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Biomedical subjects

N D Krivanek

Publications and source records attributed to N D Krivanek.

11 recordsLinked to original sources
PubMed1993

Methyl methacrylate: inhalation developmental toxicity study in rats.

Methyl methacrylate (99.9% pure) was administered by vapor inhalation exposure to five groups (27 rats/group) of presumed pregnant rats (Crl:CD) at concentrations of 0 (control), 99, 304, 1,178, and 2,028 ppm for 6 hr/day on days 6-15 of gestation (G). Maternal body weight, feed consumption, and clinical signs were recorded throughout gestation. Dams were euthanized on day 20 G. Each uterus was weighed and corpora lutea, implantation sites and resorptions were counted. The number of fetuses per litter were counted and their location within the uterus recorded. All fetuses were weighed, sexed and examined for external and skeletal alterations. One half of the fetuses from each litter were examined for visceral alterations. No treatment-related deaths were noted at any concentration tested. Treatment-related effects on maternal body weight and feed consumption were noted at all exposure levels. The decreases in maternal body weight at 99 and 304 ppm were minimal and transient since they returned to control values by the next weighing period. When exposure was discontinued, body weight gain and feed consumption in all exposure groups returned to control values. There were no treatment-related changes in the number of litters produced or in the mean number per litter of corpora lutea, implantations, resorptions, live or dead fetuses, or sex ratio. Fetal body weights were similar between the control and treated groups. There were no treatment-related increases in the type or incidence of external, visceral, or skeletal malformations, developmental variations, or variations indicative of retarded development. Exposure to methyl methacrylate concentrations up to 2,028 ppm resulted in no embryo or fetal toxicity or malformations even at exposure levels that resulted in maternal toxicity.

Administration, Inhalation↗
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↗
PubMedDate not supplied

Chronic inhalation toxicity and oncogenicity of methyl methacrylate in rats and hamsters.

Male and female Fischer 344 rats were exposed to methyl methacrylate (MMA) monomer vapours at 0, 25, 100 and 400 ppm, 6 hr/day, 5 days/wk for 24 months and male and female Golden hamsters were exposed to similar vapour concentrations of MMA for 18 months. Parameters monitored throughout the study included clinical signs, individual body weights, haematology, clinical chemistry (rats only) and urinalyses (rats only). 10 rats per sex per exposure group were killed after 13 and 52 wk of exposure and all surviving rats were killed during wk 104-106. All surviving hamsters were killed at wk 78. Mortality and haematological, clinical chemistry and urinalyses parameters were not affected by MMA exposure. Body weights of male rats were not affected by exposure to MMA while body weights of female rats exposed to 400 ppm were lower than control values after wk 52. Male and female hamsters exposed to 400 ppm had body weight decreases ranging from 9 to 12% after wk 48. The nasal cavity was identified as the target organ for chronic toxicity in male and female rats exposed to 100 or 400 ppm. The microscopic nasal cavity changes occurred primarily in olfactory epithelium lining the dorsal meatus and consisted of degeneration of neuroepithelium, basal cell hyperplasia and atrophy of Bowman's glands. Hamsters did not have demonstrable nasal cavity microscopic changes. Chronic exposure to MMA vapour did not cause tumours in either rats or hamsters.

Administration, Inhalation↗