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. 2017 Jan 26;15(1):e04655. doi: 10.2903/j.efsa.2017.4655

Table 5.

In vitro toxicity studies with T2 and HT2 and its phase I metabolites in various cell systems

Cell system Endpoint Effective concentrations (relative molar toxicity)g Reference
Primary human lymphocytes Inhibition of mitogen‐induced blastogenesis; 72‐h exposure; EC50

T2: 3.2 nM (1)

HT2: 8.3 nM (0.39)

T2‐triol: 390 nM (0.008)

T2‐tetraol: 500 nM (0.006)

19‐Hydroxy‐T2: 8.3 nM (0.39)

19‐Hydroxy‐HT2: 115 nM (0.028)

 Forsell et al. (1985)
Kidney epithelial cell line (Vero cells, African green monkey) Inhibition of protein synthesis (3H‐leucin incorporation); 1‐h exposure; EC50

T2: 24 nM (1)

hAcetyl‐T2: 19,500 nM (0.0012)

T2‐tetraol: 22,800 nM (0.0011)

 Ehrlich and Daigle (1985)
Mouse erythroleukaemia cell line Inhibition of protein synthesis (3H‐leucin incorporation), 1‐h exposure; EC50

T2: 6 nM (1)

hAcetyl‐T2: 3,500 nM (0.0017)

T2‐tetraol: 6,400 nM (0.00094)

 Ehrlich and Daigle (1985)
Kidney epithelial cell line (Vero cells, African green monkey) Inhibition of protein synthesis (3H‐leucin incorporation): 1.5 h exposure; EC50

T2: 14 nM (1)

HT2: 65 nM (0.22)

NEO: 273 nM (0.051)

T2‐triol: 1,120 nM (0.013)

T2‐tetraol: 5,856 nM (0.0024)

hAcetyl‐T2: 5,792 nM (0.0024)

 Thompson and Wannemacher (1986)
Primary rat spleenocytes Inhibition of protein synthesis (3H‐leucin incorporation); 1.5‐h exposure; EC50

T2: 6 nM (1)

HT2: 10 nM (0.60)

NEO: 127 nM (0.047)

T2‐triol: 151 nM (0.040)

T2‐tetraol: 7,832 nM (0.0008)

hAcetyl‐T2: 1,036 nM (0.006)

 Thompson and Wannemacher (1986)
Rabbit reticulocytes Inhibition of protein synthesis (3H‐leucin incorporation); 1.5‐h exposure; EC50

T2: 21.5 nM (1)

HT2: 70.8 nM (0.30)

NEO: 654 nM (0.033)

T2‐triol: 5,240 nM (0.004)

T2‐tetraol: 8,390 nM (0.002)

 Ueno et al. (1986)
Tetrahymen pyroformis Inhibition of protein synthesis (3H‐leucin incorporation); 1.5‐h exposure; EC50

T2: 53.6 nM (1)

HT2: 118 nM (0.45)

NEO: 1,310 nM (0.041)

T2‐triol: 5,240 nM (0.010)

T2‐tetraol: 8,390 nM (0.006)

 Ueno et al. (1986)
Human acute promyelocytic leukaemia cell line (HL 60) Cell viability (trypan blue exclusion);concentrations required to kill 100% of the cells in 5 days

T2: 17 nM (1)

HT2: 19 nM (0.89)

NEO: 340 nM (0.050)

T2‐triol: 262 nM (0.065)

T2‐tetraol: 470 nM (0.036)

hAcetyl‐T2: 39 nM (0.44)

h9,10‐Epoxy‐T2: 207 nM (0.082)

h9,10‐Dihydro‐T2: 280 nM (0.061)

 Samara et al. (1987)
Brine shrimp (Artemia salina) bioassay Cytotoxicity; 24‐h exposure of eggs; lethality of hatched shrimps; LC50

T2: 240 nM (1)

HT2: 610 nM (0.39)

T2‐triol: 3,600 nM (0.067)

T2‐tetraol: 3,200 nM; (0.075)

De‐epoxy‐HT2: > 14,700 nM (< 0.016)

De‐epoxy‐T2‐triol: > 13,700 (< 0.018)

De‐epoxy‐T2‐tetraol: > 21,300 (< 0.011)

 Swanson et al. (1987)
Adult human liver cell line (Chang liver) Cell viability; 6‐day exposure; amido black 10B; EC50

T2: 5 nM (1)

HT2: 10 nM (0.50)

NEO: 200 nM (0.025)

T2‐triol: 105 nM (0.048)

T2‐tetraol: 800 nM (0.0062)

hIso‐T2a: 49 nM (0.10)

hAcetyl‐T2: 26 nM (0.19)

hTetraacetyl‐T2‐tetraol: 150 nM (0.033)

h4,8‐Diacetyl‐T2‐tetraolb: 110 nM (0.045)

 von Milczewski (1987)
Human epidermoid carcinoma cell line (HEp‐2) Cell viability; 6‐day exposure; amido black 10B; EC50

T2: 5 nM (1)

HT2: 10 nM (0.5)

NEO: 180 nM (0.028)

T2‐triol: 86 nM (0.058)

T2‐tetraol: 670 nM (0.0075)

hIso‐T2a: 59 nM (0.017)

hAcetyl‐T2: 16 nM (0.31)

hTetraacetyl‐T2‐tetraol: 150 nM (0.033)

h4,8‐Diacetyl‐T2‐tetraolb: 86 nM (0.058)

 von Milczewski (1987)
Girardi human heart cell line (clone GHc7) Cell viability; 6‐day exposure; amido black 10B; EC50

T2: 9 nM (1)

HT2: 12 nM (0.75)

NEO: 210 nM (0.043)

T2‐triol: 76 nM (0.12)

T2‐tetraol: 470 nM (0.019)

hIso‐T2a: 28 nM (0.32)

hAcetyl‐T2: 70 nM (0.13)

hTetraacetyl‐T2‐tetraol: 100 nM (0.090)

h4,8‐Diacetyl‐T2‐tetraolb: 400 nM (0.023)

 von Milczewski (1987)
Pig kidney cell line (clone Amc6sc8) Cell viability; 6‐day exposure; amido black 10B; EC50

T2: 10 nM (1)

HT2: 11.3 nM (0.88)

NEO: 3–6 nM (3.33–1.67)c

T2‐triol: 39 nM (0.26)

T2‐tetraol: 540 nM (0.019)

hIso‐T2a: 3.4 nM (2.94)

hAcetyl‐T2: 50 nM (0.20)

hTetraacetyl‐T2‐tetraol: 9.4 nM (1.06)

h4,8‐Diacetyl‐T2‐tetraolb: 6 nM (1.67)

 von Milczewski (1987)
Mouse lymphoma cell line (L5178Y) Cell viability; 3‐day exposure; EC50

T2: 3.9 nM (1)

HT2: 7.1 nM (0.55)

NEO: 105 nM (0.037)

T2‐triol: 260 nM (0.015)

T2‐tetraol: 340 nM (0.012)

hIso‐T2a: 43 nM (0.090)

h3‐Acetyl‐T2: 40 nM (0.097)

h8‐Acetyl‐NEO: 3.2 nM (1.22)

h3‐Acetyl‐NEO: 47 nM (0.083)

hTetraacetyl‐T2‐tetraol: 43 nM (0.091)

h3,4,8‐Triacetyl‐T2‐tetraol: 190 nM (0.021)

h4,8‐Diacetyl‐T2‐tetraolb: 160 nM (0.024)

h15‐Deacetyl‐NEOd: 60 nM (0.065)

 Anderson et al. (1989)
Human fibroblast cell line (GM5757) Cell viability; 48‐h exposure; MTTe assay; EC50

T2: 122 nM (1)

HT2: 383 nM (0.32)

NEO: 342 nM (0.36)

T2‐tetraol: 6,540 nM (0.019)

hAcetyl‐T2: 1,970 nM (0.062)

 Kim et al. (1991)
Human liver cell line (HepG2) Cell viability, 48‐h exposure; neutral red uptake; EC50

T2: 21 nM (1)

HT2: 37 nM (0.57)

T2‐triol: 1,040 nM (0.020)

T2‐tetraol: 1,490 nM (0.014)

 Babich and Borenfreund (1991)
Baby hamster kidney cell line (BHK‐21 cells) Cytotoxicity; 24‐h exposure; approximate LC100

T2: 10.7 nM (1)

HT2: 240 nM (0.045)

NEO: 26.2 nM (0.41)

T2‐tetraol: 33,500 nM (0.0003)

19‐Hydroxy‐T2: 10.3 nM (1.03)

h8‐Acetyl‐T2‐tetraol: 294,000 nM (0.00004)

h4,8‐Diacetyl‐T2‐tetraolb: 2,620 nM (0.0041)

h8‐Acetyl‐NEO: 1,180 nM (0.009)

 Senter et al. (1991)
Primary human renal proximal tubule epithelial cells Cell viability; 48‐h exposure; CCK‐8f assay; EC50

T2: 200 nM (1)

HT2: 800 nM (0.25)

NEO: 3,000 nM (0.067)

T2‐triol: 14,600 nM (0.014)

T2‐tetraol: 25,100 nM (0.008)

 Königs et al. (2009)
Primary human lung fibroblasts Cell viability; 48‐h exposure; CCK‐8f assay; EC50

T2: 500 nM (1)

HT2: 700 nM (0.71)

NEO: 2,000 nM (0.25)

T2‐triol: 10,600 nM (0.047)

T2‐tetraol: 8,300 nM (0.060)

 Königs et al. (2009)
Lung fibroblast cell line from male Chinese hamster (V79) Cell viability; 48‐h exposure; neutral red uptake; EC50

T2: 3 nM (1)

HT2: 14 nM (0.21)

 Behm et al. (2012)

RPF: relative potency factor with respect to T2; EC50: Half‐maximal effective concentration; LC: left‐censored; NEO: neosolaniol.

a

Also designated as 3‐acetyl‐HT2.

b

Also designated as NT‐1 toxin.

c

Considered an outlier (only range given, very different from results of numerous other studies on NEO).

d

Also designated as NT‐2 toxin.

e

MTT: 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide.

f

Cell Counting Kit‐8, using reduction of 2‐(2‐methoxy‐4‐nitrophenyl)‐3‐(4‐nitrophenyl)‐5‐(2,4‐disulfophenyl)‐2H‐tetrazolium monosodium salt.

g

The doses used have been recalculated from weight to molar units. Relative toxicity (effective molar dose) has been set as 1 for T2.

h

Hypothetical metabolite (i.e. not identified occurring naturally).