### PHYS 

### - C HEM 

### S CREENING 

### :

S MALL 

### S TUDIES 

### ........... B IG 

### C ONSEQUENCES Gordon SANDERS Givaudan International SA, Geneva, Switzerland US - EPA / Industry Workshop, Arlington VA, 10 – 11 September 20142 

## “ Chemicals are used to make most of the

products that we rely on in our daily lives. 

## When used safely, chemicals significantly contribute to the improvement of our quality of life, health, and well -being.”3 

## “ Chemicals are used to make most of the

products that we rely on in our daily lives. 

# When used safely

, chemicals significantly contribute to the improvement of our quality of life, health, and well -being.” US - EPA : CDR – Basics Fact Sheet (June, 2014)



### - Strict minimum of product comprehension required



### - Intrinsic properties + Environmental Release  Acceptable Risk

## PHYS 

## - C HEM 

## S CREENING 

## :

S MALL 

## S TUDIES 

## ........... B IG 

## C ONSEQUENCES

4 

## Content

Be Prepared - Chemical Composition and Identity The Utility of Phys - Chem Data Deriving Phys - Chem Data for Difficult to Test Substances and Challenges Related to Interpretation and Application 

### 1 2 

### 3 Impact on Other Testing and Needs Moving Forward 

### 4

## PHYS 

## - C HEM 

## S CREENING 

## :

S MALL 

## S TUDIES 

## ........... B IG 

## C ONSEQUENCES

5 

## Content

Be Prepared - Chemical Composition and Identity The Utility of Phys - Chem Data Deriving Phys - Chem Data for Difficult to Test Substances and Challenges Related to Interpretation and Application 

### 1 2 

### 3 Impact on Other Testing and Needs Moving Forward 

### 4

## B E 

## PREPARED

6  Chemical Identity : 

### Class 1 “Well Defined” Class 2 UVCB Polymers Non - Ionic, Anionic, Cationic, Amphoteric

- Low Mol. Wt.

- Low + High Mol. Wt.



### - High Mol. Wt.

- Mono- or Multi - Constituent ?

- Chem. Abs. n omenclature(s)

- CAS No(s)

- Molecular Formula

- Molecular Weight

- Structure(s) - Precursor(s) + CAS No(s)

- Description of process

- Detail of typical composition

- Structures / partial structures - MWn

- LMW (500, 1000)

- Details of Monomer and reactants

## REPRESENTATIVE 

## S AMPLE 

## + S PECTRAL 

## ANALYSES

7 Signal Apex RT Area % Area 1 57.39 92780026 99.69 Constituent A MW 220, C 13 H 16 O 3 

### UV -VIS Scan FT - IR

1 

### H, 13 

### C - NMR
M S8

## IMPURITIES 

## – DEFINITION AND 

## A SSESSMENT

9  

### Definition :  

### CAS RN + CA nomenclature if known  

### Source material if appropriate  

### Class or Structural range

 

### Class 1 – How low ?  

### List all present ; regardless of percentage  

### Knowns and Unknowns should be included

 

### Characterize using :  

### Chemical and instrumental analyses  

### Knowledge of manufacturing process chemistry  

### Quality Control procedures

## PHYS 

## - C HEM 

## S CREENING 

## :

S MALL 

## S TUDIES 

## ........... B IG 

## C ONSEQUENCES

10 

## Content

Be Prepared - Chemical Composition and Identity The Utility of Phys - Chem Data Deriving Phys - Chem Data for Difficult to Test Substances and Challenges Related to Interpretation and Application 

### 1 2 

### 3 Impact on Other Testing and Needs Moving Forward 

### 4

## WHERE ARE 

## PHYS 

## - C HEM 

## V ALUES 

## USED 

## ?

11 

## EPI SuiteTM 

## ECOSAR TM 

### logKow WS VP MPt BPt Acute & Chronic AquaTox Acute - COC Chronic- COC Acute & Chronic AquaTox Acute - COC Chronic- COC 

### P REDICTED 

### M EASURED 

# E - FAST

- PEC -
- ExceedenceSTP Removal Rate BCF Environmental Distribution 

# ! PRIMORDIAL for AquaTox Planning 

# !

## PHYS 

## - C HEM 

## S CREENING 

## :

S MALL 

## S TUDIES 

## ........... B IG 

## C ONSEQUENCES

12 

## Content

Be Prepared - Chemical Composition and Identity The Utility of Phys - Chem Data Deriving Phys - Chem Data for Difficult to Test Substances and Challenges Related to Interpretation and Application 

### 1 2 

### 3 Impact on Other Testing and Needs Moving Forward 

### 4

### DERIVING 

### PHYS 

### - C HEM 

### DATA FOR 

### DIFFICULT TO 

### TEST 

### S UBSTANCES

13 l ow Kow, soluble high Kow, l ow solubility soluble insoluble volatile n on -volatile Formation of octanol micro droplets in aqueous phase Efficient, practical, useable with UVCBs

Separation and filtration issues, hydrolytic stability Correct choice of method for VP range, thermal stability, avoid extrapolation from high - to lowtemps

### C HALLENGES 

### RELATED TO 

### INTERPRETATION AND 

### APPLICATION

14  Octanol -Water Partition Coefficient :  Intrinsic error stated as +/- 0.5 log units !

Measured logKow Linalyl Acetate d - Limonene Musk Xylene

3.90 4.38 4.90 Potential logKow Range 3.40 – 4.40 3.88 – 4.88 4.40 – 5.40 EPISuite : STP Removal Rate BCF - Regression

Range Range 53% 74% 94% 46 – 66% 51 – 87% 93 – 95% 174 L/kg 794 L/kg 361 L/kg 81 – 372 L/kg 372 - 1700 L/kg 169 – 771 L/kg

### C HALLENGES 

### RELATED TO 

### INTERPRETATION AND 

### APPLICATION

15  Water Solubility Determinations :  Sub - ppm substances : Separation of dissolved from non - soluble Application to AquaTox studies

0 0.2 0.4 0.6 0.8 1 1.2

Water Solubility Time 0 24hr Renewal ppm

### C HALLENGES 

### RELATED TO 

### INTERPRETATION AND 

### APPLICATION

16  Water Solubility Determinations :  Sub - ppm substances : Separation of dissolved from non - soluble Application to AquaTox studies

0 5 10 15 20

Water Solubility Time 0 24hr Renewal Pre-Test ppm

## PHYS 

## - C HEM 

## S CREENING 

## :

S MALL 

## S TUDIES 

## ........... B IG 

## C ONSEQUENCES

17 

## Content

Be Prepared - Chemical Composition and Identity The Utility of Phys - Chem Data Deriving Phys - Chem Data for Difficult to Test Substances and Challenges Related to Interpretation and Application 

### 1 2 

### 3 Impact on Other Testing and Needs Moving Forward 

### 4

### IMPACT ON 

### O THER 

### TESTING AND 

### NEEDS 

### M OVING 

### F ORWARD

I

18 

###  

## logKow :  

### Directly related to Bioaccumulation potential  

### Is the main driver for Bioaccumulation QSARs  

### Is NOT, however, the main influencing characteristic logKow 

### 830.7550 830.7560 830.7570 Fish - BCF 

### 850.1730
S9 fractions (-80 ° C) larger debris removed 

### Liver Homogenate In- vitro

## IMPACT ON 

## O THER 

## TESTING AND 

## NEEDS 

## M OVING 

## F ORWARD

19 

###  

## W ATER 

## S OLUBILITY 

## : AquaTox Studies Exposure Medium Prep Analytics

- Direct Analysis -
- Extraction / Concentration Direct Dissolution in Media Use of Solvent Saturated Solns . & WAFs Reproducibility Stirring time vs Stability

## IMPACT ON 

## O THER 

## TESTING AND 

## NEEDS 

## M OVING 

## F ORWARD

20 

###  

## V APOUR 

## P RESSURE 

## :  

### AquaTox  

## A DAPTED 

## G UIDANCE FOR 

## P HYS

## - C HEM 

## T ESTING AND 

## I NTERPRETATION OF 

## :  

### UVCB S  

### I ONISABLES 

### What are the effects of using closed test systems ?

## C ONCLUSIONS

21  Determined Phys - Chem values are prone to intrinsic errors : + / - significant  Some test substances ARE more difficult to test than others  increased relative error: low water solubility, high vapour pressure, UVCBs, ionisables

The World that we live in is not ideal .........

BUT Comprehension of our products is our responsibility .........  Prepare the terrain well : test substance quality, QSAR modelling / read - across, pre -test trials  Use existing guidelines or adapt where possible with justification  Phys - chem values may not be suitable “surrogate” for extrapolation (e.g. logKow  BCF)

– Development of parallel approach, or, move to higher-tier  More guidance from Phys - Chem values through to AquaTox media preparation22