T. R. Torkelson

1,4-Dioxane. I. Results of a 2-year ingestion study in rats

Abstract Four groups of rats, 60/sex/level, were maintained on drinking water containing 0, 1.0, 0.1, or 0.01% 1,4-dioxane for up to 716 days. Male and female rats receiving 1% dioxane (equivalent to approximately 1015 and 1599 mg/kg/day, respectively) showed decreases in body weight gains, survival rates, and water consumption. Hepatocellular and renal tubular degenerative changes, accompanied by regenerative activity, were similar to those reported in previous studies following exposure to toxic levels of dioxane. Hepatocellular and nasal carcinomas, occurring at this dose level, were considered related to the lifetime exposure to these massive toxic dosages of dioxane. Male and female rats receiving 0.1% dioxane (equivalent to approximately 94 and 148 mg/kg/day, respectively) in the drinking water had variable degrees of renal and hepatic degenerative changes, but there was no indication of treatment-related tumor occurrence. Male and female rats receiving 0.01% dioxane in the drinking water (equivalent to approximately 9.6 and 19.0 mg/kg/day, respectively) showed no evidence of tumor formation or other toxic effects considered to be related to treatment. These data indicate a dose response for the toxicity of dioxane.

The toxicity of vinyl chloride as determined by repeated exposure of laboratory animals.

Abstract Groups of laboratory animals were exposed repeatedly for up to six months to either 500, 200, 100 or 50 ppm vinyl chloride in air. Detectable changes occurred at all but the lowest concentration. The results are discussed and handling precautions suggested.

The toxicity of chloroform as determined by single and repeated exposure of laboratory animals

The acute and chronic toxicity of chloroform has been studied in laboratory animals. An acute oral LD50 of 2.0 (1.0-3.8) g/kg was determined for male rats. When applied to the skin of rabbits, chloroform produced slight to moderate irritation and delayed healing of abraded sking. Absorption of chloroform through the skin of rabbits was apparent but absorption is not expected to present a practical acute hazard. Liquid chloroform produced slight injury to the eyes of rabbits which took over a week to heal. Repeated 1-hour exposures five days per week for six months to either 85.50 or 25 ppm of the vapor of chloroform resulted in adverse effects in all or some species studied: rats, rabbits, guinea pigs and dogs. The effects at 25 ppm were slight and reversible. Rats exposed to 25 ppm for 4.2 or 1 hour/day for 6 months were not adversely affected. Based on experimental data and published reports on human experience as well as industrial experience with carbon tetrachloride, the authors suggest that when workers exposures can be expected to be repeated and prolonged, the exposure concentrations be maintained below 25 ppm vapor and that the time weighted average not exceed 10 ppm.

The toxicity of 1,3-dichloropropene as determined by repeated exposure of laboratory animals.

In a preliminary experiment, exposure of rats and guinea pigs to 50 or 11 ppm (v/v) 1,3-dichloropropene vapor for seven hours/day, five days/week for one month had been found to produce liver and kidney injury. In order to determine the effects of more prolonged, repeated exposure to lower concentrations, four species of laboratory animals were exposed repeatedly to nominal concentrations of either 3 or 1 ppm (13.6 or 4.5 mg/m3) 1,3-dichloropropene in air. Rats, guinea pigs, rabbits and dogs received seven-hour daily exposure five days/week to 1 ppm (v/v) (0.9 ppm recovered analytically) for six months with no adverse effect. The only effect in any group exposed to 3 ppm (v/v) (2.6 ppm recovered analytically) was a slight, apparently reversible change seen microscopically in the kidneys of male rats exposed seven or four hours daily. Female rats, male and female rabbits, male and female guinea pigs and female dogs exposed repeatedly to 3 ppm seven hours/day showed no adverse effect. No effects were appare...

Experimental human exposure to vapor of propylene glycol monomethyl ether. Experimental human exposure.

The monomethyl ether of propylene glycol (PGME) is used as a radiator coolant Simulation of PGME coolant leakage on the engine of an idling truck resulted in a breathing zone concentration of 5 ppm in the cab. Under grossly exaggerated leakage conditions, a concentration of 460 ppm was reached when the coolant was pumped into the heater of an unventilated truck cab. In controlled human exposure studies to PQME vapor concentrations ranging from 50 to 2,000 ppm, the odor became transiently objectionable above 100 ppm. Eye, nasal, and throat irriation became objectionable prior to the first signs of central nervous system (CNS) impairment, which occurred at 1,000 ppm in one of two subjects. Alveolar breath samples must be obtained within 10 to 20 minutes following exposure because of the rapid decrease in solvent concentration.

A comparison of the lethality of chlorinated pyridines and a study of the acute toxicity of 2-chloropyridine☆

The single-dose intraperitoneal LD50, meq/kg, of the chlorinated pyridines in mice is as follows: 2,6-dichloro-, 0.78; 2,3,6-trichloro-, 0.82; 2,3-dichloro-, 0.91; 2,3,4,5,6-pentachloro-, 0.94; 2-chloro-, 1.14; 2,4,6-trichloro-, 1.54; 2,3,4,5-tetrachloro-, 1.96; 3-chloro-, 2.05; 2,3,5-trichloro-, 2.36; 4-chloro-, 2.46; 2,3,5,6-tetrachloro-, 5.30; 3,5-dichloro-, 7.98; and 2,5-dichloro-, 11.42. 2-Chloropyridine is somewhat more toxic to mice when given orally than when given by intraperitoneal injection. Concurrent administration of methionine but not cysteine to mice has a protective effect against the toxicity of 2-chloropyridine while nicotinamide augments the toxicity. In studies using rabbits, 2-chloropyridine was essentially as toxic when applied to the skin as when given by intraperitoneal injection. The single-dose inhalation toxicity of 2-chloropyridine was determined using rats. Following vapor exposure, histopathologic examinations revealed that this compound caused central lobular necrosis, hemorrhage, and fatty degeneration as well as cellular infiltration. Maximum single-dose exposures not causing these changes were 100 ppm for 3 minutes, 50 ppm for 6 minutes, 25 ppm for 12 minutes, and 10 ppm for 30 minutes. Maximum single-dose exposures that did not cause death were 1000 ppm for 6 minutes, 500 ppm for 12 minutes, 250 ppm for 30 minutes, 100 ppm for 2 hours, and 50 ppm for 4 hours.

The Toxicity of Boron Trifluoride when inhaled by Laboratory Animals.

Abstract Rats, rabbits, and guinea pigs were exposed seven hours per day, five days per week for periods up to six months duration to atmospheres containing boron trifluoride in concentrations calculated to be 12.8, 7.7, or 3.0 ppm. Analysis showed concentrations to be about one-half of these levels. The major effect of repeated inhalation was respiratory irritation causing injury ranging from death to a slight increase in pneumonitis. On basis of the study, a value of 0.3 ppm is tentatively suggested as a threshold limit value for boron trifluoride.

Effects of Repeated Inhalation of Vinyl Bromide in Laboratory Animals with Recommendations for Industrial Handling

Twenty repeated 7-hour exposures of male rats to 10,000 ppm of vinyl bromide resulted in an observable decrease in activity during the exposures and a significant decrease in gain of body weight. No noteworthy gross or microscopic pathological changes were detected in the major organs and tissues. Repeated 6-hour daily exposures of groups of male and female rats, rabbits, and monkeys, to either 2,50 ppm or 500 ppm of vinyl bromide vapor, for a period of 6 months were also investigated. There were no compound-related effects with respect to demeanor, body and organ weights, food consumption, a number of hematological parameters, or mortality. Gross and microscopic examination of the major organs and tissues revealed no remarkable abnormal changes. Slight increases in blood bromide concentration were detected in the experimental animals. An inference from the experimental data for an industrial situation suggests that repeated exposure of workmen to vinyl bromide should not exceed 500 ppm, and that the time...

Single exposure of rats to the vapors of trace substances in methoxyflurane

The question of the acute inhalation toxicity of real and potential trace substances in methoxyflurane was studied by exposing rats to the vapors of 9 compounds. None of the compounds were of the same order of toxicity as 2,3-dichloro-1,1,1,4,4,4-hexafluoro-2- butene, which was run as a standard. The compounds were found to fall in the following order when ranked from least acutely lethal to most acutely lethal toward rat CClF2CH2Cl, CCl3CClF2, CF2CHCl, CH3OCOOCH3, CH3OCF2CH2Cl, CClF2CHCl2, CHCl2COOCH3, CCl2CF2, and CH2ClCOOCH3.

Preliminary toxicologic studies on nitrogen trifluoride.

Abstract Limited toxicologic studies on NF 3 indicate that it is of moderate to high toxicity by inhalation in single doses. Single exposure of rats to concentrations in excess of 1000 ppm caused methemoglobinemia. A concentration of 2500 ppm caused death after 4 hours of exposure. Exposures to higher concentrations resulted in shorter survival times. The recovery of survivors appeared rapid although enlarged spleens were seen in many of the surviving animals. Repeated 7-hour daily exposures of male and female rats to 100 ppm for 4 I 2 months resulted in slight to moderate pathologic changes in the livers and kidneys of both sexes. An increase in the average weight of the liver, kidneys, and spleen of the male rats was also found. No evidence of fluorosis of the teeth or deposition of fluorine in the teeth and bone was observed, although a very slight increase in total fluorine in the urine was detected. Additional experiments are necessary before a level without any adverse effect can be defined. The concentration of NF 3 in work areas where repeated human exposure is likely should be limited to well below 100 ppm until more adequate information is available. Nitrogen trifluoride does not possess warning properties adequate to prevent excessive exposure; therefore, monitoring by instruments is recommended. Analysis by infrared absorption is extremely sensitive to this material and with a suitable gas cell should provide a method suitable for monitoring.