Evaluation of NAFTA Kinetics 

Guidance

Russell L Jones1, Jane Tang1, Michael Huang2, Wenlin

Chen3, Richard Allen4, Sue Hayes3

, Robin Sur1

1Bayer CropScience

2DuPont

3Syngenta

4Valent

Exposure Modeling Public Meeting

March 24, 2014 
Introduction

• The rates at which parent and metabolites 

degrade are important input parameters to 

exposure models used in regulatory risk 

assessments

• For many assessments (for example, potential 

movement to ground water) the predicted 

concentrations are sensitive to the choice of 

degradation rates.

2
Introduction

• Most regulatory models use first order kinetics

 However, degradation of parent and metabolites is 

often not adequately described by first order kinetics

 Therefore an appropriate first-order degradation rate 

must be derived from non-first order data

• Therefore, to obtain consistency in performing 

risk assessments, consistency is needed in 

determining degradation rates from kinetic 

analyses

3
Introduction

• Two kinetics analysis approaches are currently 

used by regulatory agencies

 EU guidance document 

(2006) developed by FOCUS

 NAFTA Guidance Document, 

(2012) developed by NAFTA

Technical Working Group on

Pesticides

• Kinetic analysis tools were also developed to 

implement the respective guidance

 EU - KinGUI (other models also acceptable)

 NAFTA - PESTDF

4
Introduction

• CropLife America established a work group to 

evaluate the NAFTA kinetics guidance and the 

associated tool PESTDF

 Evaluate appropriateness of the approach and 

assumptions

 Compare results obtained by PESTDF and the 

FOCUS guidance 

5
Definitions

• DT50

 Time between application and when 50% of the 

originally applied material has degraded

• DT90

 Time between application and when 90% of the 

originally applied material has degraded

• Half-life

 Time required for half the material to degrade

 The half-life is constant as a function of time only 

when degradation follows first order kinetics

 The half-life is equal to the DT50 only when 

degradation follows first order kinetics

6
Kinetic Models

7

Model Mathematical Equations Guidance

SFO

(Single First-Order) EU-FOCUS NAFTA

FOMC

(First-Order MultipleCompartment) 

EU-FOCUS

DFOP 

(Double First-Order in 

Parallel)

EU-FOCUS NAFTA

HS

(Hockey-Stick) EU-FOCUS

IORE

(Indeterminate Order Rate 

Equation/nth order rate 

equation)

NAFTA

Equivalent to FOMC

n
Note on the DFOP Kinetic Model

• Use of DFOP kinetics in exposure models

 While exposure models require SFO, kinetics, DFOP 

kinetics can be simulated in most models by using 

two compounds

One compound is assigned the fast phase degradation 

rate and the other the slow phase degradation rate

Slight inconsistency when the Freundlich isotherm is 

used to model sorption

8
NAFTA Guidance

9

Source:http://www.epa.gov/oppefed1/ecorisk_ders/degradation

_kinetics/NAFTA_Degradation_Kinetics.htm

Half-life of a SFO model that passes through a 

hypothetical DT90 of the IORE fit 

*

*

Acceptability criteria 

• test if n =1 of IORE by 

F-test at 50% level 
Differences in NAFTA and FOCUS

• Acceptability criteria for first order kinetics

 Difference of most practical significance

 The NAFTA acceptance criteria are more strict

• Procedures when DT90 not reached

 While procedures are different the end result is often 

the same

• Use of IORE rather than FOMC

 Mathematically equivalent expressions but this 

difference influences the acceptability criteria

10
Comparison Simulations 

• Twenty data sets were used for the evaluations

 All the data sets were taken from EU approved 

registration documents, indicating that the kinetic 

endpoints derived were accepted by the EU

• Based on the FOCUS approach:

 11 data sets fit SFO

 6 data sets fit DFOP

 3 data sets fit FOMC

11
Endpoint Comparison for SFO Fits by FOCUS

12

Data Set

FOCUS NAFTA

Half-life Model Half-life Model

#1 60 SFO 94 DFOP (slow phase)

#2 39 SFO 53 IORE tR

#3 55 SFO 102 IORE tR

#4 211 SFO 282 DFOP (slow phase)

#5 232 SFO 1,070 DFOP (slow phase)

#6 62 SFO 97 IORE tR

#7 66 SFO 94 DFOP (slow phase)

#8 41 SFO 74 IORE tR

#9 43 SFO 87 IORE tR

#10 2.9 SFO 2.5 IORE tR

#11 2.2 SFO 2.2 SFO
Endpoint Comparison for SFO Fits by FOCUS

• In 10 out of 11 cases, PESTDF chose IORE or 

DFOP kinetics when FOCUS guidance 

indicated SFO kinetics provided an adequate fit 

of the data

 In 9 of these 10 cases, the representative half-life 

chosen by PESTDF was significantly longer than 

obtained with FOCUS kinetics

Up to a factor of four

 Especially problematic for laboratory studies where 

microbes can slow with time due to removal from their 

natural environment 

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Example - PESTDF

14

Data set #11

 SFO is the best fit based on both guidance, 

therefore, the half-life is the same
Example - PESTDF

15

Data set #3

SFO is not a best fit statistically, but 

appears to adequately describe the main 

portion of the degradation
Example - PESTDF

16

Data set #5

 SFO and IORE/DFOP kinetics describe the observed 

degradation quite similarly

 However, the half-life from IORE is 4 times higher than SFO

 The parameters describing DFOP have wide confidence 

intervals
Endpoint Comparison from Different Tools

17

Tools

SFO DFOP IORE

t1/2

(d)

Overall 

DT90 (d)

Slow-phase (k2) 

t1/2 (d)

Overall 

DT90 (d) tR, IORE (d)

KinGUII 228 779 238 - -

Model Maker - 778 238 2,503 754

NAFTA 228 2,931 1,070 5,397 1,620

Data set #5

 Half-lives for SFO fits are comparable

 Endpoints for DFOP fits derived from KinGUII and 

ModelMaker are comparable, and are 4 times shorter than 

those from NAFTA

 Endpoints for IORE fits derived from ModelMaker were 

significant different than those from NAFTA
Endpoint Comparison for FOMC Fits by FOCUS

18

Data Set

FOCUS NAFTA

Endpoint Model Endpoint Model

#12 57 FOMC 46 DFOP (slow phase)

#13 30 FOMC 30 IORE tR

#14 65 FOMC 58 DFOP (slow phase)

Data sets described by FOCUS guidance with 

FOMC kinetics are described with DFOP or IORE 

kinetics based on the NAFTA guidance

The derived half-lives are comparable when IORE 

tR, IORE was used, and slightly shorter when the slow 

phase of DFOP is selected based on the NAFTA 

guidance
Endpoint Comparison for DFOP Fits by FOCUS

19

Data Set FOCUS NAFTA FOCUS/NAFTA Model

#15 158 160 DFOP (slow phase)

#16 169 170 DFOP (slow phase)

#17 210 210 DFOP (slow phase)

#18 142 143 DFOP (slow phase)

#19 90 91 DFOP (slow phase)

#20 434 434 DFOP (slow phase)

 Data sets are described by DFOP using both 

FOCUS and NAFTA guidance; therefore the 

derived half-lives are comparable
Conclusions

• The most significant difference between 

FOCUS and NAFTA kinetic guidance is the 

criteria for acceptability of SFO fits

 The NAFTA criteria for acceptability of SFO fits is 

more strict, resulting in longer half-lives when the data 

is described by IORE and DFOP kinetics

These longer half-lives are made even longer when 

NAFTA specifies the degradation rate to be the upper 

bound of the 90th percentile confidence interval 

compared to the mean value specified in the FOCUS 

guidance

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Conclusions

• For data sets described by DFOP or FOMC 

according to FOCUS guidance, similar halflives are obtained with FOCUS and NAFTA 

guidance 

• In one of the test cases, PESTDF did not reach 

an optimum solution

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Recommendations

• When SFO kinetics provides an adequate fit of 

the data, its use should be considered, even if 

an improved fit is obtained with other types of 

kinetics

 In laboratory experiments, degradation rates often 

slow down near the end due to decreased bioavailability and slow down of microbial activity, which 

would not be representative of behavior under field 

conditions

• Perform model/parameter significance test to 

reject/accept non-first order, and avoid 

endpoints determined from a model fit with 

broad confidence intervals

22
Recommendations

• Options to include non-first order degradation 

patterns should be considered in NAFTA 

refined exposure assessments

 Modeling non-first order degradation using DFOP

Modeling fast and slow degradation rates as two 

different compounds each with SFO kinetics

 Non-first order degradation resulting from timedependent sorption

 When data is available for individual metabolites, nonfirst order degradation patterns in TTR (total toxic 

residue) simulations can often be more appropriately 

addressed by using a formation-decline approach 

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