TIM Version 3.0 beta Technical Description and User Guide - Appendix H - Dermal Toxicity Estimation
In the March 2000 SAP for the implementation of probabilistic risk assessments, one question posed to the panel concerned dermal toxicity estimation. The SAP was concerned about the potential approach of applying the ratio of oral-to-dermal toxicity from mammals to birds. A limited set of data exists for evaluating the relationship between dermal toxicity and oral toxicity in birds (Table H-1). Definitive oral and dermal LD50's are available for 42 individual studies. These studies were conducted across a variety of species and several classes of chemicals.
Regression analysis was used to predict the dermal LD50 based on the oral LD50. In addition, pesticide chemical properties were included into the regression model in an attempt to improve the model fit, similar to the approach taken by Mineau (2002). Prior to regression analysis, the dermal LD50 data and the oral LD50 data to were transformed to the log-base10 scale to better meet assumptions of normality and homogeneous variance.
In the log transformed scale, the correlation coefficient between the dermal and oral LD50 values was 0.55 (Figure H-1). The correlation coefficients between dermal LD50 and the evaluated chemical properties were much lower: -0.11, -0.03, and -0.03 for molecular weight (MW), density, and molecular volume (MV), respectively.
A summary of the evaluated regression models is provided in Table H-2. This analysis indicates that the addition of these chemical properties into the regression model do not significantly improve its predictive ability. The adjusted R-square (a modified R-square with a correction for the number of parameters included in the model) ranged between 0.2575 and 0.2857, indicating little difference in the predictive ability among the fitted models. The best fitting model to predict dermal LD50 was one based solely on oral LD50:
log Dermal LD50 = 0.84 + 0.62 * log Oral LD50
standard errors: (0.14)(0.15)
The p-value for the slope was 0.0002 and the R-square was 0.30. The chemical properties that were included did not provide significant improvement in the predictive ability of the model.
Compound | Class | Species | Oral LD50 (mg/kg) |
Dermal LD50 (mg/kg) |
Footnotea | Molecular Weight | Density | Molar Volume (mol/cm3) |
---|---|---|---|---|---|---|---|---|
Aldicarb | Carbamate | Mallard | 3.4 | 60.0 | 1 | 190.26 | 1.195 | 159.21 |
Carbofuran | Carbamate | House sparrow | 1.3 | 100.0 | 2 | 221.26 | 1.18 | 187.51 |
Carbofuran | Carbamate | Quelea | 0.42 | 100.0 | 2 | 221.26 | 1.18 | 187.51 |
Coumaphos | OP | House sparrow | 10 | 75.0 | 2 | 362.80 | 1.47 | 246.80 |
Coumaphos | OP | Quelea | 3.2 | 7.5 | 2 | 362.80 | 1.47 | 246.80 |
Demeton | OP | Mallard | 7.19 | 24 | 1 | 258.34 | 1.18 | 218.93 |
Demeton | OP | House sparrow | 5.6 | 13.0 | 2 | 258.34 | 1.18 | 218.93 |
Demeton | OP | Quelea | 1.3 | 1.8 | 2 | 258.34 | 1.18 | 218.93 |
Dicrotophos | OP | Mallard | 4.24 | 14.2 | 1 | 237.19 | 1.216 | 195.06 |
Dicrotophos | OP | House sparrow | 4.2 | 1.8 | 2 | 237.19 | 1.216 | 195.06 |
Dicrotophos | OP | Quelea | 1.3 | 1.3 | 2 | 237.19 | 1.216 | 195.06 |
Disulfoton | OP | Mallard | 6.54 | 192.0 | 1 | 274.39 | 1.144 | 239.85 |
Disulfoton | OP | Starling | 133 | 13.3 | 3 | 274.39 | 1.144 | 239.85 |
Disulfoton | OP | Red-winged Blackbird | 3.2 | 1.00 | 3,4 | 274.39 | 1.144 | 239.85 |
Endrin | OChl | Mallard | 5.64 | >140.0b | 1 | 380.93 | 1.7 | 224.08 |
EPN | OP | Mallard | 7.09 | 400.0 | 1 | 323.31 | 1.3 | 248.70 |
Ethoprop | OP | Mallard | 12.6 | 10.6 | 1 | 242.3 | 1.094 | 221.48 |
Fenamiphos | OP | Mallard | 1.68 | 23.8 | 1 | 303.36 | 1.15 | 263.79 |
Fenitrothion | OP | Mallard | 1190 | 504.0 | 1 | 277.23 | 1.33 | 208.44 |
Fensulfothion | OP | Mallard | 0.749 | 2.86 | 1 | 308.35 | 1.202 | 256.53 |
Fensulfothion | OP | House sparrow | 0.32 | 1.00 | 2 | 308.35 | 1.202 | 256.53 |
Fensulfothion | OP | Quelea | 0.24 | 0.42 | 2 | 308.35 | 1.202 | 256.53 |
Fenthion | OP | Mallard | 5.94 | 44.0 | 1 | 278.32 | 1.25 | 222.66 |
Fenthion | OP | House sparrow | 5.6 | 2.40 | 2 | 278.32 | 1.25 | 222.66 |
Fenthion | OP | Quelea | 1.3 | 1.80 | 2 | 278.32 | 1.25 | 222.66 |
Methamidophos | OP | Starling | 10.0 | 17.8 | 3 | 141.13 | 1.343 | 105.09 |
Methamidophos | OP | Red-winged Blackbird | 1.73 | 31.6 | 3 | 141.13 | 1.343 | 105.09 |
Methiocarb | Carbamate | House sparrow | 18 | >100.0b | 2 | 225.31 | 0.6 | 375.52 |
Methiocarb | Carbamate | Quelea | 4.2 | 100.0 | 2 | 225.31 | 0.6 | 375.52 |
Methyl parathion | OP | Mallard | 60.5 | 53.6 | 1 | 263.21 | 1.358 | 193.82 |
Mevinphos | OP | Mallard | 4.63 | 11.1 | 1 | 224.15 | 1.25 | 179.32 |
Monocrotophos | OP | Mallard | 4.76 | 30.0 | 1 | 223.17 | 1.3 | 171.67 |
Monocrotophos | OP | House sparrow | 1.3 | 18.0 | 2 | 223.17 | 1.3 | 171.67 |
Monocrotophos | OP | Quelea | 1.3 | 4.2 | 2 | 223.17 | 1.3 | 171.67 |
Paraquat Dichloride | Bipyridinium | Mallard | 199 | 600.0 | 1 | 257.20 | 1.25 | 205.76 |
Parathion | OP | Mallard | 2.34 | 28.3 | 1 | 291.26 | 1.267 | 229.88 |
Parathion | OP | House sparrow | 1.3 | 1.8 | 2 | 291.26 | 1.267 | 229.88 |
Parathion | OP | Quelea | 1.8 | 1.8 | 2 | 291.26 | 1.267 | 229.88 |
Phorate | OP | Mallard | 2.55 | 203.0 | 1 | 260.38 | 1.167 | 223.12 |
Phosfolan | OP | House sparrow | 2.4 | 18.0 | 2 | 255.28 | 1.3 | 196.37 |
Phosfolan | OP | Quelea | 1.8 | 10.0 | 2 | 255.28 | 1.3 | 196.37 |
Phosphamidon | OP | Mallard | 3.81 | 26.0 | 1 | 299.69 | 1.2132 | 247.02 |
TEPP | OP | Mallard | 3.56 | 64.0 | 1 | 290.20 | 1.2 | 241.83 |
Thionazin | OP | Mallard | 1.68 | 7.07 | 1 | 248.26 | 1.207 | 205.68 |
Footnotes:
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Hudson, R.H., M.A. Haegele, and R.K. Tucker. 1979. Acute oral and percutaneous toxicity of pesticides to mallards: Correlations with mammalian toxicity data. Toxicology and Applied Pharmacology 47:451-460.
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Schafer, E.W., R.B Brunton, N.F. Lockyer, and J.W. DeGrazio. 1973. Comparative toxicity of seventeen pesticides to the quelea, house sparrow, and redwing blackbird. Toxicol. Appl. Pharmacol. 26:154-157.
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Schafer, E.W. 1984. MRID 00146286
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Schaefer, E.W. 1972. The acute oral toxicity of 369 pesticidal, pharmaceutical, and other chemicals to wild birds. Toxicol. Appl. Pharmacol. 21:315-330.
b Data value was censored (50% mortality not obtained at highest dose) and was not used in the statistical analysis.
Model | Included Dependent Variables | Adjusted R-square | Variables with p-value < 0.25 |
---|---|---|---|
1 | Logoral, MW, density, MV | 0.2575 | Logoral |
2 | Logoral, MW, density | 0.2678 | Logoral |
3 | Logoral, MW, MV | 0.2741 | Logoral |
4 | Logoral, density, MV | 0.2634 | Logoral |
5 | Logoral, MW | 0.2812 | Logoral |
6 | Logoral, density | 0.2762 | Logoral |
7 | Logoral, MV | 0.2677 | Logoral |
8 | Logoral | 0.2857 | Logoral |
Literature Cited
Mineau, Pierre. 2002 Estimating the probability of bird mortality from pesticide sprays on the basis of the field study record. Environmental Toxicology and Chemistry 21:1497-1506.