Inhaled studies

Formaldehyde is classified as a probable human carcinogen by the International Agency for Research on Cancer (lARC) and as a suspected human carcinogen by the American Conference of Governmental Industrial Hygienists (ACGIH). This is based on limited human evidence and on sufficient evidence in experimental animals (136). Lifetime inhalation studies with rodents have shown nasal cancer at formaldehyde concentrations that overwhelmed cellular defense mechanisms, ie, 6 to 15 ppm. No nasal cancer was seen at 2 ppm or lower levels (137). 

Eadier reports of a link between testicular cancer and DMF exposure have not been corroborated ia a study of 4000 Du Pont employees (34). Very recendy, inhalation studies ia mice and rats have shown no oncogenic effect from DMF (35). The International Agency for Research on Cancer (lARC) has concluded that evidence associating DMF with cancer ia animals is "iaadequate," but has classified DMF as "possibly carciaogenic to humans" (Group 2B) (36). 

Toxicity Data on Af- Vinyl-2-Pyrrolidinone. Results of a chronic inhalation study in rats warrant a review of industrial hygiene practices to assure that VP vapor concentrations are maintained at a safe level. One of the manufacturers, ISP, recommends that an appropriate workplace exposure limit be set at 0.1 ppm (vapor) (9). Additionally, normal hygienic practices and precautions are recommended, such as prompt removal from skin and avoidance of ingestion. In case of accidental eye contact, immediately flush with water for at least 15 minutes and seek medical attention. Refer to the manufacturers Material Safety Data Sheets for more detailed information. Table 3 provides some toxicity data. 

Inhalation of high concentrations of monochlorotoluenes will cause symptoms of central nervous system depression. Inhalation studies produced an LC q (rat, 4 h) of 7119 ppm for o-chlorotoluene (68). o- and Chlorotoluene are both considered moderately toxic by ingestion (Table 2). A study of the relationship between the electronic stmcture and toxicity parameters for a series of mono-, di-, and tri-chlorotoluenes has been reviewed (72). A thin-layer chromatographic method has been developed to assess the degree of occupational exposure of workers to chlorotoluenes by determining j -cblorobippuric... 

A. Wiedow, Results of Inhalation Studies on PT810 and PT810 Containing Powders, paper presented at CIBA GEIGY PT810 Health Safety Seminar, Greenville, S.C., Sept. 23—24, 1991. 

In an animal study of rats exposed by inhalation to ethylene oxide at 10, 33, or 100 ppm for approximately two years (245), and in a separate chronic rat study in which rats were exposed to 50 or 100 ppm of ethylene oxide (240), increased incidences of mononuclear cell leukemia, peritoneal mesothelioma, and various brain tumors have been reported. In an NTP (246) two-year inhalation study of mice at 50 and 100 ppm, alveolar/bronchiolar carcinomas and adenomas, papillary cystadenomas of the harderian gland, and malignant lymphomas, uterine adenocarcinomas, and mammary gland tumors were increased in one or both exposure groups. 

If an inhalation study in animals, list conversion factors used in determining human equivalent concentration NA... 

Exposure Period Three exposure periods - acute (less than 15 days), intermediate (15-364 days), and chronic (365 days or more) are presented within each relevant route of exposure. In this example, an inhalation study of intermediate exposure duration is reported. For quick reference to health effects occurring from a known length of exposure, locate the applicable exposure period within the LSE table and figure. 

PBPK models have also been used to explain the rate of excretion of inhaled trichloroethylene and its major metabolites (Bogen 1988 Fisher et al. 1989, 1990, 1991 Ikeda et al. 1972 Ramsey and Anderson 1984 Sato et al. 1977). One model was based on the results of trichloroethylene inhalation studies using volunteers who inhaled 100 ppm trichloroethylene for 4 horns (Sato et al. 1977). The model used first-order kinetics to describe the major metabolic pathways for trichloroethylene in vessel-rich tissues (brain, liver, kidney), low perfused muscle tissue, and poorly perfused fat tissue and assumed that the compartments were at equilibrium. A value of 104 L/hour for whole-body metabolic clearance of trichloroethylene was predicted. Another PBPK model was developed to fit human metabolism data to urinary metabolites measured in chronically exposed workers (Bogen 1988). This model assumed that pulmonary uptake is continuous, so that the alveolar concentration is in equilibrium with that in the blood and all tissue compartments, and was an expansion of a model developed to predict the behavior of styrene (another volatile organic compound) in four tissue groups (Ramsey and Andersen 1984). 

Freni and Bloomer 1988 Lagakos et al. 1986a). Available inhalation studies in animals do not fully characterize the reproductive effects following inhalation exposure. Only abnormal sperm morphology has been reported after inhalation exposure however reproductive performance was not evaluated in these studies... 

Kligerman AD, Bryant MF, Doerr CL, et al. 1994. Inhalation studies of the genotoxicity of trichloroethylene to rodents. Mutat Res 322 87-96. 

If an inhalation study in animals, list the conversion factors used in determining human equivalent dose Va male Wistar rat = 0.23 mVday, BW = 0.217 kg Va human = 20 mVday, BW = 70 kg... 

Mewhinney JA, Griffith WC, Muggenburg BA. 1979. Comparison of metabolic models used to describe the fate of inhaled 241Am02 based on inhalation studies in the beagle dog. Health Phys 37(6) 830. 

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