Based on the above discussions of critical effects, appropriate effect levels, and uncertainty factors, separate RfDs, one for each degradate, were developed by the panel. For alachlor ESA, the high dose in the dietary study of 12,000 ppm serves as the appropri ate NOAEL for the RfD, since it is lower than that seen in the drink ing water study. An uncertainty factor of 1000 is applied to the NOAEL for males of 788 mg/kg day, the lower of both sexes, result ing in an RfD of 8 E 1 mg/kg day. Alachlor ESA was similar to alachlor OXA in that no statistically significant effects were judged to be adverse in the 90 day feeding study with alachlor OXA. The high dose of 13,000 ppm serves as the appropriate NOAEL. Applying a composite UF of 1000 to the lower of the NOAELs results in an RfD of 8 E 1 mg/kg day.
2 An argument could be made for a UF of 3000, where the 30_ UF represents the combined uncertainties in the duration extrapolation and database insufficiency because of the lack of a reproductive toxicity study for any degradate, the lack of a second species developmental toxicity study for any degradate, and the lack of a second species standard subchronic systemic Angiogenesis toxicity study for any degradate. For acetochlor ESA, the NOAEL of 3000 ppm in the 90 day feeding study was identified as the appropriate point of departure. Applying an uncertainty factor of 1000 to the lower NOAEL results in an RfD of 2 E 1 mg/kg day. For acetochlor OXA, the NOAEL of 3000 ppm in the 90 day feeding study was identified as the appropriate point of departure.
Applying the composite UF of 1000 to the NOAEL in males of 230 mg/kg day results in an RfD of 2 E 1 mg/kg day. For each degradate, the confidence in the RfD is judged to be low to medium and additional studies that might reduce the overall uncertainty factor would be a bioassay in a second mammalian species and comparative toxicokinetics Apoptosis information in humans. The RfDs for the parent compounds, from the Tolerance Reas sessment Eligibility Decision Document for acetochlor and the Reregistration Eligibility Decision for alachlor are 2 E 2 mg/kg day for acetochlor based on clinical signs and microscopic find ings in the liver, testes and kidney in dogs, and 1 E 2 mg/kg day for alachlor, based on hemosiderosis and hemolytic anemia in dogs.
These RfDs are 10 and 80 fold lower than those for the Dasatinib corre sponding degradates, which agrees with the consensus opinion that the toxicity of the degradates is significantly less than the tox icity of the parent chemicals. Today, more than 500 compounds have been registered worldwide as pesticides or metabolites of pesticides. These pesticides are broadly applied to crops at various stages of cultivation to provide protection against pests and thus to prevent/reduce agricultural losses and to improve the production yield. Every 2 years, more than 5 billion pounds pesticides were used for agriculture, and herbicides accounted for the largest portion, being 1. 9 billion pounds. Acetanilide herbicides are the most commonly used herbicides, mainly used in corn, soybean and many other cereal crops which are staple foods of some countries, for preemergence control of annual grasses and broadleaf.
However, a number of these pesticides have been demon strated to be mutagenic and carcinogenic. Acetochlor can carry strong genotoxicity activity in vitro. Butachlor was a suspected carcinogen capable c-Met Signaling Pathway of stimulating cell prolifera tion and inducing malignant transformation in vitro. In recent years, increasing attention has been paid to the risk posed to consumers, and lower maximum recommended limits have been set for more and more kinds of pesticides. The MRLs of some acetanilide herbicides in cereal crops were in the range of 0. 01 0. 2 mg/ kg established by European Union and Japan, the detailed information is described in Table 1. Therefore, the development of simple and sensitive methods for acetanilide herbicide residues analysis in cereal crops is necessary and valuable.
However, researches about these herbicides are concentrated on water and Sampling and sample pretreatment usually account for over 60% of the total analysis time, and the quality of these steps largely determines the success of an analysis from complex matrices. VEGF Hence, sample preparation should be as simple as possible. The conventional and classical method for the extraction of acetanilide herbicides from environmental samples is shake ask extraction and sonication extraction, which are characteristically time and solvent consuming, and their sample throughput is low. As an alternative, some novel techniques have been developed such as microwave assisted extraction, supercritical uid extraction and accelerated solvent extraction. Compared with the classical method, MAE, SFE and ASE require less solvent and extraction time, but SFE requires expensive instrumentation and recoveries can be somewhat lower for markedly polar pesticides, MAE gave lower recoveries to unpolar compounds. ASE was first performed for the extraction of organic substances by Richter et al., which significantly streamlines sample preparation.