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                                                                     EXHIBIT 4.3

                        CHARLES RIVER LABORATORIES, INC.

                                   AS ISSUER,

                                       AND

                       STATE STREET BANK AND TRUST COMPANY

                                   AS TRUSTEE

                                 ---------------

                          FIRST SUPPLEMENTAL INDENTURE

                          DATED AS OF JANUARY 30, 2002

           SUPPLEMENTING THE INDENTURE DATED AS OF SEPTEMBER 29, 1999

                                 ---------------

                   13 1/2% SENIOR SUBORDINATED NOTES DUE 2009

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     FIRST SUPPLEMENTAL INDENTURE, dated as of January 30, 2002, between CHARLES
RIVER LABORATORIES, INC., a Delaware corporation, as Issuer (the "COMPANY"), and
STATE STREET BANK AND TRUST COMPANY as Trustee (the "TRUSTEE"). All capitalized
terms which are used herein and not otherwise defined herein shall have the
meanings assigned thereto in the Indenture referred to below.

     WHEREAS, the Company has heretofore executed and delivered an Indenture
dated as of September 29, 1999, among the Company, SBI Holdings, Inc., Sierra
Biomedical, Inc., Sierra Biomedical San Diego, Inc., as the guarantors, and the
Trustee (the "INDENTURE"), providing for the issuance of the Company's 13 1/2%
Senior Subordinated Notes Due 2009 (the "SECURITIES");

     WHEREAS, subsequent to executing the Indenture, SBI Holdings, Inc., Sierra
Biomedical, Inc. and Sierra Biomedical San Diego, Inc. merged into the Company;

     WHEREAS, Section 9.02 of the Indenture provides, subject to certain
exceptions, that with the written consent of the Holders of a majority in
principal amount of the Securities then outstanding, the Company and the Trustee
may amend or supplement the Indenture; and

     WHEREAS, this First Supplemental Indenture, and the amendment to the
Indenture set forth herein, have received the consent of the Holders of a
majority in principal amount of the Securities outstanding;

     WHEREAS, all other acts and things necessary to make this First
Supplemental Indenture a valid, binding and enforceable instrument have been
done and performed; and

     WHEREAS, this First Supplemental Indenture does not adversely affect the
Trustee's own rights, duties or immunities under the Indenture;

     NOW, THEREFORE, in consideration of the premises, the Company, the
Guarantors and the Trustee mutually covenant and agree for the equal and
proportionate benefit of the respective Holders from time to time of the
Securities as follows:

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                                   ARTICLE ONE

                           AMENDMENTS TO THE INDENTURE

     1.1. The Indenture is hereby amended by deleting Sections 4.03, 4.05, 4.07,
4.08, 4.09, 4.10, 4.11, 4.12, 4.13, 4.15, 4.16 and 4.17 thereof, and all
references thereto, in their entirety and replaced with the following:

     "[Intentionally Deleted by Amendment]".

     1.2. The Indenture is hereby amended by deleting Article 5 thereof, and all
references thereto, in its entirety and replaced with the following:

     "[Intentionally Deleted by Amendment]".

     1.3. The Indenture is hereby amended by deleting paragraphs (e) and (f) of
Section 6.01, and all references thereto, in their entirety. and replaced with
the following:

     "[Intentionally Deleted by Amendment]".

                                   ARTICLE TWO

                                  MISCELLANEOUS

     2.1. The First Supplemental Indenture shall become a binding agreement
between the parties hereto when counterparts hereof shall have been executed and
delivered by each of the parties hereto. The amendment set forth in Article One
shall become operative at such time as the Company shall accept Securities for
purchase pursuant to the Offer to Purchase and Consent Solicitation Statement
dated January 16, 2002, relating to the Company's offer to purchase all
outstanding Securities.

     2.2. This First Supplemental Indenture is executed as and shall constitute
an indenture supplemental to the Indenture and shall be construed in connection
with and as part of the Indenture and the Securities.

     2.3. The First Supplemental Indenture may be executed in any number of
counterparts, each of which shall be an original, but such counterparts shall
together constitute but one and the same instrument.

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     2.4. This First Supplemental Indenture shall be governed by, and construed
in accordance with, the laws of the State of New York.

     2.5. All the covenants, stipulations, promises and agreements in this First
Supplemental Indenture contained by or on behalf of the Company shall bind its
respective successors and assigns, whether so expressed or not.

     2.6. Nothing in this First Supplemental Indenture, express or implied,
shall give or be construed to give any person, firm or corporation, other than
the parties hereto and their successors and the Holders of the Securities, any
legal or equitable right, remedy or claim under this First Supplemental
Indenture or under any covenant or provision herein contained, all such
covenants and provisions being for the sole benefit of the parties hereto and
their successors and of the Holders of the Securities.

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     IN WITNESS WHEREOF, the parties hereto have caused this First Supplemental
Indenture to be duly executed as of January 30, 2002.

                                      CHARLES RIVER LABORATORIES, INC.

                                      By:
                                         ------------------------
                                         Name:
                                         Title:

Attest:
       ------------------------
       Name:
       Title:

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                                      STATE STREET BANK AND TRUST
                                      COMPANY, as Trustee

                                      By:
                                         ------------------------
                                         Name:
                                         Title:

Attest:
       ------------------------
       Name:
       Title:

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STATE OF MASSACHUSETTS      )
                            : ss.:
COUNTY OF                   )

     On the _______ day of _______________, 2001, before me personally
____________________________, came to me known, who, being by me duly sworn, did
depose and say that (s)he resides at ________________________________; that
(s)he is a ______________________________________________,of CHARLES RIVER
LABORATORIES, INC., one of the corporations described in and which executed the
foregoing instrument; that (s)he knows the common seal of said corporation; that
the seal affixed to said instrument is such common seal; that it was so affixed
by authority of the Board of Directors of said corporation; and that (s)he has
signed his (her) name thereto by like authority.

                                          ---------------------------
                                                 Notary Public

[NOTARIAL SEAL]

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STATE OF                    )
                            : ss.:
COUNTY OF                   )

     On the _______ day of ____________, 2001, before me personally came
___________________________, to me known, who, being by me duly sworn, did
depose and say that (s)he resides at _______________________________________;
that (s)he is a ____________________________ of STATE STREET AND TRUST COMPANY,
one of the corporations described in and which executed the foregoing
instrument; that (s)he knows the common seal of said corporation; that the seal
affixed to said instrument is such common seal; that it was so affixed by
authority of the Board of Trustees of said corporation; and that (s)he has
signed his (her) name thereto by like authority.

                                          ---------------------------
                                                 Notary Public

[NOTARIAL SEAL]<Page>

                                                                     EXHIBIT 4.6

                   AMENDMENT NO. 2 TO THE AMENDED AND RESTATED
                              INVESTORS' AGREEMENT

     AMENDMENT NO. 2 dated as of November 19, 2001 to the Amended and Restated
Investors' Agreement dated as of June 19, 2000, as amended (the "INVESTORS'
AGREEMENT").

                              W I T N E S S E T H:

     WHEREAS, Charles River Laboratories International, Inc., a Delaware
corporation (the "COMPANY"), and several stockholders from time to time parties
thereto have entered into the Investors' Agreement; and

     WHEREAS, in order to permit a transfer by a Management Stockholder (as
defined in the Investors' Agreement) to a charitable organization, the Company,
DLJ Merchant Banking II, Inc. and B&L CRL, Inc. desire to amend the Investors'
Agreement as provided hereunder in accordance with Section 6.06 thereof.

     NOW, THEREFORE, it is agreed as follows:

     SECTION 1. DEFINED TERMS; REFERENCES. Unless otherwise specifically defined
herein, each term used herein which is defined in the Investors' Agreement has
the meaning assigned to such term in the Investors' Agreement. Each reference to
"hereof," "hereunder," "herein" and "hereby" and each other similar reference
and each reference to "this Agreement" and each other similar reference
contained in the Investors' Agreement shall, after this Amendment becomes
effective, refer to the Investors' Agreement as amended hereby.

     SECTION 2. DEFINITIONS. Section 1.01(a) is hereby amended by adding the
following subclause (D) after subclause (iii)(C) of the definition "Permitted
Transferee":

     ", or (D) a charitable organization"

     SECTION 3. GOVERNING LAW. THIS AMENDMENT SHALL BE GOVERNED BY AND CONSTRUED
IN ACCORDANCE WITH THE LAWS OF THE STATE OF DELAWARE WITHOUT REGARD TO THE
CONFLICTS OF LAW RULES OF SUCH STATE.

     SECTION 4. EFFECTIVENESS. This Amendment will be effective as of the date
hereof when signed by the Company, DLJ Merchant Banking II, Inc. and B&L CRL,
Inc.

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     IN WITNESS WHEREOF, the undersigned have executed this Amendment as of the
19th day of November 2001.

                                              CHARLES RIVER LABORATORIES,
                                              INTERNATIONAL, INC.

                                              By:
                                                 -------------------------------
                                                  Name:
                                                  Title:

                                              DLJ MERCHANT BANKING II, INC.

                                              By:
                                                 -------------------------------
                                                  Name:
                                                  Title:

                                              B&L CRL, INC.

                                              By:
                                                 -------------------------------
                                                  Name:
                                                  Title:

                                        2

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