Sphingosine N-acyltransferase/ceramide synthase

The fumonisin B mycotoxins (FB1 and FB2) have been purified and characterized from corn cultures of Fusarium moniliforme strain MRC 826. Fumonisin B1 (FB1), the major fumonisin produced in culture, has been shown to be responsible for the major toxicological effects of the fungus in rats, horses and pigs. Recent investigations on the purification of compounds with chromatographic characteristics similar to FB1 have led to the identification of two new fumonisins, FB3 and FB4. Fumonisins A1 and A2, the N-acetyl derivatives of FB1 and FB2 respectively, were also purified and shown to be secondary metabolites of the fungus. Short-term carcinogenesis studies in a rat liver bioassay indicated that over a period of 15 to 20 days, at dietary levels of 0.05-0.1%, FB2 and FB3 closely mimic the toxicological and cancer initiating activity of FB1 and thus could contribute to the toxicological effects of the fungus in animals. In contrast, no biological activity could be detected for FA1 under identical experimental conditions. These studies and others have indicated that the fumonisin B mycotoxins, although lacking mutagenicity in the Salmonella test or genotoxicity in the DNA repair assays in primary hepatocytes, appear to induce resistant hepatocytes similar to many known hepatocarcinogens [1].

A liquid chromatographic (LC) method for simultaneous determination of fumonisins B1 (FB1), B2 (FB2), and B3 (FB3) in corn was subjected to a collaborative study involving 12 participants from 10 countries, in which the accuracy and reproducibility characteristics of the method were established. Mean analyte recoveries from corn ranged from 81.1 to 84.2% for FB1 (at a spiking range of 500 to 8000 ng/g), from 75.9 to 81.9% for FB2 (at a spiking range of 200 to 3200 ng/g), and from 75.8 to 86.8% for FB3 (at a spiking range of 100 to 1600 ng/g). The valid data were statistically evaluated after exclusion of outliers. Relative standard deviations for within-laboratory repeatability ranged from 5.8 to 13.2% for FB1, from 7.2 to 17.5% for FB2, and from 8.0 to 17.2% for FB3. Relative standard deviations for between-laboratory reproducibility varied from 13.9 to 22.2% for FB1, from 15.8 to 26.7% for FB2, and from 19.5 to 24.9% for FB3. HORRAT ratios, calculated for the individual toxin analogues, ranged from 0.75 to 1.73. The LC method for determination of fumonisins B1, B2, and B3 in corn (at concentrations of 800-12800 ng total fumonisins/g) has been adopted by AOAC INTERNATIONAL [2].

The Committee reviewed studies available since the last assessment in 2011 and concluded that these studies do not alter the Committee’s previous overall toxicological assessment. Therefore, the Committee maintained the previously established PMTDI for FB1, FB2, and FB3 (alone or in combination) at 2 µg/kg body weight. The Committee noted that the international exposure estimates for FB1 and total fumonisins were lower than those estimated at the Committee’s seventy-fourth session in 2011. In this assessment, a higher proportion of incidence data from WHO European Region countries compared to 2011 led to a decrease in the overall level of fumonisins in maize. Information on fumonisin levels in maize from countries in the African, Eastern Mediterranean, or Southeast Asian regions, where high concentrations of fumonisins are typically detected, was not available in this assessment. Given these limitations of the incidence data used in the exposure assessment, and the high exposure levels reported in some countries in the literature, fumonisin exposure levels in areas where maize is a major food crop and where high concentrations of fumonisin contamination may exist are likely higher than the Committee’s estimates at this session, as demonstrated in previous assessments based on larger, more representative datasets. At its eighty-third session, the Committee also assessed the co-exposure to aflatoxin and fumonisin. Both fumonisin and aflatoxin are common contaminants in cereals and cereal products. Aflatoxin is a common contaminant in peanuts and nuts. In areas where these foods are frequently consumed, co-exposure to these two mycotoxins is likely. Although previous and current assessments have provided evidence in laboratory animals suggesting an additive or synergistic effect of co-exposure to fumonisin and aflatoxin on the development of precancerous lesions or hepatocellular carcinoma, there are currently no data on such effects in humans. The Committee concluded that the existing data are insufficient to support that co-exposure is a contributing factor to human disease. However, the interaction between aflatoxin B1 (AFB1), a compound known to be genotoxic, and fumonisin, which has the potential to induce regenerative cell proliferation (especially at exposure levels above PMTDI), remains a concern. This is because in some parts of the world, exposure to both mycotoxins is high, and the presence of co-exposure has been confirmed by biomarkers, in areas with high rates of chronic liver disease and developmental delays.

[1]. Fumonisins: isolation, chemical characterization and biological effects. Mycopathologia. 1992 Feb;117(1-2):11-6.

[2]. Liquid chromatographic determination of fumonisins B1, B2, and B3 in corn: AOAC-IUPAC Collaborative Study. J AOAC Int. 1996 May-Jun;79(3):688-96.

(2R)-2-[2-[(5R,6R,7S,9S,11R,18S,19S)-19-amino-6-[(3R)-3,4-dicarboxybutyryl]oxy-11,18-dihydroxy-5,9-dimethyleicosano-7-yl]oxy-2-oxoethyl]succinic acid has been reported in Fusarium fujikuroi and Fusarium verticillioides, and related data have been published. See also: Fumonisin B3 (note moved to).

C34H59NO14

705.830572366714

705.393

C, 57.86; H, 8.43; N, 1.98; O, 31.73

1422359-85-0

Fumonisin B3-13C34;2819816-90-3

42608358

Typically exists as solid at room temperature

0.8

7

15

31

49

1040

9

CCCC[C@@H](C)[C@H]([C@H](C[C@@H](C)C[C@@H](CCCCCC[C@@H]([C@H](C)N)O)O)OC(=O)C[C@@H](CC(=O)O)C(=O)O)OC(=O)C[C@@H](CC(=O)O)C(=O)O

CPCRJSQNWHCGOP-STOIETHLSA-N

InChI=1S/C34H59NO14/c1-5-6-11-21(3)32(49-31(43)19-24(34(46)47)17-29(40)41)27(48-30(42)18-23(33(44)45)16-28(38)39)15-20(2)14-25(36)12-9-7-8-10-13-26(37)22(4)35/h20-27,32,36-37H,5-19,35H2,1-4H3,(H,38,39)(H,40,41)(H,44,45)(H,46,47)/t20-,21+,22-,23+,24+,25+,26-,27-,32+/m0/s1

(2R)-2-[2-[(5R,6R,7S,9S,11R,18S,19S)-19-amino-6-[(3R)-3,4-dicarboxybutanoyl]oxy-11,18-dihydroxy-5,9-dimethylicosan-7-yl]oxy-2-oxoethyl]butanedioic acid

Fumonisin B3; 1422359-85-0; (2R)-2-[2-[(5R,6R,7S,9S,11R,18S,19S)-19-amino-6-[(3R)-3,4-dicarboxybutanoyl]oxy-11,18-dihydroxy-5,9-dimethylicosan-7-yl]oxy-2-oxoethyl]butanedioic acid; 1,2,3-Propanetricarboxylic acid, 1,1'-[(1S,2R)-1-[(2S,4R,11S,12S)-12-amino-4,11-dihydroxy-2-methyltridecyl]-2-[(1R)-1-methylpentyl]-1,2-ethanediyl] ester, (2R,2'R)-; Fumonisin B3 (>90%); DTXSID20891856; 1,2,3-Propanetricarboxylic acid, 1,1'-[(1S,2R)-1-[(2S,4R,11S,12S)-12-amino-4,11-dihydroxy-2-methyltridecyl]-2-[(1R)-1-methylpentyl]-1,2-ethanediyl] ester, (2R,2'R)-; FB3; Fumonisin B3; Fumonisin B3 50 microg/mL in Acetonitrile/Water;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

---

Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

View More

Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

---

Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

View More

Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

---

Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

---

 (Please use freshly prepared in vivo formulations for optimal results.)