Approval of Mycogen Seeds c/o Dow AgroSciences LLC and Pioneer Hi-Bred International, Inc

APHIS evaluated the results of several studies submitted that were designed to evaluate the sensitivity of representative nontarget organisms to Cry1F as expressed in different test substrates: i.e., line 1507 corn grain or pollen expressing modified Cry1F protein; or Cry1F purified from a Cry-minus bacterial strain engineered to express the protein toxin. The results of these studies are included in Appendix C of this Environmental Assessment. Data supporting these studies was submitted to the EPA in support of the registration of the plant-pesticide. APHIS concluded that the petitioner adequately demonstrated that the bacterially-produced Cry1F, as purified and prepared for these studies, was similar enough in its biochemical properties (molecular weight, amino acid sequence, and lack of glycosylation) and in its biological activity against lepidopteran larvae to warrant its use as a test substance comparable to Cry1F as produced in line 1507 corn. In both cases, the predominant active protein purified from these sources was a protease-resistant core protein with a molecular weight of approximately 65 kDa. Tests included acute dietary toxicity studies with beneficial arthropods such as honeybee larvae, predatory ladybird beetle (Hippodamia convergens) and green lace wing (Chrysopa carnea), and parasitic hymenoptera (Nasonia vitripennis); a 28 day chronic effects study on survival and reproduction of the soil-dwelling arthropod Collembola (springtails) (Folsomia candida); and acute toxicity studies with other nontarget organisms including earthworms, the freshwater invertebrate Daphnia magna, Northern bobwhite, and mice. Results of these studies indicate that no deleterious effects on these organisms would be expected due to incidental exposure or feeding on line 1507 corn. This takes into consideration the levels of the Cry1F protein measured in different tissues of line 1507 corn, the environmental fate and likely routes and levels of exposure to line 1507 corn plant tissue or residues of this tissue that contain the active toxin, and dietary preferences.

In addition to the laboratory studies, results of a small scale field study conducted in 1999 in Johnston, Iowa (Petition, Vol. 16) demonstrated that there was no consistent pattern of differences in abundance of several categories of beneficial arthropod predators observed in plots planted to two transgenic corn lines expressing the Bt. Cry1F (one of which was line 1507 corn) or the non-transformed genetically similar corn^[1].

Potential impacts on monarch butterflies

Laboratory studies have suggested that monarch butterfly larvae may be adversely effected by feeding on their host plant (milkweed) when it is exposed to pollen from transgenic corn plants expressing other B.t. Cry proteins (Losey et al., 1999; Hansen and Obrycki, 2000). Several different Bt toxins, Cry1Ab, Cry1Ac, and Cry9C, have been conditionally registered as plant-pesticides as expressed in different Bt corn transformation events, but the status of some of these registrations has recently changed. Transformation events containing Cry1Ac and Cry9C will no longer be available due to voluntary cancellations (U.S. EPA, 2000a). In December of 1999, the EPA subsequently issued a monarch butterfly adverse effects data call in for all registrants of Bt corn products and presented current and possible new data requirements to evaluate ecological effects, including the risk to monarch butterflies (U.S. EPA, 2000b). An analysis of recent data, literature, and information on the monarch butterflies, milkweed, pollen movement, and the toxicity of purified Cry proteins against monarch larvae, is presented by the EPA in their preliminary risk and benefit assessment of transgenic plants (U.S. EPA, 2000a). Their preliminary conclusion is that there is a low probability of adverse effects of Bt corn on monarch larvae. Milkweeds located within 1 meter of cornfields are unlikely to be dusted with toxic levels of Bt pollen from the two most widely planted Bt corn varieties whose registrations are not being withdrawn or canceled, Monsanto=s MON 810 and Novartis Seeds, Inc. Bt11 (both of which express Cry1Ab).

The toxicity to monarch larvae of Cry1F as expressed in line 1507 is even lower than the currently registered Bt corn plant-pesticides. Data provided in the petition (Vol. 5) indicate that the estimated environmental concentration (EEC) of Cry1F due to line 1507 pollen exposure does not exceed the no effect level (10 micrograms/g) for monarch larvae at any point inside or outside of maize fields. In addition, the EEC of Cry1F on milkweed leaves due to surface deposits of pollen from hybrids of Bt Cry1F line 1507 is estimated to be less than the LC₅₀ (that concentration at which 50% mortality is observed) for greater than 90% of Lepidoptera species at distances greater than 0.2 m from the field edge. This estimate is probably representative of what one would expect for pollen disposition on other weeds or plants growing in and around corn fields. Therefore, cultivation of line 1507 corn is not expected to harm monarch butterfly larvae, nor is it expected to significantly affect the majority of other nontarget lepidopteran larvae beyond the field margins.

Potential impacts on threatened and endangered arthropods.

Because of the lack of toxicity of the PAT protein and the demonstrated toxicity of Cry1F to only certain species of lepidopteran larvae, APHIS focused its analysis of impacts on threatened and endangered lepidopteran species. A Biological Opinion from the Department of Interior Fish and Wildlife Service was issued on December 18, 1986, concerning possible effects of foliar spray of B. t. subsp. kurstaki on threatened and endangered species. Based on difference in exposure routes between foliar spray and expression in plants, APHIS believes that the Biological Opinion is inapplicable. The majority of endangered lepidopterans have very restrictive habitat ranges; and their larvae typically feed on specific host plants, none of which include corn or its sexually compatible relatives. An examination of county distribution of endangered lepidopterans shows that, for the most part, they do not occur in agricultural settings where corn is grown (Petition, Figure 14). The only possible exceptions are Karner blue butterfly and Mitchell=s satyr butterfly. APHIS examined the potential for impact on these two species due to exposure to corn pollen expressing Cry1F landing on their host plants. The assessment of risk to monarch butterfly associated with non-target exposure to maize pollen containing Cry1F on their milkweed host plant indicates rapid fall-off in exposure with distance, and consequently there is limited potential for non-target effects beyond the immediate field extremity (Petition Vol. 5).

Mitchell=s satyr butterfly occur in northern wetlands fed by seeps and springs known as fens, and their larvae, which are present throughout the summer, feed primarily on sedges (USFWS, 1999). Some of the populations have been observed within 800 meters of corn fields (Wayne Wheling, APHIS Entomologist, personal communication to Susan Koehler). This distance should be sufficient to preclude exposure to toxic concentrations of pollen containing Cry1F. Pollen drift onto sedges in these fens will be further inhibited by the pines and oaks that typically surround these habitats.

4. Line 1507 corn is substantially equivalent in whole plant forage composition and in kernel composition, quality and other characteristics to nontransgenic corn and should have no adverse impact on raw or processed agricultural commodities.

5. Line 1507 corn will not have a significant adverse impact on nontarget organisms, including those beneficial to agriculture; and it will not affect threatened or endangered species.

6. Compared to current agricultural practices, cultivation of line 1507 corn should not reduce the ability to control insects or weeds in corn or other crops.

VII. LITERATURE CITED

Baker, H. G. 1965. Characteristics and modes of origin of weeds, pp. 147‑168. In: The Genetics of Colonizing Species. Baker, H. G., and Stebbins, G. L. (eds.), Academic Press, New York.

Beadle, G. 1980. The ancestry of corn. Sci. American 242:112-119.

Canadian Food Inspection Agency. 1994. Regulatory Directive Dir 94-11: The Biology of Zea mays L. ( Corn/Maize). CFIA, Plant Products Division, Plant Biotechnology Office, Ottawa.

Carpenter, J. and Gianessi, L. 1999. Why U.S. Farmers are Adopting Genetically Modified Crops. Economic Perspectives. An Electronic Journal of the U.S. Department of State, Vol. 4, No. 4, October 1999 [http://usinfo.state.gov/journals/ites/1099/ijee/bio‑toc.htm]

Crockett, L. 1977. Wildly Successful Plants: North American Weeds. University of Hawaii Press, Honolulu, Hawaii. 609 pp.

Davidson, R.H. and Lyon, W.F. 1987. Insect Pests of Farm, Garden, and Orchard. John Wiley & Sons, Inc., New York. 640 pp.

Doebley, J. 1990a. Molecular evidence for gene flow among Zea species. BioScience 40:443-448.

Doebley, J. 1990b. Molecular systematics of Zea (Gramineae). Maydica 35(2):143-50.

Fernandez-Cornejo, J. and Jans, S., 1999. Pest Management in U.S. Agriculture. Resource Economics Division, Economic Research Service, U.S. Department of Agriculture. Agricultural Handbook No. 717.

Fernandez-Cornejo, J. and McBride, W.D. [with contributions from Klotz-Ingram, D., Jans, S., and Brooks, N.] 2000. Genetically Engineered Crops for Pest Management in U.S. Agriculture: Farm-Level Effects. U.S. Department of Agriculture, Economic Research Service, Resource Economics Division. Agricultural Economic Report No. 786.

Galinat, W.C. 1988. The Origin of Corn, pp. 1-31. In: Corn and Corn Improvement, Third Edition. Sprague, G. F., Dudley, J. W. (eds.). American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Madison, Wisconsin

Gray, M. and Steffey, K. 1999. Insect pest management for field and forage crops. Chapter 1 pp.1-22, In: 2000 Illinois Agricultural Pest Management Handbook. College of Agricultural, Consumer and Environmental Sciences, University of Illinois at Urbana-Champaign. University of Illinois Board of Trustees. ISBN 1-883097-25-8. Available at: http://www.ag.uiuc.edu/%7Evista/abstracts/aiapm2k.html

Haack, R.A., 1993. The Endangered Karner Blue Butterfly (Lepidoptera: Lycaenidae): Biology, management considerations, and data gaps. In: Proceedings, 9th Central hardwood forest conference; 1993 March 8-10; West Lafayette, IN. Gillespie, A.R; Parker, G.R.; Pope, P.E.; Rink, G. (eds.), Gen. Ech. Rep. NC-161. St. Paul, MN: U.S. Department of Agriculture, Forest Service, North Central Forest Experiment Station. 515 p.

Hansen, L.C., Obrycki, J.J. 2000. Field deposition of Bt transgenic corn pollen: lethal effects on the monarch butterfly. Oecologia (Published online).

Heap, I.M. 1997. The Occurrence of Herbicide‑Resistant Weeds Worldwide. Pesticide Science, 51, 235‑243. Available at: http://www.weedscience.com/paper/resist97.htm, and last updated in February 1999.

Heap, I.M. 2000. International Survey of Herbicide Resistant Weeds. Online. Internet. October 06, 2000 . Available at: http://www.weedscience.com

Heimlich, R.E., Fernandez-Cornejo, J., McBride, W., Klotz-Ingram, C., Jans, S., Brooks, N. 2000. Genetically Engineered Crops: Has adoption reduced pesticide use? Agricultural Outlook, Economic Research Service/USDA. August 2000: 13-17. Available at: http://www.ers.usda.gov/whatsnew/issues/gmo/

Hitchcock, A.S. (revisions by Agnes Chase) 1971. Tripsacum L. Gamagrass, In: Manual of the Grasses of the United States (Miscellaneous Publication 200, U.S. Department of Agriculture), 2nd Edition, pp. 790-792, Dover, NY, NY (ISBN 0-486-22718-9).

Hofmann, C., Luthy, P., Hutter, R., Piska, V. 1988a. Binding of the Delta Endotoxin from Bacillus thuringiensis to Brush-Border Membrane Vesicles of the Cabbage Butterfly (Pieris brassicae). Eur. J. Biochem. 173:85-91.

Hofmann, C., Vanderbruggen, H., Hofte, H., Van Rie, J., Jansens, S., Van Mellaert, H. 1988b. Specificity of B. thuringiensis Delta-Endotoxins is Correlated with the Presence of High Affinity Binding Sites in the Brush-Border Membrane of Target Insect Midguts. Proc. Natl. Acad. Sci. USA 85:7844-7448.

Holm, L., Pancho, J. V., Herbarger, J. P., Plucknett, D. L. 1979. A Geographical Atlas of World Weeds. John Wiley and Sons, New York. 391 pp.

Kato Y., T.A. 1997 Review of introgression between maize and teosinte. In: Gene Flow Among Maize Landraces, Improved Maize Varieties, and Teosinte: Implications for Transgenic Maize. pp. 44-53. Serratos, J.A., Willcox, M.C., and Castillo-González, F. (eds.). Mexico, D.F., CIMMYT.

Keeler, K. 1989. Can genetically engineered crops become weeds? Bio/Technology 7:1134-1139.

Knake, E.L. 1998. New developments aid corn weed control. 1998 Weed Control Manual. Vol. 31. pp. 92-93.

Lambert, B., Buysse, L., Decock, C., Jansens, S., Piens, C., Saey, B., Seurinck, J., Van Audenhove, K., Van Rie, J., Van Vliet, A., Peferoen, M. 1996. A Bacillus thuringiensis insecticidal crystal protein with a high activity against members of the family Noctuidae. Appl. Envir. Microbiol. 62(1):80-86.

Losey, J.E., Rayor, L.S., Carter, M.E. 1999. Transgenic pollen harms monarch larvae. Nature 399: 214.

McGlamery, M., Hager, A., and Sprague, C. 1999. Toxicity of Herbicides. Chapter 16, pp. 287- 290. In:2000 Illinois Agricultural Pest Management Handbook. College of Agricultural, Consumer and Environmental Sciences, University of Illinois at Urbana-Champaign. University of Illinois Board of Trustees. ISBN 1-883097-25-8. Available at: http://www.ag.uiuc.edu/%7Evista/abstracts/aiapm2k.html

Muenscher, W.C. 1980. Weeds. Second Edition. Cornell University Press, New York and London. 586 pp

Munkvold, G.P., and Hellmich, R.L. 1999. Genetically modified, insect resistant corn: Implications for disease management. APSnet Feature, October 15 thru November 30, 1999. American Phytopathological Society, St. Paul, Minnesota. http://www.scisoc.org/feature/BtCorn/Top.html

OECD, 1999. Consensus Document on General Information Concerning the Genes and Their Enzymes that Confer Tolerance to Phosphinothricin Herbicide. OECD Environmental Health and Safety Publications Series on Harmonization of Regulatory Oversight in Biotechnology. ENV/JM/MONO(99)13 No. 11.

Pike, D. 1999. Environmental Toxicities and Properties of Common Herbicides. Chapter 18, pp. 309-313. In: 2000 Illinois Agricultural Pest Management Handbook. College of Agricultural, Consumer and Environmental Sciences, University of Illinois at Urbana-Champaign. University of Illinois Board of Trustees. ISBN 1-883097-25-8. Available at: http://www.ag.uiuc.edu/%7Evista/abstracts/aiapm2k.html

Raynor, G.S., Ogden, E.C., Hayes, J.V. 1972. Dispersion and deposition of corn pollen from experimental sources. Agronomy Journal 64:420-427.

Sánchez G., J.J., Ruiz C., J.A. 1997. Teosinte Distribution in Mexico. In: Gene Flow Among Maize Landraces, Improved Maize Varieties, and Teosinte: Implications for Transgenic Maize. pp. 18-39. Serratos, J.A., Willcox, M.C., and Castillo-González, F. (eds.). Mexico, D.F., CIMMYT

Smith, C.M. 1997. An overview of the mechanisms and bases of insect resistance in maize. In: Mihm, J.A. (ed.). 1997. Insect Resistant Maize: Recent Advances and Utilization; Proceedings of an International Symposium held at the International Maize and Wheat Improvement Center (CIMMYT) 27 November -3 December, 1994. Mexico, D.F.: CIMMYT.

USDA. 1999. United States Department of Agriculture, National Agricultural Statistics Service, Economic Research Service. Agricultural Chemical Usage, 1998 Field Crops Summary report AG CH 1 (99) available at http://usda.mannlib.cornell.edu/usda/

U.S. EPA, 2000a. Biopesticides Registration Action Document. Preliminary Risks and Benefits Sections. Bacillus thuringiensis Plant-Pesticides. U.S. Environmental Protection Agency, Office of Pesticide Programs, Biopesticides and Pollution Prevention Division. Available at the EPA website: http://www.epa.gov/scipoly/sap

U.S. EPA, 2000b. SAP report No 99-06, ASets of Scientific Issues being considered by the Environmental Protection Agency regarding: section I - Characterization and non target organism data requirements for protein plant pesticides@. Dated February 4, 2000. Available at the EPA website: http://www.epa.gov/scipoly/sap/1999/index.htm#December.

USFWS. 1999. Endangered Species Fact Sheet: Mitchell's Satyr Butterfly. U.S. Fish and Wildlife Service, Division of Endangered Species, Region 3, Fort Snelling, Minnesota. Available at: http://midwest.fws.gov/eco_serv/endangrd/insects/mitchell.html

USFWS. 2000a. The karner blue butterfly. U.S. Fish and Wildlife Service, Division of Endangered Species, Region 3, Fort Snelling, Minnesota. Available at: http://www.fws.gov/r3pao/eco_serv/endangrd/news/karnerbl.html

USFWS. 2000b. Wild lupine and the karner blue butterfly. U.S. Fish and Wildlife Service, Division of Endangered Species, Region 3, Fort Snelling, Minnesota. Available at: http://www.fws.gov/r3pao/eco_serv/endangrd/news/lupine.html

Van Rie, J. Jansens, S., Hofte, H., Degheele, D., Van Mellaert, H. 1989. Specificity of Bacillus thruringiensis δ-Endotoxins, Importance of Specific Receptors on the Brush Border Membrane of the Mid-Gut of Target Insects. Eur. J. Biochem. 186:239-247.

Van Rie, J. Jansens, S., Hofte, H., Degheele, D., Van Mellaert, H. 1990. Receptors on the Brush Border Membrane of the Insect MidGut as Determininants of the Specificity of Bacillus thruringiensis Delta-Endotoxins. Appl. Environ. Microbiol. 56:1378-1385.

Wilkes, H. G. 1967. Teosinte: the closest relative of maize. Bussey Inst., Harvard Univ., Cambridge, Massachusetts.

Wilkes, H. G. 1977. Hybridization of maize and teosinte in Mexico and Guatemala and the improvement of maize. Econ. Bot. 31:254-293.

Wolfersberger, M.G., Hofmann, C., Luthy, P. 1986. In Bacterial Protein Toxins. (eds. Falmagne, P., Alout, J.E., Fehrenbach, F.J., Jeljaszewics, J. And Thelestam, M.) pp. 237-238. Fischer, New York.

VIII. PREPARERS AND REVIEWERS

Permits and Risk Assessment Staff

Mike Firko, Ph.D, Assistant Director

David S. Heron, Ph.D., Biotechnologist

Karen Hokanson, Ph.D., Biotechnologist (Reviewer)

Susan Koehler, Ph.D., Biotechnologist (Preparer)

Craig Roseland, Ph.D., Biotechnologist (Reviewer and Preparer, Appendix A)

John Turner, Ph.D., Biotechnologist

James L. White, Ph.D., Senior Operations Officer

Safeguarding and Pest Management

Michael A. Lidsky, J.D., LL.M., Assistant Director

Shirley P. Ingebritsen, M.A., Regulatory Analyst (Reviewer)

IX. AGENCY CONTACT

Ms. Kay Peterson, Regulatory Analyst

USDA, APHIS, Plant Protection and Quarantine (PPQ)

4700 River Road, Unit 147

Riverdale, MD 20737-1237

Phone: (301) 734-4885

Fax: (301) 734-8669

kay.peterson@usda.gov

Appendix A: USDA Approved Field Tests of B.t. Cry1F Corn Line 1507¹

USDA Notification #

Company

Reference #

Planting Dates

Acreage²

Field Trial Location

Company

00-088-37n Notification still open. Field data report not yet submitted.³

MS132

5/13/00

5/14/00

5/23-27/00

5/24/00

5/11-25/00

5/11/00 - 6/2/00

Pending

5/12/00

5/25 & 31/00

5/22 & 29/00

21.8

19.4

23.0

19.88

21.54

15.86

1.0

6.0

18.3

13.4

Renville County, MN

“

Dakota County, MN

“

Grundy County, IA

“

Story County, IA

Fillmore County, NE

“

Mycogen

00-068-02n

Notification still open. Field data report not yet submitted.

MS123

5/4/00

5/3/00

5/6/00

4/25/00

5/3/00

5/2/00

5/3/00

5/2/00

4/27/00

5/25/00

5/23/00

4/28/00

5/5/00

5/12/00

5/22/00

5/4/00

4/29/00

5/6/00

5/22/00

5/3/2000

4/28/00

5/4/00

4/25/00

5/3/00

5/15/00

5/5/00

5/5-11/00

4/29/00

5/23/00

4/26/00

5/3/00

5/5/00

5/1/00

5/9/00

5/17/00

6/7/00

6/9/00

5/9/00

6/7/00

6/1/00

5/11/00

5/2/00

0.02

0.32

0.018

0.819

0.18

0.344

0.5

0.046

1.38

0.05

0.023

0.005

0.9

0.1

1.7

0.36

0.5

0.8

0.6

0.79

0.02

0.275

0.1

0.5

0.1

0.011

1.0

0.8

0.6

0.18

.021

1.01

0.11

1.1

0.2

0.6

0.5

0.1

0.017

0.055

0.95

Wilkin County, MN

“

Renville County, MN

“

Winona County, MN

Jackson County, MN

Brown County, MN

Sac County, IA

“

Story County, IA

“

Plymouth County, IA

Marshall County, IA

Page County, IA

Scott County, IA

Boone County, IA

Clay County, SD

Cass County, ND

Pierce County, WI

“

Columbia County, WI

“

Jefferson County, WI

Dane County, WI

York County, NE

“

Dixon County, NE

Butler County, NE

Savoy, IL

Dekalb County, IL

Champaign County, IL

“

Massac County, IL

Macon County, IL

Logan County, IL

Mycogen

USDA Notification #

Company

Reference #

Planting Dates

Acreage

Field Trial Location

Company

00-068-02n

(continued)

Notification still open. Field data report not yet submitted.

MS123

5/3/00

5/4/00

4/20/00

4/29/00

9/01/00

4/29/00

5/25/00

5/3/00

5/5/00

5/4/00

4/24/00

pending

11/22/00

5/15/00

5/31/00

8/31/00

9/12/00

9/15/00

9/25/00

4/28/00

5/8/00

5/25/00

5/02/00

5/22/00

7/8/00

5/31/00

5/1/00

6/7/00

5/10/00

pending

4/24/00

5/4/00

5/30/00

5/5/00

4/26/00

5/16/00

pending

5/15/00

5/11/00

1.14

1.2

0.64

0.0275

0.0046

0.82

0.006

0.01

1.1

0.22

0.037

0.0173

30.0

3.0

5.0

0.11

0.048

0.1

0.022

0.01

0.03

0.06

0.1

0.137

0.2

0.027

0.78

0.02

0.01

0.2

0.02

0.17

LaSalle County, IL

Knox County, IL

Tipton County, IN

Benton County, IN

“

Tippecanoe County, IN

“

Decatur County, IN

White County, IN

Moore County, TX

Swisher County, TX

Santa Isabel, PR

Oahu County, HI

Maui County, HI

(total for all plantings

is 5 acres)

Haskell County, KS

Ford County, KS

Finney County, KS

Riley County, KS

Fayette County, KY

“

Caldwell County, KY

Callaway County, MO

Holt County, MO

“

Boone County, MO

Mississippi County, MO

Pike County, MO

Saline County, MO

Ingham County, MI

Lenawee County, MI

Washington County, MS

“

Tiff County, GA

Clark County, OH

“

Weld County, CO

“

Mycogen

00-010-07n

MS121

5/11/00

0.03

Saunders County, NE only, not planted in Lancaster, Dixon, or

Clay Counties

Mycogen

USDA Notification #	Company Reference #	Planting Dates	Acreage	Field Trial Location	Company
99-357-08n Still open, report not yet submitted.	MS113	pending pending pending pending	0.5 0.3 0.3 8.9	Huxley, IA; Arlington, WI; Fowler, IN; Santa Isabel, PR	Mycogen
99-110-05n	MS083	5/14/99 5/4/99 5/12/99 5/25/99 5/3/99	0.57 0.8 0.82 0.62 1.1	Wilkin County, MN Renville County, MN Jackson County, MN Brown County, MN Winona County, MN	Mycogen
99-078-10n	MS082	5/2/99 5/4/99 5/13/99 4/30/99 5/8/99 5/3/99 5/8/99 5/11/99 5/7/99 5/1/99 5/3/99 5/4/99 5/12/99 4/30/99 4/28/99 5/12/99 5/12/99 5/19/99 5/10/99 5/27/99 5/14/99 4/22/99 5/14/99 4/26/99	3.0 1.5 1.5 0.58 0.76 0.76 1.4 0.84 1.28 2.6 0.75 0.62 1.0 0.7 0.83 0.28 1.6 0.87 0.75 0.01 0.25 2.15 0.62 0.62	Columbia County, WI Jackson County, WI Jefferson County, WI Richland County, ND Cass County, IL Champaign County, IL Scott County, IA LaSalle County, IL Dawson County, NE Story County IA Madison County, IA Pierce County, WI Sac County, IA Plymouth County, IA Calhoun County, MI Decatur County, IN Benton County, IN York County, NE Butler County, NE Clay County, SD Dixon County, NE Santa Isabel, PR Dane County, WI Cass County, ND	Mycogen
98-267-02n	MS059	12/11/98 2/17/99 4/1/99 4/5/99 4/15/99	5.28	Santa Isabel, PR (total for all plantings is 5.28 acres)	Mycogen
98-127-07n	MS052	6/6/98	0.05, 0.5	Marshalltown, IA Huxley, IA	Mycogen
98-027-02n	MS043	2/26/98 3/13/98 7/3/98 9/18/98 10/9/98 10/27/98	1.7 1.9 2.5 1.2 0.44 0.51	Santa Isabel, PR “ “ “ “ “	Mycogen
97-178-02n	MS032a	7/27/97	0.25	Del Mar, DE	Mycogen
97-059-04n	MS028	4/15/97	2.0	Huxley, IA	Mycogen
97-059-02n	MS026	7/1/97	3.0	Santa Isabel, PR	Mycogen

USDA Notification #	Company Reference #	Planting Dates	Acreage	Field Trial Location	Company
98-040-10n	CRN-US-TX-98-49	5/6/98	0.07	Hale County, TX	Pioneer
98-040-12n	CRN-US-HI-98-52	6/18/98	0.45	Kekaha, HI	Pioneer
98-040-13n	CRN-US-PR-98-75	6/1/98	0.12	Salinas, PR	Pioneer
98-072-20n 98-128-19n	CRN-US-IA-98-42 CRN-US-IA-98-	5/4/98 5/19/98	1.08	Polk County, IA “	Pioneer
98-155-01n	CRN-US-HI-98-191	7/8/98 7/27/98	0.38 0.20	Kekaha, HI “	Pioneer
98-296-03n	CRN-US-HI-98-270	3/16/98 4/16/98 6/17/98	0.009 0.001 0.001	Kekaha, HI “ “	Pioneer
99-028-01r Comprehensive permit.	CRN-US-CP-99-007	3/31/99 – 4/30/00	1.65 0.08 0.62 0.71 0.67 0.03 0.60 0.06 0.01 0.01 0.06 0.01 0.03 0.23 0.01 0.01 0.01 0.02 0.01	Kauai County, HI Kossuth County, IA Linn County, IA Polk County, IA Bureau County, IL Champaign County, IL McDonough County, IL Tipton County, IN Gratiot County, MI Kandiyohi County, MN Saline County, MO Cass County, ND York County, NE Salinas, PR Beadle County, SD Obion County, TN Hale County, TX Eau Claire, WI Rock County, WI	Pioneer

¹ Includes only those authorizations under which plantings actually took place at the time of petition submission. No plantings of line 1507 corn occurred under the notification 99-274-10n, Mycogen’s reference number MS095, in Huxley, IA; Arlington, WI; Fowler, IN; and Santa Isabel, PR.

² Acreage reflects the approximate amount planted to corn derived from line 1507.

³ Field data reports are due six months after termination of all field trials for a given notification or permit.

Unless otherwise noted, all field data reports have been submitted.

	Cry1F ¹ [Bt protein]	Dimethoate² (Cygon7) [organophosphate]	Chlorpyrifos³ (Lorsban 7) [organophosphate]	Permethrin⁴ (Ambush/Pounce7) [pyrethroid]	λ-cyhalothrin⁵ (Darate7) [pyrethroid]
Environmental Fate	Cry1F protein is expressed in minute quantities and is retained within the plant. Therefore, common modes of toxicity or routes of exposure are generally not relevant to consideration of the cumulative exposure to Bacillus thuringiensis Cry1F insect control protein. The product has demonstrated low toxicity to a large number of organisms listed in this table. In addition, the protein is not likely to be present in drinking water because the protein is deployed in minute quantities within the plant. The time-dependent loss in bioavailability of CrylF protein following incorporation into a typical maize-growing soil was determined under laboratory conditions (Halliday, 1998).The results of this study indicated that soil-applied CrylF protein exhibited a greater than 20-fold decline in biological activity over the 28-day test period. The estimated DT₅₀ was 3.13 days. These results are consistent with those for CrylA(b) protein using essentially the same experimental design; a soil DT₅₀ of 1.6 days was reported for the CrylA(b) protein.	Dimethoate is of low persistence in the soil environment. Soil half‑lives of 4 to 16 days, or as high as 122 days have been reported, but a representative value may be on the order of 20 days. Because it is rapidly broken down by soil microorganisms, it will be broken down faster in moist soils. Dimethoate is highly soluble in water, and it adsorbs only very weakly to soil particles so it may be subject to considerable leaching. However, it is degraded by hydrolysis, especially in alkaline soils, and evaporates from dry soil surfaces. Losses due to evaporation of 23 to 40% of applied dimethoate have been reported. Biodegradation may be significant, with a 77% loss reported in a nonsterile clay loam soil after 2 weeks. In water, dimethoate is not expected to adsorb to sediments or suspended particles, nor to bioaccumulate in aquatic organisms. The half‑life for dimethoate in raw river water was 8 days, with disappearance possibly due to microbial action or chemical degradation.	In soils: Chlorpyrifos is moderately persistent with a half‑life of usually 60 and 120 days, and a range from 2 wks - > 1 yr., depending on the soil type, climate, and other conditions . It was less persistent in soils with a higher pH (greater than 7.4). Soil half‑life was not affected by soil texture or organic matter content. Adsorbed chlorpyrifos is subject to degradation by UV light, chemical hydrolysis and by soil microbes. When applied to moist soils, the volatility half‑life was 45 to 163 hours, with 62 to 89% of the applied chlorpyrifos remaining on the soil after 36 hours. In another study, 2.6 and 9.3% of the chlorpyrifos applied to sand or silt loam soil remained after 30 days . Chlorpyrifos adsorbs strongly to soil particles and it is not readily soluble in water. It is therefore immobile in soils and unlikely to leach or to contaminate groundwater. TCP, the principal metabolite of chlorpyrifos, is moderately mobile and persistent in soils. In water: The concentration and persistence of chlorpyrifos will vary depending on the type of formulation. The increase in the concentration of insecticide is slower for granules and controlled release formulations in the water, but the resulting concentration persists longer . Volatilization is probably the primary route of loss of chlorpyrifos from water. Volatility half‑lives of 3.5 and 20 days have been estimated for pond water. The photolysis half‑life is 3 to 4 weeks during midsummer in the U.S. Research suggests that in water the rate at which it is hydrolyzed decreases by 2.5‑ to 3‑fold with each 10 C drop in temperature. The rate of hydrolysis increases in alkaline waters. In water at pH 7.0 and 25 C, it had a half‑life of 35 to 78 days. In vegetation: Chlorpyrifos may be toxic to some plants. Residues remain on plant surfaces for ~ 10 to 14 days. This insecticide and its soil metabolites can accumulate in certain crops.	Permethrin is of low to moderate persistence in the soil environment, with reported half‑lives of 30 to 38 days. Permethrin is readily broken down, or degraded, in most soils except organic types. Soil microorganisms play a large role in the degradation of permethrin in the soil. The addition of nutrients to soil may increase the degradation of permethrin. It has been observed that the availability of sodium and phosphorous decreases when permethrin is added to the soil. Permethrin is tightly bound by soils, especially by organic matter. Very little leaching of permethrin has been reported. It is not very mobile in a wide range of soil types. Because permethrin binds very strongly to soil particles and is nearly insoluble in water, it is not expected to leach or to contaminate groundwater. The results of one study near estuarine areas showed that permethrin had a half‑life of less than 2.5 days. When exposed to sunlight, the half‑life was 4.6 days. Permethrin degrades rapidly in water, although it can persist in sediments. Breakdown in vegetation: Permethrin is not phytotoxic, or poisonous, to most plants when it is used as directed. No incompatibility has been observed with permethrin on cultivated plants.	λ- cyhalothrin is moderately persistent in the soil environment. Reported field half‑lives range from four to 12 weeks. Its field half‑life is probably close to 30 days in most soils. It shows a high affinity for soil and so is not expected to be appreciably mobile in most soils. There is little potential for groundwater contamination. Soils with high sand content or with very low organic matter content may tend to retain the compound to a lesser degree. In field studies of Karate, leaching of λ- cyhalothrin and its degradates from the soil were minimal. Breakdown rates of both the technical product and Karate were similar under aerobic and anaerobic conditions. λ- cyhalothrin has extremely low water solubility and is tightly bound to soil, it is therefore not expected to be prevalent in surface waters. One possible source of infiltration into surface waters would be surface runoff. In this event, the compound would most probably remain bound to the solid particle and settle to the bottom.
Avian toxicity	A summary value for acute toxicity for bobwhite quail chicks shows an LC₅₀>100,000 mg of grain from Cry1F corn/kg diet (the highest concentration tested). This is equivalent to 10% or 100,000 ppm of the diet being derived from Cry1F corn.	Dimethoate is moderately to very highly toxic to birds. In Japanese quail, a 5‑day dietary LC₅₀ of 341 ppm is reported. It may be very highly toxic to other birds; reported acute oral LD₅₀ values are 41.7 to 63.5 mg/kg in mallards and 20.0 mg/kg in pheasants. Birds are not able to metabolize dimethoate as rapidly as mammals do, which may account for its relatively higher toxicity in these species.	Chlorpyrifos is moderately to very highly toxic to birds. Its oral LD₅₀ is 8.41 mg/kg in pheasants, 112 mg/kg in mallard ducks, 21.0 mg/kg in house sparrows, and 32 mg/kg in chickens. The LD₅₀ for a granular product (15G) in bobwhite quail is 108 mg/kg. At 125 ppm, mallards laid significantly fewer eggs. There was no evidence of changes in weight gain, or in the number, weight, and quality of eggs produced by hens fed dietary levels of 50 ppm of chlorpyrifos.	Effects on birds: Permethrin is practically non‑toxic to birds. The oral LD₅₀ for the permethrin formulation, Pramex, is greater than 9900 mg/kg in mallard ducks, greater than 13,500 mg/kg in pheasants, and greater than 15,500 mg/kg in Japanese quail.	λ- cyhalothrin's toxicity to birds ranges from slightly toxic to practically non‑toxic. In the mallard duck, the reported oral LD₅₀ is greater than 3,950 mg/kg, and the reported dietary LC₅₀ is 3,948 ppm. In bobwhite quail the reported dietary LC₅₀ is greater than 500 ppm. There is evidence that it does not accumulate in the eggs or tissues of birds.
Aquatic Data	There is no evidence for sensitivity of endangered aquatic species to Cry1F delta endotoxin. Low potential for exposure to Cry1F through drifting Cry1F maize pollen or other tissues derived from Cry1F maizeand toxicity studies with aquatic invertebrates show very limited hazard for fish or invertebrates exposed to Cry1F. The measured effect level (EC₅₀) for the 48 hr. acute dietary toxicity study with Daphnia magna was greater than 100 mg Cry1F pollen/liter. This level is several fold higher than the estimated concentration of 1.25 μg Cry1F/liter from pollen drift into fresh water ponds.	Dimethoate is moderately toxic to fish, with reported LC₅₀ values of 6.2 mg/L in rainbow trout, and 6.0 mg/L in bluegill sunfish. It is more toxic to aquatic invertebrate species such as stoneflies and scuds.	Chlorpyrifos is very highly toxic to freshwater fish, aquatic invertebrates and estuarine and marine organisms. Cholinesterase inhibition was observed in acute toxicity tests of fish exposed to very low concentrations of this insecticide. Application of concentrations as low as 0.01 pounds of active ingredient per acre may cause fish and aquatic invertebrate deaths. Chlorpyrifos toxicity to fish may be related to water temperature. The 96‑hour LC₅₀ for chlorpyrifos is 0.009 mg/L in mature rainbow trout, 0.098 mg/L in lake trout, 0.806 mg/L in goldfish, 0.01 mg/L in bluegill, and 0.331 mg/L in fathead minnow]. Chlorpyrifos accumulates in the tissues of aquatic organisms. Studies involving continuous exposure of fish during the embryonic through fry stages have shown bioconcentration values of 58 to 5100. Due to its high acute toxicity and its persistence in sediments, chlorpyrifos may represent a hazard to sea bottom dwellers. Smaller organisms appear to be more sensitive than larger ones .	Effects on aquatic organisms: Aquatic ecosystems are particularly vulnerable to the impact of permethrin. A fragile balance exists between the quality and quantity of insects and other invertebrates that serve as fish food. The 48‑hour LC₅₀ for rainbow trout is 0.0125 mg/L for 24 hours, and 0.0054 mg/L for 48 hours. As a group, synthetic pyrethroids were toxic to all estuarine species tested. They had a 96‑hour LC₅₀ of less than or equal to 0.0078 mg/L for these species. The compound has a low to moderate potential to accumulate in these organisms.	λ- cyhalothrin is very highly toxic to many fish and aquatic invertebrate species. Reported LC₅₀ in these species are as follows: bluegill sunfish, 0.21 μg/L; rainbow trout, 0.24 μg/L; Daphnia magna, 0.36 μg/L; mysid shrimp, 4.9 ng/L; sheepshead minnow, 0.807 ng/L. Bioconcentration is possible in aquatic species, but bioaccumulation is not likely. Bioconcentration in channel catfish has been reported as minimal, with rapid depuration (elimination). A bioconcentration factor of 858 has been reported in fish (species unspecified), but concentration was confined to non‑edible tissues and rapid depuration was observed.
Nontarget and beneficial insects	Results indicated that Cry1F delta endotoxin (produced microbially) has an acute LC₅₀ greater than 320 μg Cry 1F/g diet for parasitic hymenoptera (Nasonia vitripennis), and an acute LC₅₀ greater than 480 μg Cry 1F/g diet for green lacewing (Chrysopa carnea) and lady bird beetle (Hippodamia convergens). These concentrations are several fold higher than the upper bound estimate of 32 μg Cry 1F/g pollen derived from line 1507 corn, and indicate low potential for toxicity due to exposure.	Survival of Microplitis croceipes (Cresson) adults, parasitoids of the cotton pests H.zea and H.virescens, exposed to residues of insecticides applied at recommended rates to cotton was measured in 1989. In unsprayed cheek treatments, survival was 91.4% after 24 h. The organophosphates profenofos and acephate and the new‑generation pyrethroid bifenthrin were highly toxic to M. croceipes. All other compounds tested showed some selectivity, including esfenvalerate, cypermethrin, thiodicarb, oxamyl, dicrotophos, dimethoate, and cyhalothrin in order of decreasing survival. The effectiveness of M. croceipes as a biocontrol agent of the bollworm and tobacco budworm might be improved through selective use of insecticides to which the parasitoid is tolerant.	Aquatic and general agricultural uses of chlorpyrifos pose a serious hazard to wildlife and honeybees.	Effects on other organisms: Permethrin is toxic to wildlife. It should not be applied, or allowed to drift, to crops or weeds in which active foraging takes place. The International Organization for Biological Control tested the acute toxicity of permethrin to 13 species of beneficial arthropods and found that permethrin caused 99 percent mortality of 12 of the species, and over 80 percent mortality of the other. Effects were persistent, lasting over 30 days. Sublethal doses also impact beneficial arthropods: permethrin inhibited the emergence of a parasitoid wasp from eggs of the rice moth Corcyra cephalonica and disrupted the foraging pattern of another parasitoid wasp as it searched for its aphid prey.	Data not available from sources consulted.
Honeybee toxicity	A petition by Dow-Mycogen to deregulate Cry1F maize contains details of this analysis in a CBI appendix, and the petition summary indicates an acute dietary toxicity (honeybees) LD₅₀> 640 ng Cry1F/larvae.	Dimethoate is highly toxic to honeybees. The 24‑hour topical LD₅₀ for dimethoate in bees is 0.12 μg per bee	Aquatic and general agricultural uses of chlorpyrifos pose a serious hazard to honeybees.	Permethrin is extremely toxic to bees. Severe losses may be expected if bees are present at treatment time, or within a day thereafter.	λ- cyhalothrin is highly toxic to bees, with a reported oral LD₅₀ of 38 ng/bee and reported contact LD₅₀ of 909 ng/bee (0.9 μg/bee).
Nontarget soil organisms	A 28-day study to determine the chronic effects of microbially-derived CrylF protein on survival and reproduction of Collembola was conducted with three treatment levels of the CrylF test substance (0.63, 3.1, and 12.5 mg/kg of test diet). At the conclusion of the test, there was less than 10% mortality associated with exposure to either the CrylF protein test substance or the assay control. Reproduction of Collembola was not significantly affected by exposure to the test substance when compared to the assay control. No mortality and no reduction in the number of progeny was observed following exposure to the test materials for 28 days. The results of this study indicate Collembola were not affected by chronic exposure to CrylF at treatment levels exceeding those expected to be found in maize fields based on the calculated worst-case, post-harvest exposure estimates of 0.350 mg Cry1F protein/kg of whole plant material at senescence or 0.063 mg Cry1F protein/kg dry soil. Acute toxicity for earthworm was established by exposure to microbially-produced Cry1F protein in soil. The LC₅₀ was > 2.5 mg Cry1F/kg dry soil. This concentration is also considerably higher than the worst-case estimate of Cry1F post-harvest exposure in the soil.	A study of the effects of soil moisture and toxicity of dimethoate was conducted with an enchytraeid worm. Laboratory experiments used dimethoate and small Enchytraeus sp. as the test species. Substrate was natural agricultural field soil cultivated without pesticides for several years. Experimental design consisted of three soil moistures (40, 55, and 70% of water holding capacity) and five pesticide concentrations, plus controls. Measured parameters were survival, size of the parent worms and number and size of juveniles produced. Dimethoate was relatively non‑toxic to this species. Dimethoate did not decrease survival, but sublethal effects on adult size and number of juveniles were observed. Adverse conditions in dry soil masked these effects; dimethoate appeared to be less toxic in dry soil than in moist soil.	Data not found in sources consulted.	Data not found in sources consulted.	Data not found in sources consulted
EPA toxicity class (Class I -highly toxic to Class IV-relatively nontoxic)	Not yet assigned.	Dimethoate is a moderately toxic compound in EPA toxicity class II. Labels for products containing dimethoate must bear the Signal Word WARNING. Dimethoate is a General Use Pesticide (GUP).	Chlorpyrifos is toxicity class II ‑ moderately toxic. Products containing chlorpyrifos bear the Signal Word WARNING or CAUTION, depending on the toxicity of the formulation. It is classified as a General Use Pesticide (GUP). The EPA has established a 24‑hour reentry interval for crop areas treated with emulsifiable concentrate or wettable powder formulations of chlorpyrifos unless workers wear protective clothing.	Permethrin is a moderately to practically non‑toxic pesticide in EPA toxicity class II or III, depending on the formulation. Formulations are placed in class II due to their potential to cause eye and skin irritation. Products containing permethrin must bear the Signal Word WARNING or CAUTION, depending on the toxicity of the particular formulation. All products for agricultural uses (except livestock and premises uses) are Restricted Use Pesticides (RUPs) because of their possible adverse effects on aquatic organisms.	λ- cyhalothrin is a Restricted Use Pesticide and so may be purchased and used only by certified applicators. It is in EPA Toxicity Class II, and products containing it must bear the signal word WARNING.
EDF - Integrated Environmental Rankings⁶ - Combined human & ecological scores	not ranked	65 to 100% ranked.on the least to most hazardous scale with 100% being the most hazardous	50 to 75%	0 to 25%	not ranked
Mammalian toxicity	Toxicology studies conducted to determine the toxicity of Cry1F insect control protein demonstrated that the protein has very low toxicity. In an acute oral toxicity study in the mouse, the estimated acute LD₅₀ by gavage was determined to be >5,050 mg of the microbially produced test substance containing 576 mg Cry1F/kg body weight. This dose is 12,190 x greater than the estimated 95th percentile for human dietary exposure to Cry1F protein resulting from consumption of foods derived from Cry1F protected corn. In an in vitro study, Cry1F protein was rapidly and extensively degraded in simulated gastric conditions in the presence of pepsin. This indicates that the potential for adverse health effects from chronic exposure is virtually nonexistent. A search of relevant databases indicated that the amino acid sequence of the Cry1F protein exhibits no significant homology to the sequences of known allergens or protein toxins. Thus, Cry1F is highly unlikely to exhibit an allergic response. Collectively, the available data on Cry1F protein along with the safe use history of microbial Bacillus thuringiensis products establishes the safety of the plant pesticide Bacillus thuringiensis subspecies aizawai Cry1F insect control protein and the genetic material necessary for its production in all raw agricultural commodities.	Acute toxicity: Dimethoate is moderately toxic by ingestion, inhalation, and dermal absorption. The reported acute oral LD₅₀ values for the technical product range from 180 to 330 mg/kg in the rat; although an oral LD₅₀ of as low as 28 to 30 mg/kg has been reported. Reported dermal LD₅₀ values for dimethoate are 100 to 600 mg/kg in rats, again with a much lower value for an earlier product . Dimethoate is reportedly not irritating to the skin and eyes of lab animals. Severe eye irritation has occurred in workers manufacturing dimethoate, although this may be due to impurities. Via the inhalation route, the reported 4‑hour LC₅₀ is greater than 2.0 mg/L, indicating slight toxicity. Effects of acute exposure are those typical of organophosphates. Chronic toxicity: There was no cholinesterase inhibition in an adult human who ingested dimethoate for 21 days. No toxic effects and no cholinesterase inhibition were observed in individuals who ingested dimethoate for 4 weeks. Repeated or prolonged exposure to organophosphates may result in the same effects as acute exposure, including the delayed symptoms. Reproductive effects: When mice were given 9.5 to 10.5 mg/kg/day dimethoate in their drinking water, there was decreased reproduction, pup survival, and growth rates of surviving pups. Teratogenic effects: Dimethoate is teratogenic in cats and rats. It is not likely that teratogenic effects will be seen in humans under normal circumstances. Mutagenic effects: Mutagenic effects due to dimethoate exposure were seen in mice. Mutagenic effects are unlikely in humans under normal circumstances. Carcinogenic effects: An increase in malignant tumors was reported in rats given oral doses of dimethoate for over a year; but the increases were not dose dependent. Thus the evidence of carcinogenicity, even with high‑dose, long‑term exposure, is inconclusive. This suggests carcinogenic effects in humans are unlikely. Fate in humans and animals: Dimethoate is rapidly metabolized by mammals.	Acute toxicity: Chlorpyrifos is moderately toxic to humans. Poisoning may affect the central nervous system, the cardiovascular system, and the respiratory system. It is also a skin and eye irritant. Studies in humans suggest that skin absorption of chlorpyrifos is limited. The oral LD₅₀ for chlorpyrifos in rats is 95 to 270mg/kg, 60 mg/kg in mice,1000 mg/kg in rabbits, 32 mg/kg in chickens, 500 to 504 mg/kg in guinea pigs, and 800 mg/kg in sheep. The dermal LD₅₀ is greater than 2000 mg/kg in rats, and 1000 to 2000 mg/kg in rabbits. The 4‑hour inhalation LC₅₀ for chlorpyrifos in rats is greater than 0.2 mg/L. Chronic toxicity: Repeated or prolonged exposure to organophosphates may result in the same effects as acute exposure including the delayed symptoms. Human volunteers who ingested for 4 weeks 0.1mg/kg/day of chlorpyrifos showed significant plasma cholinesterase inhibition. Reproductive effects: Current evidence indicates that chlorpyrifos does not adversely affect reproduction. No effects were seen in 2 studies where animals were tested at doses up to 1.2 mg/kg/day. Teratogenic effects: Available evidence suggests that chorpyrifos is not teratogenic. Three studies in pregnant rats or mice indicate that no significant teratogenic effects were seen at doses up to 25 mg/kg/day for 10 days. Mutagenic effects: No evidence was found in any of four tests performed that chlorpyrifos is mutagenic. Carcinogenic effects: There is no evidence that chlorpyrifos is carcinogenic. There was noincrease in the incidence of tumors when rats were fed 10 mg/kg/day for 104 weeks. Fate in humans and animals: Chlorpyrifos is readily absorbed into the bloodstream through the gastro-intestinal tract if it is ingested, through the lungs if it is inhaled, or through the skin if there is dermal exposure. In humans, chlorpyrifos and its principal metabolites are eliminated rapidly. After a single oral dose, the half‑life of chlorpyrifos in the blood appears to be about 1 day.	Acute toxicity: Permethrin is moderately to practically non‑toxic via the oral route. Via the dermal route, it is slightly toxic, with a reported dermal LD₅₀ in rats of over 4000 mg/kg, and in rabbits of greater 2000 mg/kg. Permethrin caused mild irritation of both the intact and abraded skin of rabbits. It also caused conjunctivitis when it was applied to the eyes. The 4‑hour inhalation LC₅₀ for rats was greater than 23.5 mg/L, indicating practically no inhalation toxicity. Chronic toxicity: No adverse effects were observed in dogs fed permethrin at doses of 5 mg/kg/day for 90 days. Rats fed 150 mg/kg/day for 6 months showed a slight increase in liver weights. Reproductive effects: The fertility of female rats was affected when they received very high oral doses of 250 mg/kg/day of permethrin during the 6th to 15th day of pregnancy. It is not likely that reproductive effects will be seen in humans under normal circumstances. Teratogenic effects: Permethrin is reported to show no teratogenic activity. Mutagenic effects: Permethrin is reported to show no mutagenic activity. Carcinogenic effects: The evidence regarding the carcinogenicity of permethrin is inconclusive. Organ toxicity: Permethrin is suspected of causing liver enlargement and nerve damage. Fate in humans and animals: Permethrin is efficiently metabolized by mammalian livers. Breakdown products, or "metabolites," of permethrin are quickly excreted and do not persist significantly in body tissues. Permethrin may persist in fatty tissues, with half‑lives of 4 to 5 days in brain and body fat.	λ- cyhalothrin is moderately toxic in the technical form, but may be highly toxic via some routes in formulation (e.g., as Karate). Cyhalothrin is moderately toxic via the oral route in test animals. Data indicate a moderate to high toxicity via the inhalation route for the formulated product Karate. It may cause mild eye irritation in rabbits. Chronic Toxicity: The principal toxic effects noted in chronic studies with rates were decreased body weight gain and decreased food consumption. It is unlikely that cyhalothrin would cause chronic effects in humans under normal conditions. Reproductive Effects: Cyhalothrin caused reduced numbers of viable offspring at doses of 50 mg/kg/day in the second and third generations in the three-generational rat study noted above. It is unlikely that cyhalothrin would cause reproductive effects in humans under normal conditions. Teratogenic Effects: No teratogenic or fetotoxic effects were observed in teratology studies of lambda cyhalothrin in rats and rabbits at the highest doses tested in both species (15 mg/kg/day and 30 mg/kg/day, respectively). Mutagenic Effects: Cyhalothrin produced negative results in Ames mutagenicity assays and other in-vitro cytogenetic assays and chromosomal structural aberration tests indicated no mutagenic or genotoxic effects. Carcinogenic Effects: Evidence is inconclusive, but suggests that it is probably not carcinogenic. Organ Toxicity: No specific target organs or organ systems have been identified in the available studies of chronic toxicity. Fate in Humans & Animals: In rat studies, lambda cyhalothrin is rapidly metabolized and excreted via the urine and feces.

Cry1F ¹

[Bt protein]

Dimethoate²

(Cygon7)

[organophosphate]

Chlorpyrifos³

(Lorsban 7)

[organophosphate]

Permethrin⁴ (Ambush/Pounce7)

[pyrethroid]

λ-cyhalothrin⁵ (Darate7)

[pyrethroid]

Environmental

Fate

Cry1F protein is expressed in minute quantities and is retained within the plant. Therefore, common modes of toxicity or routes of exposure are generally not relevant to consideration of the cumulative exposure to Bacillus thuringiensis Cry1F insect control protein. The product has demonstrated low toxicity to a large number of organisms listed in this table. In addition, the protein is not likely to be present in drinking water because the protein is deployed in minute quantities within the plant. The time-dependent loss in bioavailability of CrylF protein following incorporation into a typical maize-growing soil was determined under laboratory conditions (Halliday, 1998).The results of this study indicated that soil-applied CrylF protein exhibited a greater than 20-fold decline in biological activity over the 28-day test period. The estimated DT₅₀ was 3.13 days. These results are consistent with those for CrylA(b) protein using essentially the same experimental design; a soil DT₅₀ of 1.6 days was reported for the CrylA(b) protein.

Dimethoate is of low persistence in the soil environment. Soil half‑lives of 4 to 16 days, or as high as 122 days have been reported, but a representative value may be on the order of 20 days. Because it is rapidly broken down by soil microorganisms, it will be broken down faster in moist soils. Dimethoate is highly soluble in water, and it adsorbs only very weakly to soil particles so it may be subject to considerable leaching. However, it is degraded by hydrolysis, especially in alkaline soils, and evaporates from dry soil surfaces. Losses due to evaporation of 23 to 40% of applied dimethoate have been reported. Biodegradation may be significant, with a 77% loss reported in a nonsterile clay loam soil after 2 weeks. In water, dimethoate is not expected to adsorb to sediments or suspended particles, nor to bioaccumulate in aquatic organisms. The half‑life for dimethoate in raw river water was 8 days, with disappearance possibly due to microbial action or chemical degradation.

In soils: Chlorpyrifos is moderately persistent with a half‑life of usually 60 and 120 days, and a range from 2 wks - > 1 yr., depending on the soil type, climate, and other conditions . It was less persistent in soils with a higher pH (greater than 7.4). Soil half‑life was not affected by soil texture or organic matter content. Adsorbed chlorpyrifos is subject to degradation by UV light, chemical hydrolysis and by soil microbes. When applied to moist soils, the volatility half‑life was 45 to 163 hours, with 62 to 89% of the applied chlorpyrifos remaining on the soil after 36 hours. In another study, 2.6 and 9.3% of the chlorpyrifos applied to sand or silt loam soil remained after 30 days . Chlorpyrifos adsorbs strongly to soil particles and it is not readily soluble in water. It is therefore immobile in soils and unlikely to leach or to contaminate groundwater. TCP, the principal metabolite of chlorpyrifos, is moderately mobile and persistent in soils.

In water: The concentration and persistence of chlorpyrifos will vary depending on the type of formulation. The increase in the concentration of insecticide is slower for granules and controlled release formulations in the water, but the resulting concentration persists longer . Volatilization is probably the primary route of loss of chlorpyrifos from water. Volatility half‑lives of 3.5 and 20 days have been estimated for pond water. The photolysis half‑life is 3 to 4 weeks during midsummer in the U.S. Research suggests that in water the rate at which it is hydrolyzed decreases by 2.5‑ to 3‑fold with each 10 C drop in temperature. The rate of hydrolysis increases in alkaline waters. In water at pH 7.0 and 25 C, it had a half‑life of 35 to 78 days.

In vegetation: Chlorpyrifos may be toxic to some plants. Residues remain on plant surfaces for ~ 10 to 14 days. This insecticide and its soil metabolites can accumulate in certain crops.

Permethrin is of low to moderate persistence in the soil environment, with reported half‑lives of 30 to 38 days. Permethrin is readily broken down, or degraded, in most soils except organic types. Soil microorganisms play a large role in the degradation of permethrin in the soil. The addition of nutrients to soil may increase the degradation of permethrin. It has been observed that the availability of sodium and phosphorous decreases when permethrin is added to the soil. Permethrin is tightly bound by soils, especially by organic matter. Very little leaching of permethrin has been reported. It is not very mobile in a wide range of soil types. Because permethrin binds very strongly to soil particles and is nearly insoluble in water, it is not expected to leach or to contaminate groundwater.

The results of one study near estuarine areas showed that permethrin had a half‑life of less than 2.5 days. When exposed to sunlight, the half‑life was 4.6 days. Permethrin degrades rapidly in water, although it can persist in sediments.

Breakdown in vegetation: Permethrin is not phytotoxic, or poisonous, to most plants when it is used as directed. No incompatibility has been observed with permethrin on cultivated plants.

λ- cyhalothrin is moderately persistent in the soil environment. Reported field half‑lives range from four to 12 weeks. Its field half‑life is probably close to 30 days in most soils. It shows a high affinity for soil and so is not expected to be appreciably mobile in most soils. There is little potential for groundwater contamination. Soils with high sand content or with very low organic matter content may tend to retain the compound to a lesser degree. In field studies of Karate, leaching of λ- cyhalothrin and its degradates from the soil were minimal. Breakdown rates of both the technical product and Karate were similar under aerobic and anaerobic conditions.

λ- cyhalothrin has extremely low water solubility and is tightly bound to soil, it is therefore not expected to be prevalent in surface waters. One possible source of infiltration into surface waters would be surface runoff. In this event, the compound would most probably remain bound to the solid particle and settle to the bottom.

Avian toxicity

A summary value for acute toxicity for bobwhite quail chicks shows an LC₅₀>100,000 mg of grain from Cry1F corn/kg diet (the highest concentration tested). This is equivalent to 10% or 100,000 ppm of the diet being derived from Cry1F corn.

Dimethoate is moderately to very highly toxic to birds. In Japanese quail, a 5‑day dietary LC₅₀ of 341 ppm is reported. It may be very highly toxic to other birds; reported acute oral LD₅₀ values are 41.7 to 63.5 mg/kg in mallards and 20.0 mg/kg in pheasants. Birds are not able to metabolize dimethoate as rapidly as mammals do, which may account for its relatively higher toxicity in these species.

Chlorpyrifos is moderately to very highly toxic to birds. Its oral LD₅₀ is 8.41 mg/kg in pheasants, 112 mg/kg in mallard ducks, 21.0 mg/kg in house sparrows, and 32 mg/kg in chickens. The LD₅₀ for a granular product (15G) in bobwhite quail is 108 mg/kg. At 125 ppm, mallards laid significantly fewer eggs. There was no evidence of changes in weight gain, or in the number, weight, and quality of eggs produced by hens fed dietary levels of 50 ppm of chlorpyrifos.

Effects on birds: Permethrin is practically non‑toxic to birds. The oral LD₅₀ for the permethrin formulation, Pramex, is greater than 9900 mg/kg in mallard ducks, greater than 13,500 mg/kg in pheasants, and greater than 15,500 mg/kg in Japanese quail.

λ- cyhalothrin's toxicity to birds ranges from slightly toxic to practically non‑toxic. In the mallard duck, the reported oral LD₅₀ is greater than 3,950 mg/kg, and the reported dietary LC₅₀ is 3,948 ppm. In bobwhite quail the reported dietary LC₅₀ is greater than 500 ppm. There is evidence that it does not accumulate in the eggs or tissues of birds.

Aquatic Data

There is no evidence for sensitivity of endangered aquatic species to Cry1F delta endotoxin. Low potential for exposure to Cry1F through drifting Cry1F maize pollen or other tissues derived from Cry1F maizeand toxicity studies with aquatic invertebrates show very limited hazard for fish or invertebrates exposed to Cry1F. The measured effect level (EC₅₀) for the 48 hr. acute dietary toxicity study with Daphnia magna was greater than 100 mg Cry1F pollen/liter. This level is several fold higher than the estimated concentration of 1.25 μg Cry1F/liter from pollen drift into fresh water ponds.

Dimethoate is moderately toxic to fish, with reported LC₅₀ values of 6.2 mg/L in rainbow trout, and 6.0 mg/L in bluegill sunfish. It is more toxic to aquatic invertebrate species such as stoneflies and scuds.

Chlorpyrifos is very highly toxic to freshwater fish, aquatic invertebrates and estuarine and marine organisms. Cholinesterase inhibition was observed in acute toxicity tests of fish exposed to very low concentrations of this insecticide. Application of concentrations as low as 0.01 pounds of active ingredient per

acre may cause fish and aquatic invertebrate deaths. Chlorpyrifos toxicity to fish may be related to water temperature. The 96‑hour LC₅₀ for chlorpyrifos is 0.009 mg/L in mature

rainbow trout, 0.098 mg/L in lake trout, 0.806 mg/L in goldfish, 0.01 mg/L in bluegill, and 0.331 mg/L in fathead minnow]. Chlorpyrifos accumulates in the tissues of aquatic organisms. Studies involving continuous exposure of fish during the embryonic through fry stages have shown bioconcentration values of 58 to 5100. Due to its high acute toxicity and its persistence in sediments, chlorpyrifos may represent a hazard to sea bottom dwellers. Smaller organisms appear to be more sensitive than larger ones .

Effects on aquatic organisms: Aquatic ecosystems are particularly vulnerable to the impact of permethrin. A fragile balance exists between the quality and quantity of insects and other invertebrates that serve as fish food. The 48‑hour LC₅₀ for rainbow trout is 0.0125 mg/L for 24 hours, and 0.0054 mg/L for 48 hours. As a group, synthetic pyrethroids were toxic to all estuarine species tested. They had a 96‑hour LC₅₀ of less than or equal to 0.0078 mg/L for these species. The compound has a low to moderate potential to accumulate in these organisms.

λ- cyhalothrin is very highly toxic to many fish and aquatic

invertebrate species. Reported LC₅₀ in these species are as follows: bluegill sunfish, 0.21 μg/L; rainbow trout, 0.24 μg/L; Daphnia magna, 0.36 μg/L; mysid shrimp, 4.9 ng/L; sheepshead minnow, 0.807 ng/L. Bioconcentration is possible in aquatic species, but bioaccumulation is not likely. Bioconcentration in channel catfish has been reported as minimal, with rapid depuration (elimination). A bioconcentration factor of 858 has been reported in fish (species unspecified), but concentration was confined to non‑edible tissues and rapid depuration was observed.

Nontarget and beneficial insects

Results indicated that Cry1F delta endotoxin (produced microbially) has an acute LC₅₀ greater than 320 μg Cry 1F/g diet for parasitic hymenoptera (Nasonia vitripennis), and an acute LC₅₀ greater than 480 μg Cry 1F/g diet for green lacewing (Chrysopa carnea) and lady bird beetle (Hippodamia convergens). These concentrations are several fold higher than the upper bound estimate of 32 μg Cry 1F/g pollen derived from line 1507 corn, and indicate low potential for toxicity due to exposure.

Survival of Microplitis croceipes (Cresson) adults, parasitoids of the cotton pests H.zea and H.virescens, exposed to residues of insecticides applied at recommended rates to cotton was measured in 1989. In unsprayed cheek treatments, survival was 91.4% after 24 h. The organophosphates profenofos and acephate and the new‑generation pyrethroid bifenthrin were highly toxic to M. croceipes. All other compounds tested showed some selectivity, including esfenvalerate, cypermethrin, thiodicarb, oxamyl, dicrotophos, dimethoate, and cyhalothrin in order of decreasing survival. The effectiveness of M. croceipes as a biocontrol agent of the bollworm and tobacco budworm might be

improved through selective use of insecticides to which the parasitoid is tolerant.

Aquatic and general agricultural uses of chlorpyrifos pose a serious hazard to wildlife and honeybees.

Effects on other organisms: Permethrin is toxic to wildlife. It should not be applied, or allowed to drift, to crops or weeds in which active foraging takes place.

The International Organization for Biological Control tested the acute toxicity of permethrin to 13 species of beneficial arthropods and found that permethrin caused 99 percent mortality of 12 of the species, and over 80 percent mortality of the other. Effects were persistent, lasting over 30 days. Sublethal doses also impact beneficial arthropods: permethrin inhibited the emergence of a parasitoid wasp from eggs of the rice moth Corcyra cephalonica and disrupted the foraging pattern of another parasitoid wasp as it searched for its aphid prey.

Data not available from sources consulted.

Honeybee toxicity

A petition by Dow-Mycogen to deregulate Cry1F maize contains details of this analysis in a CBI appendix, and the petition summary indicates an acute dietary toxicity (honeybees) LD₅₀> 640 ng Cry1F/larvae.

Dimethoate is highly toxic to honeybees. The 24‑hour topical LD₅₀ for dimethoate in bees is 0.12 μg per bee

Aquatic and general agricultural uses of chlorpyrifos pose a serious hazard to honeybees.

Permethrin is extremely toxic to bees. Severe losses may be expected if bees are present at treatment time, or within a day thereafter.

λ- cyhalothrin is highly toxic to bees, with a reported oral LD₅₀ of 38 ng/bee and reported contact LD₅₀ of 909 ng/bee (0.9 μg/bee).

Nontarget soil organisms

A 28-day study to determine the chronic effects of microbially-derived CrylF protein on survival and reproduction of Collembola was conducted with three treatment levels of the CrylF test substance (0.63, 3.1, and 12.5 mg/kg of test diet). At the conclusion of the test, there was less than 10% mortality associated with exposure to either the CrylF protein test substance or the assay control. Reproduction of Collembola was not significantly affected by exposure to the test substance when compared to the assay control. No mortality and no reduction in the number of progeny was observed following exposure to the test materials for 28 days. The results of this study indicate Collembola were not affected by chronic exposure to CrylF at treatment levels exceeding those expected to be found in maize fields based on the calculated worst-case, post-harvest exposure estimates of 0.350 mg Cry1F protein/kg of whole plant material at senescence or 0.063 mg Cry1F protein/kg dry soil.

Acute toxicity for earthworm was established by exposure to microbially-produced Cry1F protein in soil. The LC₅₀ was > 2.5 mg Cry1F/kg dry soil. This concentration is also considerably higher than the worst-case estimate of Cry1F post-harvest exposure in the soil.

A study of the effects of soil moisture and toxicity of dimethoate was conducted with an enchytraeid worm. Laboratory experiments used dimethoate and small Enchytraeus sp. as the test species.

Substrate was natural agricultural field soil cultivated without pesticides for several years. Experimental design consisted of

three soil moistures (40, 55, and 70% of water holding capacity) and five pesticide concentrations, plus controls. Measured

parameters were survival, size of the parent worms and number and size of juveniles produced. Dimethoate was relatively non‑toxic to this species. Dimethoate did not decrease survival, but sublethal effects on adult size and number of juveniles were observed. Adverse conditions in dry soil masked these effects; dimethoate appeared to be less toxic in dry soil than in

moist soil.

Data not found in sources consulted.

Data not found in sources consulted

EPA toxicity class

(Class I -highly toxic to Class IV-relatively nontoxic)

Not yet assigned.

Dimethoate is a moderately toxic compound in EPA toxicity class II. Labels for products containing dimethoate must bear the Signal Word WARNING. Dimethoate is a General Use Pesticide (GUP).

Chlorpyrifos is toxicity class II ‑ moderately toxic. Products

containing chlorpyrifos bear the Signal Word WARNING or CAUTION, depending on the

toxicity of the formulation. It is classified as a General Use Pesticide (GUP). The EPA has established a 24‑hour reentry interval for crop areas

treated with emulsifiable concentrate or wettable powder formulations of chlorpyrifos unless

workers wear protective clothing.

Permethrin is a moderately to practically non‑toxic pesticide in EPA toxicity class II or III, depending on the formulation. Formulations are placed in class II due to their potential to cause eye and skin irritation. Products containing permethrin must bear the Signal Word WARNING or CAUTION, depending on the toxicity of the particular formulation. All products for agricultural uses (except livestock and premises uses) are Restricted Use Pesticides (RUPs) because of their possible adverse effects on aquatic organisms.

λ- cyhalothrin is a Restricted Use Pesticide and so may be purchased and used only by certified applicators. It is in EPA Toxicity Class II, and products containing it must bear the signal word WARNING.

EDF - Integrated Environmental Rankings⁶ -

Combined human & ecological scores

not ranked

65 to 100% ranked.on the least to most hazardous scale with 100% being the most hazardous

50 to 75%

0 to 25%

not ranked

Mammalian toxicity

Toxicology studies conducted to determine the toxicity of Cry1F insect control protein demonstrated that the protein has very low toxicity. In an acute oral toxicity study in the mouse, the estimated acute LD₅₀ by gavage was determined to be >5,050 mg of the microbially produced test substance containing 576 mg Cry1F/kg body weight. This dose is 12,190 x greater than the estimated 95th percentile for human dietary exposure to Cry1F protein resulting from consumption of foods derived from Cry1F protected corn. In an in vitro study, Cry1F protein was rapidly and extensively degraded in simulated gastric conditions in the presence of pepsin. This indicates that the potential for adverse health effects from chronic exposure is virtually nonexistent. A search of relevant databases indicated that the amino acid sequence of the Cry1F protein exhibits no significant homology to the sequences of known allergens or protein toxins. Thus, Cry1F is highly unlikely to exhibit an allergic response. Collectively, the available data on Cry1F protein along with the safe use history of microbial Bacillus thuringiensis products establishes the safety of the plant pesticide Bacillus thuringiensis subspecies aizawai Cry1F insect control protein and the genetic material necessary for its production in all raw agricultural commodities.

Acute toxicity: Dimethoate is moderately toxic by ingestion, inhalation, and dermal absorption. The reported acute oral LD₅₀ values for the technical product range from 180 to 330 mg/kg in the rat; although an oral LD₅₀ of as low as 28 to 30 mg/kg has been reported. Reported dermal LD₅₀ values for dimethoate are 100 to 600 mg/kg in rats, again with a much lower value for an earlier product . Dimethoate is reportedly not irritating to the skin and eyes of lab animals. Severe eye irritation has occurred in workers manufacturing dimethoate, although this may be due to impurities. Via the inhalation route, the reported 4‑hour LC₅₀ is greater than 2.0 mg/L, indicating slight toxicity. Effects of acute exposure are those typical of organophosphates.

Chronic toxicity: There was no cholinesterase inhibition in an adult human who ingested dimethoate for 21 days. No toxic effects and no cholinesterase inhibition were observed in individuals who ingested dimethoate for 4 weeks. Repeated or prolonged exposure to organophosphates may result in the same effects as acute exposure, including the delayed symptoms.

Reproductive effects: When mice were given 9.5 to 10.5 mg/kg/day dimethoate in their drinking water, there was decreased reproduction, pup survival, and growth rates of surviving pups.

Teratogenic effects: Dimethoate is teratogenic in cats and rats. It is not likely that teratogenic effects will be seen in humans under normal circumstances. Mutagenic effects: Mutagenic effects due to dimethoate exposure were seen in mice. Mutagenic effects are unlikely in humans under normal circumstances.

Carcinogenic effects: An increase in malignant tumors was reported in rats given oral doses of dimethoate for over a year; but the increases were not dose dependent. Thus the evidence of carcinogenicity, even with high‑dose, long‑term exposure, is inconclusive. This suggests carcinogenic effects in humans are unlikely.

Fate in humans and animals: Dimethoate is rapidly metabolized by mammals.

Acute toxicity: Chlorpyrifos is moderately toxic to humans. Poisoning may affect the central nervous system, the cardiovascular system, and the respiratory system. It is also a skin and eye irritant. Studies in humans suggest that skin absorption of chlorpyrifos is limited. The oral LD₅₀ for chlorpyrifos in rats is 95 to 270mg/kg, 60 mg/kg in mice,1000 mg/kg in rabbits, 32 mg/kg in chickens, 500 to 504 mg/kg in guinea pigs, and 800 mg/kg in sheep. The dermal LD₅₀ is greater than 2000 mg/kg in rats, and 1000 to 2000 mg/kg in rabbits. The 4‑hour inhalation LC₅₀ for chlorpyrifos in rats is greater than 0.2 mg/L.

Chronic toxicity: Repeated or prolonged exposure to organophosphates may result in the same effects as acute exposure including the delayed symptoms. Human volunteers who ingested for 4 weeks 0.1mg/kg/day of chlorpyrifos showed significant plasma cholinesterase inhibition.

Reproductive effects: Current evidence indicates that chlorpyrifos does not adversely affect reproduction. No effects were seen in 2 studies where animals were tested at doses up to 1.2 mg/kg/day. Teratogenic effects: Available evidence suggests that chorpyrifos is not teratogenic. Three studies in pregnant rats or mice indicate that no significant teratogenic effects were seen at doses up to 25 mg/kg/day for 10 days.

Mutagenic effects: No evidence was found in any of four tests performed that chlorpyrifos is mutagenic. Carcinogenic effects: There is no evidence that chlorpyrifos is carcinogenic. There was noincrease in the incidence of tumors when rats were fed 10 mg/kg/day for 104 weeks.

Fate in humans and animals: Chlorpyrifos is readily absorbed into the bloodstream through the gastro-intestinal tract if it is ingested, through the lungs if it is inhaled, or through the skin if there is dermal exposure. In humans, chlorpyrifos and its principal metabolites are eliminated rapidly. After a single oral dose, the half‑life of chlorpyrifos in the blood appears to be about 1 day.

Acute toxicity: Permethrin is moderately to practically non‑toxic via the oral route. Via the dermal route, it is slightly toxic, with a reported dermal LD₅₀ in rats of over 4000 mg/kg, and in rabbits of greater 2000 mg/kg. Permethrin caused mild irritation of both the intact and abraded skin of rabbits. It also caused conjunctivitis when it was applied to the eyes. The 4‑hour inhalation LC₅₀ for rats was greater than 23.5 mg/L, indicating practically no inhalation toxicity.

Chronic toxicity: No adverse effects were observed in dogs fed permethrin at doses of 5 mg/kg/day for 90 days. Rats fed 150 mg/kg/day for 6 months showed a slight increase in liver weights.

Reproductive effects: The fertility of female rats was affected when they received very high oral doses of 250 mg/kg/day of permethrin during the 6th to 15th day of pregnancy. It is not likely that reproductive effects will be seen in humans under normal circumstances.

Teratogenic effects: Permethrin is reported to show no teratogenic activity.

Mutagenic effects: Permethrin is reported to show no mutagenic activity.

Carcinogenic effects: The evidence regarding the carcinogenicity of permethrin is inconclusive.

Organ toxicity: Permethrin is suspected of causing liver enlargement and nerve damage.

Fate in humans and animals: Permethrin is efficiently metabolized by mammalian livers. Breakdown products, or "metabolites," of permethrin are quickly excreted and do not persist significantly in body tissues. Permethrin may persist in fatty tissues, with half‑lives of 4 to 5 days in brain and body fat.

λ- cyhalothrin is moderately toxic in the technical form, but may be highly toxic via some routes in formulation (e.g., as Karate). Cyhalothrin is moderately toxic via the oral route in test animals. Data indicate a moderate to high toxicity via the inhalation route for the formulated product Karate. It may cause mild eye irritation in rabbits.

Chronic Toxicity: The principal toxic effects noted in chronic studies with rates were decreased body weight gain and decreased food consumption. It is unlikely that cyhalothrin would cause chronic effects in humans under normal conditions.

Reproductive Effects: Cyhalothrin caused reduced numbers of viable offspring at doses of 50 mg/kg/day in the second and third generations in the three-generational rat study noted above. It is unlikely that cyhalothrin would cause reproductive effects in humans under normal conditions.

Teratogenic Effects: No teratogenic or fetotoxic effects were observed in teratology studies of lambda cyhalothrin in rats and rabbits at the highest doses tested in both species (15 mg/kg/day and 30 mg/kg/day, respectively).

Mutagenic Effects: Cyhalothrin produced negative results in Ames mutagenicity assays and other in-vitro cytogenetic assays and chromosomal structural aberration tests indicated no mutagenic or genotoxic effects.

Carcinogenic Effects: Evidence is inconclusive, but suggests that it is probably not carcinogenic. Organ Toxicity: No specific target organs or organ systems have been identified in the available studies of chronic toxicity.

Fate in Humans & Animals: In rat studies, lambda cyhalothrin is rapidly metabolized and excreted via the urine and feces.