Ib 13-lub lim tiam Subchronic Toxicity Study Of 2-(l-menthoxy)ethanol hauv F344 Rats

Taw qhia

2-(1-menthoxy) ethanol (CAS No. 38618-23-4) yog cov kua ntshiab thiab tsis muaj xim nrog cov ntxhiab tsw thiab siv dav los ua tus neeg sawv cev. Lub Koom Haum Koom Tes FAO/WHO Cov Kws Tshaj Lij Tshaj Lij rau Khoom Noj Ntxiv (JECFA) tau soj ntsuam 2-(l-methoxy) ethanol ua tus neeg sawv cev flavoring, categorized li cov khoom muaj feem xyuam nrog menthol1. Raws li cov qauv txheej txheem ntawm cov tshuaj tsw qab, 2-(l-methoxy) ethanol raug xa mus rau Chav Kawm I. Hauv Tebchaws Meskas thiab Europe, cov qib tau txais ntawm 2-(l-methoxy) ethanol los ntawm tib neeg tau kwv yees li 12 ug / tus neeg / hnub thiab 0.01 ug / tus neeg / hnub, raws li, ob qho tib si qis dua Chav Kawm I qhov pib ntawm 1,800 ug / tus neeg / hnub. Raws li cov kev kwv yees no, nws raug txiav txim siab tias 2-(1-menthoxy) ethanol yuav tsis muaj kev txhawj xeeb txog kev nyab xeeb thaum lub sij hawm niaj hnub siv los ua tus neeg sawv cev tsw qab.

NATURAL CISTANCHE TUBULOSA rau kev txhim kho kev sib deev PHGS75% ECH 30% ACT 12%

As part of the risk assessment, it has been revealed that 2-(1-menthoxy)ethanol was not mutagenic in the Ames test, and the only in vivo study performed to date was an oral acute toxicity study in male and female rats (LD50: >2,000 mg/kg lub cev hnyav [BW])1. Txawm hais tias siv 2-(1-menthoxy) ethanol ua tus neeg sawv cev tsw, cov ntaub ntawv txwv tsis pub muaj txog qhov rov ua tshuaj lom ntawm cov tshuaj no. Peb lub chaw soj nstuam tau tshawb xyuas cov tshuaj lom ntawm ntau yam khoom noj ntxiv, suav nrog cov neeg sawv cev ntawm cov tshuaj tsw qab los ntawm txhua pawg, hauv cov qauv nas 2-7. Txhawm rau kom paub meej txog toxicological profile thiab tsim kom muaj qhov tsis pom qhov tsis zoo-qhov cuam tshuam (NOAEL), peb tau ua 13-lub limtiam subchronic toxicity kawm ntawm 2-(1-menthoxy) ethanol, uas yog hais lus rau F344 nas los ntawm gavage.

Cov ntaub ntawv thiab cov txheej txheem

Kuaj tshuaj

2-(1-menthoxy)ethanol (Lot No. 5I0002, purity 99.9%) tsim los ntawm Takasago Int. Corp. (Tokyo, Nyiv) yog muab los ntawm Division of Standards and Evaluation, Department of Food Safety, Ministry of Health, Labor thiab Welfare, Nyiv, nrog kev txhawb nqa los ntawm Nyiv Flavor & Fragrance Materials Association (Tokyo, Nyiv). Txawm hais tias cov tshuaj ntsuam xyuas tau muab los ua kev sib xyaw ntawm optical isomers (CAS No. 38618-23-4), nws tau lees paub tias yog l-enantiomer (CAS No. 75443-64-0) ​​los ntawm cov chaw tsim khoom. Qhov ncauj gavage nrog pob kws roj (Wako Pure Chemical Industries, Osaka, Nyiv) raws li lub tsheb tau raug xaiv raws li txoj kev ntawm kev tswj hwm vim muaj dej insolubility thiab volatility ntawm 2-(1-menthoxy) ethanol. Kev daws teeb meem ntawm 2-(1-menthoxy) ethanol tau npaj txhua hnub, tam sim ua ntej kev tswj hwm. Tom qab khaws cia rau 2 teev ntawm chav tsev kub, qhov seem seem ntawm 2-(1-menthoxy) ethanol hauv 4, 40, thiab 400 mg / mL daws tau lees paub tias yog 96.8%, 99.8%, thiab 96.5% , raws li, los ntawm cov roj chromatography (Japan Inspection Association of Food and Food Industry Environment, Tokyo, Nyiv).

Kev sim tsiaj

Nyob rau hauv tag nrho, 40 txiv neej thiab 40 poj niam tshwj xeeb cov kab mob tsis muaj nas (F344 / DuCrlCrlj, 5 lub lis piam) tau yuav los ntawm Charles River Laboratories Nyiv (Yokohama, Nyiv) thiab siv tom qab acclimation rau ib lub lis piam. Thaum lub sij hawm txoj kev tshawb no, cov tsiaj tau nyob rau hauv polycarbonate tawb nrog mos mos ntaub pua txaj, khaws cia nyob rau hauv ib chav tsev nrog ib tug barrier system tswj lub teeb / tsaus voj voog (12 h), qhov cua (cua-hloov tus nqi ntawm 18 zaug / h), kub ( 24 ± 1 degree ), thiab txheeb ze av noo (55 ± 5%). Cov tawb thiab cov txaj txaj tau hloov ob zaug hauv ib lub lis piam. Txhua tus tsiaj muaj kev nkag tau dawb rau dej kais dej thiab noj zaub mov (CRF-1; Oriental Poov xab, Tokyo, Nyiv). Thaum pib ntawm qhov kev sim, cov tsiaj tau random faib rau plaub pawg ntawm 10 tus txiv neej thiab poj niam nas txhua, raws li lub cev hnyav ntsuas tam sim ua ntej pib kho nrog cov tshuaj ntsuam xyuas.

Kawm tsim qauv

Hauv kev tshawb fawb ua ntej {{0}}hnub kev tshawb fawb soj ntsuam 2-(1-menthoxy) ethanol muab tshuaj ntawm koob tshuaj 0, 200, 400, thiab 800 mg/kg BW/ hnub, qhov tseeb thiab txheeb ze lub siab hnyav tau nce ntxiv hauv txhua pab pawg kho mob ntawm ob leeg poj niam txiv neej (cov ntaub ntawv tsis qhia). Raws li cov txiaj ntsig no, peb xaiv 2-(1-menthoxy) ethanol koob tshuaj 0, 15, 60, thiab 250 mg/kg BW/hnub rau kev tswj hwm rau txiv neej thiab poj niam nas nyob rau tam sim no {{ 13}}txoj kev tshawb fawb tshuaj lom.

Cov xwm txheej dav dav thiab kev tuag tau raug ntsuas txhua hnub. Lub cev hnyav, nrog rau cov khoom noj khoom haus thiab cov khoom seem, tau ntsuas ib zaug ib lub lim tiam thaum lub sijhawm sim. Txhua tus nas tau yoo mov ib hmos thaum ua tiav kev kho mob, thiab kuaj ntshav rau hematology thiab serum biochemistry tau sau los ntawm lub plab aorta hauv qab nqus nqus tshuaj loog siv isoflurane. Txoj kev tshawb no tsim los ntawm Cov Lus Qhia rau Kev Tsim Cov Khoom Noj Ntxiv thiab Kev Kho Cov Qauv rau Kev Siv Khoom Noj Ntxiv ntawm Nyiv (1996) thiab tau pom zoo los ntawm Pawg Saib Xyuas Tsiaj thiab Kev Siv Khoom ntawm National Institute of Health Sciences, Nyiv.

Hematology thiab serum biochemistry

Cov kab mob hematological hauv qab no tau txheeb xyuas siv ProCyte Dx tsis siv neeg hematology analyzers (IDEXX Laboratories, Westbrook, ME, USA): cov qe ntshav dawb suav (WBC), cov ntshav liab suav (RBC), hemoglobin concentration (HGB), hematocrit (HCT), txhais tau tias corpuscular ntim (MCV), txhais tau tias corpuscular hemoglobin (MCH), txhais tau tias corpuscular hemoglobin concentration (MCHC), platelet suav (PLT), thiab sib txawv leukocyte hlwb, suav nrog neutrophils (Neut), lymphocytes (Lymph), monocytes (Mono), eosinophils (Eosino), thiab basophils (Baso). Kev soj ntsuam biochemical hauv ntshav tau ua los ntawm Oriental Poov rau cov hauv qab no: tag nrho cov protein (TP), albumin (Alb), albumin / globulin ratio (A / G), tag nrho bilirubin (Bil), qabzib, tag nrho cov cholesterol (T-Chol), triglyceride (TG), urea nitrogen (BUN), creatinine (Cre), calcium (Ca), inorganic phosphorus (IP), sodium (Na), potassium (K), chlorine (Cl), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), thiab -glutamyl transpeptidase (-GTP).

Lub cev hnyav thiab kev ntsuas histopathological

Kev ua tiav necropsy tau ua tiav rau txhua tus tsiaj, thiab lub hlwb, thymus, ntsws, lub plawv, spleen, siab, qog adrenal, ob lub raum, testes, thiab zes qe menyuam tau hnyav. Cov kab mob no, nrog rau cov ntaub so ntswg los ntawm qaum qaum, trigeminal paj hlwb, pituitary caj pas, lub qhov ntswg kab noj hniav, qog nqaij hlav, tus nplaig, txoj hlab pas, trachea, aorta, thyroid caj pas, parathyroid caj pas, pancreas, plab, me thiab loj hnyuv, submandibular thiab mesenteric. lymph nodes, qhov chaw mos, tsev menyuam, zis zais zis, prostate caj pas, seminal vesicles, epididymis, femur thiab sternum nrog cov pob txha pob txha, vertebrae, skeletal leeg, sciatic paj hlwb, daim tawv nqaij, thiab mammary caj pas, tau tsau nyob rau hauv 10% nruab nrab-buffered; Tom qab ntawd, paraffin-embedded seem tau npaj thiab stained nrog hematoxylin thiab eosin rau kev kuaj histopathological. Cov noob qes thiab qhov muag nrog cov qog Harderian tau kho nyob rau hauv Bouin's fixative thiab Davidson txoj kev daws teeb meem, feem. Cov ntaub so ntswg, nrog rau lub qhov ntswg kab noj hniav, vertebrae, sternum, thiab femur, tau decalcified siv cov sib tov ntawm 10% formic acid thiab 10% buffered formalin mus txog 2 lub lis piam. Kev ntsuam xyuas histopathological tau ua rau tag nrho cov ntaub so ntswg tau txais los ntawm cov tsiaj hauv pawg tswj hwm thiab pab pawg tau muab cov koob tshuaj ntau tshaj tshwj tsis yog tias muaj kev kho mob ntsig txog qhov mob.

NATURAL CISTANCHE TUBULOSA rau kev txhim kho kev tiv thaiv kab mob PHGS75% ECH 30% ACT 12%

Immunohistochemistry rau 2u-globulin

Hauv cov txiv neej nas, tsub zuj zuj ntawm 2u-globulin nyob rau hauv lub raum tau soj ntsuam los ntawm immunohistochemical tsom xam ntawm paraffin-embedded seem. Rau kev tshawb nrhiav antigen, cov seem tau los ntawm 5 nas nyob rau hauv txhua pab pawg tau incubated nrog proteinase K (DAKO, Glostrup, Denmark) rau 1 min ntawm chav tsev kub. Tag nrho cov seem tau muab tso rau hauv 3% H2O2 / methanol tov rau 10 min ntawm chav tsev kub rau inactivation ntawm endogenous peroxidase kev ua. Tom qab thaiv cov tshuaj tiv thaiv tsis tshwj xeeb nrog 10% ib txwm luav cov ntshav, cov ntu tau tsim nrog thawj cov tshuaj tiv thaiv rau 2uglobulin (diluted 1: 400; anti-rat 2u-globulin antibody; R&D Systems, Minneapolis, MN, USA) hmo ntuj ntawm 4 degree 8. Kev pom cov tshuaj tiv thaiv kab mob tau ua tiav siv VectaStain Elite ABC Cov Khoom Siv (Vector Laboratories, Burlingame, CA, USA) thiab 3,3′-diaminobenzidine. Tag nrho cov seem tau counterstained nrog hematoxylin.

Kev txheeb cais

Kev sib txawv ntawm cov ntaub ntawv muaj txiaj ntsig rau lub cev hnyav thaum lub sijhawm sim, nrog rau kev kuaj ntshav, ntshav biochemistry, thiab qhov hnyav ntawm lub cev, raug soj ntsuam rau homogeneity siv Bartlett's test. Ib-txoj kev tsom xam ntawm qhov sib txawv thiab Kruskal-Wallis xeem, feem, tau ua haujlwm rau homogeneous thiab heterogeneous cov ntaub ntawv. Hauv kev txiav txim siab qhov sib txawv tseem ceeb, Dunnett ntau qhov kev sim sib piv tau siv los sib piv cov tswj thiab kev kho mob. Kev sib piv ntawm cov xwm txheej histopathological thiab qib tau txheeb xyuas los ntawm kev siv Fisher qhov tseeb qhov tshwm sim thiab Mann-Whitney's U test, feem. P tus nqi ntawm<0.05 were considered statistically significant.

Cov txiaj ntsig

Nyob rau hauv lub neej parameters, hematology, thiab serum biochemistry

Tsis muaj cov tsos mob tseem ceeb tau raug sau tseg thoob plaws lub sijhawm sim, thiab txhua tus tsiaj muaj sia nyob mus txog rau lub sijhawm teem tseg necropsy. Tsis tas li ntawd, tsis muaj qhov sib txawv ntawm lub cev hnyav thiab kev noj zaub mov txhua hnub hauv cov txiv neej thiab poj niam nas (Daim duab 1A thiab B).

Hematology thiab serum biochemistry cov ntaub ntawv qhia nyob rau hauv Tables 1 thiab 2, raws li. Hematological analyses tau txo qis HGB, HCT, MCV, thiab MCH thiab nce PLT hauv cov txiv neej nas noj 250 mg / kg BW / hnub 2-(1-menthoxy) ethanol (Table 1). Hauv cov ntshav biochemistry, qhov tseem ceeb nce hauv TP, T-Chol, thiab Ca thiab txo qis hauv Bil thiab ALP tau pom hauv cov txiv neej ntawm 250 mg / kg pawg (Table 2). Kev nce ntxiv hauv Cre thiab qhov txo qis hauv A / G tau pom hauv cov txiv neej ntawm 60 thiab 250 mg / kg pawg. Hauv cov poj niam, qhov nce ntxiv hauv Ca thiab qhov txo qis hauv ALP tau sau tseg hauv 60 thiab 250 mg / kg pawg, thaum nce T-Chol thiab txo A / G, Bil, TG, AST, thiab ALT tau kuaj pom hauv 250 mg. /kg pab. Txawm hais tias muaj kev nce ntxiv hauv TG thiab qhov txo qis hauv Cl tau pom hauv cov txiv neej tau tswj hwm 60 mg / kg, qhov tsis muaj kev sib raug zoo ntawm koob tshuaj qhia tias qhov sib txawv no tsis cuam tshuam nrog kev raug rau cov tshuaj ntsuam xyuas.

Lub cev hnyav

Cov ntaub ntawv hais txog qhov hnyav ntawm lub cev tau muab sau tseg rau hauv Table 3. Qhov hnyav ntawm daim siab thiab cov txheeb ze sib txheeb tau nce ntxiv hauv ob leeg poj niam txiv neej ntawm 250 mg / kg pawg (Table 3). Ib qho kev nce ntxiv hauv cov txheeb ze lub siab hnyav tau pom hauv cov txiv neej ntawm 60 mg / kg pawg. Hauv cov txiv neej, qhov hnyav ntawm lub raum tsis txaus ntseeg tau nce ntxiv hauv 60 thiab 250 mg / kg pawg. Hauv cov txiv neej 250 mg / kg pawg, qhov tseem ceeb nce hauv qhov hnyav thiab txheeb ze ntawm cov qog adrenal thiab qhov hnyav ntawm tus po thiab cov qe ntshav tau raug sau tseg.

Histopathology thiab immunohistochemistry

Cov ntaub ntawv rau kev tshawb pom histopathological thiab immunohistochemical tau sau tseg hauv Cov Lus 4 thiab 5, feem. Cov kev tshawb pom histopathological tau qhia tias qhov ntau zaus ntawm eosinophilic granules (Fig. 2A-D), basophilic tubules, thiab hyaline cam khwb cia, nrog rau focal interstitial o hauv lub raum, tau nce ntau ntxiv hauv txhua pawg txiv neej kho mob thaum piv nrog kev tswj hwm. pab pawg (Table 4). Raws li kev tshuaj ntsuam xyuas immunohistochemical, cov txiv neej nas kho nrog cov tshuaj ntsuam xyuas tau nthuav tawm qhov nce hauv 2u-globulin immunoreactivity nyob rau hauv epithelial hlwb ntawm proximal tubules, ua kom pom tseeb koob tshuaj-dependency (Daim duab 2E–H) (Table 5).

Ntawm necropsy, ib tug txiv neej nas nyob rau hauv 250 mg / kg pab pawg tau pom qhov loj ntawm lub raum sab xis vim muaj tus yam ntxwv ntawm tus mob nephroblastoma. Txawm hais tias nephroblastoma tsis tshua muaj tshwm sim nyob rau hauv feem ntau cov kab mob nas9, qhov teeb meem no tau suav tias yog qhov xwm txheej, vim tsis muaj lwm yam tsiaj uas muaj cov kab mob zoo sib xws. Tsis tas li ntawd, nyob rau hauv kev tshawb fawb ntawm qhov ncauj carcinogenicity, qhov tshwm sim ntawm spontaneous nephroblastoma nyob rau hauv txiv neej F344/DuCrlCrlj nas tau tshaj tawm nyob rau ntawm 0-2.0% 10. Txawm hais tias ob peb qhov mob tau kuaj pom nyob rau hauv lwm yam kabmob, tsis muaj kev kho mob tseem ceeb-raws li kev hloov pauv hauv qhov tshwm sim ntawm cov kab mob no tau pom meej.

Kev sib tham

Txog rau tam sim no, 24 cov tshuaj tsw qab, suav nrog 2-(1-menthoxy) ethanol, tau raug soj ntsuam los ntawm JECFA raws li cov khoom muaj feem cuam tshuam nrog menthol, thiab tag nrho cov tau teev tseg tias "tsis muaj kev txhawj xeeb txog kev nyab xeeb" ntawm qib kwv yees tam sim no ntawm intake1, 11. 2-(1-Menthoxy) ethanol yog cais nyob rau hauv ib pab pawg neeg ntawm alicyclic cawv los yog ethers thiab yog suav tias yog feem ntau conjugated nrog glucuronic acid, ua raws li los ntawm urinary excretion1. Txawm hais tias qhov ncauj LD50 qhov tseem ceeb ntawm cov tshuaj no hauv cov nas yog qhov siab, cov ntaub ntawv los ntawm cov kev tshawb fawb tshuaj toxicity rov qab tseem txwv. Ib 13-lub limtiam txoj kev tshawb nrhiav tshuaj toxicity ntau dua ib zaug tau qhia tias menthyl pyrrolidone carboxylate (CAS No. 68127-22-0), ib qho kev sib xyaw ua ke uas cuam tshuam nrog menthol, tuaj yeem cuam tshuam nrog cov txheeb ze ntawm daim siab thiab lub raum hnyav hauv txiv neej thiab poj niam. Wistar nas. Kev sib sau ntawm 2u-globulin hauv cov tubules ze ntawm cov txiv neej nas kuj tau pom ntawm koob tshuaj 1,111 mg / kg BW / hnub, thiab NOAEL tau txiav txim siab li 109 mg / kg BW / hnub 1.

Nyob rau hauv tam sim no 13-lub lim tiam subchronic toxicity kawm ntawm 2-(1-menthoxy) ethanol, tsis muaj kev hloov toxicological hauv cov xwm txheej, lub cev hnyav, thiab kev noj zaub mov. Tom qab kev ntsuam xyuas hematological, peb pom qhov txo qis hauv HGB (96.6% rau qhov ntsuas qhov ntsuas), HCT (96.3%), MCV (98.4%), thiab MCH (98.2%) thiab nce PLT (111%) hauv txiv neej 250 mg/kg pab pawg, uas tau suav tias yog toxicologic influences ntawm 2-({14}}menthoxy) ethanol kev kho mob. Ob qho tag nrho (115% ntawm ob leeg poj niam txiv neej) thiab cov txheeb ze (119% ntawm cov txiv neej thiab 111% ntawm poj niam) daim siab hnyav tau nce siab hauv ob leeg poj niam hauv 250 mg / kg pawg. Txawm hais tias tsis muaj kev hloov pauv hauv lub siab, nce qib ntawm T-Chol (110% hauv cov txiv neej thiab 121% poj niam) thiab TP (105% ntawm cov txiv neej) thiab txo TG (60.1% poj niam) hauv 250 mg / kg pawg qhia txog kev hloov pauv tshuaj lom cuam tshuam nrog lipid metabolism thiab protein synthesis hauv daim siab. Txo HGB thiab MCH thiab nce PLT, T-Chol, thiab TP hauv cov txiv neej thiab txo TG thiab nce qhov hnyav ntawm lub siab thiab cov txheeb ze ntawm ob leeg poj niam txiv neej kuj tau tshawb pom, nrog rau qhov tseem ceeb ntawm cov ntaub ntawv hauv 28-hnub kev tshawb fawb ua ntej (cov ntaub ntawv tsis qhia. ), corroborating tias cov hloov pauv hematological thiab serum biochemical tsis, nrog rau lub siab hnyav, tsis yog qhov xwm txheej tab sis kuaj cov tshuaj muaj feem cuam tshuam. Nyob rau hauv sib piv, qhov tseem ceeb nce nyob rau hauv cov txheeb ze lub siab hnyav uas kuaj pom nyob rau hauv cov txiv neej 60 mg / kg pawg nyob rau hauv txoj kev tshawb no tsis tau nrog ib tug nce nyob rau hauv qhov hnyav tag nrho los yog hloov nyob rau hauv muaj feem xyuam rau biochemical parameters, qhia hais tias qhov kev nce no yog ib tug adaptive hloov.

NATURAL CISTANCHE TUBULOSA rau kev txhim kho kev sib deev PHGS75% ECH 30% ACT 12%

Qhov tseem ceeb nce ntxiv (120%) thiab cov txheeb ze (118%) qhov hnyav ntawm cov qog adrenal hauv cov txiv neej 250 mg / kg pawg tau suav tias yog txuam nrog cov tshuaj ntsuam xyuas. Tsis tas li ntawd, nce qhov hnyav thiab qhov hnyav ntawm cov qog adrenal nyob rau hauv ob qho tib si poj niam txiv neej tau pom qhov pom tseeb ntawm koob tshuaj nyob ntawm 28-hnub kev kawm ua ntej (cov ntaub ntawv tsis qhia), qhia txog kev koom tes nrog kev sim tshuaj. Txawm hais tias adrenal hypertrophy tuaj yeem tshwm sim los ntawm kev ntxhov siab, tsis muaj kev tshawb pom qhia txog kev ntxhov siab, xws li txo lub cev qhov hnyav los yog atrophy ntawm thymus thiab lwm yam kab mob lymphoid, hauv ob qho tib si tam sim no thiab kev tshawb fawb ua ntej. Txij li thaum tej zaum yuav tsis muaj kev hloov pauv hauv cov qog adrenal txawm tias muaj kev cuam tshuam ntawm glucocorticoid ntau lawm thaum muaj kev cuam tshuam ntawm steroidogenesis ntsig txog enzymes12, qhov ua tau tias qhov hnyav ntawm lub qog adrenal yog qhov kev tshawb pom tsis tuaj yeem raug cais tawm. Hauv qhov sib piv, nce qhov hnyav ntawm tus po thiab cov qe ntshav hauv cov txiv neej 250 mg / kg pawg, tsis tau pom nyob rau hauv kev tshawb fawb ua ntej, tau suav tias yog toxicologically insignificant vim tsis muaj cov kab mob histopathological lossis qhov hnyav hnyav ntxiv. Ib yam li ntawd, ntshav biochemistry tau qhia txog qhov txo qis hauv A / G thiab nce Ca hauv ob leeg poj niam txiv neej, uas tau txiav txim siab tias tsis muaj qhov tseem ceeb ntawm toxicological, txiav txim siab tsis muaj qhov txawv txav hauv qhov cuam tshuam. Tsis tas li ntawd, txo qis Bil thiab ALP qib hauv ob leeg poj niam txiv neej thiab txo qis AST thiab ALT hauv cov poj niam yog qhov sib piv rau qhov xav tau cov tshuaj lom thiab suav tias tsis muaj txiaj ntsig.

Cov kab mob nephropathy mob ntev tshwm sim los ntawm basophilic tubules, hyaline cam khwb cia, thiab focal interstitial o tau pom nrog qhov tseem ceeb hauv cov txiv neej ntawm txhua pab pawg kho. Tsis tas li ntawd, nce ntshav cre thiab lub raum tsis zoo thiab qhov hnyav ntawm lub raum tau kuaj pom hauv cov txiv neej 60 thiab 250 mg / kg pawg; Cov kev hloov no tsis tau pom nyob rau hauv pawg poj niam kho mob. Nyob rau hauv cov ntaub ntawv no, lub degree ntawm tsub zuj zuj ntawm eosinophilic granules nyob rau hauv proximal tubular epithelial hlwb tau nce nyob rau hauv ib tug meej koob tshuaj-nyob ntawm seb. Cov granules tau lees paub tias yog 2u-globulin los ntawm immunohistochemistry, qhia qhov tshwm sim ntawm 2u-globulin nephropathy. 2u-Globulins khi rau qee yam tshuaj, xws li d-limonene, sib sau hauv lysosomes thiab pom nyob rau hauv cov tubules ze ze li eosinophilic lossis hyaline granules9. Qhov kev txuam nrog no tuaj yeem ua rau cov hlwb epithelial puas tsuaj, ua rau mob nephropathy mob ntev thiab ua rau cov qog tsim tawm 9. Yog li, txawm hais tias NOAEL rau 2-(1-menthoxy) ethanol txuam nrog 2u-globulin nephropathy hauv txiv neej nas lub raum tsis tau txheeb xyuas, hom nephropathy no tau tshaj tawm tshwj xeeb rau txiv neej nas thiab yog li tsis cuam tshuam rau tib neeg. Kev soj ntsuam kev pheej hmoo 13. Kev pheej hmoo siab ntawm lub raum tsis ua haujlwm los ntawm cov txheej txheem cuam tshuam nrog 2u-globulin tsub zuj zuj yog qhov ua tsis tau zoo, vim tias cov protein no tsis nyob hauv tib neeg14. Yog li ntawd, nws tau txiav txim siab tias tsim nyog los tshem tawm cov kev hloov pauv cuam tshuam nrog kev mob ntshav qab zib nephropathy nyob rau hauv cov txiv neej los ntawm kev txiav txim siab ntawm NOAEL.

Nyob rau hauv xaus, tam sim no 13-lub lim tiam subchronic toxicity kev tshawb fawb pom tau hais tias 250 mg/kg BW/hnub 2-(1-}menthoxy) ethanol kev kho mob ua rau muaj kev hloov tshuaj lom nyob rau hauv hematology, serum biochemistry, thiab lub cev hnyav. hauv txiv neej thiab poj niam F344 nas. Raws li cov txiaj ntsig tau pom, NOAEL ntawm 2-(1-menthoxy) ethanolraug soj ntsuam raws li 60 mg / kg BW / hnub rau ob leeg poj niam.

NATURAL CISTANCHE TUBULOSA rau kev txhim kho kev sib deev PHGS75% ECH 30% ACT 12%