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Calculate an Rdf based on dose - response data A rat liver pathology study was conducted over a two - year period on animals exposed

Calculate an Rdf based on dose-response data
A rat liver pathology study was conducted over a two-year period on animals exposed to Aroclor 1254(Polychlorinated Biphenyl). The findings are displayed below.
Dose mg/kg-d Mean
Enzyme Level Organ Wt
Change % Animals with focal necrosis
0- control
12
2550
100
200
5
10
20*
35*
42*
40*
--
-2%
+6%
+13%*
+10%*
+12%
--
0
0
2
8*
* Significantly (statistically) different from control
The agency you work for (based on information from the literature) has made the policy decisions that an "enzyme level" value of 25 or greater is defined as adverse and an organ weight change of 10% or greater is adverse.
1.a. Using the above table and your agency's policies, fill in the following table. The read is an example of what I am looking for in the asweres.
LEVEL Define What is the value? Explain
NOEL
No Observed Effect Level
12 mg/kg-d There was a statistically significant
change in mean enzyme levels at 25 mg/kg-d but not at 12 mg/kg-d.
LOEL
NOAEL
LOAEL
1.b. Based on the information provided above which uncertainties (Uncertainty factors) would need to be accounted for in the derivation of an RfD or MRL (Minimal Risk level) from this study?
1.c. Calculate an RfD from this study using uncertainty factors as appropriate to account for 1) animal-human extrapolation, 2) LOAEL to NOAEL extrapolation, 3) Human variability. Show your work and provide a brief explanation for the uncertainty/modification factors. Use your best judgement to estimate the uncertainty factors (They should be 1,3, or 10)

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