NHDC's Toxicological Assessment System
Kev soj ntsuam cov ntsiab lus ntawm European Food Safety Authority (EFSA)
European Food Safety Authority (EFSA) yog ib lub koom haum tshaj lij rau kev soj ntsuam kev nyab xeeb ntawm Neohesperidin Dihydrochalcone hmoov. EFSA Food Additives and Flavorings Panel (FAF Panel) thiab Feed Additives and Products Vaj Huam Sib Luag (FEEDAP Vaj Huam Sib Luag) tau ua qhov kev ntsuam xyuas ntawm NHDC raws li cov khoom noj ntxiv thiab cov khoom noj ntxiv, feem.
• Siv ua zaub mov ntxiv (E 959)
Xyoo 2022, EFSA FAF Vaj Huam Sib Luag ua tiav qhov kev ntsuam xyuas ntawm NHDC ua cov khoom qab zib (E 959). Qhov kev ntsuam xyuas yog ua raws li 13-lub lim tiam txoj kev tshawb fawb ntawm nas toxicity (Lina li al., 1990). Tsis muaj cov tshuaj toxicologically cuam tshuam loj heev tau pom nyob rau hauv qhov siab tshaj - pawg koob tshuaj (4000 mg/kg bw/hnub). Raws li cov kev tshawb pom no, FAF Vaj Huam Sib Luag tau tsim kom muaj kev noj haus txhua hnub (ADI) ntawm 20 mg / kg Neohesperidin Dihydrochalcone hmoov bw / hnub. Tus nqi no tau suav nrog siv 4000 mg / kg bw / hnub raws li qhov taw qhia siv. A 100-fold interspecies thiab intraspecies uncertainty factor thiab 2-fold extrapolation factor rau cov teebmeem subchronic-to-chronic.
Lub Koom Haum Koom Tes FAO/WHO Cov Kws Tshaj Lij Tshaj Lij rau Cov Khoom Noj Ntxiv (JECFA) tau soj ntsuam tib txoj kev tshawb fawb hauv xyoo 2012. Nws tau txheeb xyuas qhov tsis muaj -saib xyuas - tsis zoo- theem cuam tshuam (NOAEL) ntawm 760 mg/kg Neohesperidin Dihydrochalcone hmoov { bw.5} hnub los ntawm pawg neeg nruab nrab Qhov sib txawv ntawm ob qhov kev ntsuam xyuas feem ntau yog los ntawm kev txhais lus sib txawv ntawm cov tshuaj lom neeg muaj feem cuam tshuam ntawm kev hloov pauv tau pom nyob rau hauv qib siab - koob tshuaj. Cov kev hloov pauv no suav nrog txo lub cev hnyav, nce qib plasma alkaline phosphatase, thiab nce bilirubin concentrations.
• Siv raws li Pub Ntxiv
Neohesperidin Dihydrochalcone hmoov tau raug tso cai nyob rau hauv European Union raws li ib tug sensory pub additive nyob rau hauv lub flavoring qeb. Nws raug pom zoo siv rau hauv pub rau npua, ua tiav npua, nyuj, yaj, ntses, thiab dev.
Hauv 2025, EFSA FEEDAP Vaj Huam Sib Luag ua tiav qhov kev ntsuam xyuas kev tso cai tshiab ntawm NHDC. Lub vaj huam sib luag xaus lus tias Neohesperidin Dihydrochalcone NHDC tseem muaj kev nyab xeeb rau hom tsiaj hom, cov neeg siv khoom, thiab ib puag ncig. NHDC kuj tau pom tias tsis yog - ua rau khaus ntawm daim tawv nqaij thiab qhov muag thiab tsis ua rau tawv nqaij. Qhov siab tshaj plaws tso cai concentration yog 35 mg / kg ntawm tag nrho pub.
Kev ntsuam xyuas Genotoxicity
Genotoxicity yog qhov taw qhia tseem ceeb hauv kev ntsuas kev nyab xeeb ntawm zaub mov. Hauv nws qhov kev ntsuam xyuas FGE.420, EFSA xaus lus tias Neohesperidin Dihydrochalcone hmoov thiab nws cov qauv analogues tsis ua rau muaj kev txhawj xeeb txog genotoxicity. Qhov kev txiav txim siab no yog los ntawm kev tshuaj xyuas dav dav ntawm cov ntaub ntawv mutagenicity rau NHDC thiab lwm yam flavonoids.
JECFA tau mus txog qhov zoo sib xws. Nws tau tshaj tawm tias NHDC tau pom cov txiaj ntsig tsis zoo hauv ntau qhov hauv vitro thiab hauv vivo genotoxicity kev tshawb fawb.
Metabolism thiab excretion
Txoj kev metabolic ntawm Neohesperidin Dihydrochalcone hmoov tau pom meej meej. Raws li EFSA cov ntaub ntawv ntsuam xyuas, NHDC yog metabolized sai thiab tawm hauv cov tsiaj txhu. Nws tsis khaws cia hauv cov ntaub so ntswg.
Kev tshawb fawb ntawm cov tsiaj hauv dej, suav nrog ntses, tau pom cov qauv metabolic zoo sib xws. NHDC ua raws txoj hauv kev piv rau cov uas tau pom hauv cov tsiaj nyeg thiab tsis sib sau ua ke hauv cov ntaub so ntswg. Yog li ntawd, nws siv raws li ib tug pub additive tsis xav tias yuav ua rau kom cov neeg tau txais kev pab.
Hesperetin dihydrochalcone, daim ntawv aglycone ntawm Neohesperidin Dihydrochalcone NHDC, ua raws li txoj hmoo metabolic zoo sib xws hauv vivo. Nws yog metabolized rau hauv cov khoom tsis muaj teeb meem nkaus xwb.
Kev tshawb fawb txog kev ruaj ntseg kawg
Cytotoxicity Study
Ib txoj kev tshawb fawb luam tawm hauv Food Bioscience thaum Lub Peb Hlis 2026 tau soj ntsuam cov cellular kev nyab xeeb ntawm NHDCs hauv vitro. Txoj kev tshawb no siv tib neeg hepatocellular carcinoma cell kab Hep3B thiab human umbilical vein endothelial cells (HUVECs) ua qauv los soj ntsuam cov teebmeem cytotoxic ntawm NHDCs. Cov txiaj ntsig tseem ceeb suav nrog:
• Kev cuam tshuam rau cov hlwb noj qab haus huv:
Hauv HUVEC qauv, Neohesperidin Dihydrochalcone hmoov tshwm sim tsuas yog mob cytotoxicity. Tsis muaj cov cim qhia ntawm apoptosis tau pom. Cov cim qhia no suav nrog kev poob ntawm mitochondrial membrane muaj peev xwm thiab kev hloov pauv hauv nuclear morphology. Cov txiaj ntsig tau qhia tias NHDCs muaj cov tshuaj toxicity tsawg rau tib neeg lub cev nyob rau hauv qhov kev sim siab ntau.
• Cov teebmeem ntawm cov qog nqaij hlav cancer:
Neohesperidin Dihydrochalcone NHDC tsis tau qhia txog kev tiv thaiv kabmob tseem ceeb tiv thaiv Hep3B hepatocellular carcinoma cells. Ntawm qhov ntsuas siab tshaj plaws (300 ug / mL), tus nqi inhibition tsuas yog 25.47%. Qhov no tsis ncav cuag 50% inhibition (IC50) pib. Txoj kev tshawb no xaus lus tias NHDCs tsis muaj kev tiv thaiv kab mob tseem ceeb tab sis qhia tias tsis muaj tshuaj lom rau cov hlwb noj qab haus huv. Cov kws sau ntawv tau hais tias "NHDC zoo li yog qhov chaw nyab xeeb uas tsis muaj zog tiv thaiv kab mob."
• Kev cai ntawm kev tsiv teb tsaws ntawm tes:
Cov kev tshawb fawb pom tias Neohesperidin Dihydrochalcone hmoov txo cov peev xwm tsiv teb tsaws ntawm HUVEC hlwb. Qhov no qhia tau tias lawv cov dej num lom neeg yuav koom nrog tsis yog - txoj hauv kev apoptotic cuam tshuam nrog kev txav ntawm tes. Qhov tseem ceeb toxicological ntawm qhov kev tshawb pom no tseem tsis meej. Txawm li cas los xij, qhov teebmeem no tsis tau muab cais ua qhov tsis zoo.
Kev sib tham txog kev hloov pauv hauv cov thyroid hormones
Hauv 90-hnub toxicity txoj kev tshawb fawb ntawm hesperidin dihydrochalcone, ib qho aglycone ntawm NHDC, kev hloov pauv hauv cov thyroid hormones tau pom nyob rau hauv txhua pawg tshuaj (100-1000 mg / kg bw / hnub). EFSA FAF Vaj Huam Sib Luag ua tib zoo tshuaj xyuas cov kev tshawb pom no. Lub vaj huam sib luag tau xaus lus tias kev hloov pauv hormonal tsis tau nrog cov cim qhia ntawm hypothyroidism. Tsis muaj kev hloov pauv histopathological lossis cov tsos mob tshwm sim. Yog li ntawd, cov teebmeem hormonal no tsis suav tias yog qhov tsis zoo. Qhov kev txiav txim siab no yog qhov tseem ceeb rau kev nkag siab txog kev nyab xeeb ntawm endocrine ntawm Neohesperidin Dihydrochalcone hmoov thiab cov khoom sib txuas.
Embryonic Developmental Toxicity
Tsis muaj leej niam lossis tus menyuam hauv plab toxicity tau pom nyob rau hauv kev tshawb fawb txog kev loj hlob toxicity ua ntej yug menyuam. Cov kev tshawb pom no qhia tias Neohesperidin Dihydrochalcone hmoov tsis ua rau muaj kev pheej hmoo rau kev loj hlob ntawm tus menyuam hauv plab thaum cev xeeb tub. Qhov no txhawb nqa tag nrho kev nyab xeeb profile ntawm NHDC hauv cov pej xeem.
Kev ntsuam xyuas raug thiab thaj tsam kev nyab xeeb
Kev ntsuam xyuas raug rau kev siv zaub mov
EFSA tau siv Added Portions Exposure Technique (APET) thiab Ib Leeg Muaj Peev Xwm Txheej Txheem (SPET) hauv nws qhov kev ntsuam xyuas FGE.420 los kwv yees kev noj zaub mov raug rau Neohesperidin Dihydrochalcone hmoov thiab lwm yam tshuaj. Raws li qhov taw qhia siv ntawm 1000 mg / kg bw / hnub, cov npoo ntawm qhov raug (MOE) rau cov neeg laus thiab cov menyuam yaus nyob rau hauv qhov kev pom zoo. Qhov no qhia tau hais tias qib raug nyob rau hauv cov kev siv tiag tiag yog nyob deb ntawm cov tshuaj tsis zoo.
Rau hesperidin dihydrochalcone, JECFA suav ib qho MOE ntawm 15,000. Qhov kev suav no yog ua raws li NOAEL ntawm 750 mg / kg bw / hnub rau cov khoom muaj feem xyuam nrog NHDC thiab kwv yees kev noj zaub mov raug 3000 ug / hnub siv SPET. Tus nqi no ntau dua li qhov feem ntau lees txais kev nyab xeeb ntawm 100.
Kev ntsuam xyuas raug rau kev siv pub
Rau cov ntawv thov pub, EFSA FEEDAP Vaj Huam Sib Luag tau lees paub tias kev tso cai siv NHDC hauv kev pub tsiaj tsis ua rau muaj kev cuam tshuam loj ntxiv rau cov neeg siv khoom. Qhov kev txiav txim siab no yog nyob ntawm ob yam. Ua ntej, Neohesperidin Dihydrochalcone hmoov yog tawm sai sai los ntawm cov tsiaj. Qhov thib ob, NHDC tsis khaws cov ntaub so ntswg ntawm cov tsiaj hauv dej.
Xaus:
Neohesperidin Dihydrochalcone hmoov yog cov khoom qab zib thiab tsw qab hloov pauv uas tau dhau xyoo lawm ntawm kev tshawb fawb toxicological thiab kev ntsuas kev tswj hwm. Tsis muaj pov thawj tias Neohesperidin Dihydrochalcone NHDC ua rau genotoxicity, mutagenicity, lossis carcinogenicity. Nws tsis yog- khaus khaus rau ntawm daim tawv nqaij thiab ob lub qhov muag thiab qhia tau hais tias tsis tshua muaj toxicity nyob rau hauv cov hlwb noj qab haus huv. EFSA tau tsim kom muaj kev noj qab haus huv txhua hnub (ADI) ntawm 20 mg / kg lub cev hnyav / hnub thiab qhov siab tshaj plaws tso cai ntawm 35 mg / kg rau daim ntawv thov pub. Cov kev tshawb fawb tsis ntev los no tau luam tawm xyoo 2026 ntxiv txhawb nqa nws qhov kev nyab xeeb zoo.
NHDC tau pom zoo siv rau hauv cov khoom noj, pub, thiab siv tshuaj hauv ntau lub tebchaws thiab cheeb tsam. Cov ntaub ntawv tshaj tawm los ntawm National Health Commission ntawm Tuam Tshoj hais txog nws cov ntawv thov hauv 2025 qhia tau hais tias cov txheej txheem tswj hwm rau NHDC tau nce mus tsis tu ncua.
Guanjie Biotech yog tus kws tshaj lij Neohesperidin Dihydrochalcone tsum. Lub tuam txhab muab cov khoom ua raws NHDC rau cov neeg siv khoom thoob ntiaj teb los ntawm kev tswj hwm nruj thiab cov qauv ua raws li thoob ntiaj teb. Raws li kev pom zoo siv, Neohesperidin Dihydrochalcone hmoov muaj qhov zoo - tsim kom muaj kev nyab xeeb profile thiab tuaj yeem suav tias yog cov khoom sib xyaw ua ke rau kev tsim kho.
Cov ntaub ntawv:
[1] EFSA FEEDAP Vaj Huam Sib Luag (2011). Kev xav txog kev nyab xeeb thiab kev ua tau zoo ntawm neohesperidine dihydrochalcone ua cov khoom noj ntxiv rau piglets, npua rau fattening, calves, yaj, ntses thiab dev.
[2] EFSA FEEDAP Vaj Huam Sib Luag (2014). Nqe lus hais txog kev nyab xeeb ntawm neohesperidine dihydrochalcone rau ntses.
[3] EFSA FAF Panel (2022). Re-Kev ntsuam xyuas ntawm neohesperidine dihydrochalcone (E 959) ua cov khoom noj ntxiv.
[4] EFSA FEEDAP Vaj Huam Sib Luag (2025). Kev soj ntsuam ntawm cov khoom noj ntxiv neohesperidine dihydrochalcone (2b959) rau npua, npua rau fattening, nyuj, yaj, ntses thiab dev rau kev rov ua dua tshiab ntawm nws qhov kev tso cai. EFSA Journal, 23(10): e9681.
[5] EFSA FAF Panel (2024). Kev ntsuam xyuas pab pawg Flavoring 420 (FGE.420): Hesperetin dihydrochalcone. EFSA Journal, 22(12): e9091.
[6] Neohesperidine dihydrochalcone qhia tias tsis muaj cov tshuaj tiv thaiv kab mob tseem ceeb ntawm cov hlwb Hep3B tab sis pom tau tias muaj kev nyab xeeb zoo vim tsis muaj tshuaj lom hauv HUVEC hlwb thiab Artemia salina. Food Bioscience, 2026, 108736.
[7] Wei Jing, Song Ruolan, Chen Xiang, et al. Kev tshawb fawb nce qib ntawm cov tshuaj pharmacological ntawm Neomethylhesperidin dihydrochalcone thiab nws cov khoom siv ua ntej [J]. Food Industry Technology, 2022, 43(23): 436-449.
[8] JECFA (2012, 2021, 2022). Specifications rau flavoring tshuaj.
[9] National Health Commission Government Service Platform. Kev Tshaj Tawm Txog Kev Txais Cov Khoom Noj Ntxiv Tshiab (Lub Kaum Ib Hlis 26, 2025; Lub Kaum Ob Hlis 12, 2025).
