Safety evaluation and fluorine concentration of pu''er brick tea and bianxiao brick tea

Pu'er brick tea and Bianxiao brick tea are both compressed types of tea. Fluorine analysis was carried out on samples of Pu'er brick tea produced at different times in Yunnan Province and on samples of Bianxiao brick tea made in Hunan and Sichuan Province for supply especially to minority ethnic groups in border areas of China. The levels of water-soluble and water-insoluble fluorine were measured in the tea samples using an ion-specific electrode potentiometer. The concentration of water-soluble fluorine was much greater in Bianxiao brick tea than in Pu'er brick tea (mean levels 441 and 77 mg/kg, respectively). According to these figures, the fluorine intake associated with consuming an infusion of 30 g Pu'er brick tea/person/day is safe because it does not exceed the maximum recommended daily allowance (RDA) of up to 4.0 mg for adults. In contrast, the almost six times higher intake of fluorine from Bianxiao brick tea greatly exceeds the 4 mg RDA and is unsafe. The difference in the fluorine levels of the two types of brick tea can be attributed to differences in the materials used to make them: Pu'er brick tea is made from tender leaves whereas Bianxiao brick tea is made from old tough leaves in which fluorine has accumulated. We conclude that consumption of Pu'er brick tea is unlikely to induce fluorosis, which has been associated with consumption of Bianxiao brick tea.     

Brick tea fluoride as a main source of adult fluorosis.

An epidemiological survey was conducted in Naqu County, Tibet in September 2001 to investigate the manifestations of fluorosis in adults caused by the habitual consumption of brick tea. Profiles were obtained for the total daily fluoride intake, environmental fluoride levels and average urinary fluoride concentration, and a physical examination and a skeletal radiographic study were conducted. One hundred and eleven 30-78-year-old adults were enrolled. It was found that the fluoride level of water sources in Naqu County was 0.10+/-0.03 mg/l; no evidence of fluoride air pollution was found, but the brick tea water processed foods--zamba and buttered tea--had fluoride contents of 4.52+/-0.74 mg/kg and 3.21+/-0.65 mg/l, respectively. The adult daily fluoride intake reached 12 mg, of which 99% originated from the brick tea-containing foods. The positive rate of clinical symptoms by physical examination was 89%; furthermore, 42 of the 111 subjects were diagnosed by X-ray. The positive examination rate was 83%. Although the osteosclerosis-type skeletal fluorosis (overall increased bone matrix density) affected 74%, arthropathy and arthritis affected a significant number of the patients, resulting in functional disability. The results suggest that this brick tea-type fluorosis had even more severe adverse effects on human health compared with both the water-type and coal combustion-type fluorosis that occurred in other areas of China.     

Assessment of fluoride concentration and daily intake by human from tea and herbal infusions.

The fluoride content in infusions of commercially available black, green, oolong, pu-erh and white teas was determined by ion-selective electrode. Herbal infusions as well as instant tea and ready-to-drink tea beverages were also examined. It is found that brewing time (5, 10 and 30 min) does increase the fluoride content, which in infusions of black tea (5 min brewing) was higher than that in the other types of tea, with contents ranging between 0.32 and 4.54 mg/l for black tea to 0.37-0.54 mg/l for white tea and with even lower values for herbal tea infusions of 0.02-0.09 mg/l. On the basis of the results obtained, the daily intake of fluoride provided from tea and herbal beverages was estimated for an adult person and for children in comparison with the Polish SAI (Safe and Adequate Daily Intake) of fluoride which is strictly attributable to ADI (Acceptable Daily Intake). The fluoride intake resulted from the regular consumption of black tea infusions was raised as compared to the other types of teas as well as herbal teas. For adult and children tea drinkers consuming five cups of black tea per day the intake of fluoride will be in the range of 8.0-303% and 12-303% of the SAI, respectively. People are often exposed to multiple sources of fluoride, such as in food, water, air and excessive use of toothpaste. The control of tea quality is important to protect human against too high uptake of this element from black tea, which is the most popular beverage. Excessive intake of fluoride with black tea, especially in the regions with its high level in the drinking water, increases the risk of dental fluorosis in children during the years of tooth development. The long-term exposure to large amounts of fluoride can lead to potentially skeletal fluorosis (WHO, 1984).     

Aluminium and fluoride contents of tea,with emphasis on brick tea and their health implications

Tea plant takes up a large quantity of aluminium (Al) and fluoride (F) from acidic soils. It has been known that fluorosis can be developed for people who consume a large quantity of tea made from brick tea, a low quality tea consisting mainly of old tea leaves in China. In addition, it has been claimed that Alzheimer's disease (AD) is linked with the Al content in the human brain. Therefore, the high Al content in tea, especially brick tea is also a concern. This article reviews the basis background on tea including classification, growth conditions, types of tea leaves and their production, and processing of tea. Special emphasis is made on the transfer of Al and F from soil to tea plant and then to tea liquor. Health implications of drinking a large quantity of tea liquor especially those made from brick tea are discussed. Recommendations are suggested to reduce the uptake of these two elements by tea plant, and lower their contents in tea products.     

慢性氟中毒大鼠肾脏自由基含量与形态学变化

目的研究慢性氟中毒大鼠肾脏自由基含量与形态学变化的关系。方法wistar大鼠随机分为三组。正常对照组,未作任何处理;染氟组,自由饮用含氟化钠132．6mg／L的含氟水;抗氧化中药一染氟组,自由饮用含氟化钠132．6mg／L的含氟水,同时每日经腹腔内注射抗氧化中药丹参绞股蓝复方3．125毫克／公斤／天,实验6个月时检查动物。用电子自旋共振的方法检测肾组织内自由基的含量,并观察肾脏的形态学变化。结果与正常对照组动物相比,染氟组自由基明显升高,电镜下见肾小管上皮细胞有巨大线粒体及髓鞘样结构形成,内质网扩张,粗面内质网上核糖体脱落,细胞浆内游离核糖体增加,胞核内异染色质有向核膜下聚集的趋势;光镜下呈颗粒性变,偶见坏死。抗氧化中药一染氟组肾组织中自由基含量不增高,光镜及电镜下均未见明显病变。结论慢性氟中毒时肾脏病变与自由基含量增多有密切关系。     

Processing procedures of brick tea and their influence on fluorine content.

China is the only country that produces brick tea, and more than 90% of the brick tea is consumed in the western minority nationality regions of China. The high fluorine content of brick tea is possibly associated with the special processing procedures, but no investigation has been conducted in this field. To explore the characteristic features of brick tea manufacturing and the alterations in fluorine content during the processing procedures, we performed a field survey involving two brick tea factories and the nearby tea plantations. For the fluorine contents of the initial, intermediate and final processing products, altogether eight types of specimens were collected and determined by using the ion-selective electrode standard curve technique. It was found that the raw material tea leaf for brick tea processing was old, coarse and not the tender delicate tea leaf used for ordinary green or black tea processing. For the fluorine content of the raw material tea leaf, the intermediate and the final products showed that the fresh raw leaf contained a fluorine content as high as 489.31-512.68 mg/kg. During one fermentation-like processing procedure, the fluorine content rose by 4.67% and 1.88% in the specimens from the two factories, respectively, which revealed no statistical significance (P>0.5). These results suggest that the high fluorine content in brick tea might be due to the high content in the raw material and not related with the processing procedures.     

Fluoride levels in various black tea,herbal and fruit infusions consumed in Turkey

The fluoride contents were determined by ion-selective electrode in 26 black tea samples originally produced in Turkey, Sri Lanka, India and Kenya, and in 14 herbal and seven fruit infusions originated from Turkey. Fluoride content in black tea infusions ranged from 0.57 to 3.72 mg/L after 5 min of brewing. Higher fluoride levels were found in black teas originated from Turkey when compared with teas originated from Sri Lanka. Moreover higher fluoride levels were determined in black tea bags compared with granular and stick-shaped black teas. However, herbal and fruit infusions were characterized by low values of fluoride (0.02–0.04 mg/L) after 5 min of brewing and increasing brewing time to 10 min caused only slight increases in some infusions. As a result, consuming tea infusions prepared from some black tea available in Turkish market, especially black tea bags, in large quantities may lead to exposion to a high amount of fluoride which may cause dental fluorosis. Although fruit and herbal infusions are safer to consume their fluoride contents are too low for caries prevention. In countries such as Turkey where tea is traditionally consumed, the fluoride concentration and daily safety precautions should be indicated on tea products.     

Fluoride levels in various black tea commodities: measurement and safety evaluation.

In order to determine the fluoride content of various products of black tea and to make safety evaluations, 37 commodities in the different manufactured forms of tea were assessed by means of ion-selective electrode and spectrophotometric methods. The results showed wide differences in fluoride levels. The fluoride content was found 0.95-1.41 mg/L in black tea sticks, 0.70-2.44 mg/L in black tea granules and 1.15-6.01 mg/L in black tea bags. Of the products tested, the fluoride content was greatest in black tea bags, presumably because black tea bags are made of low cost, and older tea leaves. According to WHO's recommendation, fluoride exposure threshold for children is 2mg of daily intake and for adult, 4 mg. Assuming that children's daily intake of black tea was 800 ml and adult's 1500 ml, 56% of black tea bags should be considered unsafe for children and 44% should be considered unsafe for adults. At average rates of consumption, 24% of the black tea bags could result in an increasing risk of osteofluorosis and fractures (WHO). In the areas with drinking water fluoridation or other fluoride supplements, excessive fluoride exposure can become even more severe with even lower intake tea made from black tea bags. The potential hazards of fluoride arising from consumption of black tea has not aroused due public attention. Therefore, it is necessary to establish reliable fluoride surveillance in food and beverage commodities and conduct additional epidemiological research on fluoride hazards. In addition, it is urgent that governmental and international agencies adopt safe standards of fluoride content in tea commodities.     

燃煤型氟中毒对大鼠睾丸超微结构的影响

目的研究燃煤型氟中毒对SD大鼠睾丸超微结构的影响。方法以SD大鼠为研究对象,按体质量均衡随机分为7组:对照组、高氟组、中氟组、低氟组、高氟加营养组、中氟加营养组、低氟加营养组。各染毒组喂饲含不同比例的燃煤型氟中毒病区煤烘玉米的饲料,复制燃煤型氟中毒动物模型。分3批(90 d,120 d,180 d)以股动脉放血法处死动物,查看氟斑牙,测尿氟。常规制作睾丸超薄切片,用透射电镜观察睾丸超微结构的变化。结果 (1)建成氟中毒动物模型,90 d各染毒组均出现氟中毒表现,对照组正常。中毒程度随氟剂量增加和染毒时间延长而加重;氟剂量相同时,营养好,中毒程度轻。(2)对照组结构正常。染毒组曲精小管内各级生精细胞生成减少,精子数量减少,各级生精细胞、睾丸间质细胞、肌样细胞、支持细胞的超微结构均有不同程度的病理变化。随氟剂量增加和染毒时间延长,病变加重。相同染氟剂量和加营养组比较,加营养组病变程度减轻。结论 (1)燃煤型氟中毒对SD大鼠睾丸组织超微结构有明显的损伤作用,随氟剂量和染毒时间延长,病变加重。(2)降低摄氟量及改善营养状况,可改善氟中毒对大鼠睾丸超微结构的损伤。     

Probe on the biomarker to substitute the dental fluorosis for deriving fluoride threshold by animal study

Dental fluorosis had been used for deriving the fluoride acceptable threshold for a long time. However, it was diagnosed on the color or defect degree of tooth, like Dean’s Index, which would be easily influenced by lifestyle, like smoking and drinking tea. Hence, some biomarkers had already tried to assess the fluoride exposure risk with the development of bio-monitor technique, and this paper probed on an available biomarker, which based on a systematic biochemical indicator group relating to different biological function from animal experiment, to take place the old one. The experiment animals had been treated with different levels of NaF, and biochemical indicators were analyzed after three months later. The correlations between changes of biochemical indicators and the exposure levels were analyzed subsequently, and a comprehensive indicator was developed. Both the NOAEL/LOAEL and the Benchmark Dose approach were applied in this article to derive the suitable threshold and for indicator comparison. Our findings indicated that a better dose-response relationship was shown between the comprehensive indicator and exposure dose (R=0.811, R square=0.657) than single indicator (R<0.4, R square<0.2) and Dean’s Index (R=0.737, R square= 0.543). Furthermore, the available threshold of the comprehensive indicator was 1.70 mg/(kg.d) lower than it from dental fluorosis (2.00 mg/(kg.d)) which can protect animals from fluoride damage at rather low exposure level. Even the scientificity of the comprehensive indicator should be verified in further epidemiology research, its advantage can’t be ignored that it cannot only avoid the personally error during clinical diagnosis, but also present a new method to quantize the gap risk from dental fluorosis to skeletal fluorosis for those people cannot be diagnosed by dental fluorosis clinically.     

The influence of chronic fluorosis on mitochondrial dynamics morphology and distribution in cortical neurons of the rat brain

The present study was designed to evaluate the effects of chronic fluorosis on the dynamics (including fusion and fission proteins), fragmentation, and distribution of mitochondria in the cortical neurons of the rat brain in an attempt to elucidate molecular mechanisms underlying the brain damage associated with excess accumulation of fluoride. Sixty Sprague–Dawley rats were divided randomly into three groups of 20 each, that is, the untreated control group (drinking water naturally containing <0.5 mg fluoride/l, NaF), the low-fluoride group (whose drinking water was supplemented with 10 mg fluoride/l) and the high-fluoride group (50 mg fluoride/l). After 6 months of exposure, the expression of mitofusin-1 (Mfn1), fission-1 (Fis1), and dynamin-related protein-1 (Drp1) at both the protein and mRNA levels were detected by Western blotting, immunohistochemistry, and real-time PCR, respectively. Moreover, mitochondrial morphology and distribution in neurons were observed by transmission electron or fluorescence microscopy. In the cortices of the brains of rats with chronic fluorosis, the level of Mfn1 protein was clearly reduced, whereas the levels of Fis1 and Drp1 were elevated. The alternations of expression of the mRNAs encoding all three of these proteins were almost the same as the corresponding changes at the protein levels. The mitochondria were fragmented and the redistributed away from the axons of the cortical neurons. These findings indicate that chronic fluorosis induces abnormal mitochondrial dynamics, which might in turn result in a high level of oxidative stress.     

Cataractogenic Effect of Fluorosis in an Animal Model

Endemic fluorosis is a chronic, crippling, skeletal and dental disease caused by ingesting large amounts of fluoride either through water or rarely from foods of endemic areas. Although systemic disorders of fluorosis have a wide variety of appearances, little attention has been given to the spectrum of lenticular findings.

Thirty rats were given commercially available spring water either with 100 ppm fluoride (Experimental group, n=15 rats, 30 eyes) or 0.07 ppm fluoride (control group, n=15 rats, 30 eyes) for 24 weeks. The examinations revealed various levels of opacifications and histopathologic changes in 12 eyes of the high fluoride intake group, whereas none of the eyes were affected in the control group. Differences between groups were statistically significant (p<0.05).

Our study demonstrates that fluoride is a potential cataractogenic agent. Hence, we believe that dilution of fluoride in tap waters in endemic areas is an important measure for ophthalmic health. We suggest that ophthalmologic examinations should be performed on patients with documented endemic dental and skeletal fluorosis.     

硒、钼、硼对氟中毒大鼠氟斑牙发生的影响

目的 研究硒、钼、硼对氟中毒大鼠的氟斑牙发生的影响.方法 Wristar大鼠随机分为8组(雌雄各半):硒1组、硒2组、钼1组、钼2组、硼1组、硼2组、氟组、对照组.各组均喂以舍F-45mg/L的蒸馏水及舍不同浓度微量元素的饲料,观察大鼠的一般情况,氟斑牙的发生.结果 硒组体质量增加与对照组接近,优于钼组和硼组(P＜0....     

Effect of dog food containing 460 ppm fluoride on rat reproduction

A one-generation, two-litter rat reproduction study was done in a kennel in Allegan County, Michigan, as part of an investigation of reproductive problems in Shetland sheepdogs (shelties). Since 1970, at least 115 sheltie litters at this kennel have been grossly deformed and/or have died, generally within 3 d of birth. The causative factor(s) appears to be associated with the environment, as the shelties have had successful pregnancies elsewhere. There was some concern that a potential threat to human reproduction also might exist in this area. After it was discovered that fluoride in the dog food had apparently caused mottled teeth and bony exostoses in dogs at this and at least two other kennels, dog-food fluoride content and local well water were investigated as possible causes of the reproductive problems. A two-way factorial statistical design allowed assessment of dietary fluoride content and water source and interaction between the two. UPj:TUC(SD)spf rats, 9 males and 18 females in each group, were assigned to treatment with high-fluoride dog food (460 ppm) and well water; high-fluoride dog food and distilled water; low-fluoride dog food (56 ppm) and well water; and low-fluoride dog food and distilled water. After 60 d in the kennel, the rats were mated. Even after two litters, the only adverse effect was dental fluorosis in the high-fluoride groups. The results indicated that rats cannot be used in the search for the cause(s) of reproductive problems in dogs in this kennel.     

Subchronic fluoride intake induces impairment in habituation and active avoidance tasks in rats

Since clinical case reports suggest that sodium fluoride (NaF) intoxication may impair learning and memory, the objective of the present study was to evaluate the effects of NaF on two memory tasks: open-field habituation and two-way active avoidance. Adult male rats were exposed to NaF in drinking water at three concentrations for 30 days: 1.54 (control, tap water), 50 and 100 ppm NaF (corresponding to an intake of 0.10+/-0.005, 5.15+/-0.14, and 10.77+/-0.39 mg/kg of NaF, respectively). At day 30, the rats were placed in an open-field and retested after 24 h (test session) to measure habituation. In the two-way active avoidance task, another three groups of rats were trained in a 30-trial training session and tested again 24 h later (test session). Dental fluorosis was also evaluated. Habituation was impaired by 50 and 100 ppm, but not by 1.54 ppm NaF. Moreover, 100 ppm NaF reduced the number of avoidance responses in the active avoidance task. No locomotor impairment was observed. Mild dental fluorosis in rat incisor teeth was found in the 50 and 100 ppm NaF groups. Overall, these results suggest that moderate intoxication with sodium fluoride has potentially deleterious effects on learning and memory.     

Dietary fluoride intake from infant and toddler formulas in Poland

Risk of enamel fluorosis associated with excessive fluoride intake during infancy and early childhood has been widely reported in literature. Results of several studies indicate that infant formula consumption, especially in the form of powdered concentrate, may appreciably increase children’s fluoride exposure in optimally fluoridated communities. The aim of the study was to measure fluoride content of infant and toddler formulas available in Poland and to discuss implications of the results. Twenty nine brands of powdered formulas were evaluated. Analyzes were performed with the use of ionselective fluoride electrode (09-37 type) and a RAE 111 chloride-silver reference electrode (MARAT). Results revealed that concentration of fluoride in all products was low (mean 29.0 μg/100 g), and that the formula itself is not a significant source of fluoride exposure. However, when reconstituted with water containing more than 0.5 ppm of fluoride, starting formulas and follow-on formulas may provide a daily fluoride intake of above the suggested threshold for fluorosis. Thus, fully formula-fed infants consuming mother milk substitutes prepared with optimally fluoridated water may be at increased risk of dental fluorosis.     

Increased level of apoptosis in rat brains and SH-SY5Y cells exposed to excessive fluoride--a mechanism connected with activating JNK phosphorylation

In order to reveal the mechanism of the brain injury induced by chronic fluorosis, the levels of apoptosis and c-Jun N-terminal kinases (JNK) in brains of rats and SH-SY5Y cells exposed to different concentrations of sodium fluoride (NaF) were detected. The dental fluorosis and fluoride contents in blood, urine and bones of rats were measured to evaluate the exhibition of fluorosis. The apoptotic death rate was measured by flow cytometry and the expression of JNK at protein level by Western blotting. The results showed that as compared with controls, the apoptotic death rate was obviously increased in brains of the rats exposed to high-fluoride (50ppm) for 6 months with a concentration dependent manner, but no significant change for 3 months. In SH-SY5Y cells treated with high concentration (50ppm) of fluoride, the increased apoptotic death rate was obviously observed as compared to controls. In addition, the expressions of phospho-JNK at protein level were raised by 20.5% and 107.6%, respectively, in brains of the rats exposed to low-fluoride (5ppm) and high-fluoride for 6 months; while no significant changes were found between the rats exposed to fluoride and the controls for 3 months. The protein level of phospho-JNK was also increased in SH-SY5Y cells exposed to high-fluoride. There were no changes of total-JNK both in the rats and in the SH-SY5Y cells exposed to excessive fluoride as compared to controls. When SH-SY5Y cells were singly treated with SP600125, an inhibitor of phospho-JNK, the decreased expression of phospho-JNK, but no apoptosis, was detected. Interestingly, after JNK phosphorylation in the cultured cells was inhibited by SP600125, the treatment with high-fluoride did not induce the increase of apoptosis. In addition, there was a positive correlation between the expression of phospho-JNK and the apoptotic death rate in rat brains or SH-SY5Y cells treated with high-fluoride. The results indicated that exposure to excessive fluoride resulted in the increase of apoptosis in rat brains and SH-SY5Y cells, in which one of the mechanisms might be activating JNK phosphorylation.     

Anti-ulcer effect of tea catechin in rats

Oral administration of tea catechin dose-dependently prevented absolute ethanol-induced (50, 100, 200 mg/kg) or restraint plus water immersion stress-induced acute gastric mucosal injury (300, 400 mg/kg) in rats. When the effect of test compound was evaluated on the 15th day after acetic acid injection to rats, repeated oral administration of tea catechin (25, 50, 100 mg/kg twice daily) dose-dependently accelerated the healing of acetic acid-induced chronic gastric ulcers. Tea catechin (10(-5)-10(-1) g/100 ml) concentration-dependently scavenged superoxide anions in vitro. Tea catechin (100, 200 mg/kg orally) markedly inhibited the increase in thiobarbituric acid-reactive substances in the injured mucosa of rats treated with 50% ethanol. Tea catechin (50, 100 mg/kg twice orally, daily) markedly inhibited the increase in content of thiobarbituric acid-reactive substances in the ulcerated region of acetic acid-induced gastric ulcers on the 7th and 15th days. In addition, at 50, 100 and 200 mg/kg orally, it dose-dependently prevented the decrease in gastric mucosal hexosamine content induced by absolute ethanol, although it failed to inhibit the basal gastric acid secretion. These results suggest that tea catechin may primarily protect gastric mucosa from acute gastric mucosal injury and promote the healing of chronic gastric ulcers by its antioxidant activity and gastric mucus-increasing actions.     

The dose-time effects of fluoride on the expression and DNA methylation level of the promoter region of BMP-2 and BMP-7 in rats

Skeletal fluorosis is a chronic metabolic bone disease caused by excessive exposed to fluoride. Recent studies have shown that fluoride causes abnormal bone metabolism through disrupting the expression of Bone Morphogenetic Proteins (BMPs). However, the relationship between fluoride and BMPs is not fully understood, and the mechanism of fluoride on BMPs expression is still unclear. This study investigated the dose-time effects of fluoride on BMP-2 and BMP-7 levels and DNA methylation status of the promoter regions of these two genes in peripheral blood of rats. Eighty Wistar male rats were randomly divided into four groups and treated for 1 month and 3 months with distilled water (control), 25 mg/L, 50 mg/L or 100 mg/L of sodium fluoride (NaF). Rats exposed to fluoride had higher protein expression of BMP-2 and BMP-7 in plasma at 1 month and 3 months. An increase in BMP-2 expression was also observed with an increase of fluoride exposure time. Significant hypomethylation was observed in 2 CpG sites (CpGs) of BMP-2 and 1 CpG site of BMP-7 promoter regions in the fluoride treatment groups. It concludes that fluoride has a dose-response effect on BMP-2 in fluorosis rats, and fluoride-induced hypomethylation of specific CpGs may play an essential role in the regulation of BMP-2 and BMP-7 expression in rats.     

Effect of green tea extracts on liver functions in Wistar rats.

An herbal medicinal product (Exolise) containing as active ingredient an hydro-alcoholic extract of green tea named AR25 (standardized to 25% catechins) has been implicated in hepatic failures, leading to the withdrawal of the marketing authorization. The active ingredient of Exolise being manufactured with 80% ethanol, the question to know whether the extraction solvent could introduce some toxic components was hypothesized. Two investigations were conducted in Wistar rats to determine if repeated oral administration of different green tea extracts could corroborate the reported hepatotoxicity in humans. In a preliminary 6 week-study, experimental groups (n=9/group) received either the vehicle or a methylene chloride extract (2500 mg/kg body weight) where potential non-polar hepatotoxin(s) could be concentrated. In a second experiment (12 week-study), rats were divided in three groups (n=10/group) and treated with either the vehicle, or an aqueous extract (1400 mg/kg) or AR25 green tea extract (2000 mg/kg). Rat liver functions were assessed by serum biochemistry of hepatotoxicity markers. No sign of evidence of characteristic hepatotoxicity was found in rats treated with very high amount of different green tea extracts in these two experiments (respectively a daily dosage, which was about 900 and 80 times higher to the therapeutic daily dosage of Exolise.