Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants Volume 2 (2008) / Chapter Skim
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Pages 64-87
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From page 64... ...
. The in vitro findings are consistent with the clinical signs associated with DBNP exposure and suggest that DBNP is an
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From page 65... ...
. No inhalation reference concentration has been calculated for inhalation exposure to 2,4-DNP because of the lack of adequate data (EPA 2005)
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From page 66... ...
At lethal doses, rats showed general depression of activity starting 3 h after dosing; deaths occurred 4 h to 3 days after dosing. The oral LD50 value in male guinea pigs was reported to be 800 mg/kg (Vesselinovitch et al.
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From page 67... ...
Necropsy examination of animals that died after DBNP dosing revealed edema or congestion of the thoracic cavity and lung hemorrhages. Animals that survived 40 mg/kg showed prostration, no auditory-startle response, reduced locomotor activity, and muscular rigidity for up to 8 days after dosing.
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From page 68... ...
The change in BST suggests that DBNP exposure resulted in an altered expression of this endocrine-modulated enzyme. Chronic Toxicity No chronic-toxicity information was identified.
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From page 69... ...
The rapid phase of clearance that occurs in the first hour after ip dosing is followed by a pseudosteady state that continues for a week and results in the removal of 4-6% of the radiolabel from the blood. The rapid phase is due to distribution of DBNP to body tissues and elimination in the urine and feces.
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From page 70... ...
respiration. INHALATION EXPOSURE LEVELS FROM THE NATIONAL RESEARCH COUNCIL AND OTHER ORGANIZATIONS The occurrence of DBNP in the submarine environment is due to the unintended release of DBP from submarine steam-turbine systems that use TEP 2190 as a lubricating oil.
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From page 71... ...
. Clinical signs and histopathologic lesions associated with DBNP and 2,4-DNP are very similar; the male rat oral LD50s of DBNP (50 mg/kg)
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From page 72... ...
The animal-toxicity database available for assessment of hazard and risk includes only single or repeat-dose studies, primarily via the oral route, with a small number of end points assessed. The committee considered deriving exposure guidance levels on the basis of noninhalation exposure routes, but there were insufficient data to support the route-to-route extrapolation.
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From page 73... ...
2,6-Di-tert-butyl-4-nitrophenol Prepublication Copy 73 Human Services, Atlanta, GA. August 1995 [online]
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From page 74... ...
and other agencies are also presented. The committee considered all that information in its evaluation of the Navy's current and proposed 1-h, 24-h, and 90-day exposure guidance levels for Freon 12.
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From page 75... ...
In general, the few data in humans are consistent with data in animals in the types of effects and effect levels. Because administered doses of epinephrine that caused cardiac arrhythmia with Freon 12 exposure were considerably higher than would occur endogenously, under normal conditions, neurologic or other effects -- such as pulmonary effects -- are more likely than cardiac effects at lower Freon 12 concentrations.
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From page 76... ...
, bradycardia, and increased variability in heart rate were reported for the individual compounds, and mixtures had stronger respiratory and cardiac effects. Exposure to Freon 12 at 27,000 ppm for 45 sec was reported to cause reductions in MEF50 and MEF75 of 3.4% and 5.6%, respectively.
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From page 77... ...
1977 (pulmonary tests) disease; pulmonary effects -- 3.4% decrease in MEF50, 5.6% decrease in Prepublication Copy 15 sec, 60 sec MEF75; cardiac effects -- reduced heart rate and respiratory sinus (EKG tests)
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From page 78... ...
No clinically significant changes from reactions in clean air were measured in blood and urine (hematology and clinical chemistry) 24 h after exposure; in blood pressure, pulse, and EKG before, during, or after exposure; or in lung function (peak expiratory flow)
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From page 79... ...
. In general, at equivalent air concentrations of Freon 12, effects noted after brief exposure (for example, 5 min)
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From page 80... ...
in myocardial force -- Dog (3) 5 min Anesthetized before exposure; increased pulmonary -- 100,000, Belej and Aviado 1975 resistance and heart rate at both concentrations; reduced 200,000 minute volume at 200,000 ppm; no significant effect on aortic blood pressure Prepublication Copy
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From page 81... ...
1975a animals with tracheal cannula 500,000 and 20% O2 Prepublication Copy Rat (4) 15 min once a Decrease in operant performance at 140,000 ppm; 40,000, 60,000, 140,000 Richie et al.
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From page 82... ...
1983 days/week for water consumption, body weight, clinical measures, 90 days heart rate, EKG, blood pressure, sight, hearing, dentition, organ weights, or histologic examinations Rat (40) 6 h/day, 7 No adverse effects on behavior and appearance, food or 10,000 -- Leuschner et al.
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From page 83... ...
b Reported as a dose; equivalent air concentration for 24-h exposure for a human in parentheses. Abbreviations: CFC, chlorofluorocarbon; CNS, central nervous system; EC50, the concentrations at which a specified effect is observed in 50% of a test population; EKG, electrocardiography; EEG, electroencephalography; MEF50 and MEF25-forced expiratory flow at 50% or 25% of vital capacity; FEV1, forced Prepublication Copy expiratory volume at 1 sec; FVC, forced vital capacity; NOAEL, no-observed-adverse-effect level.
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From page 84... ...
Hematologic characteristics were measured before and after exposure, body weights were measured monthly, and visible signs of toxicity (behavior, physical appearance, respiration pattern, locomotor activity, and prostration) were monitored during the exposure period.
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From page 85... ...
Assuming an inhalation rate of 20 m3/day and 70-kg body weight, those doses would be equivalent to 24h air concentrations for a human of 686 ppm and 1,584 ppm. Mice exposed 5 min/day at the specified dose 5 days/week for 23 months showed no signs of toxicity or lung tumors.
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From page 86... ...
, the mechanism of chlorofluorocarbon toxicity originates in irritation of the respiratory tract, which by a simple reflex response influences the heart rate before absorption of the compound. That is followed by depression of cardiac function after chlorofluorocarbon absorption and by sensitization of the heart to sympathomimetic amines (Aviado 1994)
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From page 87... ...
Selected values are summarized in Table 5-4. TABLE 5-4 Selected Inhalation Exposure Levels for Freon 12 from the NRC and Other Agenciesa Organization Type of Level Exposure Level (ppm)
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