ENVIRONMENTAL

Pimephales promelas LC50 96h

 

Endpoint

 

The acute aquatic toxicity model predicts the concentration of chemicals that kill 50% (LC₅₀) of the test fish Pimephales promelas  (Fathead minnow) within a designated period.

 

Data

 

The training set consists of LC₅₀ values for 628 chemicals [1-6]:

 

• Test duration - 96 hours,
• Test species - Pimephales promelas (Fathead minnow).

 

The tested chemicals belong to the following categories:

 

• Narcotic toxicants - 221 chemicals,
• Phenols and anilines - 93 chemicals,
• Narcotic amines - 55 chemicals,
• Esters - 26 chemicals,
• Aldehydes - 46 chemicals,
• α, β- unsaturated alcohols - 9 chemicals,
• Reactive unspecified chemicals - 151 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 [7]. 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 [8].  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/LC50 = 1.66(±0.07)+1.09(±0.03) logBCFmax -0.18(±0.02)E_LUMO

  

Phenols and anilines

log 1/LC50 = 2.25(±0.10)+0.97(±0.04) logBCFmax -0.23(±0.06)E_LUMO

 

Narcotic amines

log 1/LC50 = 2.28(±0.08)+0.89(±0.05) logBCFmax 

 

Esters

log 1/LC50 = 2.51(±0.21)+0.87(±0.10) logBCFmax -0.20(±0.09)E_LUMO

 

Aldehydes

log 1/LC50 = 0.47(±2.11)+0.69(±0.09) logBCFmax +9.01(±7.08)E_LUMO

 

α, β- Unsaturated alcohols

log 1/LC50 = 4.22(±0.25)+0.58(±0.23) logBCFmax -24.78(±12.11)E_LUMO

 

 

where BCF_Max is the maximum bioconcentration factor [9],  E_LUMO is the energy of the lowest unoccupied molecular orbital, O_DDI is the donor delocalizability 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 by the model for narcotic chemicals ( log 1/EC50 ≥ log 1/EC50   of narcotics).

 

Domain

 

The stepwise approach [10] 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 (R²), mean squared error (estimate of error variance, s²), F value:

 

Narcotic toxicants

 

• Coefficient of determination R² = 0.89,
• Mean squared error (estimate of error variance) s² = 0.19,
• F value = 869,
• Number of chemicals, n = 221.

 

Phenols and anilines

 

• Coefficient of determination R² = 0.86,
• Mean squared error (estimate of error variance) s² = 0.16,
• F value = 270,
• Number of chemicals, n = 93.

 

Narcotic amines

 

• Coefficient of determination R² = 0.86,
• Mean squared error (estimate of error variance) s² = 0.25,
• F value = 322,
• Number of chemicals, n = 55.

 

Esters

 

• Coefficient of determination R² = 0.79,
• Mean squared error (estimate of error variance) s² = 0.22,
• F value = 44,
• Number of chemicals, n = 26.

 

Aldehydes

 

• Coefficient of determination R² = 0.60,
• Mean squared error (estimate of error variance) s² = 0.23,
• F value = 32,
• Number of chemicals, n = 46.

 

α, β- Unsaturated alcohols

 

• Coefficient of determination R² = 0.59,
• Mean squared error (estimate of error variance) s² = 0.38,
• F value = 4.3,
• Number of chemicals, n = 9.

 

References

 

1. DL. Geiger, LT. Brooke, DJ. Call. Acute toxicities of organic chemicals to fahhead minnows, vol 5. University of wisconsin- superior, WI, USA, p 332, (1990)
2. DL. Geiger, CE. Northcott, DJ. Call, LT. Brooke. Acute toxicities of organic chemicals to fahhead minnows, vol 2. University of wisconsin- superior, WI, USA, p 326, (1985)
3. LT. Brooke, DJ. Call, DL. Geiger, CE. Northcott. Acute toxicities of organic chemicals to fahhead minnows, vol 1. University of wisconsin- superior, WI, USA, p 414, (1984)
4. VR. Mattson, JW. Arthur, CT. Walbridge. Acute toxicity of selected organic compounds to fathead minnows. EPA-600/3-76-097. U.S. Environmental protection agency, duluth, mn, (1976)
5. DL. Geiger, SH. Poirier, LT. Brooke, DJ. Call. Acute toxicities of organic chemicals to fahhead minnows, vol 4. University of wisconsin- superior, WI, USA, p 354, (1988)
6. DL. Geiger, SH. Poirier, LT. Brooke, DJ. Call. Acute toxicities of organic chemicals to fahhead minnows, vol 3. University of wisconsin- superior, WI, USA, p 328, (1986)
7. J.W. McFarland, J. Med. Chem. 13 (1970) 1092-1196.
8. S.D. Dimitrov, O.G. Mekenyan, G.D. Sinks, T.W. Schultz, Journal of Molecular Structure (Theochem, 622 (2003) 63-70.
9. S. Dimitrov, N. Dimitrova, D. Georgieva, K. Vasilev, T. Hatfield, J. Straka, O. Mekenyan, SAR and QSAR in Environmental Research, 23 (2012) 17-36.
10. S. Dimitrov, G. Dimitrova, T. Pavlov, N. Dimitrova, G. Patlevisz, J. Niemela and O. Mekenyan, J. Chem. Inf. Model. 45 (2005)  839-849.