Inhalation unit risk

No studies were located regarding cancer incidence in animals after inhalation exposure to hexachloroethane. EPA has derived an inhalation unit risk (cancer slope factor) of 1.4x102 (mg/kg/day) 1 for hexachloroethane (IRIS 1995). This inhalation unit risk was calculated using data from oral studies (see Section 2.2.2.8) and Figure 2-2. 

Hazard identihcation, oral slope factors, and oral and inhalation unit risks for carcinogenic effects... 

Calculated from the inhalation unit risk (1.5x10" ... 

ORNL also considered calculating an SF on the basis of the U.S. Environmental Protection Agency s (EPA 1991) estimated inhalation unit risk (8.5 x 10 per pg/m ) of sulfur mustard. Normalizing the inhalation unit risk for a 70-kg person inhaling 20 m of air per day would yield an SF of 0.3 per pg/kg per day. ORNL decided not to use this method because the inhalation study (McNamara et al. 1975) used to estimate the inhalation unit risk resulted in rat skin tumors that appeared to be caused by dermal exposure rather than by systemic absorption and distribution to the skin, and inhalation-to-oral extrapolation was not considered appropriate. Furthermore, the McNamara et al. (1975) study contained a number of deficiencies, such as outdated testing protocols, brief exposures, and small numbers of animals, which made quantitative analysis difficult. 

The subcommittee agrees with ORNL that calculating an SF for sulfur mustard using the relative potency approach was more appropriate than using estimates from inhalation unit risk. The subcommittee notes, however, that a recent study by Culp et al. (1998) reported a lower carcinogenic potency value for B[a]P. That chronic exposure study of B[a]P in feed was conducted under Good Laboratory Practice conditions in B6C3Fi female mice (Culp et al. 1998). The incidence of forestomach tumors was found to be 1 of 48, 3 of 47, and 36 of 46 at concentrations... 

Inhalation Unit Risk Derived from Experimental Animal Data 20... 

Oral Slope Factor Derived from Inhalation Unit Risk 23... 

Inhalation unit risks have been derived for sulfur mustard directly from experimental animal data as weU as from an analysis of the relative carcinogenic potency of sulfur mustard in comparison with that of known carcinogens for which there are both long-and short-term data. Epidemiological and long-term animal data are not available to directly derive an oral slope factor for sulfur mustard. Estimates of the oral slope factor are made from the inhalation unit risk and from the relative potency method. 

U.S. EPA (1991) derived a cancer inhalation unit risk for sulfur mustard based on the results of inhalation animal studies conducted by McNamara et al. (1975, see Section 3.7.2) however, it was emphasized in the EPA report that the studies of McNamara et al. (1975) contained deficiencies which made a quantitative analysis difficult. Conducted in 1970, the studies do not conform to the modem norms of acceptable experimental protocol, and it is likely that there was bias in the assignment of the animals to the test categories (U.S. EPA, 1991). In addition, many of the exposures were very brief, included only a few animals, and many of the animals were sacrificed (and some were replaced) before their capacity to develop late-appearing tumors was fully developed (U.S. EPA, 1991). Despite these shortcomings, it was noted by EPA that the McNamara et al. data are the best available for estimating the carcinogenic potency of sulfur mustard. The authors of the EPA report analyzed two sets of McNamara s data one from a toxicity study and one from a carcinogenicity study (see Section 3.7.2). 

To derive an oral slope factor in the absence of long-term experimental data, two non-standard approaches can be considered. One involves the direct conversion of the inhalation unit risk to an oral slope factor, and the other involves the use of relative potency methods. Both approaches are summarized in the foUowing sections. 

The U.S. EPA (1991) identified an "inhalation" unit risk of 8.5 x 10 per fig/w , derived from the Weibull time-to-tumor model, as the most appropriate estimate of the carcinogenic potency of sulfur mustard. This unit risk can be converted to a slope factor by normalizing the value for a 70 kg man inhahng 20 m of air per day. The resulting slope factor is 0.3 (ug/kg/day). ... 

As described in section 5.1.2, U.S. EPA (1991) derived an inhalation unit risk for sulfur mustard using the relative potency method in which sulfur mustard was considered to be 10-13 times more potent than BaP. The oral slope factor for BaP, as currently listed on IRIS, is 7.3 (mg/kg/day) (U.S. EPA, 1996). Multiplying this slope factor by the relative potency range of 10-13, results in an oral slope factor of 0.073-0.095 (ug/kg/day)" for sulfur mustard. 

Carcinogenic inhalation unit risk Carcinogenic classification NESHAR—HAR... 

Health-based guidance values for 1,2-diphenylhy-drazine include an inhalation unit risk of 2.2 x 10 " (pg/m ) and a drinking water unit risk of 2.2 X 10 (pg/l) . The US Environmental Protection Agency (EPA) classifies 1,2-diphenylhydrazine as a probable human carcinogen (B2). The cancer slope factor for 1,2-diphenylhydrazine is 8.0x10 (mg/ kg/day). No regulatory values or guidance values are available for 1,1-diphenylhydrazine. 

The EPA has derived an inhalation unit risk of 0.0049 ( g/m )" for hydrazine based on nasal cavity tumors, and an inhalation unit risk ofO.OOl ( g/m )" for 1,1-dimethylhydrazine based on tumor ofthe respiratory system (HEAST 1992 IRIS 1995). Although no studies were located regarding the carcinogenic effects of 1,2-dimethylhydrazine following inhalation exposures, EPA has derived an inhalation unit risk of 0.011 ( g/m ) for 1,2-dimethylhydrazine (HEAST 1992), based on extrapolation of cancer data for oral exposures (see Section 2.2.2.8). The concentrations of hydrazine,... 

The toxicological basis of SSLs are oral cancer slope factors, non-cancer reference doses, inhalation unit risk factors and reference concentrations. Drinking water and health based standards are used to determine screening levels in groundwater.21... 

HUMAN TOXICITY DATA skin-human 1538 mg/24H toxic effect severe irritation inhalation-man TCLo 88ppb/8H toxic effect reproductive effects oral-woman LDLo 90mg/kg toxic effect gastrointestinal tract, systemic effect LD50 (man) 65 mg/kg EPA Cancer Risk Level 5x10 mg/m inhalation unit risk estimate 2.2 x 10 pg/m. ... 

HUMAN TOXICITY DATA inhalation-human TCLo 17mg/m /30M toxic effect eye, pulmonary system inhalation-man TCLo 300p,g/m toxic effect nose, central nervous system unreported man LDLo 477 mg/kg oral-woman LDLo 108mg/kg skin-human 150 pg/3D eye-human 4 ppm/5M eye-human 1 ppm/6M EPA Caneer Risk Level (1 in a million excess lifetime risk) 8 x 10 mg/m inhalation unit risk 1.3 x 10 pg/m. ... 

HUMAN TOXICITY DATA RfD (reference dose) 0.001 mg/kg/day inhalation unit risk estimate 4.0 x 10 (pg/mY Group C, possible human carcinogen of low carcinogenic hazard. 

Toxicologists generally posit that no threshold exists for some effects, notably for most carcinogens. Such effects are characterized by a derived minimal effect level (DMEL) in the European Union in the parlance used in the United States, risks are characterized using oral slope factors and oral or inhalation unit risks. A DMEL represents the exposure level that corresponds to a specified level of risk to the exposed population. In the case of a chemical known or suspected to be a human carcinogen, this exposure level corresponds to a risk of one excess case of cancer in an exposed population. For a hypothetically exposed population of one million people, for example, this risk level of one excess case of cancer in the population of one million is abbreviated... 

As the toxicities (carcinogenicity and mutagencity) of individual PAHs differ considerably, toxicity assessments of PAHs are complex. A number of approaches have been developed for evaluating the potencies of the various PAHs with regard to the possible inhalation cancer risk to humans (lARC, 1983). One approach is to calculate the inhalation unit risk for excess lung cancer over the risk posed by BaP for each of its copollutant carcinogenic PAH in the polluted ambient air divided the particular PAH s risk by the risk... 

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