Document:

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                                                                  EXHIBIT 10.160

                                FIRST AMENDMENT
                            TO AND REAFFIRMATION OF
                   SUBORDINATION AND INTERCREDITOR AGREEMENT
                   -----------------------------------------

     THIS FIRST AMENDMENT TO AND REAFFIRMATION OF SUBORDINATION AND
INTERCREDITOR AGREEMENT (this "Amendment") is made and executed as of the 17th
day of October, 2000 by APPLIED BIOSCIENCE INTERNATIONAL INC., a Delaware
corporation ("ABI"), PPD UK HOLDINGS LIMITED, a private company incorporated in
England and Wales (collectively, the "Subordinate Creditors"), ENVIRON HOLDINGS,
INC., a Delaware corporation ("EHI"), ENVIRON INTERNATIONAL CORPORATION
(formerly known as APBI Environmental Sciences Group, Inc.), a Virginia
corporation ("EIC") and ENVIRON FACILITY SERVICES CORPORATION, a Virginia
corporation (the "New Borrower", together with EHI and EIC, collectively, the
"Borrowers"), and FIRST UNION NATIONAL BANK, a national banking association, its
successors and assigns (the "Bank").

                                    RECITALS

     WHEREAS, the Bank has previously agreed, inter alia, to make a certain term
                                              ----- ----
loan to EHI and EIC in the maximum outstanding principal amount of $6,708,333.34
(the "Term Loan") and a revolving credit loan to EHI and EIC in the maximum
outstanding principal amount of $3,500,000 (the "Revolving Loan", together with
the Term Loan, the "Loans") pursuant to that certain Credit and Security
Agreement by and among EHI, EIC and the Bank dated March 30, 1999 as amended by
that certain First Amendment to Credit and Security Agreement (the "First
Amendment") dated November, 1999 and as further amended pursuant to that certain
Second Amendment to Credit and Security Agreement (the "Second Amendment") of
even date herewith (as hereafter amended, restated, modified or renewed from
time to time, the "Credit Agreement"); and

     WHEREAS, ABI has previously agreed, inter alia, to make a certain
                                         ----- ----
acquisition loan to EHI and EIC in the original principal amount of $18,000,000
pursuant to a Credit and Security Agreement by and among ABI, EHI and EIC dated
February 2, 1999, as amended by that certain Amendment No. 1 to Credit and
Security Agreement dated March 30, 1999 (the "ABI First Amendment"), that
certain Amendment No. 2 and Restatement of Credit and Security Agreement dated
November 24, 1999 (the "ABI Second Amendment") and that certain Amendment No. 3
to Credit and Security Agreement (the "ABI Third Amendment") of even date
herewith (said Credit Agreement, as heretofore and hereafter amended, restated,
modified or renewed from time to time, the "ABI Credit Agreement"); and

     WHEREAS, pursuant to a plan of corporate restructuring approved by EIC's
Board of Directors, EIC has created a separate legal entity for its facilities
group in the form of the New Borrower and has transferred all of its assets
related to the facilities group to the New Borrower pursuant to that certain
Asset Purchase Agreement dated January 1, 2000 by and between EIC and the New
Borrower (the "Facilities Group Spin Off") and the Borrowers have requested that
the Bank consent to the Facilities Group Spin Off, and the Bank has consented
upon the conditions, among others, that the New Borrower be added as a co-
borrower under the Credit Agreement, the Restated Revolving Note (as defined in
the Second Amendment) and the
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Restated Term Note (as defined in the Second Amendment) pursuant to the Second
Amendment and that the parties hereto execute this Amendment; and

     WHEREAS, the Borrowers have requested that the Subordinate Creditors
consent to the Facilities Group Spin Off, and the Subordinate Creditors have
consented upon the conditions, among others, that the New Borrower be added as a
co-borrower under the ABI Credit Agreement and the Seller Note (as defined in
the ABI Credit Agreement) pursuant to the ABI Third Amendment and that the
parties hereto execute this Amendment; and

     WHEREAS, in connection with the execution of the Credit Agreement, the
Subordinate Creditors, EHI, EIC and the Bank entered into that certain
Subordination and Intercreditor Agreement dated as of March 30, 1999
(collectively, the "Agreement"); and

     WHEREAS, the Bank is not willing to consent to the Facilities Group Spin
Off or enter into the Second Amendment unless the Subordinate Creditors and the
Borrowers each unconditionally reaffirm their obligations under the Agreement as
modified below and consent to such amendments; and

     WHEREAS, the Subordinate Creditors are not willing to consent to the
Facilities Group Spin Off or enter into the ABI Third Amendment unless the Bank
and the Borrowers each unconditionally reaffirm their obligations under the
Agreement as modified below and consent to such amendments.

                                   AGREEMENT

     NOW THEREFORE, as an inducement for the Bank and the Subordinate Creditors
to consent to the Facilities Group Spin Off, for the Bank to enter into the
Second Amendment, for ABI to enter into the ABI Third Amendment, and for other
good and valuable consideration, the receipt and sufficiency of which are hereby
acknowledged, the parties do hereby agree as follows:

     1.   Capitalized terms used herein and not otherwise defined shall have the
meanings ascribed to them in the Agreement.

     2.   The Recitals set forth hereinabove are hereby incorporated by this
reference with the same force and effect as it fully set forth herein.

     3.   The parties hereto each acknowledge and agree that (a) the term
"Borrower" and "Borrowers" as used in the Agreement shall include the New
Borrower, (b) the definitions of the terms "Bank Credit Agreement," "Level 1
Senior Creditor Loan Documents" and "Senior Creditor Loan Documents" set forth
in the Agreement include the First Amendment, the Second Amendment, the Restated
Revolving Note and the Restated Term Note and any other respective amendments of
each of said documents being executed and delivered simultaneously herewith in
connection with the Second Amendment, copies or originals of which have been
received and reviewed by the Subordinate Creditors and the Borrowers, and (c)
the definition of the term "Subordinate Creditor Loan Documents" as set forth in
the Agreement includes the ABI First Amendment, the ABI Second Amendment, the
ABI Third Amendment, the Restated Seller Note

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(as defined in the ABI Third Amendment) and any other respective amendments of
each of said documents being executed and delivered simultaneously herewith in
connection with the ABI Third Amendment, copies or originals of which have been
received and reviewed by the Bank and the Borrowers.

     4.   Each of the Subordinate Creditors and each of the Borrowers hereby
unconditionally reaffirm all of their respective obligations to Bank under the
Agreement.

     5.   The Borrowers each certify that the representations and warranties
contained in the Agreement remain true, correct and complete in all material
respects as of the date hereof with the same force and effect as if made on the
date hereof and that each of the Borrowers has no offsets, counterclaims or
defenses to any of its obligations under the Agreement as modified hereby.

     6.   The Bank and each of the Borrowers hereby unconditionally reaffirm all
of their respective obligations to the Subordinate Creditors under the
Agreement.

     7.   The Bank and the Subordinate Creditors each certify that the
representations and warranties contained in the Agreement and made by it or
them, respectively, remain true, correct and complete in all material respects
as of the date hereof with the same force and effect as if made on the date
hereof.

     8.   Except as modified hereby, the Agreement remains unmodified and in
full force and effect.

     9.   Contemporaneously herewith, EIC has delivered to Senior Creditor the
original promissory note evidencing the purchase price for the assets conveyed
to the New Borrower in furtherance of the Facilities Group Spin Off (the "New
Borrower Note").  The New Borrower Note will be held by the Senior Creditor as
Collateral in accordance with the terms of the Senior Creditor Loan Documents.
After payment in full of the Level I Senior Creditor Obligations, Senior
Creditor shall deliver forthwith the New Borrower Note to the Subordinate
Creditor to be held by the Subordinate Creditor as Collateral in accordance with
the terms of the Subordinate Creditor Loan Documents.

                      [Signatures follow on the next page]

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     IN WITNESS WHEREOF, the undersigned have executed and delivered this
Amendment as of the day and year first hereinabove written.

WITNESS:                                     BANK:
                                             ----

                                             FIRST UNION NATIONAL BANK

 /s/ Linda Daly                         By: /s/ Monica Sevila             (SEAL)
------------------------------              ------------------------------
                                            Name: Monica Sevila
                                            Title: Vice President

                                             SUBORDINATE CREDITORS:
                                             ---------------------

                                               APPLIED BIOSCIENCE
                                               INTERNATIONAL INC.

 /s/ Joanne Teague                      By: /s/ Fred B. Davenport, Jr.    (SEAL)
------------------------------              ------------------------------
                                            Name:  Fred B. Davenport, Jr.
                                            Title:  Vice President

                                               PPD UK HOLDINGS

 /s/ Joanne Teague                      By: /s/ Fred B. Davenport, Jr.    (SEAL)
------------------------------              ------------------------------
                                            Name:  Fred B. Davenport, Jr.
                                            Title:  Director

     Each Borrower signs this Agreement under seal at the requests of Senior
Creditor and Subordinate Creditors, to acknowledge that each Borrower consents
to the terms of the foregoing Amendment and covenants and agrees to be bound
thereby for the benefit of Senior Creditor and Subordinate Creditors.

                                            ENVIRON HOLDINGS, INC.

 /s/ Margaret Breyer                    By: /s/ Joseph Highland           (SEAL)
------------------------------              ------------------------------
                                            Name:  Joseph Highland
                                            Title: Chairman, Chief Executive
                                                   Officer & Secretary

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                                            ENVIRON INTERNATIONAL CORPORATION

 /s/ Margaret Breyer                    By: /s/ Joseph Highland           (SEAL)
------------------------------              ------------------------------
                                            Name:  Joseph Highland
                                            Title: Chairman, Chief Executive
                                                   Officer & Secretary

                                            ENVIRON FACILITY SERVICES
                                            CORPORATION

 /s/ Margaret Breyer                    By: /s/ Joseph Highland           (SEAL)
------------------------------              ------------------------------
                                            Name:  Joseph Highland
                                            Title: Chairman, Chief Executive
                                                   Officer & Secretary

                                       5<PAGE>

                                                                  EXHIBIT 10.161

                       SIXTH AMENDMENT TO LOAN AGREEMENT

          THIS SIXTH AMENDMENT TO LOAN AGREEMENT (this "Amendment") is made as
of the 20th day of December, 2000, by and among PHARMACEUTICAL PRODUCT
DEVELOPMENT, INC., a North Carolina corporation (together with its successors,
the "Borrower"); PPD DEVELOPMENT, LLC, a Texas limited liability company,
formerly PPD DEVELOPMENT, INC., a Texas corporation formerly known as PPD
PHARMACO, INC., a Texas corporation (the "Guarantor"); and WACHOVIA BANK, N.A.,
a national banking association (together with its endorsees, successors and
assigns, the "Bank").

                               R E C I T A L S:
                               ---------------

          The Borrower, the Guarantor and the Bank are parties to a certain Loan
Agreement dated as of August 7, 1997, as amended pursuant to an Amendment to
Loan Agreement dated as of August 6, 1998, a Second Amendment to Loan Agreement
dated as of January 30, 1999, a Third Amendment to Loan Agreement dated as of
November 11, 1999, a Fourth Amendment to Loan Agreement dated as of February 23,
2000, and a Fifth Amendment to Loan Agreement dated as of August 1, 2000 (the
"Loan Agreement").

          Capitalized terms used in this Amendment which are not otherwise
defined in this Amendment shall have the respective meanings assigned to them in
the Loan Agreement.

          The Borrower has requested certain modifications to the Loan Agreement
and the Bank is willing to modify the Loan Agreement subject to the terms,
provisions and conditions set forth in this Amendment.

          NOW, THEREFORE, in consideration of the Recitals, the mutual promises
herein contained and other good and valuable consideration, the receipt and
sufficiency of which are hereby acknowledged, the Borrower, the Guarantor and
the Bank, intending to be legally bound hereby, agree as follows:

          SECTION 1.  Recitals.  The Recitals are incorporated herein by
                      --------
reference and shall be deemed to be a part of this Amendment.

          SECTION 2.  Amendment.  Effective from and after December 20, 2000,
                      ---------
the Loan Agreement is hereby amended as follows:

          2.1  In Section 6.9 of the Loan Agreement, subsection (d) is amended
to read as follows and subsections (h) and (i) are re-lettered as (k) and (l),
respectively, and new subsections (h), (i) and (j) are hereby added to Section
6.9 of the Loan Agreement to read as follows:
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          "(d) Investments in and to Axys Pharmaceuticals, Inc. and/or PPGx,
     Inc., in an aggregate principal amount (on a cost basis) not to exceed
     $3,500,000 at any time except as provided in subsections (i) and (j)
     below;"

          "(h) acquisition of capital stock of DNA Sciences, Inc. in an amount
     not to exceed $15,000,000;

          (i)  cash equity investment in PPGx, Inc. in an amount not to exceed
     $4,700,000 (which amount represents fifty percent (50%) of the outstanding
     amounts (principal and interest) due under the Loan Agreement dated as of
     February 1, 1999 among PPGx, Inc., the Borrower and First Union National
     Bank);

          (j)  acquisition of capital stock of PPGx, Inc. in an amount not to
     exceed $5,900,000;"

          SECTION 3.  Conditions to Effectiveness.  The effectiveness of this
                      ---------------------------
Amendment and the obligations of the Bank hereunder are subject to receipt by
the Bank of the following:

          (a)  an original Amendment, duly executed by the Borrower and the
     Guarantor;

          (b)  a certificate of incumbency satisfactory to the Bank, certifying
     as to the names, true signatures and incumbency of the officer or officers
     of the Borrower and the members or managers of the Guarantor authorized to
     execute and deliver this Amendment;

          (c)  such other documents or items as the Bank or its counsel may
     reasonably request.

The effectiveness of this Amendment and the obligations of the Bank hereunder
are further subject to the condition that no Event of Default or event or
condition which with notice or lapse of time, or both, would constitute an Event
of Default under the Loan Agreement, as hereby amended, shall have occurred and
be continuing, and the representations and warranties contained in Section 5 of
the Loan Agreement, as amended herein, are true on and as of the date hereof.

          SECTION 4.  No Other Amendment.  Except for the amendments set forth
                      ------------------
above, the Loan Agreement shall remain unchanged and in full force and effect.
This Amendment is not intended to effect, nor shall it be construed as, a
novation.  The Loan Agreement and this Amendment shall be construed together as
a single agreement.  Nothing herein contained shall waive, annul, alter, limit,
diminish, vary or affect any provision, condition, covenant or agreement
contained in the Loan Agreement, except as herein amended, nor affect or

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impair any rights, powers or remedies under the Loan Agreement as hereby
amended. The Bank does hereby reserve all of its rights and remedies against all
parties who may be or may hereafter become secondarily liable for the repayment
of the Loan. The Borrower and the Guarantor promise and agree to perform all of
the requirements, conditions, agreements and obligations under the terms of the
Loan Agreement, as hereby amended, the Loan Agreement, as amended, and the
Guaranty contained in the Loan Agreement, being hereby ratified and affirmed.
The Borrower and Guarantor hereby expressly agree that the Loan Agreement, as
amended, is in full force and effect and confirm that they have no set off,
counterclaim or defense with respect to the Loan Agreement, the Loan, the Note,
the Guaranty contained in the Loan Agreement or the Guaranteed Obligations.

          SECTION 5.  Representations and Warranties.  The Borrower and the
                      ------------------------------
Guarantor hereby represent and warrant to the Bank as follows:

          (a)  No Event of Default or event or condition which with notice or
     lapse or time, or both, would constitute an Event of Default under the Loan
     Agreement, as hereby amended, has occurred and is continuing on the date
     hereof.

          (b)  The representations and warranties contained in Section 5 of the
     Loan Agreement, as amended herein, are true on and as of the date of this
     Amendment.

          (c)  This Amendment has been duly authorized, validly executed and
     delivered by one or more authorized officers of the Borrower and the
     Guarantor, and constitutes the legal, valid and binding obligation of the
     Borrower and Guarantor enforceable against them in accordance with its
     terms.

          (d)  The execution and delivery of this Amendment and the Borrower's
     and the Guarantor's performance hereunder do not and will not require the
     consent or approval of any regulatory authority or governmental authority
     or agency having jurisdiction over the Borrower or the Guarantor, nor be in
     contravention of or in conflict with the Articles of Incorporation or
     Bylaws of the Borrower or the operating agreement or Articles of
     Organization of the Guarantor, or the provision of any statute, or any
     judgment, order or indenture, instrument, agreement or undertaking to which
     the Borrower or the Guarantor is party or by which the Borrower's or the
     Guarantor's assets or properties are or may become bound.

          SECTION 6.  Counterparts.  This Amendment may be executed in
                      ------------
counterparts, each of which shall be deemed to be an original and all of which,
taken together, shall constitute one and the same agreement.

          SECTION 7.  Governing Law.  This Amendment shall be deemed to be made
                      -------------
pursuant to the laws of the State of North Carolina with respect to agreements
made and to be

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performed wholly in the State of North Carolina and shall be construed,
interpreted, performed and enforced in accordance therewith.

          SECTION 8.  Costs and Expenses.  The Borrower shall pay any and all
                      ------------------
out-of-pocket expenses in connection with the preparation, execution and
delivery of this Amendment, including, without limitation, the fees and expenses
of the Bank's counsel in connection therewith.

          SECTION 9.  Entire Agreement.  This Amendment contains the entire
                      ----------------
agreement of the parties with respect to the subject matter hereof, and there
are no representations, inducements or other provisions among the parties
regarding such subject matter other than those expressed herein in writing.  All
changes, additions or deletions to this Amendment must be in writing and signed
by all parties.

          IN WITNESS WHEREOF, the parties hereto have caused their respective
duly authorized officers or representatives to execute and deliver this
Amendment as of the day and year first above written.

                                        BORROWER:

ATTEST:                                 PHARMACEUTICAL PRODUCT
                                        DEVELOPMENT, INC.

/s/ Fred B. Davenport, Jr.              By: /s/Fredric N. Eshelman
---------------------------------           ----------------------
Fred B. Davenport, Jr.  Secretary       Title: Chief Executive Officer

[CORPORATE SEAL]

                                        BANK:

                                        WACHOVIA BANK, N.A.

                                        By: /s/ Alex K. Turner
                                            ------------------
                                        Title:  Assistant Vice President

                                        GUARANTOR:

                                        PPD DEVELOPMENT, LLC             (SEAL)

                                        By: /s/ Fredric N. Eshelman   (SEAL)
                                            -------------------------
                                                      Manager

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