# Presentation: 910689

## Inhaled Solvent Abuse: Abuse Liability of Reformulated Products

***Department of Psychology***
***Wayne State University***

- Scott E. Bowen, Ph.D.

***Inhalant Abuse Among Children and Adolescents:***
*** ******Consultation on Building an International Research Agenda***
***Nov. 7-9, 2005***

## Approaches to Managing Abuse Potential of Consumer Products

-  Restricted distribution
- 	Labeling
-  Formulation changes

## Wite-Out© Reformulation

-  Contained 1,1,1-Trichloroethane
- Widely abused
- Depleted ozone
-  Replaced with Isopar-ETM
- Branched C8-C9 isoparaffin
_**Question**_**: Is there Abuse Potential?**

- Wite-Out© Reformulation

## Slide 4

## Investigation of Isopar ETM

- Static/Dynamic Exposure Systems
- Basic/Animal Studies
- Functional Observational Battery
- Operant (lever-pressing) performance
- Drug discrimination
- Cross dependence
- Compared to 1,1,1-trichloroethane

## Evaporation Studies:

## Exposure Systems

- Static

- Dynamic

**Note the longer time required for ISOPAR-E****TM****  to reach asymptotic concentration.**

**Note that higher flow rates through the liquid solvent were required to volatilize ISOPAR-E****TM****  than for TCE.**

## Animal Studies:

- Functional Observational Battery (FOB)

## Functional Observational Battery (FOB)

- CNS Activity
- Arousal
- Rearing
- CNS excitability
- Ease of Removal
- Handling reactivity
- Autonomic effects
- Urination
- Defecation
- Lacrimation
- Piloerection
- Muscle tone equilibrium
- Gait
- Mobility
- Righting reflex
- Forelimb grip strength
- Inverted screen
- Landing foot splay
- Sensorimotor reactivity
- Approach response
- Click response
- Touch response
- Tail Pinch response

## FOB: Arousal

- ISOPAR - ETM

- 1,1,1-TRICHLOROETHANE

**TCE dose-dependently decreases arousal.**

**ISOPAR-E****TM****  decreases arousal at only highest concentration.**

## FOB: Righting Reflex

- ISOPAR - ETM

- 1,1,1-TRICHLOROETHANE

**TCE dose-dependently eliminates the righting reflex.**

**ISOPAR-E****TM****  has no effect up to the  highest concentration tested.**

## FOB: Inverted Screen Task

- ISOPAR - ETM

- 1,1,1-TRICHLOROETHANE

**TCE dose-dependently impairs motor function.**

**ISOPAR-E****TM****  has no effect on motor function up to the highest concentration tested.**

## Functional Observational Battery (FOB)

**CNS Activity****	****	****	****	****TCE****	****	****Isopar E**
- Arousal				    *******↓****	****	****     *********↓**
- Rearing				  ********↓****	****	****     **
**CNS excitability**
- Ease of Removal			  ********↑****	****	****     **
- Handling reactivity			  ********↓****	****	****     **
**Autonomic effects**
- Urination
- Defecation
- Lacrimation
- Piloerection
**Muscle tone equilibrium**
- Gait				    *******↓****	****	****     *********↓**
- Mobility				  ********↓****	****	****     *********↓**
- Righting reflex				  ********↓**
- Forelimb grip strength			  ********↓**
- Inverted screen				  ********↓**
- Landing foot splay			  ********↑** 		    ********↓**
**Sensorimotor reactivity**
- Approach response			    *******↓****	****	****     *********↓**
- Click response				  ********↓**
- Touch response			  ********↓**
- Tail Pinch response			    *******↓**

## FOB Summary

- 1,1,1-TCE exposure produced significant behavioral disruptions on most measures.
- Isopar-E exposure (_<_ 6000 ppm) resulted in only minor behavioral disruptions.

## Animal Studies:

- Operant (Lever-Pressing) Task

## Lever Pressing Behavior

- Single 20-min exposures

- Cumulative 5-min exposures

**Single exposures to either TCE or ISOPAR-E****TM** resulted in **dose-dependent decreases in lever-responding.**

**Cumulative exposures to either TCE or ISOPAR-E****TM****  resulted in dose-dependent decreases in lever-responding.**

## Animal Studies:

- Drug Discrimination Task

## Drug discrimination studies...

- Powerful tool assessing ‘subjective’ responses to drugs.
- Indicates drug abuse potential.
- For volatile solvents
**    ****- Ethanol (ETOH) like   **
**      ****effects**

**Notes:**
It has often been suggested that the this procedure allows experimenters to investigate animal models of human ‘subjective’ responses to drugs, which are often believed to be major determinants of abuse liability (Jasinski et al., 1984).  The DD procedure is therefore often considered to provide data on drug abuse potential.

## Drug discrimination

- ISOPAR - ETM

- 1,1,1-TRICHLOROETHANE

**TCE produces ethanol-like responding at the three highest concentrations tested.**

**ISOPAR-E****TM****  produces ethanol-like responding at the three highest concentrations tested.**

## Animal Studies:

- Cross Dependency Assay

## Cross Dependency with TCE

## Conclusions

- Isopar-ETM is clearly less volatile than TCE.
- Isopar-ETM produces a different profile of effects as measured by the FOB than TCE.

- But...
- Both Isopar-ETM and TCE produced concentration related decreases in operant responding with TCE recovery quicker.
- Both Isopar-ETM and TCE produced ethanol-like responding in the drug discrimination procedure.
- Isopar-ETM produced cross-dependence with TCE.

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## Special Thanks to:

- Mary Tokarz
- Josiah Hamilton
- Eric Evans, Ph.D.
- Robert Balster, Ph.D.
- Supported by Wite-Out Office Products (Beltsville, MD) and;
- NIDA grants DA03112, DA05670, and NIEHS grant ES07087