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United StatesEnvironmental ProtectionAgencyPrevention, Pesticidesand Toxic Substances(7101)EPA 712–C–98–221August 1998
Health Effects TestGuidelinesOPPTS 870.5300
In Vitro 
Mammalian CellGene Mutation Test
 
i
I
NTRODUCTION
This guideline is one of a series of test guidelines that have beendeveloped by the Office of Prevention, Pesticides and Toxic Substances,United States Environmental Protection Agency for use in the testing of pesticides and toxic substances, and the development of test data that mustbe submitted to the Agency for review under Federal regulations.The Office of Prevention, Pesticides and Toxic Substances (OPPTS)has developed this guideline through a process of harmonization thatblended the testing guidance and requirements that existed in the Officeof Pollution Prevention and Toxics (OPPT) and appeared in Title 40,Chapter I, Subchapter R of the Code of Federal Regulations (CFR), theOffice of Pesticide Programs (OPP) which appeared in publications of theNational Technical Information Service (NTIS) and the guidelines pub-lished by the Organization for Economic Cooperation and Development(OECD).The purpose of harmonizing these guidelines into a single set of OPPTS guidelines is to minimize variations among the testing proceduresthat must be performed to meet the data requirements of the U. S. Environ-mental Protection Agency under the Toxic Substances Control Act (15U.S.C. 2601) and the Federal Insecticide, Fungicide and Rodenticide Act(7 U.S.C. 136,
et seq.
).
Final Guideline Release:
This guideline is available from the U.S.Government Printing Office, Washington, DC 20402 on disks or papercopies: call (202) 512–0132. This guideline is also available electronicallyin PDF (portable document format) from EPA’s World Wide Web site(http://www.epa.gov/epahome/research.htm) under the heading ‘‘Research-ers and Scientists/Test Methods and Guidelines/OPPTS Harmonized TestGuidelines.’’
 
1
OPPTS 870.5300 In vitro mammalian cell gene mutation test.
(a)
Scope
—(1)
Applicability.
This guideline is intended to meet test-ing requirements of both the Federal Insecticide, Fungicide, andRodenticide Act (FIFRA) (7 U.S.C. 136,
et seq.
) and the Toxic SubstancesControl Act (TSCA) (15 U.S.C. 2601).(2)
Background.
The source materials used in developing this har-monized OPPTS test guideline are OPPT 40 CFR 798.5300 Detection of gene mutations in somatic cells in culture and OECD 476,
 In Vitro
Mam-malian Cell Gene Mutation Test.(b)
Introduction.
The
in vitro
mammalian cell gene mutation testcan be used to detect gene mutations induced by chemical substances. Suit-able cell lines include L5178Y mouse lymphoma cells, the CHO, AS52and V79 lines of Chinese hamster cells, and TK6 human lymphoblastoidcells (see reference in paragraph (g)(1) of this guideline). In these celllines the most commonly-used genetic endpoints measure mutation at thy-midine kinase (TK) and hypoxanthine-guanine phosphoribosyl transferase(HPRT), and a transgene of xanthine-guanine phosphoribosyl transferase(XPRT). The TK, HPRT and XPRT mutation tests detect different spectraof genetic events. The autosomal location of TK and XPRT may allowthe detection of genetic events (e.g., large deletions) not detected at theHPRT locus on X-chromosomes (see references in paragraphs (g)(2),(g)(3), (g)(4),(g)(5), and (g)(6) of this guideline).(c)
Definitions.
The definitions in section 3 of TSCA and in 40 CFRPart 792—Good Laboratory Practice Standards (GLP) apply to this testguideline. The following definitions also apply to this test guideline.
 Base pair substitution mutagens
are substances which cause substi-tution of one or several base pairs in the DNA.
Forward mutation
is a gene mutation from the parental type to themutant form which gives rise to an alteration or a loss of the enzymaticactivity or the function of the encoded protein.
Frameshift mutagens
are substances which cause the addition or dele-tion of single or multiple base pairs in the DNA molecule.
 Mutant frequency
is the number of mutant cells observed divided bythe number of viable cells.
Phenotypic expression time
is a period during which unaltered geneproducts are depleted from newly mutated cells.
 Relative suspension growth
is an increase in cell number over theexpression period relative to the negative control.
 Relative total growth
is an increase in cell number over time com-pared to a control population of cells; calculated as the product of suspen-
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