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Asian Pacific Journal of Cancer Prevention, Vol 6, 200541Chemoprevention of Hepatocarcinogenesis by Inositol and IP6Asian Pacific J Cancer Prev, 6, 41-47RESEARCH COMMUNICATIONIntroductionPhytic acid (inositol hexaphosphate, IP6) exists in plants normally as a salt, most commonly in association with sodium or potassium. Inositol and its phosphated derivatives are found not only in plants (Clements and Darnell, 1982),but also in mammalian tissues (Sakamoto et al., 1993), where they participate in the regulation of vital cellular functions,such as signal transduction, proliferation and differentiation (Shamsuddin and Vucenik, 1999). Interestingly, several recent studies have shown that IP6 modulates prostate (Singh et al., 2004), colon (Shamsuddin et al., 1989; Shamsuddin and Ullah, 1998), mammary (Shamsuddin et al., 1989; 1995;1996), and liver (Hirose et al., 1991; 1999) carcinogenesis.The plausible mechanisms for anticancer effects of IP6,although not fully elucidated yet, include antioxidant function, control of cell signaling, inhibition of cell proliferation, induction of cell differentiation, and Dietary Administration of Inositol and/or Inositol-6-phosphate Prevents Chemically-induced Rat HepatocarcinogenesisHae-Jeung Lee, Sang-Ah Lee, Haymie Choi*Nutrition Science Lab. Dept. of Food and Nutrition, Seoul National University, Seoul 151-742, Korea*Correspondence to: Prof. Haymie Choi, Department of Food and Nutrition, Seoul National University, Seoul 151-742, Korea. Telephone : 822-880-6836, 8767; F AX : 822-877-1031 E-mail : choihm@snu.ac.krAbstractChemoprevention is considered a rational strategy for dietary approaches to prevention of cancer. Multiple lines of evidence suggest that many of our dietary principles are able to intervene in the multistage carcinogenesis process and phytic acid (inositol hexaphosphate, IP6), a phytochemical present in a variety of plant species, has been shown to prevent various cancers, including those of the mammary gland, colon and liver. However, the mechanism of chemoprevention by IP6 has not been fully elucidated. In the present study, we examined the effects of inositol and/or IP6 supplementation on rat hepatocarcinogenesis initiated by diethylnitrosamine (DEN) and promoted by partial hepatectomy (PH). Supplementation with either inositol or IP6, or their combination, starting one week prior to administration of DEN, resulted in a significant decrease in both the area and the number of placental glutathione S-transferase positive (GST-P+) foci, a preneoplastic marker for DEN-initiated hepatocarcinogenesis. The administration of inositol and/or IP6 in drinking water caused marked enhancement in the glutathione S-transferase (GST) activity.In addition, the production of thiobarbituric acid reactive substances and the catalase activity were significantly reduced in rats supplemented with inositol and /or IP6. Based on these findings, it is likely that the chemopreventive effects of inositol and/or IP6 on rat hepatocarcinogenesis initiated by DEN and promoted by PH are associated with induction of GST activity and suppression of lipid peroxidation.Key Words : Inositol - inositol hexaphosphate (IP6) - hepatocarcinogenesis - placental glutathione S - transferase positive foci - glutathione S-transferase enhancement of immune responses (Baten et al., 1989; Fox and Eberl, 2002; Vucenik and Shamsuddin, 2003).Modulation of the intracellular phosphate pool and signal transduction cascades is considered to be associated with anticarcinogenic effects of a wide spectrum of naturally occurring substances. It has been reported that administration of IP6 alters the intracellular inositol phosphate pool (Shamsuddin, 1997). Huang et al (1997) have documented evidence that IP6 inhibits the activation of activator protein 1 (AP-1) and cellular transformation by targeting phosphatidylinositol-3 kinase (PI3K), a key enzyme in the intracellular signal transduction cascade regulating cell proliferation. IP6 also reduces the rate of cellular proliferation by controlling cell division (Saied andShamsuddin, 1998) through induction of p21WAF1and p53-mediated cell cycle arrest. It has also been reported that,IP6 is capable of inducing differentiation of K-562 human erythroleukemia (Shamsuddin et al., 1992), HT-29 humanHae-Jeung Lee et alAsian Pacific Journal of Cancer Prevention, Vol 6, 200542Figure 1. Experimental ProtocolExperimental liquids were administered for 6wks : PPT (IP6 2%), PIT (1% IP6 +1% inositol), and IIT (2% inositol). All except CO group rats received a single intraperitoneal injection of diethylnitrosamine (DEN), subjected to 2/3 partial hepatectomy (PH) at week 3, and sacrificed at week 8.colon carcinoma (Yang and Shamsuddin, 1995), and prostate cancer (Shamsuddin and Yang, 1995) cells. Moreover, the transformation of HepG 2 human liver cancer cells was reversed to the normal phenotype by supplemention with IP6 (Vucenik et al., 1998).Inositol has been shown to elicit anti-cancer effect on pulmonary (Estensen and Wattenberg, 1993; Wattenberg,1999), colon (Ullah and Shamsuddin, 1990), and mammary carcinogenesis to the same extent as IP6 (Shamsuddin et al., 1995; 1998). Oral administration of inositol suppresses hepatic carcinogenesis in mice (Nishino et al., 1996) and the combination of IP6 and inositol synergistically enhanced the antineoplastic effect in Sprague-Dawley rats treated with a classical tumor initiator, 7,12-dimethylbenz(a)anthracene (Shamsuddin et al., 1995).The purpose of the present study was to evaluate inhibitory effects of inositol and/or IP6 on rat hepatocarcinogenesis and to determine whether their combination can synergistically potentiate any chemopreventive activity.Materials and MethodsAnimalsMale Sprague-Dawley rats (4 weeks) were supplied by the Animal Care Facility (Chemical Institute of Daeduk,Korea) and were acclimatized for 2 weeks before launching the study. Animals were kept for 8 weeks in plastic cages under standard conditions (room temperature 20 + 1˚C,relative humidity 55 + 1%, 12 hr light/dark cycle), given food and liquid ad libitum , recorded daily and weighed weekly. Rats were divided into five groups, each consisting of 12 animals. The basal diet was prepared as described previously (Kim et al., 2000) with slight modification and contained: 20 g casein, 54.7 g corn starch, 15 g corn oil, 1.0g vitamins and mixed without inositol, 5g α-cellulose, 4.0 gminerals, and 0.3 g DL-methionine per 100 g diet. All groups were given basal diet, which was composed of 15% (g/100g)corn oil (31% of total calories).ChemicalsDiethylnitrosamine (DEN), myo-inositol, IP6 (as dodecasodium salt from corn), reduced glutathione (GSH),1-chloro-2,4-dinitrobenzene (CDNB), thiobarbituric acid (TBA), and avidin-biotin-peroxidase complex (V ectastain Elite ABC kit) used for immunohistochemical assay were obtained from Sigma Chemical Co. (St. Louis, MO, USA).Anti-rat GST-P antibody (Vector Co., USA) was kindly provided by Prof Yeong-Soon Lee, V eterinary Public Health Lab, College of Veterinary Medicine, Seoul National University.Treatment of AnimalsHepatocarcinogenesis was initiated by DEN and was promoted by PH using a modified medium-term bioassay protocol (Ito et al., 1980; 1988; 1989). Each animal received a single intraperitoneal injection of DEN (200 mg/kg body weight) dissolved in saline. After 3 weeks of DEN administration, rats were subjected to a 2/3 PH and were sacrificed at 8 weeks. Inositol (2% w/v), or IP6 (2% w/v),or a combination of inositol and IP6 (1% w/v each) in drinking water (pH 7.4 adjusted) were given from week 2after initiation with DEN as shown in Figure 1. The actual phytic acid content in the 2% IP6 liquid was 1.4%, the pH being adjusted to pH 7.4.Sample CollectionAnimals were killed by decapitation at 8 weeks. Before sacrifice, animals were kept under fasting for 12 h (Figure 1). Livers were promptly excised, weighed, finely minced in cold 50 mM potassium phosphate buffer (pH 7.4)containing 1 mM of EDTA and homogenized. Eachhomogenate was centrifuged at 1000 ×g for 10 min, and the supernatant was further centrifuged at 10,000 ×g. Pellets were homogenized in potassium phosphate buffer (pH 7.4) for the catalase assay. The remaining supernatant was centrifuged at 105,000 ×g.Peroxisomal (including mitochondria,lysosomes, and peroxisomes), microsomal, and cytosolic fractions were prepared by differential centrifugation (Wolfe, 1993) and stored at -70˚C until used.Analysis of Placental Glutathione S-transferase Positive (GST-P+) FociAt autopsy, liver sections of 2-3 mm were cut with a razor blade and fixed in ice-cold acetone for immunohistochemical examination of GST-P+ foci. The avidin-biotin-peroxidase complex method (Vectastain ABC kit, Vector Lab. Inc., Burlingame CA; GST-P antibody,MBL Co., Japan; Hsu et al., 1981) was used toAsian Pacific Journal of Cancer Prevention, Vol 6, 200543Chemoprevention of Hepatocarcinogenesis by Inositol and IP6visualize GST-P+ foci that are commonly regarded as putative preneoplastic lesions. The areas and numbers of GST-P+ foci (> 0.2 mm in diameter) in liver sections were measured using an image analyzer (Quantinet 520,Cambridge Instruments, USA)Biochemical AssaysGST activities in the hepatic cytosolic fraction were determined according to the method of Habig et al. (1974).The conjugation of GSH with CDNB was monitored by reading absorbance changes at 340 nm using a dual beam spectrophotometer (Beckman DU650). The concentration of thiobarbituric acid reactive substances (TBARS) was determined according to the method of Buege and Aust (1978). Malondialdehyde, the product of lipid peroxidation reacts with TBA to form a chromophore that is detectable at 535 nm. The catalase activity was determined by measuring the enzymatic decomposition of H 2O 2 as reported by Abei (1984). Protein was quantified using the modified Lowry method (1951), with bovine serum albumin as the standard.Statistical AnalysisSAS 8.1 statistical software was used to analyze the data.Differences among groups were determined by analysis of variance (ANOV A) with the Duncan's multiple range test at p < 0.05.ResultsGross ObservationAnimals of all groups were kept under close observation for intake of diet and liquid throughout the study period.There was no significant difference in liquid or basal diet intake among different treatment groups. However, liquid intake was apparently lower in animals given IP6 (2%)compared with those receiving either inositol (2%) or a combination of inositol and IP6. Final body and liver weights in carcinogen treated groups did not significantly vary.Relative liver weights (%) in animals given inositol and/or IP6 were decreased, but were not significantly different between these supplemented groups.Suppression of Carcinogen-induced GST-P+ Foci Formation by Inositol and/or IP6In all groups treated with DEN, placental GST-P+ foci were developed. These foci are known to be the most effective biochemical phenotypic markers for DEN-initiated preneoplastic lesions (Sato, 1989). The areas and the numbers of the GST-P+ foci (mean diameter >0.2 mm) in inositol and/or the IP6 supplemented groups were significantly lower than those of the carcinogen treated animals (Figure 2). All three groups supplemented with inositol, IP6 plus inositol, and IP6 exhibited reduced hepatic GST-P+ foci development. The frequency of GST-P+ foci in the group supplemented with a combination of inositol and IP6 was not significantly different from that observed in groups supplemented with either inositol or IP6. Thepresent study, thus revealed a lack of synergistic effect of IP6 and inositol in terms of suppressing DEN-induced hepatocarcinogenesis in rats.Inositol and/or IP6 Induced GST Activity in Carcinogen-treated Rat LiverSince inositol and IP6 were found to inhibit DEN- and PH-induced GST-P+ foci formation, effects of inositol and IP6 on the activity of GST, a phase 2 detoxifying enzyme (Kensler, 1997), were examined. The GST activity in carcinogen-treated rat liver was increased by inositol andTable 1. Effect of Inositol and/or IP6 on Final Body Weights, Liver Weights, and Relative Liver WeightsGroup Final body Liver Relative liver weight (g)weight (g)weight (%)1 CO 465.1 + 8.90a 11.91 + 0.34a 2.56 + 0.04a CT 438.3 + 10.8b 10.77 + 0.54ab 2.49 + 0.07ab PPT 427.3 + 6.01b 9.91 + 0.36b 2.27 + 0.09c PIT 439.9 + 9.20 ab 10.53 + 0.39b 2.39 + 0.05abc IIT437.4 + 9.10b9.92 + 0.39b2.32 + 0.07bc1Relative liver weight = {Liver weight (g) / Body weight (g)} - 100Hepatocarcinogenesis was induced by DEN injection and partial hepatectomy. CO, control with saline and shame operation; CT, carcinogen treated; PPT, carcinogen treated + 2% IP6; PIT, carcinogen treated + 1%IP6 + 1% inositol; IIT, carcinogen treated + 2% inositol. Values are mean +SD. V alues with the different superscripts (a, b, c) are significantly different at p<0.05 by Duncan’s multiple range test.Figure 2. The Effect of Additional Inositol and/or IP6on the Area and Number of GST-P+ Foci in Rats Treated with DEN and Subjected to Partial Hepatectomy. CT,carcinogen treated; PPT, carcinogen treated + 2% IP6; PIT,carcinogen treated + 1% IP6 + 1% inositol; IIT, carcinogen treated + 2% inositol. Values are means +S.E. Means with different superscripts (a, b) are significantly different (by analysis of variance, p < 0.05)Hae-Jeung Lee et alAsian Pacific Journal of Cancer Prevention, Vol 6, 200544IP6 supplementation (Figure 3A). Rats supplemented with inositol alone had a relatively high hepatic GST activity compared to other supplemented groups. The GST activity also inversely correlated with the area and the number of GST-P+ foci (r = 0.76, r = 0.71, p<0.01, respectively).Inhibition of Catalase Activity by Inositol and/or IP6 in Rat Liver Treated with CarcignogenIt has been reported that reactive oxygen species (ROS)are generated in hepatocytes after treatment with DEN (Roomi et al., 1997) resulting in lipid peroxidation, and partial hepatectomy further stimulates the release of ROS by up-modulating TNF-alpha (Diehl, 2000). Hepatocytes from rats treated with DEN followed by PH are vulnerable to oxidative damage that may lead to hepatocarcinogenesis (Sanchez-Perez et al., 2005). One of the antioxidant enzymes is catalase that converts carcinogen-induced H 2O 2into H 2Oand protects cells from oxidative damage. Therefore, an attempt was made to examine the effects of inositol and/or IP6 on catalase activity in DEN- and PH-treated rat liver.The catalase activity was significantly elevated in animals treated with carcinogen alone and was significantly decreased in groups supplemented with either inositol and/or IP6 (Figure 3B).Supplementation with Inositol and/or IP6 Reduced the Level of Carcinogen-induced TBARS in Rat LiverOxidative stress is reported to be closely linked to cancerand mutation (Horton, 1987), and lipid peroxidation often leads to cell damage and even stimulates tumor promotion (Cerutti, 1985). The antioxidant property of IP6 is reported to contribute to inhibition of hydroxyl radical generation by the Fenton reaction, subsequent lipid peroxidation and DNA damage (Shamsuddin, 1995). To investigate whether the antioxidant effects of inositol and IP6 contributes to the chemopreventive effects of these phytochemicals in chemically-induced rat hepatocarcinogenesis, effects of inositol and/or IP6 on TBARS were studied. TBARS content,which is used as a lipid peroxidation index, was significantly elevated after treatment of DEN followed by PH in a positive correlation with the area and number of GST-P+ foci (r =0.67, r= 0.62, p<0.01 respectively). Animals supplemented with inositol and/or IP6 showed a lower level of TBARS than the group treated with carcinogen alone (Table 2).TBARS content was decreased in the order of IP6 < IP6plus inositol < inositol < control < carcinogen alone treated groups. Therefore, the antioxidant function of IP6 could partly contribute to the inhibition of carcinogenesis by these phytochemicals.DiscussionAccumulating evidence from laboratory-based and population studies suggest that many of our dietary phytochemicals may exploit as potential chemopreventive agents. There is growing interest in identifying new chemopreventive agents from dietary sources. Phytate (IP6)has previously been reported to inhibit the development of neoplastic lesions in the promotional stage of rat liver carcinogenesis (Hirose et al., 1999). The present study was,therefore, conducted to investigate the possible chemopreventive effects of inositol and IP6 on hepatocarcinogenesis in rats treated with DEN and subjected to PH. Our study revealed that the development of GST-P+foci, one of the biomarkers of carcinogen-induced hepatic preneoplastic leisons, was significantly inhibited by inositol and/or IP6 supplements. However, the inhibitory effects of inositol and IP6 on DEN- and PH-induced GST-P+ foci formation was not significantly different from that observed by using a combination of inositol and IP6.Table 2. The Effect of Inositol and/or IP6 on Lipid PeroxidationGroupTreatmentNo.TBARS of rat(nmole/mg protein)CO Saline90.500 + 0.024b CT DEN+PH 90.633 + 0.042a PPT DEN+PH+2% IP690.244 + 0.009c PIT DEN+PH+1% IP6+1% inositol 90.256 + 0.016cIITDEN+PH+2% inositol 90.281 + 0.010cCO, control treated with saline and sham operation; CT, carcinogen treated;PPT, carcinogen treated + 2% IP6; PIT, carcinogen treated + 1% IP6 + 1%inositol; IIT, carcinogen treated + 2% inositol. V alues are mean + SE. V alues with the different superscripts (a, b, c) are significantly different at p<0.05by Duncan’s multiple range test.Figure 3. Efects of Inositol and/or IP6 on Glutathione S-trnasferase (A) and Catalase (B) Activity in DEN-induced and PH-promoted Rat Liver. CO, control treatedwith saline and shame operation; CT, carcinogen treated; PPT,carcinogen treated + 2% IP6; PIT, carcinogen treated + 1% IP6 +1% inositol; IIT, carcinogen treated + 2% inositol. V alues are means +S.E. Means with different superscripts (a, b, c, d) are significantly different (by analysis of variance, p < 0.05).ABAsian Pacific Journal of Cancer Prevention, Vol 6, 200545Chemoprevention of Hepatocarcinogenesis by Inositol and IP6IP6 has been reported to cause a statistically significant increase in the hepatic level of GST in normal rat (Singh et al., 1997), but the role of IP6 in modulating GST activity during DEN-induced hepatocarcinogenesis has not been studied yet. Since supplementation with inositol and/or IP6reduced the formation of GST-P+ foci, attempt was made to examine the effect of these phytochemicals on hepatic GST activity in rat liver exposed to carcinogen and PH. Our study revealed that the elevated GST activity in rat liver treated with DEN- and PH, was more elevated with supplementing IP6 and/or inositol in the drinking water. Inositol induced the GST activity to a greater extent than IP6 or IP6 plus inositol did. The number and the area of the preneoplastic lesions in the liver were negatively correlated with the GST activity.On the other hand, the catalase activity was elevated in carcinogen-treated liver, which may reflect cellular endeavour to eliminate the oxidative stress induced by DEN and 2/3 PH. The catalase activities of the rats-supplemented with IP6 and/or inositol groups were significantly decreased compared with animals treated with carcinogen alone.Especially in IP6 supplemented group, the catalase activity was the lowest, suggesting no need to increase catalase activity to eliminate hydrogen peroxide because phytate already scarvenged the origin of free radicals. Catalase activity by inositol supplement was significantly decreased compared with carcinogen treated alone. Inositol phosphates,including IP6 were reported to have the capacity to scavenge ROS (Graf et al., 1987). Inositol phosphates could be synthesis from inositol and those could eliminate the origin of free radicals (Shamsuddin, 1991). In support of this assumption, inositol supplement was reported to decrease the lipid peroxidation (Raj et al., 1995).Many of the important biological activities of IP6 may be attributed to its antioxidant activity. The 1,2,3-triphosphate functional group of IP6 retains a conformation that allows specific interaction with transition metal ions such as iron, thereby inhibiting their ability to catalyze hydroxyl radical formation by Fenton reaction (Graf et al.,1987; Graf and Eaton, 1990). IP6 has been reported to decrease the content of lipid peroxides in normal rat and pig, respectively (Singh et al., 1997; Porres et al., 1999).Muraoka and Miura (2004) have suggested that lipid peroxidation of phytic acid is due to xanthine oxidase inhibition and blocking the formation of the initiator of lipid peroxidation. In our model, lipid peroxidation was dramatically decreased by IP6 supplementation, suggesting that IP6 exerts an anticarcinogenic effect through an antioxidant mechanism.Inositol supplemented group also showed a decreased lipid peroxidation level. It remains unclear how inositol suppresses lipid peroxidation. One plausible mechanism is that inositol could facilitate the synthesis of inositol phosphates (IP6, IP5, IP4, etc.), and these compounds then exert antioxidant effects. In a recent study, Miyamoto et al.(2000) have demonstrated that the hydrolysis products of IP6 possess a chelating ability. Once inside cells, inositol might undergo re-phosphorylation to form inositol phosphates, which in turn, may chelate crucial cations (Shamsuddin, 1999) involved in the generation of ROS. If this is the case, inositol could reduce the TBARS content by lowering inositol phosphates (IP3, IP4, IP5). Raj and Devis (1995) demonstrated that addition of myo-inositol decreased the peroxidant effect of hydrogen peroxide. Thus, we assume that the antioxidant effect of inositol might be mediated by lower inositol phosphates than IP6.It has been reported that inositol and IP6 decrease the hepatic concentrations of lipids and the hepatic activities of lipogenic enzymes in rat liver (Tetsuyuki, 1997), which may contribute to their ability to lower lipid peroxidation. Until now, inhibition of lipid peroxidation by IP6 and lower inositol phosphates is considered to be mediated by a chelating mechanism. Besides an antioxidant mechanism,other mechanisms, such as the suppression of p53 or the modulation of other cancer associated genes, may account for chemopreventive effects of IP6. Recently, G0/G1 arrest and S phase inhibition of human cancer cell lines by IP6were reported (Sharma et al., 2003; El-Sherbiny et al., 2001).In conclusion, inositol and/or IP6 exerts chemopreventive effects in chemically-induced rat hepatocarcinogenesis, atFigure 4. Proposed Mechanisms Underlying Chemopreventive Effects of Inositol and IP6 Against DEN-induced andPH-promoted Rat HepatocarcinogenesisHae-Jeung Lee et alAsian Pacific Journal of Cancer Prevention, Vol 6, 200546ReferencesAbei H (1984). “Catalase in vitro”,Methods in Enzymology .Academic Press, New York, 121-6.Baten A, Ullah A, Tomazic VJ, et al (1989). Inositol phosphate-induced enhancement of natural killer cell activity correlates with tumor suppression. Carcinogenesis, 10, 1595-8.Buege JA, Aust SD (1978). “Microsomal lipid peroxidation”.Methods in Enzymol, 52, 302-10.Cerutti PA (1985). Prooxidant states and tumor promotion. Science,227, 375-81.Clements RS, Darnell B (1982). Myo-inositol content of commonfoods: development of a high –myo-inositol diet. Am J Clin Nutr, 33, 1954-67.Diehl AM (2000). Cytokine regulation of liver injury and repair.Immunol Rev, 174, 160-71.El-Sherbiny YM, Cox MC, Ismail ZA, et al (2001). G0/G1 arrestand S phase inhibition of human cancer cell lines by inositol hexaphosphate (IP6). Anticancer Res, 21, 2393-403.Estensenv RD, Wattenberg LW (1993). Studies of chemopreventiveeffects of myo-inositol on ben(a )pyrene-induced neoplasia of the lung and forestomach of female A/J mice, Carcinogenesis,14, 1975-77.Fox CH, Eberl M. (2002). Phytic acid (IP6), novel broad spectrumanti-neoplastic agent: a systematic review. Complement Ther Med, 10, 229-34Graf E, Eaton JW (1990). Antioxidant function of phytic acid. FreeRadic Biol Med, 8, 61-9.Graf E, Empsom KL, Eaton JW (1987). Phytic acid- A naturalantioxidant. J Biol Chem, 25, 11647-50.Habig WH, Pabst MJ, Jakoby WB (1974). Glutathione S-transferase. J Biol Chem, 249, 7130-9.Hirose M, Ozaki K, Takaba K, et al (1991). Modifying effects ofthe naturally occurring antioxidants gamma-oryzanol, phytic acid, tannic acid and n-tritriacontane-16, 18-dione in rat a wide-spectrum organ carcinogenesis model. Carcinogenesis , 12,1917-21.Hirose M, Fukushima S, Imaida K, et al (1999). Modifying effectsof phytic acid and g-oryzanol on the promotion stage of rat.Carcinogenesis, 19, 3665-70.Horton AA, Fairhurst S (1987). Lipid peroxidation and mechanismsof toxicity. Crit Rev Toxicol, 18, 27-79.Hsu SM, Raine L, Fanger H (1981). Use of avidin-biotin-peroxidasecomplex (ABC) in immunoperoxidase techniques, A comparison between ABC and unlabeled antibody (PAP)procedure. J Histochem Cytochem, 29, 577-80.Huang C, Ma WY, Hecht SS, et al (1997). Inositol hexaphosphateinhibits cell transformation and activator protein 1 activation by targeting phosphatidylinositol –3 kinase. Cancer Res, 57,2873-78.Ito N, Tatematsu M, Hosegaena R, et al (1980). The effect of variouschemicals on the development of hyperplastic nodules in hepatectomized rats treated with N-nitrosodiethylamine or N-2-fluorenylactamide. Jpn J Cancer Res , 71, 832-42.Ito N, Tsuda H, Tatematsu M, et al (1988). Enhancing effect ofvarious hepatocarcinogens on induction of preneoplastic medium-term bioassay system. Carcinogenesis, 9, 384-94.Ito N, Imaida K, Hasegawa R, et al (1989). Rapid bioassay methodsfor carcinogens and modifiers of hepatocarcinogenesis. CRC Crit Rev Toxicol , 19, 385-415.Kensler TW (1997). Chemoprevention by inducers of carcinogendetoxication enzymes, Environ. Heath Perspect , 105, 965-70.Kim Y , Ji SK, Choi H (2000). Modulation of liver monooxygenasesystem by dietary n-6/n-3 ratios in rat hepatocarcinogenesis.Nutr Cancer , 37, 65-72.Lowry OH, Rosebrough NJ, Farr AL, et al (1951). Proteinmeasurement with the Folin phenol reagent. J Biol Chem , 193,265-75.Midorikawa K, Murata M, Oikawa S, et al (2001). Protective effectof phytic acid on oxidative DNA damage with reference to cancer chemoprevention. Biochem Biophysc Res Comm, 288,552-7.Miyamoto SA, Kuwata G, Imai M, et al (2000). Protective effectof phytic acid hydrolysis products on iron-induced lipid peroxidation of liposoaml membranes. Lipids, 35, 1411-13.Muraoka S, Miura T (2004). Inhibition of xanthine oxidase byphytic acid and its antioxidative action . Life Sci , 74, 1691-700.Nishino H, Murakoshi M, Masuda M, et al (1999). Suppression oflung and liver carcinogeneses in mice by oral administration of myo-inositol. Anticancer Res, 19, 3663-4.Porres JM, Stahl CH, Cheng WH, et al (1999). Dietary intrinsicphytate protects colon from lipid peroxidation in pigs with a moderately high dietary iron intake. Proc Soc Exp Biol Med,221, 80-6.Raj DG, Ramakrishnan S, Devi CS (1995). Myoinositol andperoxidation –an in vitro study on human cataract lens and hyman erythrocytes. Indian J Biochem Biophs, 32, 109-11.Roomi MW, Farber E, Parke DV (1997). Changes in drug-metabolizing enzymes of rats in ciprofibrate-induced hepatic nodules. Xenobiotica, 27, 951-60.Saied IT, Shamsuddin AM (1998). Up-regulation of the tumorsuppressor gene p53 and WAF 1 gene expression by IP6 in HT-29 human colon carcinoma cell line. Anticancer Res, 18,1479-84.Sakamoto K, Vucenik I, Shamsuddin AM (1993). Phytic acid(inositol hexaphosphate) is absorbed and distributed to various tissues in rats. J Nutr, 123, 13-720.Sato K (1989). Glutathione transferases as markers of preneoplasiaand neoplasia. Adv Cancer Res, 52, 204-49.Sanchez-Perez Y, Carrasco-Legleu C, Garcia-Cuellar C, et al(2005). Oxidative stress in carcinogenesis. Correlation between lipid peroxidation and induction of preneoplastic lesions in rat hepatocarcinogenesis. Cancer Lett, 217, 25-32.Schantz SP, Shillitoe EJ, Brown B, et al (1986). Natural killer cellactivity and head and neck cancer. J Natl Cancer Inst, 77, 869-75.Shamsuddin AM, Baten A, Lalwani ND (1992). Effect of inositolhexaphosphate on growth and differentiation in K-562erythroleukemia cell line. Cancer Lett, 64, 195-202.least in part, by inducing carcinogen detoxifying enzyme such as GST, and/or scavenging of ROS (Figure 4).Considering the impact of dietary prevention of cancer,further investigation should be conducted to clarify underlying mechanisms of chemoprevention by inositol and IP6.AcknowledgementsWe are truly grateful to Prof. Yong-Jun Surh (Dept. of Pharmacy, Seoul National University) for proofreading of this manuscript. This study was partly supported by a grant of the Korea Health 21 R&D Projects, Ministry of Health and Welfare, Republic of Korea (03-PJ1-PG1-CH12-0002).。

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中考英语食品安全监管机制单选题40题

中考英语食品安全监管机制单选题40题

中考英语食品安全监管机制单选题40题1. In a recent food safety incident, many people got sick because of the contaminated milk. Which of the following is the main purpose of food safety supervision mechanisms?A. To make food look more attractiveB. To ensure the safety and quality of foodC. To increase the price of foodD. To limit the variety of food答案：B。

解析：A选项让食物看起来更吸引人不是食品安全监管机制的主要目的，这可能是商家营销手段的一部分。

B选项确保食物的安全和质量是食品安全监管机制的核心目的，通过监管可以防止类似受污染牛奶导致人生病的事件发生。

C选项增加食物价格与监管机制目的无关，监管机制不是为了提高价格。

D选项限制食物种类也不是监管目的，监管是为了保障安全质量而不是限制种类。

2. After a food poisoning case in a restaurant, the local food safety supervision department took immediate action. Which of the following is a common food safety supervision agency?A. Fashion Design BureauB. Food and Drug AdministrationC. Music Copyright AssociationD. Film Censorship Board答案：B。

解析：A选项时装设计局与食品安全监管毫无关系，它主要负责时装相关事务。

对节食的看法英语作文

对节食的看法英语作文

对节食的看法英语作文Dietary Approaches to Weight Management: A Critical Examination.Throughout history, the pursuit of weight managementhas sparked a plethora of dietary approaches, eachpromising a unique pathway to achieving the desired outcome. While some diets have gained widespread popularity, others have faced skepticism and even condemnation. In this essay, we will delve into the multifaceted world of dietary approaches to weight management, examining their underlying principles, potential benefits, and limitations.Restrictive Diets: A Quick Fix with Long-Term Consequences.Restrictive diets, as their name suggests, imposestrict limitations on food intake, often excluding entire food groups. Popular examples include the ketogenic diet, the paleo diet, and intermittent fasting. While these dietsmay initially lead to rapid weight loss, they often come with a slew of potential drawbacks.One major concern is nutrient deficiencies. Severely restricting food intake can lead to a lack of essential vitamins, minerals, and other nutrients. This can havewide-ranging implications for overall health, including impaired cognitive function, compromised immune system, and digestive problems.Furthermore, restrictive diets can be difficult to adhere to over the long term. The extreme nature of these diets can lead to feelings of deprivation, increased cravings, and eventually, relapse. Research has shown that most individuals who lose weight on restrictive diets regain it within a few years.Balanced Diets: A Sustainable Approach.In contrast to restrictive diets, balanced diets emphasize the consumption of a wide variety of nutrient-rich foods. These diets are designed to provide the bodywith all the necessary nutrients while still supporting weight management goals. Examples include the Mediterranean diet, the DASH diet, and the MIND diet.Balanced diets have several advantages over restrictive diets. First, they are more likely to meet nutritional needs and prevent nutrient deficiencies. Second, they are easier to follow over the long term because they allow for flexibility and moderation. Third, balanced diets promote overall health and well-being, reducing the risk of chronic diseases such as heart disease, diabetes, and cancer.Mindful Eating: A Journey of Self-Awareness andIntuitive Choices.Mindful eating is not a specific diet but rather an approach to eating that emphasizes paying attention to the present moment, savoring food, and responding to hunger and fullness cues. Mindful eating has been shown to support weight management by promoting healthier eating habits and reducing emotional overeating.By practicing mindful eating, individuals become more aware of their hunger and fullness signals, allowing themto make more conscious choices about what and how much to eat. This approach also helps cultivate a positive relationship with food and reduces feelings of guilt or shame associated with eating.Lifestyle Modifications: Beyond Diet Alone.While diet plays an important role in weight management, it is only one component of a comprehensive approach. Sustainable weight loss requires addressing other lifestyle factors, including physical activity, sleep, and stress management.Regular physical activity not only burns calories but also builds muscle, which can boost metabolism. Aiming forat least 150 minutes of moderate-intensity exercise per week is recommended for weight management.Sleep deprivation can lead to hormonal imbalances that stimulate appetite and increase cravings. Aiming for 7-9hours of quality sleep each night is crucial for weight management.Stress can trigger emotional eating and interfere with weight loss efforts. Finding healthy ways to manage stress, such as exercise, meditation, or yoga, can support overall well-being and weight management.Personalized Approaches to Weight Management.It is important to note that there is no one-size-fits-all approach to weight management. The best diet and lifestyle modifications for one person may not be suitable for another. Factors such as age, health status, and individual preferences should be considered when choosing a weight management approach.Consultation with a healthcare professional or registered dietitian is highly recommended to develop a personalized weight management plan that addresses individual needs and goals.Conclusion.Dietary approaches to weight management encompass a wide spectrum of options, each with its own principles, benefits, and limitations. While restrictive diets mayoffer a quick fix, they often come with potential drawbacks such as nutrient deficiencies and long-term weight regain. Balanced diets, mindful eating, and lifestyle modifications provide more sustainable and comprehensive approaches to weight management, promoting overall health and well-being. It is essential to seek personalized guidance from healthcare professionals to determine the most suitable weight management strategy for individual needs and goals.。

常见职位名称 The titles of common positions

常见职位名称 The titles of common positions

常见职位名称 The titles of common positions Accountant 会计员，会计师Administration Assistant 行政助理Administrator 行政主管Apprentice 学徒Architect 建筑师Assistant Manager 副经理Assistant Production Manager 副厂长Business Manager 业务经理Cashier 出纳员Chief Accountant 总会计主任Chief Engineer 总工程师Civil Engineer 土木工程师Clerk 文员（文书）Director 董事Electrical Engineer 电气工程师Executive Director 行政董事Executive Secretary 行政秘书Financial Controller 财务总监Foreman 领班，组长General manager 总经理Junior clerk 低级文员（低级职员）Manager 经理Marketing Executive 市场部主任Marketing Manager 市场部经理Marketing Officer 市场部办公室主任Mechanical Engineer 机械工程师Merchandiser 买手（商人）Messenger 信差（邮递员）Office Assistant 写字楼助理（办事员）Plant Manager 厂长Practice Nurse 见习护士Production Manager 厂长Quality Controller 品质控制员（质量检查员）Receptionist 接线生（接线员）Sales Engineer 销售工程师Sales Executive 销售主任Sales Manager 销售经理Sales Representative 营业代表Salesman 推销员Secretary 秘书Senior Clerk 高级文员（高级职员）Skilled Worker 熟练技工Stenographer 速记员Sub-Manager 副经理Supervisor 主管Surveyor 测量员Technician 技术员Telex Operator 电传机操作员Translator 翻译员Typist 打字员会计与财务部分Accounting and FinanceAccounting Assistant 会计助理Accounting Clerk 会计文员Accounting Manager 会计经理Accounting Payable Clerk 应付帐款文员Accounts Receivable Clerk 应收帐款文员Actuarial Anaylst 保险分析员Assistant Portfolio Manager 组合基金经理助理Audit Manager 审计经理Auditor 审计师Bank Administrator 银行事务管理员Bank Clerk 银行出纳Bank Treasurer 资金调拨Billing Clerk 票据文员Billing Supervisor 票据管理员Bookkeeper 档案管理Bookkeeping Clerk 档案管理助理Budget Analyst 预算分析Certified Public Accountant 注册会计师Chief Financial Officer 首席财务官Collections Officer 收款负责人 Credit Analyst 信用分析Credit Manager 信用管理经理Financial Analyst 财务分析Financial Consultant 财务顾问Financial Manager 财务经理Financial Planner 财务计划员Insurance Underwriter 保险承销商Junior Accountant 初级会计Loan Administrator 贷款管理员Loan Servicer 贷款服务Management Accountant 管理会计Mortgage Underwriter 抵抻保险员Payroll Manager 工资经理Senior Accoutant 高级会计Staff Auditor 审计员Stock Broker 股票经纪人Tax Accountant 税务会计Tax Inspector 税务检查员Vice-President of Finance 财务副总裁Vice-President of Administration and Finance 财务行政副总裁行政部分 AdministrationAdministrative Director 行政主管Executive Assistant 行政助理Executive Secretary 行政秘书File Clerk 档案管理员General Office Clerk 办公室文员Inventory Control Analyst 存货控制分析Mail Room Supervisor 信件中心管理员Office Manager 办公室经理Order Entry Clerk 订单输入文员Receptionist 接待员Secretary秘书Shipping/Receiving Expediter 收发督导员Staff Assistant 助理Stenographer 速记员Telephone Operator 电话操作员Ticket Agent 票务代理Typist 打字员Vice-President of Administration 行政副总裁传播业部分CommunicationsAssistant Editor 编辑助理Associate Editor 助理编辑Author 作家Broadcast Producer 广播制作人Columnist 专栏作家Copy Editor 文件编辑Correspondent 通讯记者Editor 编辑Editorial Director 编辑主任Events Planner 活动策划Information Support Specialist 信息专员Journalist 新闻记者Managing Editor 执行编辑Production Editor 制作编辑Proofreader 校对Public Relations Assistant 公共关系助理Public Relations 公共关系Publicist 广告员Radio Announcer 电台播音员Radio Program Director 广播节目总监Reporter 记者Symposium Coordinator 研讨会协调员Television Director 电视导演Television Producer 电视制片人Television Production Engineer 电视制片工程师Translator 翻译员Typesetter 排字工人Writer 作者计算机部分Computers and Mathematics Applications Programmer 应用软件程序员Computer Operations Supervisor 电脑操作主管Computer Operator 电脑操作员Computer Technician 电脑技术员Developmental Engineer 开发工程师Director of Information Services 信息服务主管Hardware Engineer 硬件工程师Information Analyst 信息分析LAN Administrator 局域网管理员Manager of Network Administration 网络管理经理MIS Manager 电脑部经理Operations Analyst 操作分析Product Support Manager 产品支持经理Project Manager 项目经理Statistician 统计员Subcontractor(Programming) 承包商Systems Analyst 系统分析Systems Engineer 系统工程师Systems Programmer 系统程序员Technical Engineer 技术工程师表演艺术业部分Visual and Performing Arts Actor/Actress 男演员/女演员Art Administrator 艺术主任Art Director 艺术总监Choreographer 舞蹈教练Comedian 喜剧演员Commercial Artist/Instructor 商业艺术家Dancer 舞蹈家Fashion Designer 服装设计师Film Production Assistant 电影摄制助理Graphic Artist/Designer 画家/画面设计师Interior Designer 装饰设计师Model 模特Musician 音乐家Photographer 摄影师Production Coordinator 制片协调员Production(Tour)Manager 制片经理（外景）Theatrical Director 戏剧总监Visual Artist 视觉艺术家技术业部分TechnicalAircraft Mechanic 航行器技工Aircraft Pilot 飞行员Architect 建筑师Broadcast Technician 广播技术员Building Inspector 房屋验收Drafter 草图设计员Electrician 电学家Electronic Equipment Repairer 电子设备维修员Engineering Technician 工程技术员Landscape Architect 建筑师Precision Inspector 精密度检查员QA Test Technician 质量检测技术员Quality Control Inspector 质量管理检查员Research and Development Technician 研究发展技术员Surveyor 测量员Technical Illustrator 技术讲解员Technical Instructor 技术指导讲师Technical Support Specialist 技术支持专员Telecommunications Consultant 电信业顾问管理部分Executive and ManagerialAssistant Store Manager 商店经理助理Assistant Vice-President 副总裁助理Branch Manager 部门经理Chief Executive Officer(CEO) 首席执行官Chief Operations Officer(COO) 首席运营官Claims Examiner 主考官Controller(General) 管理员Controller(International) 国际监管Director of Operations 运营总监District Manager 市区经理Executive Marketing Director 市场行政总监Field Assurance Coordinator 土地担保协调员Food Service Manager 食品服务经理General Manager 总经理HMO Administrator 医疗保险管理Hospital Administrator 医院管理Import/Export Manager 进出口经理Insurance Claims Controller 保险认领管理员Insurance Coordinator 保险协调员Inventory Control Manager 库存管理经理Management Consultant 管理顾问Manufacturing Manager 制造业经理Operations Manager 操作经理President 总统Product Manager 产品经理Production Manager 生产经理Program Manager 程序管理经理Project Manager 项目经理Property Manager 房地产经理Regional Manager 区域经理Retail Store Manager 零售店经理Service Manager 服务经理Telecommunications Manager 电信业经理Transportation Manager 运输经理Vending Manager 售买经理Vice-President 副总裁Warehouse Manager 仓库经理Manager(Non-Profit and Charities) 非盈利性慈善机构管理人力资源部分Human ResourcesAssistant Personnel Officer 人事助理Assistant Vice-President of Human Resources 人力资源副总裁助理Benefits Coordinator 员工福利协调员Compensation Manager 薪酬经理Director of Human Resources 人力资源总监Employer Relations Representative 员工关系代表Employment Consultant 招募顾问Facility Manager 后勤经理Job Placement Officer 人员配置专员Labor Relations Specialist 劳动关系专员Personnel Consultant 员工顾问Personnel Manager 职员经理Recruiter 招聘人员Training Coordinator 培训协调员Training Specialist 培训专员Vice-President of Human Resources 人力资源副总裁市场与销售部分Marketing and SalesAccount Manager 客户经理Account Representative 客户代表Ad Copywriter(Direct Mail) 广告文撰写人Advertising Assistant 广告助理Advertising Coordinator 广告协调员Advertising Manager 广告经理Assistant Account Executive 客户管理助理Callback Representative 复查代表Director of Subsidiary Rights 分公司权利总监Insurance Agent 保险代理人Manufacturer's Representative 厂家代表Market Research Analyst 市场调查分析员Marketing and Sales Director 市场与销售总监Marketing Assistant 市场助理Marketing Consultant 市场顾问Marketing Director 市场总监Marketing Intern 市场实习Marketing Manager 市场经理Merchandising Manager 采购经理Product Developer 产品开发Purchasing Agent 采购代理Real Estate Appraiser 房地产评估师Real Estate Broker 房地产经纪人Real Estate Manager 房地产经理Regional Account Manager 地区客户经理Regional Sales Manager 地区销售经理Retail Buyer 零售采购员Sales Administrator 销售主管Sales Assistant 销售助理Sales Executive 销售执行者Sales Manager 销售经理Sales Representative 销售代表Salesperson 销售员Senior Account Manager 高级客户经理Tele-Interviewer 电话调查员Telemarketer 电话销售员Telemarketing Director 电话销售总监Travel Agent 旅行代办员Vice-President of Marketing 市场副总裁Vice-President of Sales 销售副总裁Wholesale Buyer 批发采购员医学与健康部分Health and MedicalCardiologist 心脏病专家Chiropractor 脊椎指压治疗者Clinical Director 医疗主任Dental Assistant 牙科助理Dental Hygienist 牙科保健Dental Technician 牙科技师Dentist 牙科医生Dietary Technician 食疗技师Dietician 饮食专家Emergency Medical Technician 急诊技师Fitness Instructor 健美师Health Services Coordinator 健康服务协调员Home Health Aide 家庭护理Hospital Supervisor 医院管理员Lab Technician 实验技师Medical Records Clerk 病历员Medical Technologist 医疗专家Nurse 护士Nursing Administrator 看护员 Nursing Aide 看护助手Nursing Home Manager 家护管理员Nursing Supervisor 护士长Nutritionist 营养学家Occupational Therapist 职业疗法Optician 眼科医生Orthodontist 整牙医生Pediatrician 儿科医生Pharmacist 药学师Pharmacy Technician 药品技师Physical Therapist 理疗师Physician's Assistant 助理医师Psychiatrist 精神病医师Respiratory Therapist 有氧治疗师Speech Pathologist 语言心理学家Surgeon 外科医生Veterinarian 兽医Veterinary Assistant 助理兽医原文地址：英文职位名称（A)作者：nancy公司高层职位的英文缩写:CEO： Chief Executive Officer 首席执行官CFO： Chief Financial Officer 首席财务官COO： Chief Operated Officer 首席运营官CTO ： Chief Technology Officer 首席技术官CIO ： Chief Information Officer 首席信息官CRO： Chief Risk Officer 首席风险官CEO（Chief Executive Officer），即首席执行官，是美国人在20世纪60年代进行公司治理结构改革创新时的产物，它的出现在某种意义上代表着将原来董事会手中的一些决策权过渡到经营层手中。

(完整版)美国FDA《联邦规章典集》(CFR)第21篇目录中文版

(完整版)美国FDA《联邦规章典集》(CFR)第21篇目录中文版

美国FDA《联邦规章典集》（CFR）第21篇目录中文版发布时间：2010-5-11 13:44:12 发布方：奥咨达医疗器械咨询美国《联邦规章典集》（CFR）第21篇“食品与药品”总目概述：美国《联邦规章典集》（Code of Federal Regulations，CFR）第21篇“食品与药品”（Title 21―Food and Drugs）共有9卷（Volume）、3章（Chapter）、1499部（Parts）。

其中：第1―8卷第1章第1―1299部，为健康与人类服务部食品与药品管理局（Food and Drug Administration，Department of Health and Human Services）的规章；第9卷第2章第1300―1399部，为司法部毒品强制执行局（Drug Enforcement Administration，Department of Justice）的规章；第9卷第3章第1400―1499部，为毒品控制政策办公室（Office of National Drug Control Policy）的规章。

第21篇“食品与药品”（Tit le 21―Food and Drugs）的概况卷（Volume）章（Chapter）部（Parts）规制机关（Regulatory Entity）1 Ⅰ1-99 健康与人类服务部食品与药品管理局（FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES）2 100-1693 170-1994 200-2995 300-4996 500-5997 600-7998 800-12999 Ⅱ1300-1399 司法部毒品强制执行局（Drug Enforcement Administration，Department of Justice）Ⅲ1400-1499 毒品控制政策办公室（Office of National Drug Control Policy）第21篇“食品与药品”（Title 21―Food and Drugs）的章、部目录部(Part) 中译文原英文第Ⅰ章―健康与人类服务部食品与药品管理局（CHAPTER Ⅰ―FOOD AND DRUG ADMINIST RATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES）第A分章―总则（SUBCHAPTER A―GENERAL）1 一般强制执行规章GENERAL ENFORCEMENT REGULATIONS2 一般行政规则与决定GENERAL ADMINISTRATIVE RULINGS AND DECISIONS3 产品管辖权PRODUCT JURISDICTION5 组织ORGANIZATION7 强制执行政策ENFORCEMENT POLICY10 行政规范与程序ADMINISTRATIVE PRACTICES AND PROCEDURES11 电子化记录；电子化签名ELECTRONIC RECORDS; ELECTRONIC SIGNATURES12 正式证据的公众听证FORMAL EVIDENTIARY PUBLIC HEARING13 在公众质询委员会前的公众听证PUBLIC HEARING BEFORE A PUBLIC BOARD OF INQUIRY14 在公众咨询委员会前的公众听证PUBLIC HEARING BEFORE A PUBLIC ADVISORY COMMITTEE15 在FDA局长前的公众听证PUBLIC HEARING BEFORE THE COMMISSIONER16 在FDA前的规制性听证REGULATORY HEARING BEFORE THE FOOD AND DRUG ADMINISTRATION17 行政罚款听证CIVIL MONEY PENALTIES HEARINGS19 行为标准与利益冲突STANDARDS OF CONDUCT AND CONFLICTS OF INTEREST20 公共信息PUBLIC INFORMATION21 隐私保护PROTECTION OF PRIVACY25 环境影响考虑ENVIRONMENTAL IMPACT CONSIDERATIONS26 药品良好制造规范报告、医疗器械质量体系核查报告以及某些医疗器械产品评价报告的互认：美国与欧共体MUTUAL RECOGNITION OF PHARMACEUTICAL GOOD MANUFACTURING PRACTICE REPORTS, MEDICAL DEVICE QUALITY SYSTEM AUDIT REPORTS, AND CERTAIN MEDICAL DEVICE PRODUCT EVALUATION REPORTS: UNITED STATES AND THE EUROPEAN COMMUNITY50 人类受试者的保护PROTECTION OF HUMAN SUBJECTS54 临床试验者的财务公开FINANCIAL DISCLOSURE BY CLINICAL INVESTIGATORS56 机构审查委员会INSTITUTIONAL REVIEW BOARDS58 对非临床实验室研究的良好实验室规范GOOD LABORATORY PRACTICE FOR NONCLINICAL LABORATORY STUDIES60 专利期恢复PATENT TERM RESTORATION70 色素添加剂COLOR ADDITIVES71 色素添加剂申请COLOR ADDITIVE PETITIONS73 免除认证的色素添加剂的列表LISTING OF COLOR ADDITIVES EXEMPT FROM CERTIFICATION74 适用认证的色素添加剂的列表LISTING OF COLOR ADDITIVES SUBJECT TO CERTIFICATION80 色素添加剂认证COLOR ADDITIVE CERTIFICATION81 用于食品、药品和化妆品的临时性色素添加剂的一般规范和一般限制GENERAL SPECIFICATIONS AND GENERAL RESTRICTIONS FOR PROVISIONAL COLOR ADDITIVES FOR USE IN FOODS, DRUGS, AND COSMETICS82 经认证的临时性列表的色素和规范的列表LISTING OF CERTIFIED PROVISIONALLY LISTED COLORS AND SPECIFICATIONS83-98 [预留的] [Reserved]99 已上市的药品、生物制品和器械的未经批准的/新的用途的信息的发布DISSEMINATION OF INFORMATION ON UNAPPROVED/NEW USES FOR MARKETED DRUGS, BIOLOGICS, AND DEVICES第B分章―用于人类消费的食品（SUBCHAPTER B―FOOD FOR HUMAN CONSUMPTION）100 总则GENERAL101 食品标识FOOD LABELING102 非标准化食品的普通的或者通常的名称COMMON OR USUAL NAME FOR NONSTANDARDIZED FOODS104 食品的营养质量指南NUTRITIONAL QUALITY GUIDELINES FOR FOODS105 特殊膳食用途的食品FOODS FOR SPECIAL DIETARY USE106 婴儿配方母乳替代食品质量控制程序INFANT FORMULA QUALITY CONTROL PROCEDURES107 婴儿配方母乳替代食品INFANT FORMULA108 紧急许可控制EMERGENCY PERMIT CONTROL109 在人类食品与食品-包装材料中的不可避免的污染物UNAVOIDABLE CONTAMINANTS IN FOOD FOR HUMAN CONSUMPTION AND FOOD-PACKAGING MATERIAL110 在制造、包装或者保存人类食品中的现行良好制造规范CURRENT GOOD MANUFACTURING PRACTICE IN MANUFACTURING, PACKING, OR HOLDING HUMAN FOOD113 装在密封容器中的热加工低酸食品THERMALLY PROCESSED LOW-ACID FOODS PACKAGED IN HERMETICALLY SEALED CONTAINERS114 酸化食品ACIDIFIED FOODS115 带壳蛋SHELL EGGS119 存在显著或者不合理风险的膳食补充剂DIETARY SUPPLEMENTS THAT PRESENT A SIGNIFICANT OR UNREASONABLE RISK120 危害分析与关键控制点（HACCP）体系HAZARD ANALYSIS AND CRITICAL CONTROL POINT (HACCP) SYSTEMS123 鱼与渔业产品FISH AND FISHERY PRODUCTS129 饮用水加工与装瓶PROCESSING AND BOTTLING OF BOTTLED DRINKING WATER130 食品标准：总则FOOD STANDARDS: GENERAL131 乳与奶油MILK AND CREAM133 乳酪与相关乳酪产品CHEESES AND RELATED CHEESE PRODUCTS135 冷冻点心FROZEN DESSERTS136 烘焙产品BAKERY PRODUCTS137 谷物粉与相关产品CEREAL FLOURS AND RELATED PRODUCTS139 通心粉与面条产品MACARONI AND NOODLE PRODUCTS145 罐装水果CANNED FRUITS146 罐装水果汁CANNED FRUIT JUICES150 水果黄油、果冻、防腐剂以及相关产品FRUIT BUTTERS, JELLIES, PRESERVES, AND RELATED PRODUCTS152 水果馅饼FRUIT PIES155 罐装蔬菜CANNED VEGETABLES156 蔬菜汁VEGETABLE JUICES158 冷冻蔬菜FROZEN VEGETABLES160 蛋与蛋制品EGGS AND EGG PRODUCTS161 鱼与有壳的水生动物FISH AND SHELLFISH163 可可制品CACAO PRODUCTS164 树坚果与花生制品TREE NUT AND PEANUT PRODUCTS165 饮料BEVERAGES166 人造黄油MARGARINE168 增甜剂与餐桌糖浆SWEETENERS AND TABLE SIRUPS169 食品敷料与调味料FOOD DRESSINGS AND FLAVORINGS170 食品添加剂FOOD ADDITIVES171 食品添加剂申请FOOD ADDITIVE PETITIONS172 允许直接加入用于人类消费食品的食品添加剂FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION173 在用于人类消费的食品中允许的次直接的食品添加剂SECONDARY DIRECT FOOD ADDITIVES PERMITTED IN FOOD FOR HUMAN CONSUMPTION174 间接食品添加剂：总则INDIRECT FOOD ADDITIVES: GENERAL175 间接食品添加剂：胶粘剂与涂层的组分INDIRECT FOOD ADDITIVES: ADHESIVES AND COMPONENTS OF COATINGS176 间接食品添加剂：纸与纸板组分INDIRECT FOOD ADDITIVES: PAPER AND PAPERBOARD COMPONENTS177 间接食品添加剂：聚合体INDIRECT FOOD ADDITIVES: POLYMERS178 间接食品添加剂：辅剂、生产助剂和消毒剂INDIRECT FOOD ADDITIVES: ADJUVANTS, PRODUCTION AIDS, AND SANITIZERS 179 在食品生产、加工和处理中的辐照IRRADIATION IN THE PRODUCTION, PROCESSING AND HANDLING OF FOOD180 在额外试验期间临时在食品或者在与食品接触中被允许的食品添加剂FOOD ADDITIVES PERMITTED IN FOOD OR IN CONTACT WITH FOOD ON AN INTERIM BASIS PENDING ADDITIONAL STUDY181 先前核准的食品配料PRIOR-SANCTIONED FOOD INGREDIENTS182 一般认为安全的物质SUBSTANCES GENERALLY RECOGNIZED AS SAFE184 被确认为一般认为安全的直接食品物质DIRECT FOOD SUBSTANCES AFFIRMED AS GENERALLY RECOGNIZED AS SAFE 186 被确认为一般认为安全的间接食品物质INDIRECT FOOD SUBSTANCES AFFIRMED AS GENERALLY RECOGNIZED AS SAFE 189 禁止用于人类食品的物质SUBSTANCES PROHIBITED FROM USE IN HUMAN FOOD190 膳食补充剂DIETARY SUPPLEMENTS191-199 [预留的] [Reserved]第C分章―药品：总则（SUBCHAPTER C―DRUGS: GENERAL）200 总则GENERAL201 标识LABELING202 处方药广告PRESCRIPTION DRUG ADVERTISING203 处方药销售PRESCRIPTION DRUG MARKETING205 对批发处方药销售商颁发州执照的指南GUIDELINES FOR STATE LICENSING OF WHOLESALE PRESCRIPTION DRUG DISTRIBUTORS206 人用固体口服剂型药品的印码IMPRINTING OF SOLID ORAL DOSAGE FORM DRUG PRODUCTS FOR HUMAN USE207 药品生产者的登记与商业销售的药品的列表REGISTRATION OF PRODUCERS OF DRUGS AND LISTING OF DRUGS IN COMMERCIAL DISTRIBUTION208 处方药的药物治疗指导MEDICATION GUIDES FOR PRESCRIPTION DRUG PRODUCTS210 制造、加工、包装或者保存药品的现行良好制造规范；总则CURRENT GOOD MANUFACTURING PRACTICE IN MANUFACTURING, PROCESSING, PACKING, OR HOLDING OF DRUGS; GENERAL211 对完成的药品的现行良好制造规范CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS216 药房配药PHARMACY COMPOUNDING225 对含药饲料的现行良好制造规范CURRENT GOOD MANUFACTURING PRACTICE FOR MEDICATED FEEDS226 对A型含药物品的现行良好制造规范CURRENT GOOD MANUFACTURING PRACTICE FOR TYPE A MEDICATED ARTICLES 250 对特殊人用药品的特殊要求SPECIAL REQUIREMENTS FOR SPECIFIC HUMAN DRUGS290 管制的药品CONTROLLED DRUGS299 药品；正式名称与已确定的名称DRUGS; OFFICIAL NAMES AND ESTABLISHED NAMES第D分章―人用药品（SUBCHAPTER D―DRUGS FOR HUMAN USE）300 总则GENERAL310 新药NEW DRUGS312 试验用新药申请INVESTIGATIONAL NEW DRUG APPLICATION314 为FDA批准上市新药的申请APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG315 诊断用放射性药品DIAGNOSTIC RADIOPHARMACEUTICALS316 罕见病药ORPHAN DRUGS320 生物利用度与生物等效性要求BIOAVAILABILITY AND BIOEQUIVALENCE REQUIREMENTS328 含有酒精的预期用于口部摄入的非处方药品OVER-THE-COUNTER DRUG PRODUCTS INTENDED FOR ORAL INGESTION THAT CONTAIN ALCOHOL330 一般认为安全与有效以及不错误标识的非处方人用药品OVER-THE-COUNTER (OTC) HUMAN DRUGS WHICH ARE GENERALLY RECOGNIZED AS SAFE AND EFFECTIVE AND NOT MISBRANDED331 用于非处方的人类使用的抗酸产品ANTACID PRODUCTS FOR OVER-THE-COUNTER (OTC) HUMAN USE332 用于非处方的人类使用的抗胃肠气胀产品ANTIFLATULENT PRODUCTS FOR OVER-THE-COUNTER HUMAN USE333 用于非处方的人类使用的局部抗菌药品TOPICAL ANTIMICROBIAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE335 用于非处方的人类使用的止泻药品ANTIDIARRHEAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE336 用于非处方的人类使用的止吐药品ANTIEMETIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE338 用于非处方的人类使用的帮助夜间睡眠的药品NIGHTTIME SLEEP-AID DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE340 用于非处方的人类使用的兴奋药品STIMULANT DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE341 用于非处方的人类使用的感冒、咳嗽、过敏症药、支气管扩张以及平喘药品COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE343 用于非处方的人类使用的内服的止痛、退热以及抗风湿药品INTERNAL ANALGESIC, ANTIPYRETIC, AND ANTIRHEUMATIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE344 用于非处方的人类使用的局部的耳部药品TOPICAL OTIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE346 用于非处方的人类使用的肛肠药品ANORECTAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE347 用于非处方的人类使用的皮肤保护药品SKIN PROTECTANT DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE348 用于非处方的人类使用的外部的止痛药品EXTERNAL ANALGESIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE349 用于非处方的人类使用的眼科药品OPHTHALMIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE350 用于非处方的人类使用的止汗药品ANTIPERSPIRANT DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE352 用于非处方的人类使用的遮光药品SUNSCREEN DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE [STAYED INDEFINITELY]355 用于非处方的人类使用的防龋药品ANTICARIES DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE357 用于非处方的人类使用的其他内服药品MISCELLANEOUS INTERNAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE358 用于非处方的人类使用的其他外用药品MISCELLANEOUS EXTERNAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE361 一般认为安全与有效以及不错误标识的处方人用药品：用于研究的药品PRESCRIPTION DRUGS FOR HUMAN USE GENERALLYRECOGNIZED AS SAFE AND EFFECTIVE AND NOT MISBRANDED: DRUGS USED IN RESEARCH369 在用于非处方销售的药品与器械上关于警告的解释性声明INTERPRETATIVE STATEMENTS RE WARNINGS ON DRUGS AND DEVICES FOR OVER-THE-COUNTER SALE370-499 [预留的] [Reserved]第E分章―动物药品、饮料和相关产品（SUB CHAPTER E―ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS）500 总则GENERAL501 动物食品标识ANIMAL FOOD LABELING502 非标准化的动物食品的普通的或通常的名称COMMON OR USUAL NAMES FOR NONSTANDARDIZED ANIMAL FOODS509 在动物食品与食品-包装材料中的不可避免的污染物UNAVOIDABLE CONTAMINANTS IN ANIMAL FOOD AND FOOD-PACKAGING MATERIAL510 新动物药NEW ANIMAL DRUGS511 作为试验用途的新动物药NEW ANIMAL DRUGS FOR INVESTIGATIONAL USE514 新动物药申请NEW ANIMAL DRUG APPLICATIONS515 含药饲料厂执照MEDICATED FEED MILL LICENSE520 口服剂型的新动物药ORAL DOSAGE FORM NEW ANIMAL DRUGS522 植入或者注射剂型的新动物药IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS524 眼科和局部剂型的新动物药OPHTHALMIC AND TOPICAL DOSAGE FORM NEW ANIMAL DRUGS526 乳房内的剂型INTRAMAMMARY DOSAGE FORMS529 某些其他剂型的新动物药CERTAIN OTHER DOSAGE FORM NEW ANIMAL DRUGS530 在动物中的特别标签药品使用EXTRALABEL DRUG USE IN ANIMALS556 在食品中新动物药残留的容许量TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD558 用于动物饲料的新动物药NEW ANIMAL DRUGS FOR USE IN ANIMAL FEEDS564 [预留的] [Reserved]570 食品添加剂FOOD ADDITIVES571 食品添加剂申请FOOD ADDITIVE PETITIONS573 在动物饲料与饮用水中允许的食品添加剂FOOD ADDITIVES PERMITTED IN FEED AND DRINKING WATER OF ANIMALS579 在动物饲料和宠物食品的生产、加工和处理中的辐照IRRADIATION IN THE PRODUCTION, PROCESSING, AND HANDLING OF ANIMAL FEED AND PET FOOD582 一般认为安全的物质SUBSTANCES GENERALLY RECOGNIZED AS SAFE584 在动物饲料与饮用水中被确认为一般认为安全的食品物质FOOD SUBSTANCES AFFIRMED AS GENERALLY RECOGNIZED AS SAFE IN FEED AND DRINKING WATER OF ANIMALS589 禁止用于动物食品或者饲料的物质SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEED590-599 [预留的] [Reserved]第F分章―生物制品（SUB CHAPTER F―BIOLOGICS）600 生物制品：总则BIOLOGICAL PRODUCTS: GENERAL601 颁发执照LICENSING606 对血液与血液组分的现行良好制造规范CURRENT GOOD MANUFACTURING PRACTICE FOR BLOOD AND BLOOD COMPONENTS607 对人类血液与血液制品的制造者的机构登记与产品列表ESTABLISHMENT REGISTRATION AND PRODUCT LISTING FOR MANUFACTURERS OF HUMAN BLOOD AND BLOOD PRODUCTS610 普通生物制品标准GENERAL BIOLOGICAL PRODUCTS STANDARDS630 对血液、血液组分和血液衍生物的一般要求GENERAL REQUIREMENTS FOR BLOOD, BLOOD COMPONENTS, AND BLOOD DERIVATIVES640 对人类血液和血液制品的附加标准ADDITIONAL STANDARDS FOR HUMAN BLOOD AND BLOOD PRODUCTS660 对用于实验室检测的诊断物质的附加标准ADDITIONAL STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS680 对其他产品的附加标准ADDITIONAL STANDARDS FOR MISCELLANEOUS PRODUCTS第G分章―化妆品（SUBCHAPTER G―COSMETICS）700 总则GENERAL701 化妆品标识COSMETIC LABELING710 化妆品机构的自愿登记VOLUNTARY REGISTRATION OF COSMETIC PRODUCT ESTABLISHMENTS720 化妆品配料构成声明的自愿存档VOLUNTARY FILING OF COSMETIC PRODUCT INGREDIENT COMPOSITION STATEMENTS740 化妆品警告声明COSMETIC PRODUCT WARNING STATEMENTS741-799 [预留的] [Reserved]第H分章―医疗器械（SUBCHAPTER H―MEDICAL DEVICES）800 总则GENERAL801 标识LABELING803 医疗器械报告MEDICAL DEVICE REPORTING806 医疗器械；改正与移动的报告MEDICAL DEVICES; REPORTS OF CORRECTIONS AND REMOVALS807 对器械的制造者与首次进口者的机构登记与器械列表ESTABLISHMENT REGISTRATION AND DEVICE LISTING FOR MANUFACTURERS AND INITIAL IMPORTERS OF DEVICES808 对州和地方医疗器械要求的联邦优先权的豁免EXEMPTIONS FROM FEDERAL PREEMPTION OF STATE AND LOCAL MEDICAL DEVICE REQUIREMENTS809 人用体外诊断产品IN VITRO DIAGNOSTIC PRODUCTS FOR HUMAN USE810 医疗器械召回权MEDICAL DEVICE RECALL AUTHORITY812 试验用器械豁免INVESTIGATIONAL DEVICE EXEMPTIONS813 [预留的] [Reserved]814 医疗器械的上市前批准PREMARKET APPROVAL OF MEDICAL DEVICES820 质量体系规章QUALITY SYSTEM REGULATION821 医疗器械跟踪要求MEDICAL DEVICE TRACKING REQUIREMENTS822 上市后监视POSTMARKET SURVEILLANCE860 医疗器械分类程序MEDICAL DEVICE CLASSIFICATION PROCEDURES861 性能标准制定程序PROCEDURES FOR PERFORMANCE STANDARDS DEVELOPMENT862 临床化学与临床毒理学器械CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES864 血液学与病理学器械HEMATOLOGY AND PATHOLOGY DEVICES866 免疫学与微生物学器械IMMUNOLOGY AND MICROBIOLOGY DEVICES868 麻醉学器械ANESTHESIOLOGY DEVICES870 心血管器械CARDIOVASCULAR DEVICES872 牙科器械DENTAL DEVICES874 耳、鼻和咽器械EAR, NOSE, AND THROAT DEVICES876 胃肠病学-泌尿学器械GASTROENTEROLOGY-UROLOGY DEVICES878 普通与整形外科器械GENERAL AND PLASTIC SURGERY DEVICES880 普通医院与个人使用器械GENERAL HOSPITAL AND PERSONAL USE DEVICES882 神经学器械NEUROLOGICAL DEVICES884 产科与妇科学器械OBSTETRICAL AND GYNECOLOGICAL DEVICES886 眼科器械OPHTHALMIC DEVICES888 矫形外科器械ORTHOPEDIC DEVICES890 内科学器械PHYSICAL MEDICINE DEVICES892 放射学器械RADIOLOGY DEVICES895 禁止的器械BANNED DEVICES898 电极铅线与患者电缆的性能标准PERFORMANCE STANDARD FOR ELECTRODE LEAD WIRES AND PATIENT CABLES第I分章―乳房造影质量标准法（SUBCHAPTER I―MAMMOGRAPHY QUALITY STANDA RDS ACT）900 乳房造影法MAMMOGRAPHY第J分章―放射学的健康（SUBCHAPTER J―RADIOLOGICAL HEALTH）1000 总则GENERAL1002 记录与报告RECORDS AND REPORTS1003 缺陷与未能守法的通报NOTIFICATION OF DEFECTS OR FAILURE TO COMPLY1004 电子产品的回购、修理或者置换REPURCHASE, REPAIRS, OR REPLACEMENT OF ELECTRONIC PRODUCTS1005 电子产品的进口IMPORTATION OF ELECTRONIC PRODUCTS1010 电子产品的性能标准：总则PERFORMANCE STANDARDS FOR ELECTRONIC PRODUCTS: GENERAL1020 电离辐射发生产品的性能标准PERFORMANCE STANDARDS FOR IONIZING RADIATION EMITTING PRODUCTS1030 微波与射电频率发生产品的性能标准PERFORMANCE STANDARDS FOR MICROWAVE AND RADIO FREQUENCY EMITTING PRODUCTS1040 发光产品的性能标准PERFORMANCE STANDARDS FOR LIGHT-EMITTING PRODUCTS1050 声波、次声波和超声波发生产品的性能标准PERFORMANCE STANDARDS FOR SONIC, INFRASONIC, AND ULTRASONIC RADIATION-EMITTING PRODUCTS第K分章―[预留的]（SUBCHAPTER K―[RESERVED]）第L分章―根据由食品与药品管理局行政执行的某些其他法的规章（SUBCHAPTER L―REGULATIONS UNDER CERTAIN OTHER ACTS ADMINISTERED BY THE FOOD AND DRUG ADMINISTRATION）1210 根据《联邦进口乳法》的规章REGULATIONS UNDER THE FEDERAL IMPORT MILK ACT1230 根据《联邦腐蚀性毒物法》的规章REGULATIONS UNDER THE FEDERAL CAUSTIC POISON ACT1240 传染病的控制CONTROL OF COMMUNICABLE DISEASES1250 州际运输卫生INTERSTATE CONVEYANCE SANITATION1251-1269 [预留的] [Reserved]1270 预期用于移植的人体组织HUMAN TISSUE INTENDED FOR TRANSPLANTATION1271 人体细胞、组织以及细胞的和基于组织的产品HUMAN CELLS, TISSUES, AND CELLULAR AND TISSUE-BASED PRODUCTS 1272-1299 [预留的] [Reserved]第Ⅱ章―司法部毒品强制执行局（CHAPTER Ⅱ―DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE）1300 定义DEFINITIONS1301 管制物质的制造者、分销者和调剂者的登记REGISTRATION OF MANUFACTURERS, DISTRIBUTORS, AND DISPENSERS OF CONTROLLED SUBSTANCES1302 对管制物质的标识与包装要求LABELING AND PACKAGING REQUIREMENTS FOR CONTROLLED SUBSTANCES1303 定额QUOTAS1304 登记者的记录与报告RECORDS AND REPORTS OF REGISTRANTS1305 令的格式ORDER FORMS1306 处方PRESCRIPTIONS1307 杂项MISCELLANEOUS1308 管制物质的表SCHEDULES OF CONTROLLED SUBSTANCES1309 表I化学品的制造者、分销者、进口者和出口者的登记REGISTRATION OF MANUFACTURERS, DISTRIBUTORS, IMPORTERS AND EXPORTERS OF LIST I CHEMICALS1310 列入表的化学品和某些机器的记录与报告RECORDS AND REPORTS OF LISTED CHEMICALS AND CERTAIN MACHINES 1311 [预留的] [Reserved]1312 管制物质的进口与出口IMPORTATION AND EXPORTATION OF CONTROLLED SUBSTANCES1313 前体与必要化学品的进口与出口IMPORTATION AND EXPORTATION OF PRECURSORS AND ESSENTIAL CHEMICALS1314-1315 [预留的] [Reserved]1316 行政职能、规范和程序ADMINISTRATIVE FUNCTIONS, PRACTICES, AND PROCEDURES第Ⅲ章―毒品控制政策办公室（CHAPTER Ⅲ―Office of National Drug Control Policy）1400 [预留的] [Reserved]1401 信息的公众可及性PUBLIC AVAILABILITY OF INFORMATION1402 强制性解密审查MANDATORY DECLASSIFICATION REVIEW1403 对给予州和地方政府资金和合作协议的统一行政要求UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND COOPERATIVE AGREEMENTS TO STATE AND LOCAL GOVERNMENTS1404 政府范围的排除与暂停（非获得）GOVERNMENTWIDE DEBARMENT AND SUSPENSION (NONPROCUREMENT)1405 对无毒品工作场所的政府范围的要求（财政援助）GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE)1406-1499 [预留的] [Reserved]。