EFFECT LEVELS BOUNDED

Tables (3-1, 3-2, and 3-3) and figures (3-1 and 3-2) are used to summarize health effects and illustrate graphically levels of exposure associated with those effects. These levels cover health effects observed at increasing dose concentrations and durations, differences in response by species, minimal risk levels (MRLs) to humans for noncancer end points, and EPA s estimated range associated with an upper- bound individual lifetime cancer risk of 1 in 10,000 to 1 in 10,000,000. Use the LSE tables and figures for a quick review of the health effects and to locate data for a specific exposure scenario. The LSE tables and figures should always be used in conjunction with the text. All entries in these tables and figures represent studies that provide reliable, quantitative estimates of No-Observed-Adverse-Effect Levels (NOAELs), Lowest-Observed-Adverse-Effect Levels (LOAELs), or Cancer Effect Levels (CELs).

Levels of exposure associated with the carcinogenic effects (Cancer Effect Levels, CELs) of chloroform are indicated in Figure 2-2. Because cancer effects could occur at lower exposure levels. Figures 2-1 and 2-2 also show a range for the upper bound of estimated excess risks, ranging from a risk of 1 in 10,000 to 1 in 10,000,000 (lO to 10 ), as developed by EPA. 

The lowest Cancer-Effect-Levels (CELs) in the NCI (1978) bioassay are the closes that caused hepatocellular carcinoma in rats (4 mg/kg/day) and mice (52 mg/kg/day) (Table 2-1, Figure 2-1). Using the dose-response data for the hepatocellular carcinoma in rats, EPA (1980, 1988a) derived and verified an oral slope factor (q1 ) of 8.0 x 10 (mg/kg/day) 1 for 1,2-diphenylhydrazine. Using this slope factor, the doses associated with upper-bound lifetime cancer risk levels of 10 to 10 are calculated to be 1.3 x 10 to 1.3 x 10 mg/kg/day, respectively (Figure 2-1). 

As shown in Table 2-2, 300 mg/kg/day is the cancer effect level (CEL) for renal tubular cell adenomas in male rats and 600 mg/kg/day is the CEL for hepatocellular carcinomas and hepatoblastomas in mice (NTP 1987). A qj (the upper-bound estimate of the low-dose slope of the dose-response curve as determined by the multistage procedure) of 6x10 per mg/kg/day has been calculated from the data on renal tumors in rats (Battelle and Crump 1986). The qi for the mouse liver tumor data is 2.4x10 per mg/kg/day (HEAST 1992). These values are currently under review by the EPA (HEAST 1990) and have not been included in the IRIS (1998) database. 

Phenytoin (Dilantin) [Anticenvulsant/Hydantoin] Uses Sz disorders Action X Sz spread in the motor cortex Dose Load Adults Peds. 15-20 mg/kg IV, 25 mg/min max or PO in 400-mg doses at 4-h intervals Maint Adults. Initial, 200 mg PO or IV bid or 300 mg hs then follow levels Peds. 4-7 mg/kg/24h PO or IV -s- daily-bid avoid PO susp (erratic absorption) Caution [D, +] Contra Heart block, sinus bradycardia Disp Caps, susp, inj SE Nystag-mus/ataxia early signs of tox gum hyperplasia w/ long-term use. IV BP, bradycardia, arrhythmias, phlebitis peripheral neuropathy, rash, blood dyscrasias, Stevens-Johnson synd Notes Levels Trough Just before next dose Therapeutic Peak 10-20 mcg/mL Toxic >20 mcg/mL phenytoin albumin bound, levels = bound free phenytoin w/ i albumin azotemia, low levels may be therapeutic (nl free levels) Interactions T Effects W/ amiodarone, allopurinol, chloramphenicol, disulfiram, INH, omeprazole, sulfonamides, quinolones, trimethoprim t... 

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