Rodents inhalation exposure

In humans, acute high-dose exposure leads to liver and kidney damage. In rodents, inhalation exposure causes primarily proliferative lesions in nasal cavities. After intra-gastric administration, liver and kidney were the main target organs. Some evidence of adverse effects on reproduction was observed both in humans and rodents. 

Results of chronic MTBE exposure studies are the most widely available of all studies on the ether-like fuel oxygenates (MTBE, ETBE, TAME, DIPE). Evidence from animal bioassays demonstrates that long-term, high-level exposures to MTBE by either ingestion or inhalation cause cancer in rodents. Inhalation exposure to MTBE produced an increased incidence of renal and testicular tumors in male rats and liver tumors in mice. Oral administration of MTBE produced an increased incidence of lymphomas and leukemias in female rats and testicular tumors in male rats. Chronic exposure to ethanol also produces cancers (e.g., esophageal) in laboratory animals. 

No studies addressing developmental or reproductive effects following acute inhalation exposure to aniline were located. However, because effects on development and reproduction arise after systemic uptake, oral administration of aniline can be considered for evaluating potential developmental and reproductive toxicity. Aniline (administered as aniline hydrochloride) readily crosses the placental barrier in rodents (Price et al. 1985). 

Both isomers of dimethylhydrazine have been shown to be carcinogenic in rodents following chronic oral exposure and 6-mon inhalation exposure to 1,1-dimethylhydrazine. Increased tumor incidence was observed in mice, although these findings are compromised by the contaminant exposure to dimethylnitrosamine. An increased incidence of lung tumors and hepatocellular carcinomas was also seen in rats but not in similarly exposed hamsters. The U.S. Environmental Protection Agency (U.S. EPA) inhalation slope factors are currently unavailable for dimethylhydrazine. 

Chronic inhalation exposure of rodents to 1,2-dibromoethane has been associated with neoplasms in the respiratory tract, as well as in other organ systems. Two studies have examined the carcinogenic potential of 1,2-dibromoethane in rodents after inhalation exposure (NTP 1982 Wong et al. 1982). There was also an A strain mouse assay (Adkins et al. 1986). 

Degenerative changes were observed in the liver and kidney of rodents exposed to high one-time concentrations of 0.26-1.4g/mL Nonspecific changes in the blood were also observed. Nervous system effects, including excitation, impairment of locomotor activity, listlessness, hypothermia, and convulsions, were observed in mice before death following inhalation exposure to 2 g/rsf ... 

Melnick, R.L., Sills. R.C., Roycroft. J.H., Chou, B.J., Ragan, H.A. Miller, R.A. (1994) Isoprene, an endogenous hydrocarbon and industrial chemical, induces multiple organ neoplasia in rodents after 26 weeks of inhalation exposure. Cancer Res., 54, 5333-5339... 

Interroute Extrapolation. The Sun model examined two routes of exposure, oral and inhalation. The model was found to be useful in predicting the concentrations of hemoglobin adducts in blood in rodents after oral and inhalation exposure. 

The epoxide metabolites of inhaled 1,3-butadiene, used in industry, are reported to be carcinogenic and mutagenic in rodents, and their in vivo concentration following inhalation exposure to butadiene has to be determined by gas chromatography/mass spectroscopy, the isotope dilution method utilizing 8 as an internal standard. Commercially available [De]-propylene oxide has been used previously as an internal standard to monitor in vivo blood propylene oxide levels following inhalation exposure to propylene. ... 

The oral LD50 in rodents ranges from 1 to 7 g kg and intravenous LD50 in mice and rats is lOgkg. No acute lethality information is available following either dermal or inhalation exposures. Acetamide is not a developmental toxicant and is generally inactive in genetic toxicity tests. 

Rodent and human studies have shown that MTBE is rapidly absorbed following inhalation exposure. In addition, rodent studies have shown rapid distribution of MTBE after oral and intraperitoneal exposure. Dermal absorption occurs more slowly. Evidence supports metabolic transformation of MTBE by P450 enzymes to the parent alcohol, t-butyl alcohol (TBA), and formaldehyde in rodents and humans. Further oxidative metabolism of TBA seems to be slow, and glucuronidation is a major competing pathway. Formaldehyde metabolism to formate is very rapid. The toxicokinetic parameters of MTBE and TBA depend on the dose and route of administration although they appear to be linear following inhalation exposures up to 50 ppm. 

It should be noted that evidence derived largely from animal and cell-based studies indicates that both MTBE and ETBE are oxidatively demethylated to produce t-butyl alcohol (TBA). MTBE is also metabolized to formaldehyde. Both TBA and formaldehyde are potentially carcinogenic. In all the studies with rodents, MTBE and TBA increased tumor incidence only at very high oral or inhalation exposures, levels that would not be encountered by humans for prolonged periods of time. 

Glycol ethers as a class are not acutely toxic by the oral route. Inhalation exposure to high concentrations of compounds in the ethylene series can cause lethality. However, exposure to compounds in the propylene series was not lethal to rodents even at nearly saturated concentrations. 

Acute inhalation exposure may result in pulmonary edema, coughing, and labored breathing in humans. HDI is extremely irritating to the eyes, nose, and throat. Rodent studies revealed that HDI is extremely toxic by inhalation, and moderately to highly toxic by oral ingestion. 

Acute inhalation exposure may result in sensitization and asthma in humans. Dermal contact with MDI resulted in dermatitis and eczema in plant workers. Animal studies revealed skin and eye irritation in rabbits, extreme toxicity by inhalation and moderate toxicity by oral ingestion in rodents. 

Chronic inhalation exposure to MDI is one of the leading causes of asthma in plant workers. In addition, chronic inhalation exposure can cause dyspnea, immune disorders as well as nasal and lung lesions. EPA has set the RfC for MDI at 0.0006mgm based upon irritation of nasal membranes in rodents. EPA has not established an RfD for MDI. 

The acute dermal LD50 is greater than 5000 mg kg in rodents. Dermal exposure to mancozeb leads to mild irritation to the skin. Exposure to the eye also leads to moderate irritation. Inhalation of mancozeb leads to irritation of the respiratory tract, with LC50 of greater than 5.14 mg 1. ... 

CS is absorbed very rapidly from the respiratory tract, and the half-lives of CS and its principal metabolic products are extremely short. The disappearance of CS follows first-order kinetics and spontaneously hydrolyses to malononitrile, which is transformed to cyanide in animal tissues. Metabol-ically, CS undergoes conversion to 2-chlorobenzyl malononitrile (CSH2), 2-chlorobenzaldehyde (oCB), 2-chlorohippuric acid, and thiocyanate. CS and its metabolites can be detected in the blood after inhalation exposure, but only after large doses. Following inhalation exposure of CS in rodent and nonrodent species, CS and two of its metabolites, 2-chlorobenzaldehyde and 2-chlorobenzyl malononitrile, were detected in the blood. In another study, human uptake by the respiratory tract, only 2-chlorobenzyl malononitrile was detected in trace amounts in the blood. CS and 2-chlorobenzaldehyde were not detected, even after high doses of CS of up to 90 mg min m. This finding is consistent with the... 

Other routes of exposure include inhalation exposure for atmospheric borne pollutants. In many cases of an originally atmospheric exposure, dermal exposure may occur. An alternative method of ensuring an inhalation exposure is to provide an air or watertight seal limiting exposure to the respiratory apparatus. In the case of rodents, nose-only exposures can be used to limit coat... 

Using the rodent inhalation model depicted in figure 2, mice were assessed for locomotor activity after exposure to methamphetamine vapor, antinociception after exposure to heroin, and motor coordination after exposure to PCP. Temperatures used for volatilization of these drugs are listed in table 2. These temperatures were empirically derived... 

Gastrointestinal Effects. Nausea, vomiting, and diarrhea reportedly occur in humans after acute oral or inhalation exposure to high 1,1,1-trichloroethane levels (Jones and Winter 1983 McCarthy and Jones 1983 Stewart 1971 Stewart and Andrews 1966). Vomiting and diarrhea have not been reported in animals (rodents, the most commonly used laboratory animals, cannot vomit). The mechanisms for these effects are not known. 

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