OPPTS 870.5300 In vitro mammalian cell gene mutation test.
This guideline is intended to meet test-ing requirements of both the Federal Insecticide, Fungicide, andRodenticide Act (FIFRA) (7 U.S.C. 136,
) and the Toxic SubstancesControl Act (TSCA) (15 U.S.C. 2601).(2)
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,
Mam-malian Cell Gene Mutation Test.(b)
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)
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.
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.
are substances which cause the addition or dele-tion of single or multiple base pairs in the DNA molecule.
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-