NO inhalation

Health and Safety Factors. Butanediol is much less toxic than its unsaturated analogs. It is neither a primary skin irritant nor a sensitizer. Because of its low vapor pressure, there is ordinarily no inhalation problem. As with all chemicals, unnecessary exposure should be avoided. The LD q for white rats is 1.55 g/kg. 

In low doses, inhaled NO may have a beneficial therapeutic effect, since NO in the inspired air leads to pulmonary vasodilation. In persistent pulmonary hypertension of the newborn, NO inhalation has already been used with some success. NO inhalation as the treatment for acute respiratory distress syndrome, however, has been disappointing. Only transient improvements of oxygenation were detected and the outcome of placebo-controlled trials did not show any improvement... 

Inhaled NO has been used for treatment of persistent pulmonary hypertension of newborn infants, critical respiratory failure of preterm infants, and acute hypertension of adult cardiac surgery patients. PDE-5 inhibitors such as sildenafil are also effective for treatment of pulmonary hypertension. The combination of PDE-5 and NO inhalation yields additive beneficial effects on pulmonary hemodynamics. On the other hand, measurement of exhaled NO is a noninvasive and reproducible test that is a surrogate measure of airway inflammation in patients with bronchial asthma. 

Although a number of studies have reported the effects of inhalation exposure to methyl parathion in humans, no inhalation MRLs were derived based on human data because of the lack of adequate quantitative exposure information. Animal data were also insufficient to support the derivation of an acute-, intermediate-, or chronic-duration inhalation MRL. 

The oral reference dose (RfD) for trichloroethylene is currently imder review by an EPA workgroup (IRIS 1996). No inhalation reference concentration (RfC) has been derived (IRIS 1996). The National Center for Environmental Assessment, EPA has begun an effort to reassess the health risks associated with trichloroethylene. 

No inhalation or oral MRLs were derived for americium or americium compounds. 

Two studies on intermediate-duration exposure to mineral oil hydraulic fluids are available a single oral exposure rat study to MIL-H-5606 (Mattie et al. 1993), and an inhalation-exposure study in rats to Houghto-Safe 5047F (Kinkead et el. 1991). Because no other intermediate-duration studies were located, no inhalation or oral intermediate MRLs were derived. Inhalation, oral, and dermal systemic toxicity studies examining a number of end points would be useful in identifying the targets of toxicity of mineral oil hydraulic fluids. 

Mineral Oil Hydraulic Fluids. No human or animal studies involving inhalation, oral, or dermal chronic-duration exposure were located. Because no chronic-duration studies were located, no inhalation or oral... 

No inhalation slope factor is available for aniline, and the available inhalation studies did not examine the endpoint of carcinogenicity. Based on the chronic oral administration of aniline hydrochloride to CD-F rats (CUT 1982), U.S. EPA in its Integrated Risk Information Systems (IRIS) has estimated an oral slope factor of 5.7x1 OP Vrng/kg/d (U.S. EPA 1994). In that study, spleen tumor incidences in rats administered 0, 200, 600, or 2,000 ppm in the diet were 0/64, 0/90, 1/90, and 31/90, respectively. Aniline also has genotoxic action. 

Other than the study by Weeks et al. (1979), there are no inhalation studies useful for estimating an acute inhalation MRL. 

Other than the study by Weeks et al. (1979) there are no inhalation studies useful for estimating an intermediate inhalation MRL. Studies in guinea pigs and dogs confirm that 260 ppm hexachloroethane is a serious effect concentration 4/10 guinea pigs, and 1/4 dogs died at this concentration. These studies do not clearly identify a less serious LOAEL that does not have some serious effects. The 48-ppm concentration is aNOAEL for the most sensitive toxicity endpoint in all three species. 

The critical effect of intermediate-duration exposure to -hexane in humans is neurotoxicity, specifically peripheral neuropathy. No inhalation MRL was derived for this duration because the reports of neurological effects in humans were predominantly case reports with inadequate documentation of exposure levels or comparison with unexposed groups. A large database on neurological effects in rats exists for this duration however, the design of these experiments precluded documentation of clear dose-response relationships within a single study. Because of the limited database for oral exposure to -hexane and the lack of toxicokinetic data for this route, no MRL was derived for oral exposure to -hexane. 

No inhalation MRLs were derived for either mirex or chlordecone because of the absence of reliable data following inhalation exposure. 

Studies of workers exposed to high levels of chlordecone indicate that pleuritic chest pain was a relatively common complaint (Cannon et al. 1978 Taylor 1982, 1985). Examination of workers with this complaint revealed no cause for the pains. Since oral exposure studies in animals did not identify any respiratory end points that may have been affected following ingestion of chlordecone (Larson et al. 1979b) and no inhalation exposure studies were located, a possible physiological basis for the workers complaints has not been identified. Insufficient information is available to determine whether persons exposed to low levels of chlordecone at hazardous waste sites would experience adverse respiratory effects, but the possibility cannot be discounted. 

No acute-duration inhalation MRL could be derived for mirex because no inhalation data could be located. No acute-duration oral MRL was derived for mirex because serious effects (heart block and arrhythmias in fetuses from dams exposed during gestation) were observed at the lowest dose tested (Grabowski 1983a). Studies examining the effects of mirex and chlordecone after acute-duration dermal exposure would be helpful since persons at hazardous waste sites may be exposed dermally to mirex. Additional dermal studies are certainly necessary because skin absorption of chlordecone appears to be an important route of exposure (Taylor et al. 1978). However, populations at hazardous waste sites are unlikely to be exposed via inhalation since these substances are virtually nonvolatile, so future studies using this route of exposure are not essential. 

No inhalation MRLs were derived for di-w-octylphthalatc. No data exist on the effects of acute-,... 

No inhalation MRLs were derived for 1,3-DNB or 1,3,5-TNB due to lack of human and animal data. Oral MRLs. 

As discussed in Section 2.2, estimates of levels of exposure to 2-hexanone posing minimal risk to humans (MRLs) were to have been made, where data were believed reliable, for the most sensitive noncancer effect for each route and exposure duration. Flowever, no MRLs could be derived for 2-hexanone. No data were located on effects of acute-duration or chronic-duration inhalation exposure to 2- hexanone in humans or animals. Available information concerning effects of intermediate-duration inhalation exposure in humans and animals identifies neurological effects as the most sensitive indicator of toxicity, but this information does not reliably identify the threshold for this effect. Therefore, no inhalation MRLs were derived. Available information on acute-duration oral exposure in animals does not identify the most sensitive effect, and while available information on intermediate-duration oral exposure to 2-hexanone in animals suggests that neurotoxicity may be the most sensitive effect, data do not reliably identify the threshold for neurotoxicity. No information was located on effects of chronic-duration exposure to 2-hexanone in humans or animals. Therefore, no oral MRLs were derived. Acute-duration, intermediate-duration, and chronic-duration dermal MRLs were not derived for 2-hexanone due to the lack of an appropriate methodology for the development of dermal MRLs. 

No inhalation MRLs were derived for chlorite. The only available information regarding health effects following inhalation exposure to chlorite was limited to a single study of lethality in rats exposed to aerosols of sodium chlorite, an exposure scenario not likely to be encountered in environmental or occupational settings. Furthermore, lethality is a serious effect, and therefore cannot be used as the basis for deriving an MRL. 

In the lungs, NO affects not only blood vessels but also the bronchi and bronchioles as well. In newborns with defective gas exchange, NO inhalation decreases pulmonary arterial blood pressure, enabling more blood to be oxygenated. In adults with obstructive lung diseases, NO inhalation seems to relax airway smooth muscle, thus acting as a bronchodilator. 

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