Absorption, Distribution and Excretion
Within 90 minutes of topical application of a single dose of [3H-diacetoxysqualol]([3H]DAS), rats absorbed and retained more [3H]DAS than mice, while excreting less radioactive material in urine and feces. At 24 hours post-treatment, rats absorbed, excreted, and retained approximately twice as much [3H]DAS as mice (p < 0.05 or < 0.005). At 7 days post-treatment, rats absorbed more than four times as much [3H]DAS as mice (13.1% vs 57.5%; p < 0.005). However, the proportion of administered radioactive material retained in mouse tissues (4.1%) was higher than in rats (1.0%; p < 0.05). The total excretion of the radiolabeled substance in rats was approximately six times that in mice (56% vs 9%; p < 0.005). The ratio of urine to feces excretion in rats was approximately 2:1 (37% vs 18%), while in mice it was approximately 3.5:1 (7% vs 2%). Significant differences were found in the time course of tissue distribution of [(3)H]DAS in rats and mice when the data were expressed as a percentage of absorbed dose in tissue or as specific radioactivity per gram of tissue (dpm). These results indicate that the absorption, excretion, and tissue distribution patterns of locally administered [(3)H]DAS differ between rats and mice.

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Metabolites/Metabolites
Trichothecene toxins are a class of fungal toxins primarily produced by Fusarium fungi.
Consumers are particularly concerned about the toxicity and food safety of trichothecene toxins and their metabolites in edible animals. This article reviews the metabolism of T-2 toxin, deoxynivalenol (DON), nivalenol (NIV), falciparin-X (FX), diacetoxynivalenol (DAS), 3-acetyldeoxynivalenol (3-aDON), and 15-acetyldeoxynivalenol (15-aDON) in rodents, pigs, ruminants, poultry, and humans. The metabolic pathways of these mycotoxins vary considerably. The main metabolic pathways of T-2 toxin in animals include hydrolysis, hydroxylation, de-epoxyoxidation, and conjugation. After conversion to HT-2 toxin, further hydroxylation at the C-3' position to generate 3'-hydroxy-HT-2 toxin is considered an activation pathway; while the conversion of T-2 toxin to T-2 tetraol is an inactivation pathway in animals. Typical metabolites of T-2 toxin in animals include HT-2 toxin, T-2 triol, T-2 tetraol, neosoranisol (NEO), 3'-hydroxy-HT-2 toxin, and 3'-hydroxy-T-2 toxin, while HT-2 toxin is the main metabolite in humans. Decyclization is an important detoxification pathway in animals. The decyclization products DOM-1 and decyclization-NIV are the main metabolites of DON and NIV in most animals, respectively. However, these two metabolites are not present in humans. Acetyl derivatives 3-α-DON, 15-α-DON, and FX can be rapidly deacetylated. DAS is metabolized in animals via C-4 deacetylation to 15-monoacetoxycedrinol (15-MAS), and then via C-15 deacetylation to cedrinol (SCP). Finally, the epoxy group is removed, generating decyclized-SCP. Decyclized-15-MAS is also a major metabolite of DAS. 15-MAS is a major metabolite in human skin. A review of trichothecene toxin metabolism helps to better understand the future fate of these toxins in animals and humans and provides foundational information for food safety risk assessment. Trichothecene toxins present in feed, such as T-2 toxin, diacetoxycedrinol, and deoxynivalenol, are primarily metabolized in a biphasic manner. Oxidation and hydrolysis occur in the first stage, while the conversion products bind to glucuronic acid in the second stage; additionally, the epoxide ring is cleaved by the gut microbiota. Metabolites of T-2 toxin include HT-2 toxin, 3'-hydroxy-T-2 toxin, 3'-hydroxy-HT-2 toxin, neosoraniol, 4-deacetylated neosoraniol, T-2 triol, T-2 tetraol, and deepoxide-treated T-2 tetraol. Diacetoxycedrinol is converted to 15-monoacetoxycedrinol, cedrin triol, deepoxide-treated 15-monoacetoxycedrinol, and deepoxide-treated cedrin triol. Deoxynivalenol metabolism is not extensive; it is presumed to produce only deoxynivalenol glucuronide and decyclooxydeoxynivalenol. Due to the rapid metabolism of trichothecene toxins, diagnosing poisoning by analyzing swine samples is virtually impossible. For the same reason, the likelihood of enrichment of trichothecene metabolites in edible tissues is rated as low.

Toxicity Data
LC50 (mice) = 11.3 mg/kg Interactions This study investigated the potential protective effect of a feed additive (Mycofix) against the toxicity of 4,15-diacetoxycyclohexenol (DAS) in growing broilers in a 21-day fully randomized trial. Seven dietary treatment groups were set up (control group, no DAS or Mycofix added; 1 ppm DAS group; 1 ppm DAS + 0.75 g/kg Mycofix group; 1 ppm DAS + 1.5 g/kg Mycofix group; 2 ppm DAS group; 2 ppm DAS + 0.75 g/kg Mycofix group; and 2 ppm DAS + 1.5 g/kg Mycofix group). When no feed additive was added, both concentrations of dietary DAS significantly reduced body weight and feed intake and caused oral lesions, with the 2 ppm DAS concentration having a more severe effect. When 1 ppm DAS was added to the diet, Mycofix supplementation effectively mitigated the adverse effects of DAS on feed intake and body weight (at two supplementation concentrations of 0.75 g/kg and 1.5 g/kg, respectively); however, Mycofix supplementation did not alleviate oral lesions. This result suggests that the adverse effects of DAS on production performance are not caused by oral lesions themselves, but may be due to systemic absorption of the fungal toxin. When the diet contained 2 ppm DAS, Mycofix supplementation only provided partial protection against body weight and feed intake. In lymphocyte proliferation assays, combinations of novofusarium oxytocin (NIV) with T2 toxin, diacetoxynofusarium oxytocin (DAS), or deoxynofusarium oxytocin (DON) exhibited additive toxicity, while the inhibitory effect of DON combined with T2 or DAS was slightly lower than that of the individual toxins. In summary, the tested trichothecene toxins inhibited human lymphocyte proliferation and immunoglobulin (Ig) production in a dose-dependent manner, with limited inter-individual differences in sensitivity. Enhanced Ig production was observed in cell cultures exposed to lower doses of the toxins. Co-exposure to the two toxins mainly showed additive or antagonistic effects, but a synergistic effect could not be ruled out and further investigation is needed. This study evaluated the individual and combined effects of diets containing 300 mg fumonisin B1 (FB1), 4 mg diacetoxycedoryl alcohol (DAS), or 3 mg ochratoxin A (OA) in two experiments. Female turkey chicks (Nicholas Large White turkeys) were used from hatching to 3 weeks of age. Compared with the control group, the FB1 group showed a 30% (Experiment 1) and 24% (Experiment 2) reduction in body weight gain, the DAS group a 30% reduction, the OA group an 8% reduction, the FB1 and DAS combined group a 46% reduction, and the FB1 and OA combined group a 37% reduction. In Experiment 2, all treatments except FB1 adversely affected feed utilization. All treatments except DAS significantly increased relative liver weight. Chicks fed FB1 alone, or FB1 combined with DAS or OA, showed decreased serum cholesterol levels, increased aspartate aminotransferase and lactate dehydrogenase activities, and altered multiple hematological parameters. The results indicate that when chicks were fed diets containing 300 mg FB1 and 4 mg DAS or 3 mg OA/kg, the toxicity was additive or less than additive, but no synergistic toxicity was observed.

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Non-human toxicity values
Rat intraperitoneal LD50: 750 ug/kg
Rat oral LD50: 7 mg/kg
Rat intravenous LD50: 1300 ug/kg
Mouse oral LD50: 7300 ug/kg
For more complete non-human toxicity data for diacetoxycoumarins (6 in total), please visit the HSDB records page.

[1]. In vitro effects of diacetoxyscirpenol (DAS) on human and rat granulo-monocytic progenitors. Mycopathologia. 1997;140(1):59-64.

[2]. Mycotoxicosis caused by a single dose of T-2 toxin or diacetoxyscirpenol in broiler chickens. Vet Pathol. 1981 Sep;18(5):652-64.

Anguidine has been reported in Albifimbria verrucaria, Cordyceps polyarthra, and other organisms with relevant data. Anguidine is a trichothecene toxin and a potent teratogen. It inhibits the initiation of protein synthesis, leading to the death of rapidly proliferating cells. Anguidine has also been shown to enhance the cytotoxic effects of other drugs while also providing protection. (NCI04)

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Mechanism of Action
Trichothecene toxins are toxic to actively dividing cells, such as intestinal crypt epithelial cells and hematopoietic cells. Their cytotoxicity is associated with impaired protein synthesis or cell membrane dysfunction due to the binding of the compound to eukaryotic ribosomes. Inhibition of protein synthesis is associated with the induction of unstable and regulatory proteins (such as IL-2) in immune cells. Even very low concentrations of trichothecene toxins can impair the transport of small molecules across the cell membrane. /Trichothecene Toxins/
Multiple studies have shown that the fungal toxins T-2 toxin, diacetoxycedenoyl alcohol (DAS), deoxynivalenol (DON), and novofusarium-1 (NIV) affect lymphocyte function. However, the molecular mechanisms underlying the immunomodulatory effects of these trichothecene toxins remain unclear. This study examined the ability of type A trichothecene toxins T-2 toxin and DAS, as well as type B trichothecene toxins DON (and its metabolite deepoxydeoxynivalenol; DOM-1) and NIV to reduce mitochondrial activity and induce apoptosis in Jurkat T cells (human T lymphocytes). As shown in the AlamarBlue cytotoxicity assay, T-2 toxin and DAS exhibited stronger cytotoxicity than DON and NIV at low concentrations. Furthermore, the mechanism by which DON and NIV induced cytotoxicity was primarily through apoptosis, as we observed phosphatidylserine eversion, mitochondrial release of cytochrome c, procaspase-3 degradation, and Bcl-2 degradation. In contrast, trichothecene type A toxins reduced mitochondrial activity and led to cell necrosis at concentrations approximately 1000 times lower than trichothecene type B toxins. These data suggest that the cytotoxic mechanisms of trichothecene type A and type B toxins differ. To understand the potential mechanism of T cell cytotoxicity of diacetoxyfusinol (DAS) produced by Fusarium sambucinum, we investigated its pro-apoptotic and growth-inhibiting activities in human Jurkat T cells. DAS treatment (0.01–0.15 μM) induced apoptosis, accompanied by caspase-8 activation, Bid protein cleavage, mitochondrial cytochrome c release, caspase-9 and caspase-3 activation, and PARP degradation, while Fas or FasL levels remained unchanged. No cell necrosis was observed under these conditions. The anti-Fas neutralizing antibody ZB-4 did not block the cytotoxicity of DAS. Although Bcl-xL overexpression completely inhibits DAS-induced apoptosis, cells overexpressing Bcl-xL fail to divide in the presence of DAS, likely due to cell cycle arrest caused by downregulation of cdk4 and cyclin B1 protein levels. DAS-mediated apoptosis and activation of caspase-8, -9, and -3 can be blocked by pan-caspase inhibitors (z-VAD-fmk) or caspase-8 inhibitors (z-IETD-fmk). Mitochondrial permeability transition pore inhibitors (CsA) have a slight inhibitory effect on DAS-mediated apoptosis and activation of caspase-9 and caspase-3, but have no effect on caspase-8 activation or Bid lysis. Activated normal peripheral T cells exhibit similar sensitivity to DAS cytotoxicity. These results indicate that the T-cell toxicity of DAS is not only attributed to apoptosis induced by caspase-8 activation and subsequent mitochondrial-dependent or Bcl-xL-dependent caspase cascade activation, but also to cell cycle disruption caused by downregulation of cdk4 and cyclin B1 proteins.

C19H26O7

366.41

366.167

2270-40-8

15571694

White to off-white solid powder

1.3±0.1 g/cm3

471.2±45.0 °C at 760 mmHg

162-164℃

162.8±22.2 °C

0.0±2.7 mmHg at 25°C

1.561

1.33

1

7

5

26

687

7

CC1=C[C@@H]2[C@](CC1)([C@]3([C@@H]([C@H]([C@H]([C@@]34CO4)O2)O)OC(=O)C)C)COC(=O)C

AUGQEEXBDZWUJY-NMAPUUFXSA-N

InChI=1S/C19H26O7/c1-10-5-6-18(8-23-11(2)20)13(7-10)26-16-14(22)15(25-12(3)21)17(18,4)19(16)9-24-19/h7,13-16,22H,5-6,8-9H2,1-4H3/t13-,14-,15-,16-,17-,18-,19+/m1/s1

[(1S,2R,7R,9R,10R,11S,12S)-11-acetyloxy-10-hydroxy-1,5-dimethylspiro[8-oxatricyclo[7.2.1.02,7]dodec-5-ene-12,2'-oxirane]-2-yl]methyl acetate

Anguidine; Anguidin; Diacetoxyscirpenol

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)

DMSO : ~50 mg/mL (~136.46 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.82 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (6.82 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
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.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (6.82 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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