#### Tetrahymena pyriformis IGC50 48h

Endpoint

The acute aquatic toxicity model predicts the concentration of a
substance that inhibits 50% of the growth
(*IGC _{50}*) of the test population

*Tetrahymena pyriformis*within a designated period.

Data

The training set consists of *IGC _{50}* values
for 1330 chemicals [1-17]:

- Test duration - 48 hours,
- Test species -
*Tetrahymena pyriformis*(ciliate protozoa).

The tested chemicals belong to the following categories:

- Narcotic toxicants - 351 chemicals,
- Phenols and anilines - 353 chemicals,
- Narcotic amines - 30 chemicals,
- Esters - 101 chemicals,
- Aldehydes - 94 chemicals,
- α, β- unsaturated alcohols - 32 chemicals,
- Reactive unspecified chemicals - 304 chemicals.

Model

The organism response to the presence of toxicant in the environment is considered as a consequence of the combined influence of two different processes: uptake of the chemical into the biophase and interaction with the site of action [18]. In the present model, the uptake is modeled by maximum potential of the toxicant to bioconcentrate in the fish, while the interaction of chemicals is explained by descriptors assessing the electrophilic character of the molecule [19]. Such descriptors could include the energy of the lowest unoccupied molecular orbital, electronegativity, average or maximum superdelocalizability, maximum charge at non-hydrogen atom, etc. The following models were developed based on regression analysis of the data:

Narcotic toxicants

log 1/*IGC _{50}* =
1.44(±0.04)+1.00(±0.02)log

*BCF*max

*-*0.15(±0.01)

*E*

_{LUMO}

Phenols and anilines

log 1/*IGC _{50}* =
2.17(±0.05)+0.78(±0.03)log

*BCF*max

*-*0.39(±0.03)

*E*

_{LUMO}

Narcotic amines

log 1/*IGC _{50}* =
2.05(±0.11)+0.79(±0.08)log

*BCF*max

Esters

log 1/*IGC _{50}* =
1.30(±0.09)+1.05(±0.04)log

*BCF*max

*-*0.39(±0.04)

*E*

_{LUMO}

Aldehydes

log 1/*IGC _{50}* =
-1.61(±1.21)+0.67(±0.06)log

*BCF*max

*+13.51*(±4.03)

*O*

_{DDI}

α, β- Unsaturated alcohols

log 1/*IGC _{50}* =
1.82(±0.13)+0.91(±0.09)log

*BCF*max

*-*15.97(±4.84)

*E*

_{LUMO}

where *BCF*_{Max} is the maximum bioconcentration
factor [20], *E*_{LUMO} is the energy of the lowest
unoccupied molecular orbital, *O*_{DDI} is the donor
delocalizability indices of the aldehyde O-atom and
*Q*_{C} is the charge of the C atom from α, β-
unsaturated alcohols. For the reactive unspecified chemicals,
only the minimum toxicity is determined based on the model for
narcotic chemicals (i.e., of narcotics).

Domain

The stepwise approach [21] was used to define the applicability domain of the model. It consists of the following sub-domain levels:

- General parametric requirements - includes ranges of variation
of log
*K*_{OW}and*MW*, - Structural domain - based on atom-centered fragments (ACFs).

A chemical is considered *In Domain* if its log
*K*_{OW} and *MW* are within the specified
ranges and its ACFs are presented in the training chemicals.
The information implemented in the applicability domain is
extracted from the correctly predicted training chemicals used to
build the model and in this respect the applicability domain
determines practically the interpolation space of the model.

Statistics

The precision of the regression models is characterized by the
following estimates: the 95% confidence intervals of model
parameters, coefficient of determination (*R ^{2}*),
mean squared error (estimate of error variance,

*s*),

^{2}*F*value:

Narcotic toxicants

- Coefficient of determination
*R*= 0.90,^{2} - Mean squared error (estimate of error variance)
*s*= 0.10,^{2} *F*value = 1579.39,- Number of chemicals,
*n*= 351.

Phenols and anilines

- Coefficient of determination
*R*= 0.77,^{2} - Mean squared error (estimate of error variance)
*s*= 0.15,^{2} *F*value = 574.8,- Number of chemicals,
*n*= 353.

Narcotic amines

- Coefficient of determination
*R*= 0.77,^{2} - Mean squared error (estimate of error variance)
*s*= 0.19,^{2} *F*value = 92.18,- Number of chemicals,
*n*= 30.

Esters

- Coefficient of determination
*R*= 0.89,^{2} - Mean squared error (estimate of error variance)
*s*= 0.09,^{2} *F*value = 412.7,- Number of chemicals,
*n*= 101.

Aldehydes

- Coefficient of determination
*R*= 0.61,^{2} - Mean squared error (estimate of error variance)
*s*= 0.16,^{2} *F*value = 71.90,- Number of chemicals,
*n*= 94.

α, β- Unsaturated alcohols

- Coefficient of determination
*R*= 0.81,^{2} - Mean squared error (estimate of error variance)
*s*= 0.22,^{2} *F*value = 62.44,- Number of chemicals,
*n*= 32.

References

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357-360.

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267-278.

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8.Schultz TW, Lin DT, Arnold LM. 1991. The Science of the Total
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14. Schultz TW, Lin DT, Wilke TS, Arnold LM. QSAR for the
Tetrahymena pyriformis population growth endpoint: a mechanism of
action approach. In: Practical Applications of QSAR in
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16. Jaworska JS, Hunter RS, Gabble JR, Schultz TW.
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