerous microvilli. These folds are highly vascularized. The intraluminal administration of bethanechol and norepinephrine is associated with subsequent increases and decreases of mean opening pressures. Mean opening pressures were not observed to be associated with autonomic nervous activity that was unaccompanied by changes in systemic arterial pressure. It is concluded that the terminal portion of the canine major pancreatic duct probably acts as a passive valve, the occlusive competence of which is influenced by the status of the vasculature of the lining mucosa in this region.

GI motor inhibition associated with acute exposure to methyl methacrylate vapor.

A mixture of monomeric methyl methacrylate vapor in air was delivered into the breathing air of chloralose-urethan anesthetized dogs. Fixed length exposures to 2000-ppm doses of the vapor resulted in a transient drop in arterial blood pressure and a marked inhibition of ongoing GI motor activities. Motor inhibition always continued for a variable time (approximately 10-15 min) subsequent to the cessation of methyl methacrylate vapor administration. This inhibitory response was not blocked by bilateral vagotomy, spinal transection, splanchnectomy, or the intravenous administration of tetraethylammonium chloride. Another series of experiments determined that the administration of blood from a dog receiving methyl methacrylate vapor produced GI motor inhibition in another dog not connected to the experimental gas mixture. Therefore, it is concluded that, aside from any reflex effects produced, methyl methacrylate vapor in sufficient concentration probably exerts a direct inhibitory effect upon GI smooth muscle that is mediated by the cardiopulmonary systems.