Biological Effects of Short-Term, High-Concentration Exposure to Methyl Isocyanate. II. Blood Chemistry and Hematologic Evaluations

Troup, Catherine M.; Dodd, Darol E.; Fowler, Edward H.; Frank, Fred R.

doi:10.2307/3430271

Cited by 10 publications

(17 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The morphologic changes induced by high exposure concentrations of MIC vapor in the lungs of rats and guinea pigs support the biological effects observed in other studies conducted by UCC (6,8,9). In the controlled ventilation studies (8), we have shown that within minutes there is an increase in intratracheal pressure with marked shifts in both blood gases and pH.…”

Section: Guinea Pigssupporting

confidence: 87%

See 1 more Smart Citation

Biological effects of short-term, high-concentration exposure to methyl isocyanate. V. Morphologic evaluation of rat and guinea pig lungs.

Fowler¹,

Dodd²,

Troup³

1987

Environ Health Perspect

View full text Add to dashboard Cite

The morphologic changes induced in the lungs of rats and guinea pigs exposed to high concentrations of MIC vapor (100, 600, and 1000 ppm in the rat and 25, 125, 225, and 675 ppm in the guinea pig) for a short time (15 min) in a static exposure chamber were evaluated at varying postexposure periods (0, 1, 2, 4, and 16 hr). The 675 ppm-exposed guinea pigs were evaluated only immediately following removal from the chamber. Attention was primarily focused on the intrapulmonary conducting airways and the parenchyma (gas exchange region) of the lungs. The severity of morphologic changes observed by light microscopy was directly correlated with exposure concentration and time postexposure in both species. Specifically, degenerative changes were observed in the bronchial, bronchiolar, and alveolar epithelium in both species. Quantitative differences were observed; 100 ppm of MIC in the rat resulted in much less damage than did 125 ppm of MIC in the guinea pig. Morphologic evidence of sloughing of large sheets of conducting airway epithelium with fibrin buildup and increased mucus production resulted in plugging of major airways and atelectasis. These observations support the hypothesis that tissue hypoxia was a major contributing factor resulting in death.

show abstract

Section: Guinea Pigssupporting

confidence: 87%

“…Blood samples were obtained either from anesthetized animals prior to sacrifice or immediately following sacrifice for hematologic and blood chemistry analyses (6). Blood was also obtained from selected guinea pigs for determination of complement activity.…”

Section: Methodsmentioning

confidence: 99%

Biological effects of short-term, high-concentration exposure to methyl isocyanate. V. Morphologic evaluation of rat and guinea pig lungs.

Fowler¹,

Dodd²,

Troup³

1987

Environ Health Perspect

View full text Add to dashboard Cite

show abstract

“…Union Carbide Corporation chose to investigate the following pathophysiologic mechanisms: (1) an inhibition of cholinesterase activity, (2) an alteration of hemoglobin function, (3) gas exchange impairment in the lung, (4) (12).…”

Section: Current Study Objectives and Specific Areas Of Concernmentioning

confidence: 99%

Biological Effects of Short-Term, High-Concentration Exposure to Methyl Isocyanate. I. Study Objectives and Inhalation Exposure Design

Dodd¹,

Frank²,

Fowler³

et al. 1987

Environmental Health Perspectives

Self Cite

View full text Add to dashboard Cite

Early reports from India indicated that humans were dying within minutes to a few hours from exposure to methyl isocyanate (MIC). Attempts to explain the cause(s) of these rapid mortalities is where Union Carbide Corporation concentrated its post-Bhopal toxicologic investigations. The MIC studies involving rats and guinea pigs focused primarily on the consequences of acute pulmonary damage. All MIC inhalation exposures were acute, of short duration (mainly 15 min), and high in concentration (ranging from 25-3506 ppm). MIC vapors were statically generated in a double chamber exposure design. Precautionary measures taken during exposures are discussed. Guinea pigs were more susceptible than rats to MIC exposure-related early mortality. A greater than one order of magnitude difference was observed between an MIC concentration that caused no early mortality in rats (3506 ppm) and an MIC concentration that caused partial (6%) early mortality in guinea pigs (225 ppm) for exposures of 10 to 15 min duration. For both species, the most noteworthy clinical signs during exposure were lacrimation, blepharospasm, and mouth breathing. Fifteen minute LC50 tests with 14-day postexposure follow-up were conducted, and the LC5. (95% confidence limit) values were 171 (114-256) ppm for rats and 112 (61-204) ppm for guinea pigs.Target exposure concentrations for the toxicologic investigations of MIC-induced early mortality were established. A short summary of pertinent results of Union Carbide Corporation's post-Bhopal toxicologic investigations is presented.

show abstract

“…This conclusion is at least partially supported by the studies of Troup et al (26), which reported a significant increase in plasma hematocrit levels observed in rats exposed to 1000 ppm MIC for periods of 1 hr or longer. The MIC-induced activation of C5 in vivo, as evidenced by the results presented in Tables 3 and 4, may be a major contributor to the increased hematocrit (26), neutrophilia (26), and pulmonary perivascular neutrophil extravasation (18) observed in MIC-treated animals.…”

Section: Resultsmentioning

confidence: 59%

“…The MIC-induced activation of C5 in vivo, as evidenced by the results presented in Tables 3 and 4, may be a major contributor to the increased hematocrit (26), neutrophilia (26), and pulmonary perivascular neutrophil extravasation (18) observed in MIC-treated animals. This would be the case whether C5 activation occurred in these animals as a result of sequential, physiological complement pathway activation or as an isolated event as exemplified by the activation of C5 by noncomplement proteases.…”

Section: Resultsmentioning

confidence: 98%

Biological effects of short-term, high-concentration exposure to methyl isocyanate. VI. In vitro and in vivo complement activation studies.

Kolb¹,

Savary²,

Troup³

et al. 1987

Environ Health Perspect

View full text Add to dashboard Cite

The ability of MIC to induce complement activation in vitro and in vivo was investigated. For the in vitro studies, both human and guinea pig serum or EDTA-plasma samples were exposed to 1167 to 1260 ppm MIC vapor for 15 min at room temperature. The human serum samples exposed to MIC showed significant reductions in Factor B, C2, C4, C3, C5, and total hemolytic complement CH50 activity levels. C6 functional activity was unaffected. The C3, C5, and CH50 functional activities in guinea pig serum (the only functional tests conducted on these samples) were more sensitive to MIC-mediated reduction than the corresponding activity reductions observed in the human serum samples. The human and single guinea pig EDTA-plasma samples exposed to MIC vapor showed no evidence of C3 consumption but did show significant reductions in CH50 levels. Thus, MIC vapor was able to activate, and thereby reduce serum complement C3 activity in vitro by a complement-dependent process. However, the data suggest at least one complement component other than C3 was inactivated in EDTA-plasma by a complement-independent mechanism.For the in vivo studies, five pairs of guinea pigs were exposed to 644 to 702 ppm MIC vapor until one of the pair died (11-15 min). MIC exposure was then discontinued, the surviving guinea pig was sacrificed, and EDTA-plasma was obtained from both animals and analyzed for complement consumption. Clear evidence was obtained to indicate that complement activation had occurred in these animals exposed to MIC for 11 to 15 min. In addition, the complement activation profile observed in these guinea pigs was qualitatively similar to that seen in the guinea pig serum samples exposed to MIC vapor in vitro. The total protein concentration present in plasma samples obtained from guinea pigs that had died from MIC exposure was elevated significantly (p < 0.05) above the total protein concentration present in plasma samples obtained from these same animals before MIC exposure or from paired animals which had not died (sacrificed) from MIC exposure. The possible contribution of complement activation to the fatal reaction(s) observed in these MIC-treated animals is discussed.

show abstract

Biological Effects of Short-Term, High-Concentration Exposure to Methyl Isocyanate. II. Blood Chemistry and Hematologic Evaluations

Cited by 10 publications

References 5 publications

Biological effects of short-term, high-concentration exposure to methyl isocyanate. V. Morphologic evaluation of rat and guinea pig lungs.

Biological effects of short-term, high-concentration exposure to methyl isocyanate. V. Morphologic evaluation of rat and guinea pig lungs.

Biological Effects of Short-Term, High-Concentration Exposure to Methyl Isocyanate. I. Study Objectives and Inhalation Exposure Design

Biological effects of short-term, high-concentration exposure to methyl isocyanate. VI. In vitro and in vivo complement activation studies.

Contact Info

Product

Resources

About