004 epa glp acute oral toxicity test peradoxtm hc -steriplex

8/7/2019 004 Epa Glp Acute Oral Toxicity Test Peradoxtm Hc -Steriplex

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1 I I I I I I I I I I I I I I I I I I I I I I I I I I l l ~ 1 1 1 ~ 1 1 1 1 1 1 1 1 1 1 1 1 I 16 2 X 7 cOO 4 G *

STUDY TITLEPeraDox TM HeLot Number: 022

Sample Code: 2-20-07

DATA REQUIREMENTSTest

EPA Acute Oral Toxicity TestGuideline

OPPTS 870.1100

AUTHORRobert A. Noonan, Ph.D., LATg

In Vivo ServicesPacific BioLabs

STUDY COMPLETED ONApril 2, 2007

SPONSORBrian G. Larson

PresidentsBioMed

1272 South 1380 WestOrem UT 84058

PROJECT IDENTIFICATIONReport No. X7C004GMRP Number R7COOIG

551 Linus Pauling Drive . Hercules, CA 94547 . 510.964.9000 . 510.964.0551 fax . PacificBioLabs. comF D ,A R EG IST RAnO N N o. 29-14117 R eports are sucm itted _10c_lien ts on a confidentia l basis. N o re ference to the w o~k, the resu lts. o r to P,acific Bialabs in ar j Ic rm o f a dv erti,s in g, ne ws re le as e, o r o ln erp ub jic a nn ou nc em en t m ay b e m ade w ith ou t o ur w ritte o a uth on:z atlo n. T es t results ar.e, ap~!lcable o n l r to th e ~arnples tH H ng t es te d w it hin th e ~Imas o r the I~slino procedures idenUlied a nd a re rio t neceuilrH1f nd r ca u ve c t t h e c h ar ac t er ts t tc s -0 : a ny oth er s am ples fro m th e s am e o r o th er lo ts . P ac ltloC B loL ab s s tla l n ot b e lia ble u nde r a ny C Irc um stan ce s fo r a ny am ou nt In ex ce ss o f th e c os t o f th e te st pe rfo rm ed.


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Report Number: X7C004G Page: 2 of 12

STATEMENT OF NO DATA CONFIDENTIALITY CLAIMS

No claim of confidentiality is made for any information contained in this study on the basis of its fallingwithin the scope ofFIFRA Sections 10 (d)(l)(A), (B), or (C).

Sponsor: sBioMed

Sponsor's Representative:

Name Title

Signature Date


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Report Number: X7C004G Page: 3of 12

GOOD LABORATORY PRACTICE COMPLIANCE STATEMENT

This study meets the requirements of 40 CFR Part 160, with the following exception: specific informationrelated to the stability, characterization, identity and verification of the test substance as received andtested is the responsibility of the Sponsor.

Based on the signed statements in this report of the Study Director and a representative of the PacificBioLabs Quality Assurance Department. we certify that all work performed at Pacific BioLabs for thisstudy was conducted in compliance with the Good Laboratory Practice regulations cited above (See page11 for GLP Inspection and Audit Summary),

Study Director: _ _ , M , - "~ " , ", /" - " g ;J . :: :: : ", .; o :, ,, ,- _ ,, ,, _ , _ _ _ ,. .~ ~ . - - - = - . _ . . . : . . . . . . . . ! : P - _ . " ' - . . " _ _ _ ; : , , , , ~ Date:

Sponsor's Representative: _ Date: _

Submitter (if other than sponsor): _ Date: _


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Report Number; X7C004G Page: 4 of 12

TABLE OF CONTENTS

Statement Of No Data Confidentiality Claims 2Good Laboratory Practice Compliance Statement... 3Stud y Dates . 5Test Article Identification 5Protocol 5Deviations from Protocol 5Data Disposition 5Summary of Results 5EPA Acute Oral Toxicity Test.. 6Introduction 6Materials and Methods 6Test System 6Justification for Test System 6Table 1: Supplies 7Table 2: Study Design 7Table 3: Study Schedule 8Sample Preparation and Dosing Procedure 8Observations 8

Results and Discussion 9Table 4: Summary of Clinical Observations 9Table 5: Animal Weights 10Table 6: Observations at Necropsy 10

Conclusion 10References 10Quality Statement 11Final Report Audit 11Pacific BioLabs Staff Participating in this Study 12Statement of Compliance 12


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Report Number; X7C004G Page: 5 of 12

STUDY DATESStudy Authorization:Date Sample Received:Study Initiation Date:Date On Test:Date Off Test:Report Date:

Signed ProtocolFebruary 26, 2007March 7, 2007March 9, 2007March 26, 2007April 2, 2007

TEST ARTICLE IDENTIFICATIONName: PeraDox TM HCPhysical Description: liquidTotal Quantity Received for Testing: 8 sets (Eight 500 mL bottles of test article and eight bottles of activator-shared)Total Quantity Used for This Study: 10mLLot Number: 022Sample Code: 2-20-07Sterility Status: Non-sterileStorage Condition: 20 - 25CPROTOCOLThis test was conducted according to Protocol Number X7C004G, which incorporates by referenceStandard Operating Procedure 16D-05 and is on file at Pacific Biol.abs. There were no amendments tothe protocol.

DEVIATIONS FROM PROTOCOLThere were no deviations.DATA DISPOSITIONRaw data and the final report from this study are archived at Pacific BioLabs, 551 Linus Pauling Drive,Hercules, CA 94547, under Report Number X7C004G. The test article(s) will be disposed of by PacificBioLabs, unless the client requests that the test article(s) be returned. I t is the responsibility of the clientto maintain test articles in accordance with GLP regulations.SUMMARY OF RESUL T5A single oral administration of PeraDox TM HC at a limit dose of 5000 mg/kg to three female rats resultedno mortalities or abnormalities. The study confirms that the LDso for this test article is greater than 5000mg/kg.


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EPA ACUTE ORAL TOXICITY TEST

INTRODUCTIONThis procedure is designed to determine the acute oral toxicity of the material under test.A Limit test was performed using three female Sprague Dawley rats, which received an oral Limit Doseof 5000 mg/kg of the test article. Initially, one animal was dosed. When no mortalities occurred after twodays, a second and third animal were dosed. The animals were observed for mortality, weight change andtoxic signs for a two week period.If the three rats survived for two weeks after dose administration, the LD50for the test article would beconsidered to be greater than the Limit Dose (5000 mg/kg) and no additional testing would be required.

MATERIALS AND METHODS

Test SystemSpeciesStrainSourceNumber UsedSexAgeWeightHousingFeed

WaterIdentificationPhotoperiodQuarantine Period

RatSprague-DawleyCharles River Laboratories, Hollister, CAFiveFemale7-10 weeks243 to 252 gramsIn groups of no more than three, 18-26C and 50 20% relative humidityCertified Laboratory Rodent Diet; Animals are fasted prior to treatment. Foodwas restored four hours after dosing.Provided ad libitumTail marking and Cage CardDiurnal (12 hours on - 12 hours off)Five days

Justification for Test SystemRats are the species required by the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA), ToxicSubstances Control Act (TSCA) and Health Effects Guideline OPPTS 870.1100 - Acute Oral Toxicity,December, 2002.


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Report Number: X7C004G Page: 70'12

Table 1: Supplies

. Reagents/Equipment Lot Number Manufacturer Expiration DateDeionized water 3/09/07

3/12/07PBL*PBL*

NANA

Perfektum Stainless Steel AnimalFeeding Needle ( 3 inch, 16 gauge) NA Popper & Sons NA* Pacific BioLabs

Table 2: Study DesignOral Limit Test (5000 mglkg)

: 48 Hour Outcome of Test .Total I Dose DurationNumber I Dose Volume of TestAnimals Sex (mg/kg) (mL/kg) (Days) Animal(s) Die Animal(s) Survive**

Limit Test is ended. LDso test First animal is observed for 14I F 5000 10 14 should be performed days. Additional two animalsare dosed

IIfone or both animals die, two If three animals survive, limitmore animals are dosed, one at test is stopped. The LDso is

3 i F 5000 10 14 a time. If three animals die, considered greater than 5000I limit test is terminated and an mglkg. No additional testing isII LDso test should be run needed.I If two offour are dead, an! additional animal is dosed.5 I F 5000 10 I 14 If three of four are dead, limit

If three or more of fivei I I I I testis stopped and an LDso lest: I I I animals survive, the LDsoisI 1 I should be run. considered greater than 5000I

I i If three of five are dead, themglkg. No additional testing is

I needed.5I

F 5000 10 I 14 LDso is less than the limit dose.III An LDso test should be run.!

* Deaths occurring after 48 hours are considered mortalities.** All surviving animals are observed for 14 days then undergo necropsy.


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Report Number: X7C004G Page: 8of 12

Table 3: Study ScheduleTime

Day-I

Hour Procedure

oFood withheld overnightWeighing and dosingo

0-33

Observation of animalsFood restored

7Daily observationsObservation and weighing

1-6

8 - 1314

Daily observationsObservation and weighing

Sample Preparation and Dosing ProcedureAnimal Preparation - The animals were fasted beginning approximately 15 hours before doseadministration. During the fasting they continued to receive water ad libitum. Food was not restored tothe cages until three hours after dosing in order to facilitate gastrointestinal absorption of the test article.One rat was dosed on the first day of dosing. Two days later two more rats were dosed. Because all threesurvived past 48 hours. no additional rats were dosed.Sample Preparation - The test article was diluted with deionized water to attain a 0.5 g/mL solution.Dosing Procedure - The dose was administered by means of a gavage needle attached to a hypodermicsyringe. The test animals received a 10 mL/kg solution containing the test article. There were no controlanimals. The first rat was dosed on 3/9/07. The second and third rats were dosed on 3/12107.

ObservationsClinical Observations - All of the animals were observed several times on the day of dosing and at leastonce each day for fourteen days. The animals were observed for clinical signs of toxicity such asunkempt appearance, altered feeding habits. weight loss and other signs of distress or physical depressionand for any signs of recovery from these conditions.Weights - All of the animals were weighed on Day 0 (prior to test article administration, Day 7 and at theend of the study on Day 14.Euthanasia - All animals were euthanized, if they became moribund. AU surviving animals wereeuthanized at the termination of the study. Euthanization was by IP injection of Euthasol (0.5 mL).Necropsy - Gross necropsies were performed on all animals. either at death or at the end of the study.


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Report Number: X7C004G Page: 90f12

RESULTS AND DISCUSSIONClinical Observations - Rat #2 appeared subdued and was wheezing on the first day after dosing (Day 1).On Day 2. it appeared fully recovered. Clinical observations are summarized in Table 4. All three ratsremained healthy with no toxic signs for the remainder of the study.W eights - The animal weight data is summarized in Table 5. All animals gained weight during the testperiod.Necropsy - The necropsy findings are summarized in Table 6. No abnormalities were observed in any ofthe test animals.

Table 4: Summary of Clinical Observations

2

Animal2 3

NAO NAO NAONAO NAO NAONAO NAO NAONAO NAO NAONAO NAO NAONAO Subdued and Wheezing NAONAO NAO NAONAO NAO NAONAO NAO NAONAO NAO NAONAO NAO NAONAO NAO NAONAO NAO NAONAO NAO NAONAO NAO NAONAO NAO NAONAO NAO NAONAO NAO NAONAO NAO NAO

Time after DosingDay Hour

oo +0.5o +1o +2o + : .

34567891011121314

NAO = No Abnormalities Observed


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Table 5: Animal WeightsAnimal Dose Weight (g) Weight PercentChange (g) WeightNumber (mL) Day 0 Day 7 Day 14 Days 1 to 1 4 Change

2 . 5 2 5 2 2 7 5 2 7 5 + 2 3 + 92 2 . 5 2 4 7 2 6 9 2 8 5 + 3 8 + 1 53 2.4 243 2 6 9 2 8 2 + 3 9 + 1 6

Table 6: Observations at NecropsyAnimal Findings

No Abnormalities Observed2 No Abnormalities Observed3 No Abnormalities Observed

CONCLUSIONA single oral administration of PeraDox HC at a limit dose of 5000 mg/kg to three female rats resultedno mortalities or abnormalities. The study confirms that the LDso for this test article is greater than 5000mg/kg.

REFERENCESSOP 16D-05, Acute Oral Toxicity: EPA FlFRAACUP 1 7 0 - 0 1 , Acute Oral Toxicity - RatsSOP 16A-ll. Euthanasia of Laboratory Animals40 CFR Part 160, Good Laboratory Practices, July 2 0 0 3OECD Guideline for Testing of Chemicals, Part 402: Acute Oral Toxicity - Fixed Dose Method.Office of Prevention, Pesticides and Toxic Substances (OPPTS), Health Effects Test Guideline 870.1100,Acute Oral Toxicity, December, 2002


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QUALITY STATEMENTQUALITY ASSURANCE UNIT GLP INSP,ECTION AND AUDIT SUMMARY

This study, X7C004G, was inspected by Quality Assurance at intervals adequate to assure the integrity ofthe study. The SOP/protocol that the study followed, the phase(s) of the study inspected, and the date(s)of the inspection are provided below.

SOPlProtocol Phase of Study160-05, rev. 3B.OO/X7C004G Rat #1 Dose Administration 3/9/07

QAU inspection findings are routinely reviewed by the management of Pacific BioLabs. Management isnotified immediately if there are any deviations which might affect the integrity of the study data.QAU inspection findings for this study were reported to the Study Director and Management on thefollowing date(s): March 9, 2007

FINAL REPORT AUDIT

Quality Assurance has conducted a thorough audit of the test data generated during this study. ReportNumber X7C004G represents an accurate description of the conduct and final results of the study.

Quality Assurance Date


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PACIFIC BIOLABS STAFF PART!ICIPAT!ING IN THIS STUDYSome or all of the following staff were involved in the conduct of this study:1. Sheila Healy, Ph.D., Associate Manager, Toxicology Services2. Roger O'Meara, B,S" LATg, Associate Manager, Toxicology Services3. Shannon Murphy, B.S" Associate Manager. Toxicology Services4. Robert Noonan, Ph,D., LATg, Senior Scientist, Toxicology Services5. Zobair Musa, Research Associate 2, Toxicology Services6. Jade Sanchez, Research Associate 1, Toxicology Services7. Xenia Tan, D.M.D., Research Associate 1, Toxicology Services8. Lorna Castillo-Wong, D.V.M., Research Associate 1 , Toxicology Services9. Shannon Smart, B.S . ., Research Associate 1, Toxicology Services10. Kelly McCaughey, B.S" M,S., Research Associate 1, Toxicology Services11. Jessiebel F. Saria, B,S., Research Associate 1, Toxicology Services12. Gary Lo, B,A., Research Associate 1. Toxicology Services13. Thanh Nguyen, B.S., Research Associate 1, Toxicology Services14. Darlene Magee, Lead Assistant Technician, Toxicology Services15. Noe Gonzales, Research Assistant 2, Toxicology Services16, Francisco Solano, Research Assistant 1, Toxicology ServicesJ 7. Debbie Goncalves, Research Assistant 1, Toxicology Services18. Moises de Jesus-Sil-Cano, Research Assistant 1, Toxicology Services

STATEMENT OF COMPLIANCEThis study, Report Number X7C004G, has been conducted in accordance with applicable GoodLaboratory Practice Regulations.

004 epa glp acute oral toxicity test peradoxtm hc -steriplex

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