Irie studies

Guilhot F. Sustained durability of responses plus high rates of cytogenetic responses result in longterm benefit for newly diagnosed chronic-phase chronic myeloid leukemia (CML-CP) treated with imatinib (IM) therapy update from the IRIS study, (abst 21). Blood2004 104 10a. 

Larson RA, Druker B, Guilhot F et al. Correlation of pharmacokinetic data with cytogenetic and molecular response in newly diagnosed patients with chronic myeloid leukemia in chronic phase (CML-CP) treated with imatinib-An analysis of IRIS study data (Abstract 429). B/oorf 2006 108 131a. 

Larson RA et al (2008) Imatinib pharmacokinetics and its correlation with response and safety in chronic-phase chronic myeloid leukemia a subanalysis of the IRIS study. Blood 111 4022-4028... 

EPA has derived an RfD of. 00025 mg/kg/day, based on a NOAEL of 0.025 for reduced hematocrit, erythrocyte counts, and hemoglobin (cholinesterase inhibition was also listed as a critical effect but the reason for this was not explained). This NOAEL appears to be from the same study as for the ATSDR chronic-duration oral MRL, although the study is referenced differently (IRIS 2001). 

Some advice can be formulated for the choice of organic modifier, (i) Acetonitrile as an aprotic solvent cannot interact with residual silanols, whereas the protic methanol can. Thus, when measuring retention factors, methanol is the cosolvent of choice, as it reduces the secondary interactions between the solutes and the free silanol groups, (ii) For the study of the performance of new stationary phases one should use acetonitrile, as the effects of free silanol groups are fuUy expressed [35]. (iri) Acetonitrile with its better elution capacity can be considered as the best organic modifier for Hpophilicity measurements of highly Hpophihc compounds with adequate stationary phases [36]. 

EPA has derived both an oral reference dose (RfD) and an inhalation reference concentration (RfC) for chronic exposure to hydrogen sulfide. The RfD of 0.003 mg/kg/day is based on the NOAEL of 3.1 mg/kg/day for gastrointestinal disturbance in pigs in a study by Wetterau et al. (1964) (IRIS 1998). The NOAEL value of 3.1 mg/kg/day was divided by an uncertainty factor of 1,000 to account for interspecies extrapolation (10), sensitive individuals (10), and subchronic exposure (10) (IRIS 1998). 

According to EPA (IRIS 1999), the available human epidemiological studies lack quantitative exposure data for lead and for possible confounding exposures (e.g., arsenic, smoking). Cancer excesses in the lung and stomach of lead-exposed workers that are reported are relatively small, dose-response relationships are not demonstrated neither is there consistency in the site of cancers reported. EPA (IRIS 1999) concluded that the human data are inadequate to refute or demonstrate the potential carcinogenicity of lead exposure. 

In addition to supplementation or dietary intake of the xanthophylls, several other modulators that influence the MPOD response of subjects to supplementation with xanthophylls were reported (Mares et al. 2006). Larger waist circumference and the presence of diabetes predicted a decrease of MPOD. In contrast to earlier findings, iris color was not related to MPOD. No dependence of MPOD on age was revealed in this study but this may be because of its lower age limit of 53 years. 

Reference toxicological values for HRA for the selected pollutants were obtained from ISS/ISPESL [21] and IRIS [22] databases or derived from animal in vivo studies (rat or mouse) and using appropriate safety factors while PNEC concentrations were obtained from previously selected peer-reviewed freely available databases [23] such as ECOTOX [24], ChemIDPlus advanced [25] and specific reviews. 

The CD that accompanies this book contains a well-studied set of data known as the Iris dataset. A brief description of the data is included on the CD. Write a GCS to analyze the Iris data. If you have SOM software available, compare the performance and execution time of the SOM and the GCS on this dataset. 

On the basis of induction of tumors of the spleen and the body cavity in two studies with rats, U.S. EPA (1994) in their IRIS document classified aniline as B2, a probable human carcinogen. Evidence is inadequate in humans and... 

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. 

Two oral studies in rodents demonstrated the carcinogenic potential of dimethylhydrazines. Results of an inhalation study in mice showing an increased tumor response following exposure to 1,1-dimethylhydrazine may be compromised by the contamination of the test article with dimethylnitrosamine. Both inhalation and oral slope factors for the dimethylhydrazines have been withdrawn from IRIS. 

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. 

All CELs from each reliable study are included in Table 2-2 and plotted in Figure 2-2. EPA has derived an oral slope factor of 1.4x102 (mg/kg/day)1 for hexachloroethane based on hepatocellular carcinomas in male mice (IRIS 1995). Doses that correspond to excess cancer risks of 10 4 to 107 are shown in Figure 2-2. 

EPA has derived a chronic oral RfD of 0.001 mg/kg/day for hexachloroethane (IRIS 1995). This value is based on a NOAEL of 1 mg/kg/day for atrophy and degeneration of the renal tubules in rats exposed for 16 weeks (Gorzinski et al. 1985). The NOAEL was divided by an uncertainty factor of 1,000 to account for interspecies extrapolation, human variability, and the use of a subchronic study. EPA places medium confidence in this RfD (IRIS 1995). 

Among all chlorophenols, 2,4,6-trichlorophenol (TCP) and pentachlorophenol (PCP) are listed as priority pollutants by the US Environmental Protection Agency (EPA) (IRIS electronic database) and the EU [256]. In particular, PCP has been classified as a B2 probable carcinogen for humans from animal toxicity studies and human clinical data. 

ATSDR has derived a chronic oral MRL of 0.0003 mg/kg/day based on a laboratory animal study showing neurotoxic effects in dogs (Kettering Lab 1969). The EPA reference dose for endrin is 3xl0 4 mg/kg/day, and the critical dose is 0.025 mg/kg/day (IRIS 1995). Critical effects were occasional convulsions and mild histological lesions in the liver (Kettering Lab 1969). No EPA reference concentration exists for the compound. 

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