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Biotechnology Consultation
Memorandum of Meeting
BNF No. 000013
February 27, 1995
Participants:
Monsanto:
W. Martin Strauss
Roy Fuchs
Sharon Berberich
Frank Serdy
FDA:
James Maryanski, HFS-13
Nega Beru, HFS-206
Dennis Keefe, HFS-206
Laura Tarantino, HFS-206
Vincent Zenger, HFS-206
Anita Chang, HFS-226
Carl B. Johnson, HFS-226
Louis Pribyl, HFS-226
Jeannette Glover-Glew, HFS-246
Zofia Olemska-Beer, HFS-247
Min Song, HFV-144
Bill Price, HFV-221
Mika Alewynse, HFV-226
Subject: Bt-resistant Cotton
In a submission dated November 21, 1994, Monsanto provided summary information to support their safety assessment of cotton line 531. A meeting was scheduled at Monsanto's request to discuss their safety assessment of cotton line 531.
The intended technical effect of this genetic modification of cotton plants is to confer resistance to the lepidopteran pests: cotton bollworm, tobacco budworm, and pink bollworm. Cotton is primarily used for fiber production intended for textile manufacturing. Cotton linters, cottonseed oil, and cottonseed meal are by-products that are used in human and animal foodstuffs; Cotton linters are used as a source of cellulose in food for human consumption. Cottonseed oil is commonly used as a vegetable oil in human food. Cottonseed meal is used primarily in animal feed as a source of protein.
Based on information provided by Monsanto, the crylA(c) gene from Bacillus thuringiensis subsp. kurstaki (B.t.K.) encodes for protein (Bt-toxin) that is toxic to certain lepidopteran insect pests. Monsanto claims that expression of the crylA(c) gene in cotton plants results in increased resistance to cotton bollworm, tobacco budworm, and pink bollworm. The toxicity of the Bt-toxin is reported to be very specific to lepidopterans.
Based on the restriction fragment analysis of total DNA isolated from transgenic lines intended for commercialization and control lines of cotton, Monsanto has concluded that their line has one genetic locus containing the transgenic DNA. At this locus the transgenic DNA is composed of one intact copy of the nptII gene, one copy of the aad gene, and one intact copy of the crylA(c) gene. In addition, approximately 1.3 kb of the 3' coding region, including 7S transcription termination sequences, of the crylA(c) gene was inserted ca. 1.7 kb downstream of the 3' end of the intact crylA(c) gene in a head-to-tail orientation. The nptII gene encodes for the enzyme aminoglycoside 3'-phosphotransferase (APH(3')II) which confers resistance to the antibiotic kanamycin. The crylA(c) gene encodes the Bt-toxin. The aad gene encodes the enzyme 3 (9) -0-aminoglycoside adenyltranskerase which confers resistance to the antibiotics spectinomycin and streptomycin. The aad gene is under the control of its own bacterial bacterial promoter.
According to Monsanto, the inserted DNA is capable of: expressing two proteins: 1) Bt-toxin; and 2) aminoglycoside 3'- phosphotransferase I1 (APH(3')II). Because the aad gene is under the control of a bacterial promoter, expression from this gene in cotton plants would not be anticipated. Monsanto reported that they confirmed that this gene is not expressed in cotton (Monsanto's citation: "Monsanto Report, MSL No. 13275"). Because the safe use of Bt-toxins as pesticides is regulated by the Environmental Protection Agency (EPA) under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), and because EPA has exempted from the requirement of a tolerance residues of APH(3')II and the genetic material necessary for its production when used as a plant pesticide inert ingredient (59 F;R 49351; September 28, 1994), this memorandum will not address the safe use of Bt-toxin as a pesticide or the use of APH(3')II as a pesticide inert ingredient.
Based on the genomic restriction fragment mapping and genetic analysis, Monsanto has concluded that the intact crylA(c) transgene is present in one copy, is integrated at a single locus, segregates as a single Mendelian genetic trait, and is stable over several generations.
As stated above, the only new proteins expected to be expressed in cotton line 531 are the Bt-toxin and APH(3')II; these are both subject to EPA's authority under FIFRA. Therefore, we limit our comments to the nutritional and toxicant properties of line 531.
Based on the nature of the genetic modification, it is expected that cotton line 531 would not differ significantly in composition from other cotton varieties. To confirm this expectation, Monsanto analyzed the composition of cotton linters, cottonseed oil, and cotton meal obtained from line 531 and a parental control line.
Based on their analyses, Monsanto has concluded that cotton linters derived from their cotton line 531 are not materially different from cotton linters derived from other cotton varieties. They noted that the composition of linters is >99% cellulose; and because of the extensive processing prior to food use, fiber used for food is not expected to contain any detectable genetic material or protein.
In addition, Monsanto has concluded that cotton seed derived from their cotton line 531 is not materially different froh cotton seeds derived from other cotton varieties in their content of: protein, fat (oil), carbohydrate, ash, moisture, or calories. Moreover, Monsanto has concluded that the levels of gossypol and cyclopropenoid fatty acids in cotton seed produced by line 531 is similar to levels observed in cotton seed produced by the parental line.
Monsanto has concluded that cottonseed oil derived from their cotton line 531 is not significantly different from cottonseed oil derived from other cotton varieties in the content of fatty acids (14:0, 16:0, 16:1, 17:0, 18:0, 18:1, 18:2, 18:3, 20:0, 22:0, 24:O) as well as several cyclopropanoid fatty acids (sterculic, dihydrosterculic, and malvalic).
Finally, Monsanto has concluded that cottonseed meal derived from their cotton line 531 is not materially different from cottonseed meal derived from other cotton varieties.
Monsanto described the results of a wholesomeness study with cottonseed meal they carried out in rats. Monsanto has concluded from this study that there is no material difference in the wholesomeness of cotton seeds derived from their line 531 and seeds derived from control cotton lines.
Monsanto has concluded that their cotton line 531 is iot significantly altered within the meaning of 21 CFR 170.30(f)(2) when compared to cotton varieties with a safe history of food use. At this time, based on Monsanto's description of its data and analyses, the Agency considers Monsanto's consultation their cotton line 531 to be complete.
/s/
Dennis M. Keefe, Ph.D.
