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Cry1A.105 is a Bacillus thuringiensis (Bt) protein expressed in many Bt corn hybrids for controlling moth pests including the fall armyworm (FAW), Spodoptera frugiperda (J.E. Smith). The objective of this study was to compare the inheritance and fitness costs of two Cry1A.105-resistant FAW strains (RR32 and RR67) from Florida, U.S. To assess inheritance of the resistance, larval mortality of one susceptible strain (SS), RR32, RR67, and eight FAW strains generated from various genetic crosses was assayed on Cry1A.105-treated diet and Cry1A.105 corn leaf tissues. In the fitness cost study, survival, growth, development, and fecundity of SS, RR32, RR67, and two F1 heterozygous-resistant FAW strains were evaluated on non-Bt corn leaf tissue. The Cry1A.105 resistance in both RR32 and RR67 was likely inherited as a single autosomal gene with no fitness costs. The dominance levels differed between the two strains and varied from incompletely recessive to incompletely dominant, depending on Cry1A.105 concentrations and assay materials. The results of this study indicate a relatively high risk of resistance development to single-gene Cry1A.105 corn in FAW. Together with published data, the results also show that non-recessive resistance and lack of fitness costs in resistance to Bt crops are not uncommon, which provides a cautionary evidence against the assumption that resistance is recessive in an resistance management plan for Bt crops.
With the high selection pressure imposed by the broad adoption of Bacillus thuringiensis (Bt) crops (James, 2016), evolution of resistance has become a great challenge to the continued success of Bt crops. Recently, field-evolved resistance with control problems has been reported in several major target pest species of Bt corn and Bt cotton (van Rensburg, 2007, Storer etal., 2010, Dhurua and Gujar, 2011, Gassmann etal., 2011, Farias etal., 2014a, Farias etal., 2014b, Huang etal., 2014, Kranthi, 2015, Dively etal., 2016). The fall armyworm (FAW), Spodoptera frugiperda (J.E. Smith), has developed field resistance to Cry1F Bt crops in several geographical regions of Americas (Storer etal., 2010, Farias etal., 2014a, Farias etal., 2014b, Huang etal., 2014, Li etal., 2016). Therefore, implementing effective insect resistance management (IRM) strategies is urgently needed for this important cross-crop pest species (Yang etal., 2016).
Cry1A.105 (Biosafety Clearing-House, 2014) is one of the two Bt proteins produced in the event MON 89034. In the U.S., corn hybrids containing MON 89034 were first commercialized in 2010 (US-EPA, 2010). Due to the similar gene structure among Cry1F and Cry1A proteins (e.g. Cry1A.105, Cry1Ab, Cry1Ac), studies have shown that there is a high level of cross-resistance among these proteins in FAW (Huang etal., 2014, Niu etal., 2016), hence the widespread resistance to Cry1F corn would be expected to impact the effectiveness of Cry1A.105. Because Cry1A.105 is a relatively new protein used in Bt crops, knowledge of Cry1A.105 resistance is very limited. Recently, two Cry1A.105-resistant FAW strains were successfully established using an F2 screen from field populations collected from Florida, U.S. (Huang etal., 2016). The objective of this study was to analyze the genetic basis and fitness costs of these two strains. Information generated from this study should be valuable in understanding resistance mechanisms, assessing risk of resistance evolution, and developing resistance management strategies for Bt corn.
A Cry1A.105-susceptible (SS) and two Cry1A.105-resistant (RR32 and RR67) FAW strains were used as the original insect sources for this study (Table1). SS was collected from corn fields near Weslaco, Texas in 2013 and has been shown to be susceptible to Cry1A.105, Cry2Ab2, Cry1F and Vip3A proteins in diet, as well as to corn leaf tissue and whole corn plants expressing these proteins (Huang etal., 2014, Huang etal., 2016, Niu etal., 2016, Yang etal., 2017). RR32 and RR67 were established by
Inheritance of Cry1A.105 resistance in FAW
The effect of FAW strain on larval mortality was significant for each of the three Cry1A.105 concentrations in the diet-incorporated bioassay (F8,35≥14.44, P<0.0001) and for the leaf tissue test (F10,41=20.54, P<0.0001). Larval mortality of SS ranged from 98.1 to 100% across the three Bt concentrations in the diet-incorporated and was 96.4% on Cry1A.105 corn leaf tissue (Table2). Performance of RR32 and RR67 was somewhat inconsistent between the diet-incorporated bioassay and leaf
Results of this study suggest that the Cry1A.105 resistance in both RR32 and RR67 FAW strains was likely inherited as a single (or a few tightly linked) autosomal gene and the resistance was functionally non-recessive and ranged from incomplete recessive to incomplete dominant, depending on the insect strain, Bt concentration and assay method. Both RR32 and RR67 on non-Bt leaf tissue did not show less fitness than the susceptible insect strain for all life history parameters measured,
We appreciate Drs. David Kerns, Mike Stout, and Beibei Guo for their constructive suggestions during the study. This study was partially sponsored by Monsanto Company and the United State Department of Agricultural Multistate Research Project NC246. This publication has been approved by the Associate Vice President & Program Leader of the Louisiana State University Agricultural Center as manuscript No. 2017-234-30797.
- L. Zhang et al.Fitness and stability of Cry1Ab resistance in sugarcane borer, Diatraea saccharalis (F.)
- F. Yang et al.Susceptibility of Cry1F-maize resistant Spodoptera frugiperda to Bt proteins used in the transgenic cotton
- D.S. Wangila et al.Larval survival and plant injury of Cry1Ab-susceptible, -resistant, and -heterozygous genotypes of the sugarcane borer on transgenic corn containing single or pyramided Bt genes
- Y. Niu et al.Performance of Cry1A.105-selected fall armyworm (Lepidoptera: Noctuidae) on transgenic maize plants containing single or pyramided Bt genes
- R. Nair et al.Inheritance of Cry1Ac resistance and associated biological traits in the cotton bollworm, Helicoverpa armigera (Lepidoptera: Noctuidae)
- K.R. Kranthi et al.Inheritance of resistance in indian Helicoverpa armigera (Hübner) to Cry1Ac toxin of Bacillus thuringiensis
- F. Huang et al.Frequency of Bacillus thuringiensis Cry1A.105 resistance alleles in field populations of the fall armyworm, Spodoptera frugiperda, in Louisiana and Florida
- J.R. Farias et al.Field-evolved resistance to Cry1F maize by Spodoptera frugiperda (Lepidoptera: Noctuidae) in Brazil
- V. Dangal et al.Fitness costs of Cry1F resistance in two populations of fall armyworm, Spodoptera frugiperda (JE Smith), collected from Puerto Rico and Florida
- D. Bernardi et al.Selection and characterization of Spodoptera frugiperda (Lepidoptera: Noctuidae) resistance to MON 89034× TC1507× NK603 maize technology
Amethod of computing the effectiveness of an insecticide
Cross-resistance between Cry1 proteins in fall armyworm (Spodoptera frugiperda) may affect the durability of current pyramided Bt corn hybrids in Brazil
Gene and DNA Sequence, Cry1A.105
Insecticide resistance and dominance levels
Comparative analysis of the genetic basis of Cry1F resistance in two strains of Spodoptera frugiperda originated from Puerto Rico and Florida
Dominant inheritance of field-evolved resistance to Bt Corn in Busseola fusca
Field-evolved resistance to Bt toxin Cry1Ac in the pink bollworm, Pectinophora gossypiella (Saunders) (Lepidoptera: Gelechiidae), from India
Pest Manag. Sci.
The Handy Bt Trait Tablefor U.S. Corn Production
Field-evolved resistance in corn earworm to Cry proteins expressed by transgenic sweet corn
Geographical and temporal variability in susceptibility to Cry1F toxin from Bacillus thuringiensis in Spodoptera frugiperda (Lepidoptera: Noctuidae) populations in Brazil
Dominance of Cry1F resistance in Spodoptera frugiperda (Lepidoptera: Noctuidae) on TC1507 Bt maize in Brazil
Pest Manag. Sci.
Biochemistry and genetics of insect resistance to Bacillus thuringiensis
Annu. Rev. Entomol.
Fitness costs of insect resistance to Bacillus thuringiensis
Annu. Rev. Entomol.
Field-evolved resistance to Bt maize by western corn rootworm
Fitness costs of resistance to Cry3Bb1 maize by western corn rootworm
Transgenic Bt plants: successes, challenges, and strategies
- Laboratory induced bifenthrin resistance selection in Oxycarenus hyalinipennis (Costa) (Hemiptera: Lygaeidae): Stability, cross-resistance, dominance and effects on biological fitness
2020, Crop Protection
The dusky cotton bug, Oxycarenus hyalinipennis (Costa) (Hemiptera: Lygaeidae) is a serious pest of cotton and damages cotton seed by reducing the oil content. In Pakistan, O. hyalinipennis is managed by using various insecticides and has developed resistance to several insecticides. In this study, O. hyalinipennis was selected with bifenthrin for 12 generations (G1 to G12) and developed a 55.64-fold resistance when compared with an unselected population (Unsel Pop). Bifenthrin resistance declined from 55.64 to 24.93-fold when selected population was removed from bifenthrin selection pressure for four generations (G13 to G16). Bifenthrin selected (Bifen-Sel) population showed a very low cross-resistance to profenofos (2.82-fold), deltamethrin (2.35-fold) and acetamiprid (2.21-fold) when compared with a field population (Field Pop). The bifenthrin resistance was incomplelety dominanat and autosomal. The relative fitness (Rf) of Bifen-Sel population was 0.58 along with significant decreases in average nymphal survival, fecundity, egg hatchability, intrinsic rate of population increase (rm), net reproductive rate (Ro) and biotic potential (Bp). The Rf of Cross1 and Cross2 was 1.07 and 1.22, respectively. The high fitness costs, instable resistance and a very low cross-resistance with other insecticides might be useful in slowing down the evolution of bifenthrin resistance by implementing an insecticide rotation plan.
- Survival and effective dominance level of a Cry1A.105/Cry2Ab2-dual gene resistant population of Spodoptera frugiperda (J.E. Smith) on common pyramided Bt corn traits
2019, Crop Protection
Citation Excerpt :
In contrast, the current study suggests that the Cry1A.105/Cry2b2 resistance in AABB was incompletely recessive on both leaf tissue (DML = 0.21) and whole VT-2P corn plants (DML = 0.27). In addition, our previous studies showed that the single-gene Cry1A.105 resistance in AAbb was also non-recessive on Cry1A.105 corn leaf tissue (DML = 0.097–0.579) and Cry1A.105 whole plants (DML = 0.50–0.75) (Niu et al., 2016a, 2017), while the Cry2Ab2 resistance in aaBB was found to be completely recessive on Cry2Ab2 corn leaf tissue (DML = − 0.02) (Acharya et al., 2017), but incompletely recessive on Cry2Ab2 whole plants (DML = 0.34) (Yang et al., 2017). More studies are warranted to elucidate the reasons for the differences in the effective dominance levels of the resistance between the Brazilian and United States populations.
The fall armyworm, Spodoptera frugiperda (J.E.Smith.), is an important pest that has developed resistance to Bt corn in several countries. In this study, leaf-tissue bioassays and whole-plant tests were conducted to evaluate the performance of a Bt-susceptible (aabb), a Cry1A.105/Cry2Ab2 dual-gene resistant (AABB), and a heterozygous (AaBa) genotypes of S. frugiperda on two non-Bt and five pyramided Bt corn traits. The five Bt corn traits were Genuity® VT Double Pro® (VT-2P) containing Cry1A.105 and Cry2Ab2 genes, Optimum®Intrasect® (Intrasect) containing Cry1F and Cry1Ab, Genuity® SmartStax® (SMT) containing Cry1A.105, Cry2Ab2, and Cry1F against lepidopteran pests, Optimum® Leptra® (Leptra) containing Cry1Ab, Cry1F, and Vip3A, and Trecepta ™ (Trecepta) containing Cry1A.105, Cry2Ab2, and Vip3A. Larvae of the three genotypes survived well on non-Bt corn, while few aabb survived on Bt corn plants. Survivorship of AABB on Bt leaf tissue was 43.7% for VT-2P, 29.7% for Intrasect, and 47.7% for SMT, and live larvae were recovered from 46.9% of VT-2P, 12.5% of Intrasect, and 21.9% of SMT whole plants. Some AaBb larvae also survived on these three Bt corn traits. In contrast, leaf tissue of Leptra and Trecepta killed all three genotypes, and few larvae survived on whole plants of the two Bt corn traits. The results demonstrated that AABB was highly resistant to VT-2P, and somewhat cross-resistant to Intrasect and SMT. The dual-gene resistance in AABB was non-recessive on VT-2P. Pyramided corn traits containing Vip3A were effective against the three genotypes. However, Vip3A in the current pyramided Bt corn traits apparently is the only fully active Bt protein against the Cry1/Cry2-resistant S. frugiperda. More effective resistance management plans are necessary to suppress resistance to Bt crops and sustain the value of these technologies.
- Performance of Bt-susceptible and -heterozygous genotypes of Spodoptera frugiperda (J.E. Smith) possessing single- or dual-gene resistance alleles in sequential feedings of non-Bt and Cry1A.105/Cry2Ab2 maize leaf tissues
2018, Journal of Invertebrate Pathology
Citation Excerpt :
Recently, this pest was introduced to Africa and is becoming a great threat to Africa’s food security (Goergen et al., 2016; Foodtank, 2018). The genetic basis, cross-resistance, and fitness costs of the Cry1A.105 and Cry2Ab2 resistance in the S. frugiperda strains have been characterized (Acharya et al., 2017; Niu et al., 2016b, 2018; Yang et al., 2017a). By crossing these well-documented single-gene resistant strains, a dual-gene Bt resistant strain of S. frugiperda that is resistant to both Cry1A.105 and Cry2Ab2 was developed in the laboratory (Niu, 2018; Zhu et al., 2019).
We simulated larval feeding behavior in seed blends of non-Bt and Bt maize to determine if seed blends create more favorable conditions for heterozygous-resistant insects over their Bt-susceptible counterparts. Survival, growth, development, and progeny production of four genotypes of the fall armyworm, Spodoptera frugiperda, Bt-susceptible (aabb), Cry1A.105 heterozygous resistant (Aabb), Cry2Ab2 heterozygous resistant (aaBb), and Cry1A.105/Cry2Ab2 heterozygous resistant (AaBb), were evaluated in eight feeding sequences (Seq 1–8) of non-Bt and MON89034 Bt maize leaf tissue expressing the Cry1A.105 and Cry2Ab2 proteins. We report variation in the performance of the four genotypes across the feeding sequences and biological parameters measured. Three heterozygous genotypes generally outperformed the susceptible genotype in larval survival, pupation rate, pupal weight, and progeny production. The performance was greater for Aabb over aaBb, AaBb over Aabb or aaBb, in two of the feeding sequences. The findings of this study could have important implications in assessing the risk of seed blends as refuge plantings for Bt crop resistance management where resistance in the target pest is not functionally recessive.
- Fitness costs and inheritance of Cry2Ab2 resistance in Spodoptera frugiperda (J.E. Smith)
2017, Journal of Invertebrate Pathology
Cry2Ab2 is a Bacillus thuringiensis (Bt) protein expressed in transgenic corn and cotton targeting above-ground lepidopteran pests including the fall armyworm, Spodoptera frugiperda (J.E. Smith). The objective of this study was to characterize fitness costs and inheritance of Cry2Ab2 resistance in S. frugiperda. To determine if fitness costs were associated with the resistance, life history parameters (larval survival, growth, development and egg production) of Cry2Ab2-resistant, -susceptible, and two reciprocal F1 colonies of S. frugiperda were assayed on non-toxic diet and non-Bt corn leaf tissue. The results showed that there were no significant differences among the four insect colonies for all the biological parameters measured with few exceptions, suggesting that the resistance in the colony was not associated with significant fitness costs in the test conditions. To examine the inheritance of resistance, susceptibilities of the resistant and susceptible parents, as well as eight additional colonies generated from various genetic crosses, were assayed using Cry2Ab2-treated diet and Cry2Ab2 corn leaf tissue. The Cry2Ab2 resistance in S. frugiperda in the colony was inherited as a single autosomal recessive or incompletely recessive gene. The results of the study suggest a potential risk of resistance development in S. frugiperda to the Cry2Ab2 protein and thus effective management strategies should be implemented for the sustainable use of the Bt corn technology for pest management.
Research articleDevelopment of improved disease management for powdery mildew on mango trees in Israel
Crop Protection, Volume 110, 2018, pp. 221-228
Powdery mildew, caused by Pseudoidium anacardii (formerly Oidium mangiferae Berthet), attacks panicles, young fruits, and leaves of mango trees; it may cause considerable crop loss. Mango is the only known host of this pathogen. Disease management in Israel has not been investigated extensively; it is based on field observations by the Agricultural Extension Service, which instructs growers to spray at 14-d intervals, starting from the beginning of bloom when the first flowers appear in the orchard, or after rain events; rain events during flowering promote development of the disease. The present study found that fungicides applied to panicles at 10-d intervals after they reached a length of 5 or 10cm improved disease control compared with spraying at 14-d intervals. Earlier applications did not improve disease control; later applications, beginning at the first-open-flower stage, were less effective. Foliar sprays applied before rain events provided better disease control than spraying after the rain. In Israel, about 30 fungicides against mango powdery mildew are registered, but no comparative trials for fungicide efficacy have been conducted in recent years. Efficacy trials showed that the most effective fungicides were penconazole, myclobutanil, tetraconazole, and an improved formulation of mineral oil. A tank mixture of systemic fungicide with a reduced sulfur content (up to 60%) was as effective as, or slightly more so than each component applied alone, and provided 70–90% protection compared with control untreated trees. QoI fungicides (strobilurins) were less effective and less consistent. Where there was an existing infection on panicles, two consecutive applications of sulfur or mineral oil, combined with systemic fungicides, suppressed the fungus and inhibited powdery mildew development. The main findings of the present study were implemented by growers and currently are used to develop improved disease management.
Research articleFlights of Noctuidae and Crambidae of economic importance in Southeast Missouri – 2015, 2016
Crop Protection, Volume 110, 2018, pp. 141-145
Growers of cotton and soybean in Southeast Missouri have expressed deep concern over increases in lepidopteran damage the past 2 years. Efforts to control fall armyworm, bollworm, Southwestern corn borer, and black cutworm with Bt varieties of corn or cotton and foliar insecticides generally meet with limited success. Therefore, we sought a more effective means to monitor and manage these moth populations in cotton, soybean, corn, and grain sorghum by use of pheromone traps and verification of degree-day models. Green plastic funnel traps baited with their respective lures were dispensed and monitored weekly (1 May – 1 Oct 2015, 2016) in 8 randomly selected soybean and cotton fields. Degree-days began at biofix, and a single sine method with lower and upper thresholds were used for the model. Temperature data were obtained from National Oceanic and Atmospheric Administration (NOAA). Each moth peak was assigned accumulative number of degree-days. Accumulated degree-day sums for peak flight of each moth species were estimated by averaging accumulated degree-days between counties for peaks 1–5. For direct comparison, interpretation, and incorporation into a predictive model, differences between the degree-days that flight actually occurred and predictions from models were evaluated with analysis of variance. Factors in the model were county, flight/model, peak, and degree-days. No significant differences in degree-days were found between the peak-flight in degree-days, and the degree-days of its model for the respective moth species, regardless of county. These models are a good fit for predicting catches of moths in monitoring traps and management decisions for Southeast Missouri.
Research articleEffect of three insect-resistant maizes expressing Cry1Ie, Cry1Ab/Cry2Aj and Cry1Ab on the growth and development of armyworm Mythimna separata (Walker)
Journal of Integrative Agriculture, Volume 19, Issue 7, 2020, pp. 1842-1849
Three transgenic maize events (IE09S034, Shuangkang 12–5 and C0030.3.5) produced Cry1le, Cry1Ab/Cry2Aj and G10-EPSPS, Cry1Ab and EPSPS, respectively, all of which target the Asian corn borer. The oriental armyworm Mythimna separata (Walker) is the secondary target. In this study, the effects of the three Bt maizes on the development and survival of armyworm were studied. The results showed that IE09S034 had insecticidal activity against 1st instar larvae, and the survival rate of armyworm fed with Bt maize for 10 days was 46.2%, significantly lower than that of the control. The larvae at 3rd–6th instar were more tolerant of the Bt toxin than the early instar larvae. However, Shuangkang 12-5 had good insecticidal activity against 1st–5th instar larvae. The mortality was nearly 100% when the larvae were fed with Shuangkang 12-5 before 3rd instar, and the toxin had quick-acting efficacy. This event significantly inhibited the development of armyworm; that is, the larval duration of the 3rd and 4th instar larvae fed with Shuangkang 12-5 was prolonged by 4.5 and 3.0 days, respectively. The pupal weight and egg number were also significantly lower than those of the control. For C0030.3.5, it could control 1st–5th instar larvae effectively. The mortality rates were all over 50% if 1st–3rd larvae were fed with this event. The pupal weight of 4th–6th instar larvae fed with Bt maize were only 53.9, 56.8 and 54.6%, respectively, compared to that of the control. The number of eggs laid was significantly less than the control. The results indicate that all three transgenic maize events exhibit the potential to provide effective control of early instar larvae of armyworm, which can be commercialized in future to control lepidoptera pests such as Asian corn borer and armyworm.
Research articleSpodoptera frugiperda (J.E. Smith) with field-evolved resistance to Bt maize are susceptible to Bt pesticides
Journal of Invertebrate Pathology, Volume 122, 2014, pp. 52-54
Field-evolved resistance to maize event TC1507 expressing the Cry1Fa toxin from Bacillus thuringiensis (Bt) was detected in populations of Spodoptera frugiperda from Puerto Rico. We tested for cross-resistance to purified Cry1A toxins and commercial Bt pesticides in susceptible (Benzon) and TC1507-resistant (456) strains of S. frugiperda. Larvae from the 456 strain exhibited cross-resistance to Cry1Ab and Cry1Ac toxins, while no differences in susceptibility to XenTari WG and DiPel ES pesticides were detected. These data support cross-resistance to toxins that share binding sites with Cry1Fa and no cross-resistance to Bt pesticides in S. frugiperda with field-evolved resistance to Bt maize.
Research articleField-evolved resistance to Cry1F maize by Spodoptera frugiperda (Lepidoptera: Noctuidae) in Brazil
Crop Protection, Volume 64, 2014, pp. 150-158
The Cry1F protein from Bacillus thuringiensis Berliner expressed in event TC1507 maize (Zea mays L.) was one of the most effective ways to control Spodoptera frugiperda (J. E. Smith) in Brazil. After reports of reduced effectiveness of this Bt maize event in some areas of Brazil, research was undertaken to investigate if damage to Cry1F maize was caused by resistant S.frugiperda. Additional investigations were conducted to evaluate the genetic basis of the resistance and to test if Cry1F resistant S.frugiperda selected from populations of different regions of Brazil share the same resistance locus by using complementation tests. Neonate larvae of S.frugiperda collected from TC1507 maize fields with damage in Western Bahia region in 2011 were able to survive on Cry1F maize plants under laboratory conditions and subsequently produced normal adults. Survival of Cry1F-susceptible S.frugiperda on non-Bt maize was significantly higher in leaf than plant bioassays. Resistance ratio in diet overlay bioassays was >5000-fold. A discriminating concentration of 2000ngcm−2 of Cry1F protein was defined for monitoring the frequency of resistance of S.frugiperda to Cry1F. Cry1F resistant S.frugiperda showed a recessive autosomal inheritance for alleles involved in resistance to Cry1F protein. In complementation tests, the resistant population from Western Bahia was crossed with the other seven resistant populations collected from different States of Brazil. F1 larvae from each cross had the same survival at discriminating concentration of 2000ngcm−2 of Cry1F protein, indicating that the resistance alleles in each population were likely at the same locus. Therefore, implementation of resistance management strategies is urgent to prolong the lifetime of Cry1F for controlling S.frugiperda in Brazil.
Research articleSafety of the Bacillus thuringiensis-derived Cry1A.105 protein: Evidence that domain exchange preserves mode of action and safety
Regulatory Toxicology and Pharmacology, Volume 99, 2018, pp. 50-60
The lepidopteran-active Cry1A.105 protein is a chimeric three-domain insecticidal toxin with distinct structural domains derived from the naturally occurring Cry1Ab, Cry1Ac and Cry1F proteins from the soil bacterium Bacillus thuringiensis (Bt). The X-ray crystal structure of the Cry1A.105 tryptic core at 3.0 Å resolution demonstrates its high structural similarity to the tryptic core of Cry1Ac. Bioinformatics analyses demonstrate that Cry1A.105 has no significant amino acid sequence similarity to known allergens or mammalian toxins, which is the same conclusion reached for its component domains. Like its intact donor proteins, Cry1A.105 was heat labile at temperatures ≥75 °C and degraded upon exposure to gastrointestinal proteases. No adverse effects were observed in mice when Cry1A.105 was dosed orally at 2451 mg/kg body weight. Therefore, the weight of evidence supports that Cry1A.105 is safe for human and animal consumption. These results support the conclusion that the safety of a chimeric protein for human or animal consumption can be evaluated in the context of the safety of its donor proteins.
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