Cyprinidae LC50 96h

 

Endpoint

 

The acute aquatic toxicity model predicts the concentration of chemicals that kill 50% (LC50) of the test fish which belongs to the family Cyprinidae (it is a family of freshwater fish commonly called the carp or minnow family) within a designated period.

 

Data

 

The training set consists of LC50 values for 745 chemicals. Of them 51 chemicals are confidential and are not visible in the model training set [1-7]:

 

  • Test duration - 96 hours,
  • Test species - Pimephales promelas(also Fathead minnow); Leuciscus idus (also Ide or Orfe) and Zebra fish (also Danio rerio).

 

The tested chemicals belong to the following categories:

 

  • Narcotic toxicants - 271 chemicals,
  • Phenols and anilines - 100 chemicals,
  • Narcotic amines - 59 chemicals,
  • Esters - 43 chemicals,
  • Aldehydes - 56 chemicals,
  • α, β- unsaturated alcohols - 11 chemicals,
  • Reactive unspecified chemicals - 205 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 [8]. 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 [9].  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

 

log1/ LC50 = 1.61(±0.06) + 1.1(±0.03)logBCFMax − 0.17(±0.02)ELUMO

 

 

Phenols and anilines

 

log1/ LC50 = 2.25(±0.1) + 0.95(±0.05)logBCFMax − 0.25(±0.06)ELUMO

 

 

Narcotic amines

 

log1/ LC50 = 2.29(±0.07) + 0.87(±0.05)logBCFMax

 

 

Esters

 

log1/ LC50 = 2.58(±0.19) + 0.83(±0.1)logBCFMax − 0.3(±0.08)ELUMO

 

 

Aldehydes

 

log1/ LC50 = − 1.44(±1.75) + 0.62(±0.08)logBCFMax + 15.71(±5.75)ODDI

 

 

α, β- Unsaturated alcohols

 

log1/ LC50 = 3.96(±0.6) + 0.22(±0.24)logBCFMax + 2.29(±5.73)QC

 

 

where BCFMax is the maximum bioconcentration factor [10],  ELUMO is the energy of the lowest unoccupied molecular orbital, ODDI is the donor delocalizability of the aldehyde O-atom and QC 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 (  of narcotics).

 

 

 

Domain

 

The stepwise approach [11] 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 KOW and MW,
  • Structural domain - based on atom-centered fragments (ACFs),
  • Mechanistic domain (parametric coverage) - the probability that the descriptors of a random chemical of the training set are the same as that of the target chemical.

 

A chemical is considered In Domain if its log KOW 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 = 0.9,
  • Mean squared error (estimate of error variance) s2 = 0.4,
  • F value = 1089,
  • Number of chemicals, n = 271.

 

 

 

Phenols and anilines

 

  • Coefficient of determination R2 = 0.83,
  • Mean squared error (estimate of error variance) s2 = 0.4,
  • F value = 222
  • Number of chemicals, n = 100.

 

Narcotic amines

 

  • Coefficient of determination R2 = 0.85,
  • Mean squared error (estimate of error variance) s2 = 0.5,
  • F value = 323,
  • Number of chemicals, n = 59.

 

Esters

 

  • Coefficient of determination R2 = 0.73,
  • Mean squared error (estimate of error variance) s2 = 0.49,
  • F value = 49,
  • Number of chemicals, n = 43.

 

Aldehydes

 

  • Coefficient of determination R2 = 0.56,
  • Mean squared error (estimate of error variance) s2 = 0.46,
  • F value = 32,
  • Number of chemicals, n = 56.

 

α, β- Unsaturated alcohols

 

  • Coefficient of determination R2 = 0.1,
  • Mean squared error (estimate of error variance) s2 = 0.8,
  • F value = 0.52,
  • Number of chemicals, n = 11.

 

 

 

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. Estimating environmentally important properties of chemicals from the chemical structure - Erik Furusjo, Magnus Andersson, Magnus Rahmberg, Anders Svenson - Report B1517.
  8. J.W. McFarland, J. Med. Chem. 13 (1970) 1092-1196.
  9. S.D. Dimitrov, O.G. Mekenyan, G.D. Sinks, T.W. Schultz, Journal of Molecular Structure (Theochem, 622 (2003) 63-70.
  10. S. Dimitrov, N. Dimitrovaa, D. Georgieva, K. Vasilev, T. Hatfield, J. Straka, O. Mekenyan, SAR and QSAR in Environmental Research, 23 (2012) 17-36.
  11. S. Dimitrov, G. Dimitrova, T. Pavlov, N. Dimitrova, G. Patlevisz, J. Niemela and O. Mekemyan, J. Chem. Inf. Model. 45 (2005)  839-849.

Aquatic toxicity

Model Features

 

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Cyprinidae