F. Oyen

TOXICOLOGY OF ACRYLAMIDE.

Abstract This laboratory became interested in acrylamide early in 1954, when it became apparent that the material had great potential as a monomer and comonomer to make resins with unique flocculating action, and later as a dry strength improver in the manufacture of paper and paperboard. At that time, there were no published data on the toxicity of acrylamide. Later, it was learned that American Cyanamid Com- pany was sponsoring work on the material, portions of which have been reported by Hamblin (1956) and Kuperman (1958) . It soon became quite apparent that the rather high and unusual toxicity of the monomer would require extensive toxicologic study in order that recommendations for safe industrial handling could be ascertained, and to evaluate the safety in commercial use of polymers or copolymers which might contain small amounts of residual acrylamide.

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...

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.

Toxicity of acetylene tetrabromide determined on experimental animals.

Abstract Experimental animals were exposed to acetylene tetrabromide (1,1,2,2-tetra-bromoethane) by various routes in order to obtain toxicological information necessary to assess the hazards to health associated with the production, handling and use of the material. Results show that the material does not present serious hazards from ingestion, eye contact, skin contact, or from acute inhalation. They do show, however, that the material is quite toxic when given in small repeated doses. An industrial hygiene standard of one ppm is suggested.

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.

Toxicological studies of p-chlorophenyl-p-chlorobenzenesulphonate (Ovex)

Abstract Short- and long-term feeding studies of the pesticide, p -chlorophenyl- p -chlorobenzenesulphonate (ovex), have been carried out in rats and a 6-month feeding study in dogs. The acute oral LD 50 of ovex in rats was 2·05 g/kg and ranged from 0·64 to 5·66 g/kg in guinea-pigs, rabbits, mice and chicks. In the short-term study on rats fed on a diet containing 0, 0·03, 0·1, 0·3 or 1% ovex for 130 days toxic effects became apparent at the 0·1% level as evidenced by increased liver weight and slight cloudy swelling in the central areas of the liver. At the two highest dietary levels these effects were more pronounced and in addition growth retardation and slight to moderate degeneration of the tubular epithelium of the kidney were also observed. When animals were placed on a similar regime for 164 days and then allowed to partake of the control diet for the next 152 days the histopathological changes previously seen were now absent and liver weight was restored to normal even at the 0·3% level. In a 2-generation reproduction study involving rats given dietary levels of 0, 0·01, 0·03 or 0·3% ovex for 164 days no adverse effect on the number of litters, litter size or survival of young to weaning was seen at the lowest level although there were slight reductions in litter size at the 0·03 and 0·3% levels. At the highest level the mothers poor condition was conducive to the failure of the young to survive weaning. In a 2-yr study on rats maintained on a diet containing 0·63, 1·25, 2·5, 5, 15 and 50 mg ovex/kg growth retardation was only seen in females at the two highest levels. Very slight liver and kidney changes were first observed at the 2·5 mg/kg/day level but the slight fatty metamorphosis of the liver and slight chronic glomerulonephritis of the kidney became more pronounced with increasing dosage levels. Dogs receiving in their diet 0, 5, 15 or 50 mg ovex/kg/day for 6 months exhibited no toxic effects apart from a doubtful significant increase in liver weight found in the groups on the two highest dietary levels. Analysis of various tissues showed that repeated ingestion of ovex does not result in its accumulation in the tissues of rats and dogs. At high dosage levels ovex is preferentially retained in the fat, partly in muscle with traces in the liver. The no-effect level of ovex in the rat was estimated to be 1·25 mg/kg/day, a figure which provides a very wide margin of safety for the human consumption of foodstuffs likely to contain ovex residues.