Sol_RFQ-RT-15-00061_Amd_000001.pdf

(x)

RFQ-RT-15-00061

x x copies of the amendment; (b) By acknowledging receipt of this amendment on each copy of the offer submitted; or (c) By separate letter or telegram which includes a reference to the solicitation and amendment numbers. FAILURE OF YOUR ACKNOWLEDGEMENT TO BE RECEIVED AT

THE PLACE DESIGNATED FOR THE RECEIPT OF OFFERS PRIOR TO THE HOUR AND DATE SPECIFIED MAY RESULT IN REJECTION OF YOUR OFFER. If by virtue of this amendment you desire to change an offer already submitted, such change may be made by telegram or letter, provided each telegram or letter makes reference to the solicitation and this amendment, and is received prior to the opening hour and date specified.

x

Research Triangle Park NC 27709

RTPPOD

Mail Code: AA005 109 T.W. Alexander Drive US Environmental Protection Agency

RTPPOD

07/21/2015000001

13. THIS ITEM ONLY APPLIES TO MODIFICATION OF CONTRACTS/ORDERS. IT MODIFIES THE CONTRACT/ORDER NO. AS DESCRIBED IN ITEM 14.

12. ACCOUNTING AND APPROPRIATION DATA (If required) is not extended.is extended, Items 8 and 15, and returning

Offers must acknowledge receipt of this amendment prior to the hour and date specified in the solicitation or as amended, by one of the following methods: (a) By completing

The above numbered solicitation is amended as set forth in Item 14. The hour and date specified for receipt of Offers

11. THIS ITEM ONLY APPLIES TO AMENDMENTS OF SOLICITATIONS

FACILITY CODE CODE

10B. DATED (SEE ITEM 13)

10A. MODIFICATION OF CONTRACT/ORDER NO.

9B. DATED (SEE ITEM 11)

9A. AMENDMENT OF SOLICITATION NO.

CODE

8. NAME AND ADDRESS OF CONTRACTOR (No., street, county, State and ZIP Code)

7. ADMINISTERED BY (If other than Item 6)CODE 6. ISSUED BY

PAGE OF PAGES

4. REQUISITION/PURCHASE REQ. NO.3. EFFECTIVE DATE2. AMENDMENT/MODIFICATION NO. 5. PROJECT NO. (If applicable)

1. CONTRACT ID CODE

AMENDMENT OF SOLICITATION/MODIFICATION OF CONTRACT

06/24/2015

CHECK ONE A. THIS CHANGE ORDER IS ISSUED PURSUANT TO: (Specify authority) THE CHANGES SET FORTH IN ITEM 14 ARE MADE IN THE CONTRACT

B. THE ABOVE NUMBERED CONTRACT/ORDER IS MODIFIED TO REFLECT THE ADMINISTRATIVE CHANGES (such as changes in paying office, C. THIS SUPPLEMENTAL AGREEMENT IS ENTERED INTO PURSUANT TO AUTHORITY OF:

D. OTHER (Specify type of modification and authority) appropriation date, etc.) SET FORTH IN ITEM 14, PURSUANT TO THE AUTHORITY OF FAR 43.103(b).

E. IMPORTANT: Contractor is not, is required to sign this document and return __________________ copies to the issuing office.

ORDER NO. IN ITEM 10A.

14. DESCRIPTION OF AMENDMENT/MODIFICATION (Organized by UCF section headings, including solicitation/contract subject matter where feasible.)

Notice of Intent to Sole Source

16A. NAME AND TITLE OF CONTRACTING OFFICER (Type or print)15A. NAME AND TITLE OF SIGNER (Type or print)

15C. DATE SIGNED 16B. UNITED STATES OF AMERICA 15B. CONTRACTOR/OFFEROR 16C. DATE SIGNED

(Signature of person authorized to sign) (Signature of Contracting Officer)

Nicole A. Hairston

STANDARD FORM 30 (REV. 10-83)

Prescribed by GSA

FAR (48 CFR) 53.243

NSN 7540-01-152-8070

Previous edition unusable

Except as provided herein, all terms and conditions of the document referenced in Item 9A or 10A, as heretofore changed, remains unchanged and in full force and effect.

07/21/2015

EPA Histology of Tissue Samples Notice of Intent to Sole Source

Procurement Office: U.S. Environmental Protection Agency, Research Triangle Park Procurement Operations Division (AA004) 109 T.W. Alexander Dr. RTP, NC 27711

NAICS Code: 541712 (size standard of 500 employees) Research and Development in the Physical, Engineering, and Life Sciences (except Biotechnology)

Response Date: July 31, 2015

In accordance with FAR 13.106-1(b)(1), the U.S. Environmental Protection Agency (EPA) Office of Research and Development NHEERL intends to award a sole source fixed-price purchase order to Experimental Pathologies Laboratories, Inc. to purchase histology of tissue samples services in accordance with the attached Statement of Work.

The following are required of a laboratory qualified to perform this requirement:

A. In EPA studies, in utero exposure to certain chemicals during pregnancy induces unique reproductive tract lesions that are only seen after the animals are born and reach adulthood. For this reason, the performing laboratory must have demonstrated though peer-reviewed publications or EPA reports (as an author, coauthor, or their data cited in these peer reviewed documents) that they have evaluated tissues (gross or histologically) in adult animals, exposed in utero, to vinclozolin, procymidone, diethylhexyl phthlate, dipentyl phthalate, linuron, and prochloraz. (*If other chemical, provide explanation of relation to the aforementioned)

B. The performing laboratory must also have demonstrated experience evaluating lesions of the reproductive tract of both male and female rats at different stages of the life cycle, including neonatal, infantile, pubertal and adult.

C. The specific histopathological lesions induced by the chemicals currently under investigation are expected to induce lesions similar to the aforementioned chemicals. The laboratory is required to have experience evaluating the following lesions:

1. EPIDIDYMAL AGENESIS

2. EPIDIDYMAL GRANULOMA

3. EPIDIDYMAL DEBRIS FROM TESTIS

4. TESTIS ATROPHY, FLUID FILLED TESTIS,

HYPOSPERMATOGENESIS

5. TESTICULAR TUMORS

6. TESTIS GRANULOMA

7. VENTRAL PROSTATE AND SEMINAL VESICLE

INFLAMATION/GRANULOMA AND AGENESIS

8. UTERINE EPITHELIA AND MYOMETRIAL HYPERPLASIA

NO SOLICITATION OR REQUEST FOR QUOTE (RFQ) IS AVAILABLE.

Notwithstanding, any firm that believes it is capable of meeting EPA's requirement as stated herein may submit a capability statement, which if received within ten (10) calendar days of the date of this announcement will be considered. Responses to this posting must be in writing and provide clear and convincing evidence that competition would be advantageous to the Government. A determination not to compete the proposed purchase order based upon the responses to this notice is solely within the discretion of the Government. All questions should be directed to Nicole Hairston via the e-mail link below.

All other information related to this requirement as well as any subsequent procurement notifications will be posted via FedBizOpps (FBO) and Fedconnect. All interested parties should check these sites frequently for updates.

CONTACT INFORMATION

Contracting Officer: Nicole Hairston, Contract Specialist, Hairston.Nicole@epa.gov .

NO FAXES, MAIL OR PHONE CALLS WILL BE ACCEPTED

mailto:Hairston.Nicole@epa.gov

HISTOLOGY of TISSUE SAMPLES - STATEMENT OF WORK

SECTION I – DESCTIPTION OF WORK

Task 1 - Determining the ED50 values for Bisphenol C, Bisphenol S, and Bisphenol A in rat Uterotrophic Estrogenic Bioassay – Oral exposure route

A. Background

Bisphenol S

Bisphenol S (BPS) has been hypothesized to behave as an environmental estrogen by previous studies. A recent in vitro study with the T47D-KBluc estrogen-responsive transcriptional activation luciferase reporter gene assay demonstrated that BPS induced an estrogenic response. The objective of this study is to demonstrate that BPS behaves as an environmental estrogen with an in vivo rat model and to calculate ED50 and HillSlope values for both these compounds with oral exposure. The potential estrogenicity of BPS is of interest to the NTP, supporting this work. The ED50 and HillSlope values will, in a later mixture study, be used to determine if the dose-addition model predicts the in vivo mixture interactions as well as it does in vitro. We predict the following: 1) BPS will induce an estrogenic response in the rat uterotrophic bioassay with oral exposure; 2) the BPS ED50 value will indicate that it is a considerably less potent environmental estrogen than previously tested bisphenol compounds.

Bisphenol C

Bisphenol C (BPC) has been hypothesized to behave as an environmental estrogen by previous studies. A recent in vitro study with the T47D-KBluc estrogen-responsive transcriptional activation luciferase reporter gene assay demonstrated that BPC induced an estrogenic response. The objective of this study is to demonstrate that BPC behaves as an environmental estrogen with an in vivo rat model and to calculate ED50 and HillSlope values for both these compounds with oral exposure. The potential estrogenicity of BPC is of interest to the NTP, supporting this work. The ED50 and HillSlope values will, in a later mixture study, be used to determine if the dose-addition model predicts the in vivo mixture interactions as well as it does in vitro. We predict the following: 1) BPC will induce an estrogenic response in the rat uterotrophic bioassay with oral exposure; 2) the BPC ED50 value will indicate that it is a considerably more potent environmental estrogen than previously tested bisphenol compounds.

Bisphenol A

Bisphenol A (BPA) has been hypothesized to behave as environmental estrogen by previous studies. A recent in vitro study with the T47D-KBluc estrogen-responsive transcriptional activation luciferase reporter gene assay demonstrated that BPA induced an estrogenic response. The objective of this study is to demonstrate that BPA behaves as environmental estrogens with an in vivo rat model and to calculate ED50 and HillSlope value for this compound with oral exposure. The potential estrogenicity of BPA is of interest to the NTP, supporting this work. The ED50 and HillSlope values will, on a later mixture study, be used to determine if the dose-addition model predicts the in vivo mixture interactions as well as it does in vitro. We predict the following: 1) BPA will induce an estrogenic response in the rat uterotropic bioassay; and 2) BPA will be a slightly potent environmental estrogen.

120 ovariectomized Sprague-Dawley rats were ordered from Charles River Laboratories. Each block consisted of up to 24 rats. OVX rats will be weight ranked and randomly assigned to treatment in a manner that provides similar means and variances in body weights before dosing is initiated. OVX rats will be dosed daily in the morning by oral gavage for four consecutive days with a) 0, 50, 100, 200, 400, and 800 mg/kg-bw of Bisphenol S, b) 200, 400, 600, and 800 mg/kg-bw of Bisphenol A, or c) 1.5, 4, 13.5, 45, 150, or 300 mg/kg-bw Bisphenol C. Each block of this study will have a positive control of 1 µg/day estradiol-benzoate (subcutaneous). Three hours after the final dose, OVX rats will be euthanized and uterine tissue will be excised and weighed. After the initial weight of the uterus has been recorded, the tissue will then be drained of all fluid and then re-weighed. Any observed malformations will be recorded.

B. Contractor Requirements

The contractor shall process, embed, section, stain (H&E), and evaluate a total of 119 uteri that have been fixed in Bouin’s Fixative for 24 hours, and are currently stored in a 70% ethyl alcohol solution. Each uterus shall be cut cross-sectionally once on the right horn and shall be placed on one slide and labeled with the animal’s ID number. Unused portions of the tissues and paraffin blocks must be returned to the EPA along with the slides.

Task 2 - Assessing the Postnatal Effects of Dipentyl Phthalate on Male CD-1 Mouse Reproductive Development

A. Background

Recently, our lab has conducted several in utero, ex vivo, and in vitro studies to characterize the dose-response curve of DPP, and the chemical’s effect on testosterone production in the fetal testis. Although these studies have pointed to the overall potency of DPP, little literature exists defining its dose-response curve in vivo. Foster et al.

conducted an in vivo study in 1983 which showed that treatment of young male rats with DPP produced significant decreases in testicular cytochrome P-450, cytochrome P-450 dependent microsomal steroidogenic enzymes (I~uhydroxylase, 17-20 lyase) and in the maximal binding of a natural substrate (progesterone) to testis microsomes. This effect on the enzymes responsible for androgen production is important as a mechanism of action involved in the development of phthalate-induced testicular damage.

Even less literature exists defining the dose response curve of DPP on the reproductive development of the male mouse.

The purpose of this study is to 1) treat timed-pregnant CD-1 mice with varying levels of DPP, from gestational days (GD) 8-18, 2) monitor male offspring for delayed sexual maturity, nipple/areola retention, and reproductive malformations 3) monitor female offspring for delayed vaginal opening and uterine malformations, and 4) attempt to further define the dose-response curve of DPP via its effects on mouse reproductive development.

25 timed-pregnant Charles River CD-1 mice were separated into 5 treatment groups (0, 25, 50, 100, and 200 mg DPP/kg-bw/day) with 5 pregnant mice per group. On gestational day 7, mice were weighed and assigned to one of the 5 treatment groups to ensure that the treatment groups are equally weighted. Dams were dosed in the morning by oral gavage on GD8-18.

B. Contractor Requirements

The contractor shall process, embed, section, stain (H&E), and evaluate a total of 115 livers, 230 testes and 115 epididymides that have been fixed in Bouin’s Fixative for 24 hours, and are currently stored in a 70% ethyl alcohol solution. Each tissue shall be cut cross-sectionally once. One cross-section from the liver will be taken from the medial lobe and placed on one slide, and labeled with the animal’s ID number. Two cross-sections (one from each testis, right and left) shall be placed on one slide and labeled with the animal’s ID number. One cross-section (from each epididymis) shall be placed on one slide, and labeled with the animal’s ID number. Cross-sections for each animal ID may be placed on one slide should room permit. Unused portions of the tissues and paraffin blocks must be returned to the EPA along with the slides.

Task 3 - Assessing the Postnatal Effects of a Mixture of Pyrifluquinazon and Di(n-butyl) Phthalate on Male Rat Reproductive Tract Development

A. Background

Pyrifluquinazon (PFQ)

Pyrifluquinazon (PFQ) is a new insecticide active ingredient developed by Nichino America, Inc. PFQ [1-acetyl-1,2,3,4-tetrahydro-3-[(3-pyridylmethyl)amino]-6- [1,2,2,2-tetrafluoro-1-(trifluoromethyl) ethyl]quinazolin-2-one] represents a new mode of action, characterized by modification of insect feeding behavior, which has not yet been classified by the Insecticide Resistance Action Committee (IRAC). PFQ has been registered for use in commercial greenhouses on non-food, ornamental plants for control of sap-feeding insects, including whiteflies (including problematic q-strain whiteflies), aphids, leafhoppers, thrips, and mealybugs. The end-use formulation contains 20% PFQ, for dilution at rates ranging from 1.6 fl oz – 6.4 fl oz. per gallon, and applied to plants at a rate of 10 gallons of spray solution per 1,000 square ft. per application. There is a limit of 2 applications per crop cycle.

There are currently no registered food uses for PFQ in the United States.

The acute toxicity profile of PFQ consists of moderate toxicity via the oral route of exposure and mild toxicity via the dermal and inhalation routes of exposure. It is not a skin sensitizer.

PFQ acts against insects via a novel mode of action. In vertebrate systems, PFQ’s effects and modes of action are classified as anti-androgenic. No current data supports evidence of genotoxicity or mutagenicity in mammals. In all three mammalian species tested, the primary target organs for PFQ were the liver, thyroid, hematopoietic system, kidneys, and the male and female reproductive organs.

Di(n-butyl) Phthalate (DBP)

Studies conducted previously have shown that di(n-butyl)phthalate (DBP) adversely affects fetal Leydig cell differentiation, thus delaying the production of testosterone. In contrast to some other anti-androgens that compete with testosterone for the androgen receptor (AR), DBP does not prevent testosterone from properly binding to the AR. High doses of DBP, over gestational days 14 through 18 decrease production of testosterone and insl-3, resulting in reduced weights in most reproductive organs, as well as testicular lesions.

The purpose of this study is to 1) dose animals with a mixture of PFQ and DBP and various concentration levels 2) monitor male offspring for reduced anogenital distance, nipple/areola retention, delayed sexual maturity, and gross reproductive malformations, and 3) characterize the dose additivity of the two chemicals.

Thirty timed-pregnant Sprague-Dawley rats were ordered from Charles River Laboratories and housed on pine shavings in polycarbonate cages. Animals were weight ranked and randomly assigned to treatment groups. Animals were dosed daily via oral gavage with 0, 12.5 mg PFQ + 93.75 mg DBP, 25 mg PFQ + 187.5 mg DBP, 50 mg PFQ + 375 mg DBP, 75 mg PFQ + 562 mg DBP and 100 mg PFQ + 750 mg DBP (mg/kg-bw/day) from gestational days 14 through 18, during the period of fetal sexual differentiation. Offspring were necropsied at 120 days of age and reproductive malformations were recorded.

B. Contractor Requirements

The contractor shall process, embed, section, stain (H&E), and evaluate a total of 298 testes and 149 epididymides that have been fixed in Bouin’s Fixative for 24 hours, and are currently stored in a 70% ethyl alcohol solution. Each tissue shall be cut cross-sectionally once. Two cross-sections (one from each testis, right and left) shall be placed on one slide and labeled with the animal’s ID number. One cross-section (from each epididymis) shall be placed on one slide, and labeled with the animal’s ID number.

Cross-sections for each animal ID may be placed on one slide should room permit.

Unused portions of the tissues and paraffin blocks must be returned to the EPA along with the slides.

Task 4 - Cumulative Effects of a 9 Phthalate Mixture Using DEHP, DiHP, DiBP, DBP, BBP, DCHP, D(Hexyl)P, D(Heptyl)P, and DPeP

A. Background

Studies have shown that in utero exposure to certain mixtures of phthalates, especially those that exhibit similar modes of action, inhibits male reproductive development in laboratory rodents in a dose-additive fashion. These studies have also indicated that phthalates administered to pregnant dams during the period of sexual differentiation, where reproductive malformations were observed in the male rat, correlated to significant reductions in fetal T levels. In addition, previous studies conducted in our laboratory have observed that administration of mixture of 9 phthalates (80 mg DEHP, DiHP, DiBP, DBP, BBP, DCHP, D(hexyl)P, D(heptyl)P/kg-bw/day, and 10 mg DPeP/kg-bw/day) at the appropriate dosing ratios reduced fetal T production in a dose dependent manner (Hannas et al, 2011). Therefore, the objective of the current study is to determine the “point of departure” as it correlates to reduction in fetal T levels and the potential resultant postnatal male reproductive malformations using the same mixture of 9 phthalates.

Twenty-five timed-pregnant Sprague-Dawley rats were ordered from Charles River Laboratories, and separated into 5 different treatment groups: 100% of the stock solution mentioned above, and dilutions of the stock solution at 67%, 33%, 17%, and 0% (n=5 per treatment group). Dosing solutions were administered via oral gavage for 11 days from gestational day 8 through 18. Dams were allowed to go full term and deliver, and pups were weaned at postnatal day 24. Offspring were then maintained until adulthood and then euthanized beginning postnatal day 150. Males were then assessed for external and internal reproductive malformations.

B. Contractor Requirements

The contractor shall process, embed, section, stain (H&E), and evaluate a total of 232 testes and 116 epididymides that have been fixed in Bouin’s Fixative for 24 hours, and are currently stored in a 70% ethyl alcohol solution. Each tissue shall be cut cross-sectionally once. Two cross-sections (one from each testis, right and left) shall be placed on one slide and labeled with the animal’s litter and ID number. One cross-section (from each epididymis) shall be placed on one slide, and labeled with the animal’s ID number.

Unused portions of the tissues and paraffin blocks must be returned to the EPA along with the slides.

Task 5 - Assessment of the Postnatal Effects of Pyrifluquinazon (PFQ) on Male and Female Reproductive Tract Development in Sprague-Dawley Rats

A. Background

Pyrifluquinazon (PFQ) is a new insecticide active ingredient developed by Nichino America, Inc. PFQ [1-acetyl-1,2,3,4-tetrahydro-3-[(3-pyridylmethyl)amino]-6-[1,2,2,2-tetrafluoro-1-(trifluoromethyl) ethyl]quinazolin-2-one] represents a new mode of action, characterized by modification of insect feeding behavior, which has not yet been classified by the Insecticide Resistance Action Committee (IRAC). PFQ has been registered for use in commercial greenhouses on non-food, ornamental plants for control of sap-feeding insects, including whiteflies (including problematic q-strain whiteflies), aphids, leafhoppers, thrips, and mealybugs. The end-use formulation contains 20% PFQ, for dilution at rates ranging from 1.6 fl oz – 6.4 fl oz. per gallon, and applied to plants at a rate of 10 gallons of spray solution per 1,000 square ft. per application. There is a limit of 2 applications per crop cycle.

There are currently no registered food uses for PFQ in the United States.

The acute toxicity profile of PFQ consists of moderate toxicity via the oral route of exposure and mild toxicity via the dermal and inhalation routes of exposure. It is not a skin sensitizer.

PFQ acts against insects via a novel mode of action. In vertebrate systems, PFQ’s effects and modes of action are classified as anti-androgenic. No current data supports evidence of genotoxicity or mutagenicity in mammals. In all three mammalian species tested, the primary target organs for PFQ were the liver, thyroid, hematopoietic system, kidneys, and the male and female reproductive organs.

The purpose of this study is to determine the effects of pyrifluquinazon on the development of the male and female rat reproductive tract, and to potentially define the dose-response curve of PFQ.

Twenty-five timed-pregnant Sprague-Dawley rats were ordered from Charles River Laboratories and separated into 5 different treatment groups (n=5 dams per treatment group). Four groups of timed-pregnant dams received 0, 12.5, 25, 50, or 100 mg/kg/day pyrifluquinazon from gestational day 14-18 via oral gavage.

B. Contractor Requirements

The contractor shall process, embed, section, stain (H&E), and evaluate a total of 270 testes and 135 epididymides that have been fixed in Bouin’s Fixative for 24 hours, and are currently stored in a 70% ethyl alcohol solution. Each tissue shall be cut cross-sectionally once. Two cross-sections (one from each testis, right and left) shall be placed on one slide and labeled with the animal’s litter and ID number. One cross-section (from each epididymis) shall be placed on one slide, and labeled with the animal’s ID number.

Unused portions of the tissues and paraffin blocks must be returned to the EPA along with the slides.

Task 6 - Assessment of Male Reproductive Development after In Utero Simvastatin Exposure in Charles River Sprague-Dawley Rats

A. Background

Simvastatin (SMV) is a member of the statin family of cholesterol-lowering drugs. It inhibits3-hydroxyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase, a coenzyme that facilitates the conversion of HMG-CoA to mevalonate in the cholesterol biosynthetic pathway. Exposure to statin drugs during pregnancy is associated with increased post implantation loss, decreased pup survival, and decreased fetal weight, among other effects. The mechanism by which this occurs has yet to be elucidated. As cholesterol is a precursor for steroid hormone biosynthesis, inhibition of the cholesterol biosynthetic pathway by statin drugs may adversely affect hormone-dependent processes. In particular, the development of the male reproductive tract occurs between gestational days 14-18 in the rat and is driven, in part, by fetal androgen production. Compounds that decrease fetal testicular testosterone production, such as phthalate esters, during the period of sex differentiation can cause reproductive tract malformations that become apparent later in life during adulthood (Mylchreest, Sar et al. 1999, Gray, Ostby et al.

2000, Barlow and Foster 2003).

In previous expanded fetal phthalate screens in Harlan and Charles River Sprague Dawley rats assessing the effects of simvastatin on testosterone production and gene expression in fetal testes, it was demonstrated that inhibition of the cholesterol pathway caused a reduction in fetal testicular testosterone production and circulating fetal lipids.

In other studies conducted in the lab, similar reductions in testosterone production by dipentyl phthalate resulted in reproductive tract malformations in the postnatal rat. The purpose of the present study is to determine if in utero exposure to simvastatin will correlate with postnatal effects on male reproductive development.

Twenty-five timed-pregnant Sprague-Dawley rats were ordered from Charles River Laboratories and separated into 5 different treatment groups (n=5 dams per treatment group). Four groups of timed-pregnant dams received 0, 15.6, 31.25, or 62.5 mg/kg/day simvastatin from gestational day 8-18. The fifth group received 62.5 mg/kg/day simvastatin from gestational day 14-18 in order to correlate the fetal effects on testosterone productions from previous FPS studies during that dosing period with any postnatal reproductive malformations.

B. Contractor Requirements

The contractor shall process, embed, section, stain (H&E), and evaluate a total of 218 testes and 109 epididymides that have been fixed in Bouin’s Fixative for 24 hours, and are currently stored in a 70% ethyl alcohol solution. Each tissue shall be cut cross-sectionally once. Two cross-sections (one from each testis, right and left) shall be placed on one slide and labeled with the animal’s litter and ID number. One cross-section (from each epididymis) shall be placed on one slide, and labeled with the animal’s ID number. Unused portions of the tissues and paraffin blocks must be returned to the EPA along with the slides.

SECTION II – ADDITIONAL REQUIREMENTS (Applicable to All Tasks)

A. Pathology Services

The contractor will provide the following pathology services:

a. Provide stained sections of tissue

b. Analyze stained tissue samples

c. Prepare slides for submitted tissues

d. Prepare histology reports

A Board Certified Pathologist shall be used. The results of these pathology findings are presented during scientific meetings and published in papers and journal articles. Consequently, the pathologist must be able to substantiate all findings when called upon by the EPA.

B. Transportation of Sample(s)

The contractor will pick-up the tissues form the following location:

109 TW Alexander Drive Lobby of Building C Durham, NC 27709

Due to safety concerns and the possibility of spoilage, all pathology service should be performed locally. The Government will not ship tissues to the contractor by overnight air or land transport. Overnight shipment by the contractor is at their own risk and the contractor will be held liable for any resulting spoilage or damage.

C. Government Responsibilities

EPA will provide the tissues, and inventory sheet of all tissues, and a summary of the experimental protocol for this study.

D. Reporting Requirements

The contractor must provide a written report from the pathologist of the effects observed on these tissues along with a Quality Assurance Certificate for documentation. A draft of the final report shall be mailed to the PI for review. If needed, the PI will return the draft copy of the report to the contractor for correction. Once corrected and approved, the PI will accept the final report.

E. Quality Assurance (QA)

Acceptable Quality Assurance Documentation must be submitted to the EPA Project Officer within 30 days of the acceptance of this order. No work involving direct measurements or data generation, compilation of data from literature or electronic media shall be initiated under this project until the EPA Project Officer, in concert with the EPA Quality Assurance Manager, has approved the quality assurance documentation. For such documentation, the Contractor shall provide:

(1) a Quality Management Plan which describes the organizational structure, functional responsibilities of management and staff, line of authority, and required interfaces for planning, implementing and assessing all quality assurance activities, and (2) a Quality Assurance Project Plan, which comprehensively describes the necessary QA, Quality Control (QC) and other technical activities to ensure that the results of the work performed satisfy the state performance criteria. QA guidance documents can be found on the internet at http://www.epa.gov/quality1/exmural.html http://www.epa.gov/quality1/exmural.html

HISTOLOGY of TISSUE SAMPLES – Testing Requirement

Item Description Quantity Unit Price Subtotal Histology, small animals ( 270 testes & 135 epididymides to H&E slides) 405 Patrhology (270 testes & 135 epididymides with draft/final report) 405 Histology, small animals (218 testes & 109 epididymides to H&E slides) 327 Pathology (218 testes & 109 epididymides with draft/final report) 327 Histology, small animals (232 testes & 116 epididymides to H&E stained slides) 348 Pathology ( 232 testes & 116 epididymides with draft/final report) 348 Histology (process uteri to H&E stained slides) 119 Pathology (evaluate slides and prepare a draft/final report) 119 Histology (process - 115 livers, 230 testes, & 115 epididymides to H&E slides) 460 Pathology (evaluate above tissues with draft/final report) 460 Histology (process 298 testes & 149 epididymides to H&E stained slides) 447 Pathology (evaluate above tissues with draft/final report) 447