P00016 TASK ORDER TITLE: IN VITRO MEASUREMENTS FOR TOXICOKINETICS (RTK) THE PURPOSE OF MODIFICATION NO. 16 IS TO DE-OBLIGATE FUNDS. Funding Only Action ($139) 8/28/24 P00015 TASK ORDER TITLE: IN VITRO MEASUREMENTS FOR TOXICOKINETICS (RTK) THE PURPOSE OF MODIFICATION NO. 13 IS TO DEFINITIZE A NO COST EXTENSION DUE TO GOVERNMENT CAUSED DELAYS. THE PURPOSE OF TASK ORDER (TO) 0012 IS TO OBTAIN LABORATORY SERVICES AND SUPPORT TO DEVELOP AND PERFORM SPECIFIC IN VITRO ASSAYS WHICH CAN BE USED AS KEY DETERMINANTS OF IN VIVO TOXICOKINETICS FOR A SET OF CHEMICALS. THIS TO COVERS DEVELOPMENT OF AND OBTAINING DATA FROM IN VITRO ASSAYS WHICH WILL BE INCORPORATED INTO TOXICOKINETIC MODELS TO PREDICT INTERNAL TISSUE (PLASMA/BLOOD) CONCENTRATIONS FROM THE BIOACTIVITY CONCENTRATIONS DETERMINED USING HIGH THROUGHPUT SCREENING (HTS) IN VITRO ASSAY DATA OR FROM FRANK ADMINISTERED CHEMICAL DOSE IN LEGACY ANIMAL TOXICITY STUDIES (E.G. TOXREFDB). THE DATA WILL BE OBTAINED WITH MEDIUM TO HIGH THROUGHPUT, IN VITRO MEASUREMENTS OF KEY DETERMINANTS OF IN VIVO TOXICOKINETICS. OF PRIMARY INTEREST IS PLASMA PROTEIN BINDING AND INTRINSIC HEPATIC CLEARANCE DATA. ADDITIONAL INFORMATION RELATED TO NON-SPECIFIC BINDING IN THE IN VITRO SYSTEMS AND ORAL ABSORPTION RATE, BIOAVAILABILITY, BLOOD TO PLASMA RATIO, AND ACTIVE TRANSPORT WILL BE NEEDED FOR IN VITRO-IN VIVO EXTRAPOLATION TO PREDICT TISSUE DOSES FOR ANIMALS. CHEMICAL-SPECIFIC ANALYTIC METHODS ARE ALSO NEEDED TO QUANTIFY THE PRESENCE OF COMPOUNDS IN THE ASSAY SAMPLES IN ORDER TO DETERMINE KEY PLASMA PROTEIN BINDING AND HEPATIC CLEARANCE RATES. Funding Only Action ($269k) 6/13/18 14 TASK ORDER TITLE: IN VITRO MEASUREMENTS FOR TOXICOKINETICS (RTK) THE PURPOSE OF MODIFICATION NO. 13 IS TO DEFINITIZE A NO COST EXTENSION DUE TO GOVERNMENT CAUSED DELAYS. THE PURPOSE OF TASK ORDER (TO) 0012 IS TO OBTAIN LABORATORY SERVICES AND SUPPORT TO DEVELOP AND PERFORM SPECIFIC IN VITRO ASSAYS WHICH CAN BE USED AS KEY DETERMINANTS OF IN VIVO TOXICOKINETICS FOR A SET OF CHEMICALS. THIS TO COVERS DEVELOPMENT OF AND OBTAINING DATA FROM IN VITRO ASSAYS WHICH WILL BE INCORPORATED INTO TOXICOKINETIC MODELS TO PREDICT INTERNAL TISSUE (PLASMA/BLOOD) CONCENTRATIONS FROM THE BIOACTIVITY CONCENTRATIONS DETERMINED USING HIGH THROUGHPUT SCREENING (HTS) IN VITRO ASSAY DATA OR FROM FRANK ADMINISTERED CHEMICAL DOSE IN LEGACY ANIMAL TOXICITY STUDIES (E.G. TOXREFDB). THE DATA WILL BE OBTAINED WITH MEDIUM TO HIGH THROUGHPUT, IN VITRO MEASUREMENTS OF KEY DETERMINANTS OF IN VIVO TOXICOKINETICS. OF PRIMARY INTEREST IS PLASMA PROTEIN BINDING AND INTRINSIC HEPATIC CLEARANCE DATA. ADDITIONAL INFORMATION RELATED TO NON-SPECIFIC BINDING IN THE IN VITRO SYSTEMS AND ORAL ABSORPTION RATE, BIOAVAILABILITY, BLOOD TO PLASMA RATIO, AND ACTIVE TRANSPORT WILL BE NEEDED FOR IN VITRO-IN VIVO EXTRAPOLATION TO PREDICT TISSUE DOSES FOR ANIMALS. CHEMICAL-SPECIFIC ANALYTIC METHODS ARE ALSO NEEDED TO QUANTIFY THE PRESENCE OF COMPOUNDS IN THE ASSAY SAMPLES IN ORDER TO DETERMINE KEY PLASMA PROTEIN BINDING AND HEPATIC CLEARANCE RATES. Other Administrative Action $0 11/21/17 13 TASK ORDER TITLE: IN VITRO MEASUREMENTS FOR TOXICOKINETICS (RTK) THE PURPOSE OF MODIFICATION NO. 13 IS TO DEFINITIZE A NO COST EXTENSION DUE TO GOVERNMENT CAUSED DELAYS. THE PURPOSE OF TASK ORDER (TO) 0012 IS TO OBTAIN LABORATORY SERVICES AND SUPPORT TO DEVELOP AND PERFORM SPECIFIC IN VITRO ASSAYS WHICH CAN BE USED AS KEY DETERMINANTS OF IN VIVO TOXICOKINETICS FOR A SET OF CHEMICALS. THIS TO COVERS DEVELOPMENT OF AND OBTAINING DATA FROM IN VITRO ASSAYS WHICH WILL BE INCORPORATED INTO TOXICOKINETIC MODELS TO PREDICT INTERNAL TISSUE (PLASMA/BLOOD) CONCENTRATIONS FROM THE BIOACTIVITY CONCENTRATIONS DETERMINED USING HIGH THROUGHPUT SCREENING (HTS) IN VITRO ASSAY DATA OR FROM FRANK ADMINISTERED CHEMICAL DOSE IN LEGACY ANIMAL TOXICITY STUDIES (E.G. TOXREFDB). THE DATA WILL BE OBTAINED WITH MEDIUM TO HIGH THROUGHPUT, IN VITRO MEASUREMENTS OF KEY DETERMINANTS OF IN VIVO TOXICOKINETICS. OF PRIMARY INTEREST IS PLASMA PROTEIN BINDING AND INTRINSIC HEPATIC CLEARANCE DATA. ADDITIONAL INFORMATION RELATED TO NON-SPECIFIC BINDING IN THE IN VITRO SYSTEMS AND ORAL ABSORPTION RATE, BIOAVAILABILITY, BLOOD TO PLASMA RATIO, AND ACTIVE TRANSPORT WILL BE NEEDED FOR IN VITRO-IN VIVO EXTRAPOLATION TO PREDICT TISSUE DOSES FOR ANIMALS. CHEMICAL-SPECIFIC ANALYTIC METHODS ARE ALSO NEEDED TO QUANTIFY THE PRESENCE OF COMPOUNDS IN THE ASSAY SAMPLES IN ORDER TO DETERMINE KEY PLASMA PROTEIN BINDING AND HEPATIC CLEARANCE RATES. Change Order $0 9/27/17 12 IN VITRO MEASUREMENTS FOR TOXICOKINETICS (RTK) MOD 007: THE PURPOSE OF THIS MODIFICATION IS TO: (1) OBLIGATE FUNDING, TOTALING $475,226.21, BACK TO THE TASK ORDER; (2) APPROVE THE CONTRACTOR'S REVISED PROPOSAL AND COST/PRICE ESTIMATE DATED 29 APRIL 2016 (I.E., RTI PROJECT NO. 0213211.012; RTI PROPOSAL NO. 0281600.345), WHICH IS INCORPORATED IN LINE ITEM 0001 AND WHICH HAS AN APPROVED PRICE/COST CEILING OF $262,538.00; (3) DECREASE THE PRICE AND ZERO OUT UNEXERCISED LINE ITEM NOS. 0007-0011; (4) DECREASE THE TOTAL TASK ORDER CEILING/PRICE BY $61,662.00; (5) REVISE EPA ADMINISTRATIVE PERSONNEL TO CHANGE THE ALTERNATE TASK ORDER CONTRACTING OFFICER'S REPRESENTATIVE AND ALTERNATE INVOICE APPROVING OFFICIAL FROM PATIENCE BROWNE TO SCOTT LYNN; (6) AND EXTEND THE TASK ORDER PERFORMANCE PERIOD END DATE TO 3/31/2017. MOD 006: OBLIGATE FUNDING BACK TO TASK ORDER. MOD 005: THE PURPOSE OF THIS MODIFICATION IS TO EXTEND THE TASK ORDER END DATE FROM 13 JULY 2016 TO 25 MARCH 2017 IN ORDER TO PROVIDE THE CONTRACTOR ADDITIONAL TIME TO PERFORM REQUIRED TASKS. AN EXTENSION TO THIS DATE IS PERMITTED PER CONTRACT CLAUSE I.4 FAR 52.216-22 INDEFINITE QUANTITY (OCT 1995). THE PURPOSE OF THIS MODIFICATION IS ALSO TO TEMPORARILY DEOBLIGATE $1 MILLION IN EXPIRING FUNDS FROM THE TASK ORDER. AN EQUAL AMOUNT OF NON-EXPIRING FUNDS WILL BE OBLIGATED TO THE TASK ORDER IN A SUBSEQUENT MODIFICATION IN THE NEAR FUTURE. MOD 004: THE PURPOSE OF THIS MODIFICATION IS TO REVISE THE TASK ORDER STATEMENT OF WORK IN ORDER TO REFLECT A MORE ACCURATE RECORD OF REQUIRED TASK AREAS. NO ADDITIONAL COSTS ARE ASSOCIATED WITH ANY/ALL CHANGES MADE UNDER THIS CONTRACT ACTION. Funding Only Action $773.0k 6/8/17