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Biomedical subjects

N D Krivanek

Publications and source records attributed to N D Krivanek.

8 recordsLinked to original sources
PubMed1990

A scheme for classifying carcinogens.

We present a scheme for classifying chemical carcinogens according to the weight of the evidence that each substance poses a human cancer hazard. The approach represents a logical extension of and builds upon those previously developed by the International Agency for Research on Cancer, the U.S. Environmental Protection Agency, and the so-called Tripartite Group of industrial scientists. It takes into account new scientific knowledge about chemical carcinogenesis and animal models. Eight categories are presented: known human carcinogen (Category 1), carcinogenic activity in animals, probable human carcinogen (Category 2), possible human carcinogen (Category 3), equivocal evidence for carcinogenic activity (Category 4), evidence inadequate for classification (Category 5), carcinogenic activity in animals; probably not a human cancer hazard (Category 6), carcinogenic activity in animals; considered not a human cancer hazard (Category 7), evidence of noncarcinogenicity (Category 8). Evidence useful for categorization includes human studies, animal bioassays, corroborative evidence from bioassays, and mechanistic studies relevant to determining the predictivity of animal responses for human hazard. Weighing this evidence to derive a conclusion about classification is a process that requires expert judgment; it cannot now be reduced to a simple set of decision rules. However, we identify the kinds of information that can be useful in this process, and indicate how each might most appropriately be used.

Animals↗
PubMed1983

Guinea pig respiratory response to isocyanates.

Exposure to some isocyanates (e.g., toluene diisocyanate) has been associated with development of respiratory sensitization. In this study, guinea pig respiratory response to protein conjugates of isocyanatoethyl methacrylate (IEM) and isocyanatoethyl propionate (IEP) was evaluated. Guinea pigs were exposed to daily induction exposures with an aerosol of bovine serum albumin (BSA) or BSA conjugated with IEM or IEP. After approximately 2 weeks significant increases in respiratory rate occurred in the guinea pigs exposed to the isocyanate conjugates. The number of animals responding was related to the degree of conjugation of isocyanate to protein. No response to unconjugated BSA was observed. The isocyanates conjugated to another carrier, guinea pig serum albumin (GSA), elicited responses. In guinea pigs responding to BSA-IEM, 0.01 ppm IEM monomer did not elicit responses; 0.1 to 0.4 ppm IEM vapor elicited responses similar to conjugates but which were delayed; 0.5 and 0.6 ppm induced irritation responses. An IEM polymer aerosol that contained less than 0.004% monomer did not elicit a response. These data suggest a response threshold. Guinea pig developing responses to either of the isocyanate conjugates displayed cross-reactions to challenge with the other. A conjugate of BSA with hexyl isocyanate (HI) did not induce cross-responses in guinea pigs reactive to BSA-IEM. Application of BSA-IEP or IEP monomer to the scratched skin of guinea pigs that responded by inhalation to BSA-IEP resulted in immediate wheal and flare responses not seen in unexposed animals. All of these findings suggest induction of Type I hypersensitivity (asthmatic) directed toward the isocyanate portion of the conjugate and not the protein.

Acrylates↗
PubMed1982

Comparison of unconditioned reflex and conditioned avoidance tests in rats exposed by inhalation to carbon monoxide, 1,1,1-trichloroethane, toluene or ethanol.

The sensitivity of unconditioned reflex and conditioned avoidance tests in evaluating behavioral toxicity was compared. Male rats were exposed by inhalation up to four hours to 0, 200, 400, 800 or 1600 ppm carbon monoxide (CO); 0, 1500, 3000, 6000 or 12,000 ppm 1,1,1-trichloroethane; 0, 800, 1600, 3200, or 6400 ppm toluene; or 0, 4000, 8000, 16,000 or 32,000 ppm ethanol. Animals were tested for behavioral changes at one-half, one, two and four hours during exposure and eighteen hours after exposure ended. In unconditioned reflex testing the presence or absence of specific unconditioned reflexes (such as corneal, placing, grasping and righting reflexes) and simple behavior patterns including locomotor activity and coordination were observed. The conditioned reflex task consisted of shock avoidance by lever press following simultaneous light and sound stimuli. Rats began to fail unconditioned reflex tests at 800 ppm CO, 3000 ppm trichloroethane, 800 ppm toluene and 8000 ppm ethanol. Decrements in conditioned avoidance were observed at 800 ppm CO, 6000 ppm trichloroethane, 3200 ppm toluene and 8000 ppm ethanol. Neither test was consistently more sensitive than the other in detecting behavioral changes. For both methods, the concentrations at which changes were detected in rats were two to tenfold higher than those reported for human effects.

Animals↗
PubMed1978

Monomethylformamide levels in human urine after repetitive exposure to dimethylformamide vapor.

Eight healthy male subjects were exposed to DMF vapor at a concentration of 8.79 +/- 0.33 ppm for six hours daily for five consecutive days. All urine voided by the subjects was collected from the beginning of the first exposure to 24 hours past the end of the last exposure and each sample was analyzed for monomethylformamide (MMF). MMF was rapidly eliminated from the body with urine values peaking within a few hours following the end of each exposure period. Very little was found in the 24-hour postexposure sample and none was found in a 48-hour postexposure sample. There was no increased excretion of MMF in the urine following repetitive exposure. The mean for the seven-hour (end of exposure) sample was 4.74 microgram/ml or 736.8 microgram. Lower and upper one-sided 95% tolerance limits for 95% of the population were 1.2 microgram/ml (367 microgram) and 13.9 microgram/ml (1625 microgram). The coefficient of variation (CV) for microgram MMF/ml was approximately 25 times more variable than the CV for total microgram.

Adult↗