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Dyspnoea in young adults due to pulmonary lymphangitic carcinomatosis from gastric carcinoma

Liam CK, Looi LM, Pailoor J, Alhady SF

Ann Acad Med Singap, 1989 Nov;18(6):713-6.
PMID: 2624423

Three cases of progressive dyspnoea in young female adults due to pulmonary lymphangitic carcinomatosis are reported. The underlying primary neoplasm was gastric carcinoma in all 3 cases. The diagnosis was not suspected in 2 patients because of their young age.
Effect of palm oil carotene on breast cancer tumorigenicity in nude mice

Nesaretnam K, Radhakrishnan A, Selvaduray KR, Reimann K, Pailoor J, Razak G, et al.

Lipids, 2002 Jun;37(6):557-60.
PMID: 12120953

Biological therapies are new additions to breast cancer treatment. Among biological compounds, beta-carotene has been reported to have immune modulatory effects, in particular, enhancement of natural killer cell activity and tumor necrosis factor-alpha production by macrophages. The objective of this study was to investigate the effect of palm carotene supplementation on the tumorigenicity of MCF-7 human breast cancer cells injected into athymic nude mice and to explore the mechanism by which palm carotenes suppress tumorigenesis. Forty-eight 4-wk-old mice were injected with 1 x 10(6) MCF-7 cells into their mammary fat pad. The experimental group was supplemented with palm carotene whereas the control group was not. Significant differences were observed in tumor incidence (P< 0.001) and tumor surface area and metastasis to lung (P< 0.005) between the two groups. Natural killer (NK) cells and B-lymphocytes in the peripheral blood of carotene-supplemented mice were significantly increased (P < 0.05 and P < 0.001, respectively) compared with controls. These results suggest that palm oil carotene is able to modulate the immune system by increasing peripheral blood NK cells and B-lymphocytes and suppress the growth of MCF-7 human breast cancer cells.
Safety Evaluation of Sclerotium from a Medicinal Mushroom, Lignosus cameronensis (Cultivar): Preclinical Toxicology Studies

Lee SS, Tan NH, Pailoor J, Fung SY

Front Pharmacol, 2017;8:594.
PMID: 28919858 DOI: 10.3389/fphar.2017.00594

Twenty-eight days subacute toxicity studies performed in rats using sclerotial powder of Lignosus cameronensis cultivar was conducted to assess its safety for consumption prior to other scientific investigations on its medicinal benefits, nutraceutical or pharmaceutical application of the mushroom. The study was conducted at 250, 500, and 1000 mg/kg sclerotial powder of L. cameronensis cultivar (n = 5 for each respective dose, on both male and female groups) while control groups received only distilled water. At the end of the study (29th day), the animals were sacrificed followed by blood and organs collection for analysis. Subacute toxicity studies done shows that sclerotial powder of L. cameronensis cultivar at 250, 500, and 1000 mg/kg did not induce treatment related changes on behavioral patterns, gross physical appearance, growth pattern, body weight gain, values of hematological and clinical biochemical panels as well as histopathological findings on kidney, spleen, heart, lung and liver of the experimental rats. The no-observed-adverse-effect level dose for sclerotial powder of L. cameronensis cultivar in 28-days sub-acute toxicity study is determined to be 1000 mg/kg.
Fulltext Genetic and Chromosomal Aberrations and Their Clinical Significance in Renal Neoplasms

Yap NY, Rajandram R, Ng KL, Pailoor J, Fadzli A, Gobe GC

Biomed Res Int, 2015;2015:476508.
PMID: 26448938 DOI: 10.1155/2015/476508

The most common form of malignant renal neoplasms is renal cell carcinoma (RCC), which is classified into several different subtypes based on the histomorphological features. However, overlaps in these characteristics may present difficulties in the accurate diagnosis of these subtypes, which have different clinical outcomes. Genomic and molecular studies have revealed unique genetic aberrations in each subtype. Knowledge of these genetic changes in hereditary and sporadic renal neoplasms has given an insight into the various proteins and signalling pathways involved in tumour formation and progression. In this review, the genetic aberrations characteristic to each renal neoplasm subtype are evaluated along with the associated protein products and affected pathways. The potential applications of these genetic aberrations and proteins as diagnostic tools, prognostic markers, or therapeutic targets are also assessed.
Nuclear factor-kappa B subunits and their prognostic cancer-specific survival value in renal cell carcinoma patients

Ng KL, Yap NY, Rajandram R, Small D, Pailoor J, Ong TA, et al.

Pathology, 2018 Aug;50(5):511-518.
PMID: 29935727 DOI: 10.1016/j.pathol.2018.03.003

Better characterisation and understanding of renal cell carcinoma (RCC) development and progression lead to better diagnosis and clinical outcomes. In this study, expression of nuclear factor-kappa B (NF-κB) subunits: p65 (RelA), p105/p50, p100/p52, and cRel in RCC tissue were compared with corresponding normal kidney, along with tumour characteristics and survival outcome. Ninety-six cases of RCC with paired normal kidney were analysed. Clinicopathological data, demographics and survival data were available. Immunohistochemistry (IHC) for NF-κB subtypes was analysed using the Aperio digital pathology system for overall cellular expression and localisation. The prognostic cancer-specific survival value of the subunits in RCC patients was analysed. Approximately 50% of patients had clinical stage T1, with 22 patients having metastases at presentation. RCC subtypes were: clear cell (n = 76); papillary (n = 11); chromophobe (n = 5); clear cell tubulopapillary (n = 3); and one multilocular cystic RCC. Median follow up was 54.5 months (0.2-135), with 28 deaths at time of analysis. NF-κB p65 had higher overall and nuclear expressions, with lower overall and nuclear expressions of p50, p52 and cRel in RCC compared with normal kidney. Higher expressions of p65 (nuclear), p52 (overall and nuclear) and p50 (overall) correlated significantly with worse cancer-specific survival. This is the first large series of analysis of expression of NF-κB subunits in RCC. Especially with regards to the less studied subunits (p52, p50, cRel), our results allow a better understanding the role of NF-κB in RCC development and progression, and may pave the way for future targeted NF-κB subunit specific therapies.
Tumour necrosis factor receptor-associated factor-1 (TRAF-1) expression is increased in renal cell carcinoma patient serum but decreased in cancer tissue compared with normal: potential biomarker significance

Rajandram R, Yap NY, Pailoor J, Razack AH, Ng KL, Ong TA, et al.

Pathology, 2014 Oct;46(6):518-22.
PMID: 25158810 DOI: 10.1097/PAT.0000000000000145

Renal cell carcinoma (RCC) generally has a poor prognosis because of late diagnosis and metastasis. We have previously described decreased tumour necrosis factor receptor-associated factor-1 (TRAF-1) in RCC compared with paired normal kidney in a patient cohort in Australia. In the present study, TRAF-1 expression in clear cell RCC (ccRCC) and normal kidney was again compared, but in a cohort from University Malaya Medical Centre. Serum TRAF-1 was also evaluated in RCC and normal samples.Immunohistochemistry with automated batch staining and Aperio ImageScope morphometry was used to compare TRAF-1 in 61 ccRCC with paired normal kidney tissue. Serum from 15 newly diagnosed and untreated ccRCC and 15 healthy people was tested for TRAF-1 using ELISA.In this cohort, TRAF-1 was highly expressed in proximal tubular epithelium of normal kidney, and significantly decreased in ccRCC tissue (p
Fulltext Low prevalence of 'classical' microscopic colitis but evidence of microscopic inflammation in Asian irritable bowel syndrome patients with diarrhoea

Hilmi I, Hartono JL, Pailoor J, Mahadeva S, Goh KL

BMC Gastroenterol, 2013;13:80.
PMID: 23651739 DOI: 10.1186/1471-230X-13-80

There is increasing evidence for the role of microscopic inflammation in patients with IBS. We aimed to examine the prevalence of microscopic colitis and inflammation in Malaysian IBS patients with diarrhoea (IBS-D).
Fulltext Leprosy--an imported disease

Kwan Z, Pailoor J, Tan LL, Robinson S, Wong SM, Ismail R

Lepr Rev, 2014 Sep;85(3):170-6.
PMID: 25509717

OBJECTIVES: Leprosy remains a public health concern in Malaysia and globally. We aim to review the characteristics of leprosy patients in a tertiary institution in urban Malaysia.
DESIGN: This is a case series of 27 leprosy patients who presented between 2008 and 2013.
RESULTS: The majority of our patients consisted of male (74.1%), Malaysian (63.0%), blue collar workers (51.9%) and married (59.3%) patients; 48.1% had lepromatous leprosy. All except one of the patients presented with skin lesions, 25.9% had nerve involvement and 33.3% developed lepra reactions. Forty-four point four percent (44.4%) of the cases seen initially in the primary care setup were misdiagnosed.
CONCLUSIONS: Doctors need to have a high index of suspicion for leprosy when patients present with suggestive skin, nerve or musculoskeletal lesions. Immigrants accounted for 37% of cases and these patients may become a reservoir of infection, thus accounting for the rise in incidence. An increasing trend in multibacillary cases may be attributed to the spread from migrants from countries with a high burden of leprosy.
Fulltext Chromosome 7 aneuploidy in clear cell and papillary renal cell carcinoma: detection using silver in situ hybridization technique

Pailoor J, Rajandram R, Yap NY, Ng KL, Wang Z, Iyengar KR

Indian J Pathol Microbiol, 2013 Apr-Jun;56(2):98-102.
PMID: 24056643 DOI: 10.4103/0377-4929.118688

Chromosome 7 aberrations in renal cell carcinoma (RCC) have been reported in papillary renal cell carcinoma (pRCC) and clear cell renal cell carcinoma (ccRCC). However, the implication of these anomalies on prognosis and survival is still unclear. RCC Chromosome 7 aberrations have commonly been detected by fluorescent in situ hybridization and chromogenic in situ hybridization but not silver in situ hybridization (SISH).
Characteristics of skin cancers among adult patients in an urban Malaysian population

Han WH, Yong SS, Tan LL, Toh YF, Chew MF, Pailoor J, et al.

Australas J Dermatol, 2019 Nov;60(4):e327-e329.
PMID: 31222718 DOI: 10.1111/ajd.13106

There has been a rising incidence of skin cancers among Asians in recent years. We present a retrospective analysis of 106 skin cancers and analysed the demography, clinical subtypes of skin cancers and surgical techniques used for skin cancer treatment. In our population, skin cancers were most frequently basal cell carcinomas and diagnosed among ethnic Chinese patients.
Fulltext Cutaneous malignant melanoma: clinical and histopathological review of cases in a Malaysian tertiary referral centre

Pailoor J, Mun KS, Leow M

Malays J Pathol, 2012 Dec;34(2):97-101.
PMID: 23424771 MyJurnal

Melanoma is a lethal skin cancer that occurs predominantly among Caucasians. In Malaysia, the incidence of melanoma is low. This is a retrospective study of clinical and histopathological features of patients with cutaneous melanoma who were seen at the University Malaya Medical Centre from 1998 to 2008. Thirty-two patients with cutaneous melanoma were recorded during that period. Of these, 24 had sought treatment at the onset of disease at our centre. Chinese patients constituted the largest group (19 cases). The median age of these 24 patients at the time of presentation was 62 years. 16 patients had melanoma involving the lower limb with 12 affecting the sole of the foot. None had melanoma arising from the face. Histopathology showed nodular melanoma in 22 cases (91.6%), with superficial spreading and acral lentiginous melanoma diagnosed in 1 case each. The majority of patients (62.5%) were found to be in Stage III of the disease at the time of diagnosis.
Pattern of tissue expression of CA-125 and HE4 in primary epithelial ovarian tumours and correlation with serum CA-125 levels

Devan SM, Pailoor J, Sthaneshwar P, Narayanan V

Asian Pac J Cancer Prev, 2013;14(8):4545-8.
PMID: 24083699

The objective of this study is to assess tissue expression of CA-125 and HE4 protein in primary benign and malignant epithelial tumours of the ovary and correlate with serum CA-125 levels. A total of 100 formalin-fixed, paraffin embedded sections of ovarian tumours which included serous adenoma (11), mucinous adenoma (42), serous carcinoma (20), mucinous carcinoma (12) and endometrioid carcinoma (15), histologically diagnosed between 1st January 2004 to 31st December 2012 at the University Malaya Medical Centre, were stained for HE4 (rabbit polyclonal antibody, Abcam, UK) and CA-125 (mouse monoclonal antibody clone: OC125, Cell Marque Corporation, Rocklin, California, USA). Pre-operative serum CA-125 levels were obtained from the laboratory information system. Immunoscore (I score) for HE4 and CA-125 was given based on the intensity of staining and percentage of positive tumour cells and considered significant when it was >50 (intensity of staining multiplied by percentage of positive tumour cells). Serum CA-125 levels were compared with the I score of HE4 and CA-125 in tissues. We noted that the CA-125 levels in serum and tissues were significantly raised in malignant compared to benign ovarian tumours (p value<0.05). Tissue expression of HE4 protein was also significantly raised in malignant tumours compared to benign tumours (p value<0.05). We conclude that HE4 can be a useful tissue immunomarker in addition to CA-125.
Nutritional composition, antioxidant properties, and toxicology evaluation of the sclerotium of Tiger Milk Mushroom Lignosus tigris cultivar E

Kong BH, Tan NH, Fung SY, Pailoor J, Tan CS, Ng ST

Nutr Res, 2016 Feb;36(2):174-83.
PMID: 26598045 DOI: 10.1016/j.nutres.2015.10.004

The Tiger Milk Mushroom (Lignosus spp.) is an important medicinal mushroom in Southeast Asia and has been consumed frequently by the natives as a cure for a variety of illnesses. In this study, we hypothesized that Lignosus tigris (cultivar E) sclerotium may contain high nutritional value and antioxidant properties, is nontoxic and a potential candidate as a dietary supplement. The chemical and amino acid compositions of the sclerotium were evaluated and antioxidant activities of the sclerotial extracts were assessed using ferric reducing antioxidant power; 1,1-diphenyl-2-picrylhydrazyl; and superoxide anion radical scavenging assays. Acute toxicity of the L. tigris E sclerotium was assessed using a rat model study. The sclerotium was found to be rich in carbohydrate, protein, and dietary fibers with small amounts of fat, calories, and sugar. The amino acid composition of the protein contains all essential amino acids, with a protein score of 47. The sclerotial extracts contain phenolics, terpenoids, and glucan. The ferric reducing antioxidant power values of the various sclerotial extracts (hot water, cold water, and methanol) ranged from 0.008 to 0.015 mmol min(-1) g(-1) extract, while the 1,1-diphenyl-2-picrylhydrazyl and superoxide anion radical scavenging activities ranged from 0.11 to 0.13, and -2.81 to 9.613 mmol Trolox equivalents g(-1) extract, respectively. Acute toxicity assessment indicated that L. tigris E sclerotial powder was not toxic at the dose of 2000 mg kg(-1). In conclusion, L. tigris E sclerotium has the potential to be developed into a functional food and nutraceutical.
Fulltext P53 expression in invasive pancreatic adenocarcinoma and precursor lesions

Norfadzilah MY, Pailoor J, Retneswari M, Chinna K, Noor LM

Malays J Pathol, 2011 Dec;33(2):89-94.
PMID: 22299208 MyJurnal

Patients with pancreatic adenocarcinoma are known to have a high mortality rate. The 5-year survival rate still remains low even now compared to that of the 1960's despite new advances in management including surgery, chemotherapy, pathological classification and molecular diagnostic technologies. Precursors to invasive pancreatic adenocarcinoma have been identified in the last ten years that include mucinous cystic neoplasm, intraductal papillary mucinous neoplasm and pancreatic intraepithelial neoplasia. p53 protein accumulation in the nuclei is a common molecular event in most human neoplasms. Our objective is to investigate p53 expression in pancreatic adenocarcinoma and precursor lesions and their significance. The selected study material encompassed 31 invasive ductal adenocarcinoma, 15 mucinous cystic neoplasm and papillary mucinous neoplasm, and 27 cases of pancreatic intraepithelial neoplasia including grade 1, 2 and 3. Immunoscore was given for each case based on intensity of staining and percentage of cells positive and compared between precursor lesions and invasive adenocarcinoma. A score of 50 and above was considered significant. The results showed that p53 expression increased progressively and significantly with the grade of pancreatic intraepithelial neoplasia and adenocarcinoma (p-value < 0.001). These findings support the concept of multistep carcinogenesis in pancreatic adenocarcinoma and suggest that p53 inactivation occurs in the progression of precursors to pancreatic adenocarcinoma.
Fulltext Isolated sphenoid sinus lesion: A diagnostic dilemma

Alazzawi S, Shahrizal T, Prepageran N, Pailoor J

Qatar Med J, 2014;2014(1):57-60.
PMID: 25320694 DOI: 10.5339/qmj.2014.10

Isolated sphenoid sinus lesions are an uncommon entity and present with non-specific symptoms. In this case report, the patient presented with a history of headaches for a duration of one month without sinonasal symptoms. A computed tomography scan showed a soft tissue mass occupying the sphenoid sinus. An endoscopic biopsy revealed fungal infection. Endoscopic wide sphenoidotomy with excision of the sphenoid sinus lesion was then performed however, the microbiological examination post-surgery did not show any fungal elements. Instead, Citrobacter species was implicated to be the cause of infection.
Fulltext Which is the best method of sterilization of tumour bone for reimplantation? A biomechanical and histopathological study

Singh VA, Nagalingam J, Saad M, Pailoor J

Biomed Eng Online, 2010;9:48.
PMID: 20831801 DOI: 10.1186/1475-925X-9-48

Sterilization and re-usage of tumour bone for reconstruction after tumour resection is now gaining popularity in the East. This recycle tumour bone needs to be sterilized in order to eradicate the tumour cells before re-implantation for limb salvage procedures. The effect of some of these treatments on the integrity and sterility of the bone after treatment has been published but there has yet been a direct comparison between the various methods of sterilization to determine the one method that gives the best tumour kill without compromising the bone's structural integrity.
Preclinical toxicological evaluations of the sclerotium of Lignosus rhinocerus (Cooke), the Tiger Milk mushroom

Lee SS, Enchang FK, Tan NH, Fung SY, Pailoor J

J Ethnopharmacol, 2013 May 2;147(1):157-63.
PMID: 23458920 DOI: 10.1016/j.jep.2013.02.027

Lignosus rhinocerus (Tiger Milk mushroom) is distributed in South China, Thailand, Malaysia, Indonesia, Philippines and Papua New Guinea. In Malaysia, it is the most popular medicinal mushroom used by the indigenous communities to relieve fever, cough, asthma, cancer, food poisoning and as a general tonic. In China, this mushroom is an expensive traditional medicine used to treat liver cancer, chronic hepatitis and gastric ulcers. The sclerotium of the mushroom is the part with medicinal value. This rare mushroom has recently been successfully cultivated making it possible to be fully exploited for its medicinal and functional benefits. The present study was carried out to evaluate the chronic toxicity of the sclerotial powder of Lignosus rhinocerus cultivar (termed TM02), its anti-fertility and teratogenic effects as well as genotoxicity.
Characteristics and outcome of autoimmune liver disease in Asian children

Lee WS, Lum SH, Lim CB, Chong SY, Khoh KM, Ng RT, et al.

Hepatol Int, 2015 Apr;9(2):292-302.
PMID: 25788179 DOI: 10.1007/s12072-014-9558-0

BACKGROUND: Little is known about autoimmune liver disease (AILD) in Asian children. We studied the clinical features and predictors of outcome in childhood AILD in an Asian population.

METHODS: Retrospective review of AILD [autoimmune hepatitis type 1 and 2 (AIH1, AIH2), primary sclerosing cholangitis (PSC) and autoimmune sclerosing cholangitis (ASC)] seen at two pediatric liver units in Malaysia.

RESULTS: At presentation, 17 (56%) of the 32 children [19 females, 59%; median (range) age 7.7 (1.8-15.5) years] with AILD (AIH1 = 18, AIH2 = 5, PSC = 0, ASC = 9) had liver cirrhosis. At final review [median (range) duration of follow-up 4.8 (0.4-12) years], 24 patients (75%) survived with a native liver. Twenty-one (66%) were in remission; 19 (AIH1 = 11; AIH2 = 4, ASC = 4) were on prednisolone and/or azathioprine, one on cyclosporine and another on mycophenolate mofetil. Three (AIH1 = 3) were in partial remission. Of the two who underwent liver transplantation (LT; 6.5%; both ASC), one died of primary graft failure after LT. Six patients (19%) died without LT (acute liver failure, n = 1; end-stage liver disease, n = 5). The overall survival rate (native liver and survival post-LT) was 78%. A delay in seeking treatment adversely affected the final outcome [survival with native liver vs. LT or death (duration between onset of disease and treatment; median ± standard error) = 2.5 ± 2.9 months vs. 24.0 ± 13.3 months; p = 0.012].

CONCLUSIONS: Although remission was achieved in the majority of patients with prednisolone and/or azathioprine therapy, delay in seeking diagnosis and treatment adversely affects the outcome of childhood AILD in Malaysia.
Fulltext Sub-Acute Toxicity Study of Tiger Milk Mushroom Lignosus tigris Chon S. Tan Cultivar E Sclerotium in Sprague Dawley Rats

Kong BH, Tan NH, Fung SY, Pailoor J

Front Pharmacol, 2016;7:246.
PMID: 27555822 DOI: 10.3389/fphar.2016.00246

Lignosus also known as "Tiger Milk Mushroom," is classified in the family Polyporaceae and mainly consumed for its medicinal properties in Southeast Asia and China. The sclerotium is known as the part with medicinal value and often used by the natives to treat a variety of ailments. Lignosus tigris Chon S. Tan, one of the species of the Malaysia Tiger Milk mushroom, has recently been successfully cultivated in laboratory. Earlier studies have demonstrated the L. tigris cultivar E sclerotia exhibited beneficial biomedicinal properties. This study evaluated the potential toxicity of L. tigris E sclerotia in a 28-day sub-acute oral administration in Sprague Dawley (SD) rats. L. tigris E sclerotial powder was administered orally at three different doses of 250, 500, and 1000 mg/kg to the SD rats once daily, consecutively for 28-days. Body weight of the rats was recorded and general behavior, adverse effects, and mortality were observed daily throughout the experimental period. At the end of the experiment, blood hematology and biochemistry, relative organ weights, and histopathological analysis were performed. Results showed that there were no mortality nor signs of toxicity throughout the 28-day sub-acute toxicity study. Oral administration of the L. tigris E sclerotial powder at daily dose up to 1000 mg/kg had no significant effects in body weight, relative organ weight, blood hematological and biochemistry, gross pathology, and histopathology of the organs. L. tigris E sclerotial powder did not cause any treatment-related adverse effect in the rats at different treatment dosages up to 1000 mg/kg. As the lethal dose for the rats is above 1000 mg/kg, the no-observed-adverse-effect level (NOAEL) dose is more than 1000 mg/kg.
Safety assessment of cultivated fruiting body of Ophiocordyceps sinensis evaluated through subacute toxicity in rats

Fung SY, Lee SS, Tan NH, Pailoor J

J Ethnopharmacol, 2017 Jul 12;206:236-244.
PMID: 28587826 DOI: 10.1016/j.jep.2017.05.037

ETHNOPHARMACOLOGICAL RELEVANCE: Ophiocordyceps sinensis (Berk.) G.H. Sung, J.M. Sung, Hywel-Jones & Spatafora is one of the most renowned traditional Chinese medicine used as tonic, renal, respiratory and reproductive health, promote longevity and overall improvement in quality of life. Natural production of O. sinensis is limited due to its extreme specificity in host range and confined geographic distribution. Therefore, cultivation of the fungus was developed to meet high demand for commercialization as nutraceutical. O. sinensis fruiting body has recently been successfully cultivated in large scale using rice based solid medium, providing wider source options for consumers and scientific researchers.
AIMS OF THE STUDY: The present study aims to establish safety profile for the consumption of cultivated fruiting body of O. sinensis (FBOS) by 28-days sub-acute toxicity study in Sprague Dawley rats.
MATERIALS AND METHODS: Rats were orally administered with cultivated FBOS at three graded doses (250, 500 and 1000mg/kg), once daily for 28 consecutive days. Control group received distilled water. General observations (gross behavioral changes and toxic symptoms) and body weight of each animal were monitored daily. Haematological, serum biochemical and histopathological analysis were carried out at the end of the experiment (Day 29).
RESULTS: No behavioral changes, toxic symptoms or death was observed in rats throughout the dosing period. Cultivated FBOS treatment up to 1000mg/kg did not cause any adverse effect on the growth of the animals. Results from haematology and serum biochemistry revealed no toxic effect following cultivated FBOS treatment at three graded doses for 28 days. In addition, no treatment related histopathological changes were noted in heart, spleen, kidney, lung and liver of the animals.
CONCLUSION: The present study revealed that oral administration of cultivated FBOS for 28 days, at dosage up to 1000mg/kg did not pose toxicological concern in rats. Therefore, the no-observed-adverse-effect level (NOAEL) dose of cultivated FBOS in 28-days subacute toxicity study is higher than 1000mg/kg.

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