An official website of the United States government.

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.

Figure H-1. Plot of dermal LD50 values (y-axis) vs. oral LD50 values (x-axis) in log-base 10 scale. The correlation coefficient was 0.55.Figure H-1. Plot of dermal LD50 values vs. oral LD50 values in log-base 10 scale. The correlation coefficient was 0.55.

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.

Table H-1: Raw Data from Regression Analysis of Avian Dermal LD50 and Oral LD50
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:

  1. 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.

  2. 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.

  3. Schafer, E.W. 1984. MRID 00146286

  4. 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.

Table H-2. Summary of fitted regression models to predict dermal LD50 from oral LD50 and the chemical properties molecular weight (MW), density, and molecular volume (MV).
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.

Top of Page