Document ID: EPA-HQ-OAR-2003-0118-0229
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2009-09-18T04:00Z

Significant New Alternatives Policy Program

Refrigeration and Air Conditioning Sector

Risk Screen on Substitutes for CFC-113 in 

Non-Mechanical Heat Transfer

Substitute: Novec™ 649

This risk screen does not contain Clean Air Act (CAA) Confidential
Business Information (CBI) and, therefore, may be disclosed to the
public.

INTRODUCTION

Ozone-depleting substances (ODS) are being phased out of production in
response to a series of diplomatic and legislative efforts that have
taken place over the past decade, including the Montreal Protocol and
the Clean Air Act Amendments of 1990 (CAAA).  The U.S. Environmental
Protection Agency (EPA), as authorized by Section 612 of the CAAA, is
developing a program to evaluate the human health and environmental
risks posed by alternatives to ODS.  The main purpose of EPA's program,
called the Significant New Alternatives Policy (SNAP) Program, is to
identify acceptable and unacceptable substitutes for ODS in specific end
uses.  

EPA’s decision on the acceptability of a substitute is based largely
on the findings of a screening assessment of potential human health and
environmental risks posed by the substitute in specific applications. 
EPA has already screened a large number of substitutes in many end uses
within all of the major ODS-using sectors, including refrigeration and
air conditioning, solvent cleaning, foam blowing, aerosols, fire
suppression, adhesives, coatings and inks, and sterilization. The
results of these risk screens are presented in a series of Background
Documents that are available in EPA's docket.

The purpose of this report is to supplement EPA’s Background Document
on the refrigeration and air conditioning sector (EPA 1994) (hereinafter
referred to as the Background Document). This risk screen evaluates the
potential use of Novec™ 649, a C6 fluoroketone, as a substitute for
CFC-113 to be used as a non-mechanical heat transfer fluid for a small
class of electrical transformers.   REF _Ref173102842 \h  \* MERGEFORMAT
 Table 1  presents information on the proposed substitute.

Table   SEQ Table \* ARABIC  1 . Chemical Information for Proposed
Substitute.

Proposed Substitute	Chemical Name	CAS Number	Chemical Formula

Novec™ 649	1,1,1,2,2,4,5,5,5,
-Nonafluoro-4-(trifluoromethyl)-3-pentanone	756-13-8	C6F12O

This risk screen addresses potential toxicity risks to workers during
equipment use.  Consumer or general population exposures are not
expected to occur.  Novec™ 649 is not flammable, so a flammability
analysis was not conducted.  

Section 2 of this report summarizes the results of the risk screen for
the proposed substitute.  The remainder of the report is organized into
the following sections:

Section 3: Atmospheric Assessment

Section 4: Toxicity Assessment

Section 5: Volatile Organic Compound Assessment 

Section 6: References

SUMMARY OF RESULTS

™ 649 is recommended for SNAP approval for use as a non-mechanical
heat transfer fluid.  EPA's risk screen indicates that the use of the
proposed substitute will be less harmful to the atmosphere than the
continued use of CFC-113.   No significant toxicity risks to workers,
consumers or the general population are expected.

ATMOSPHERIC ASSESSMENT

This section presents an assessment of the potential risks to
atmospheric integrity posed by the use of Novec™ 649 as a
non-mechanical heat transfer fluid.  The ODP, GWP, and atmospheric
lifetime (ALT) of the proposed substitute are presented in   REF
_Ref175036149 \h  \* MERGEFORMAT  Table 1 .  The substitute is
substantially less harmful to the ozone layer and has less climate
impact than CFC-113.

Novec™ 649 Compared to CFC-113.

Heat Transfer Fluid	Ozone Depleting Potential (ODP)	Global Warming
Potential (GWP)	Atmospheric Lifetime years (ALT)

Novec™ 649	0a	0.6-1.8a	0.04a

CFC-113	0.8b	6,130c	85c

a  ICF 2003  

b Available at: http://www.epa.gov/ozone/ods.html.

c IPCC 4th Assessment Report (Forster et al. 2007).

TOXICITY ASSESSMENT

4. 1.  Toxicity Reference Values

To assess potential health risks from exposure to this substitute, ICF
(2009) evaluated available toxicity data for this substitute and
developed a recommended acceptable exposure limit.   The long-term
exposure limit developed in ICF (2009) is presented in   REF
_Ref222734171 \h  \* MERGEFORMAT  Table 3 .  The reader is referred to
Attachment 1 for a detailed explanation of the development of the AEL
(note that in the attachment the substitute is referred to as
“C6-perfluoroketone”). 

Table   SEQ Table \* ARABIC  3 .  Recommended Toxicity Limit for
Novec™ 649

Substance	Long-Term Exposure Limit

(ppm)

Novec™ 649	250

4. 2.  Occupational Exposure 

Novec™ 649 are expected to be minimal.  To further minimize potential
exposures, it is recommended that all technicians be properly trained in
working with the transformers and related recovery equipment and that
the requirement of possessing EPA 608 certification be strictly
enforced.

4. 3.  Consumer Exposure

Consumer exposure to the substitute is not expected. 

4. 4.  General Population Exposure

Chronic exposures to the substitute are not expected for the general
population. 

VOLATILE ORGANIC COMPOUND (V䍏 十䕓卓䕍呎

Novec™ 649 produced in one year were to leak to the atmosphere over
the course of the year (extremely unlikely given the hermetic seals on
the transformers and the caution used during recovery to minimize
emissions), the resulting annual VOC emissions would be only about
2x10-5 percent of all annual anthropogenic VOC emissions.  As these
emissions of Novec™ 649 are several orders of magnitude less than
other anthropogenic emissions, the environmental impacts of these VOCs
are not considered a threat.

REFERENCES

3M. 2009a. Significant New Alternatives Policy (SNAP) Approval for C6
Perfluoroketone in Non-mechanical Heat Transfer Use.  June 2009. 

3M.  2009b.  Follow-Up Email Regarding Significant New Alternatives
Policy (SNAP) Approval for C6 Perfluoroketone in Non-mechanical Heat
Transfer Use.  July 2009. 

EPA 2008.  Volatile Organic Compounds – National Summary of VOC
Emissions.  Last updated 21 October 2008.  Accessed 4 March 2009.
Available at <http://www.epa.gov/air/emissions/voc.htm>.

EPA. 1994.  Significant New Alternatives Policy Technical Background
Document:  Risk Screen on the Use of Substitutes for Class I
Ozone-depleting Substances: Refrigeration and Air Conditioning. 
Stratospheric Protection Division.  March 1994.

Forster, P., V. Ramaswamy, P. Artaxo, T. Berntsen, R. Betts, D.W. Fahey,
J. Haywood, J. Lean, D.C. Lowe, G. Myhre, J. Nganga, R. Prinn, G. Raga,
M. Schulz and R. Van Dorland. 2007.  Changes in Atmospheric Constituents
and in Radiative Forcing. In: Climate Change 2007:The Physical Science
Basis. Contribution of Working Group I to the Fourth Assessment Report
of the Intergovernmental Panel on Climate Change [Solomon, S., D. Qin,
M. Manning, Z. Chen, M. Marquis, K.B. Averyt, M.Tignor and H.L. Miller
(eds.)]. Cambridge University Press, Cambridge, United Kingdom and New
York, NY, USA.

ICF.  2009.  Recommendation for an Acceptable Exposure Limit for
C6-Perflouroketone.  Deliverable under EPA Contract EP-W-06-008, TO 038,
Task 6.  September 2009.

ICF.  2003.  Re-evaluation of a C-6 Oxyfluorocarbon (trade name Novec™
1230) and References.  Deliverable under EPA Contract Number
68-3-00-266, Work Assignment 2-05 Task 03.  Available online at: <
http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064
800bb086&disposition=attachment&contentType=pdf>.Development of AEL
for C6-Perfluoroketone

ICF has developed a revised AEL for C6-perfluoroketone based on a review
of recent additional studies in the C6-perfluoroketone toxicity
database.  These studies are

Sub-chronic (13-week) inhalation toxicity study with MTDID 5789 in rats
(TNO, 2007)

Reproduction/ developmental toxicity screening text after inhalatory
exposure to MTDID 5789 in rats (TNO, 2007) 

In the subchronic inhalation study, groups of 10 each male and female
Wistar rats were exposed to 0, 300, 1000 or 3000 ppm (target
concentrations) C6-perfluoroketone for 6 hours/day, 5 days/week for 13
weeks.  In addition, two recovery groups of 10 each male and female rats
were exposed to 0 or 3000 ppm of the test compound as with the main
groups of the study and were allowed to recover for 28-days post
exposure.  This recovery period was intended to investigate the
reversibility of noted adverse effects.

The study evaluated typical parameters for subchronic toxicity studies
including clinical/cageside observations, food consumption/efficiency,
body weight changes, hematology/clinical chemistry, localized effects,
gross necropsy, organ changes, and organ histopathology.  No
exposure-related effects were noted in the following parameters:
clinical/cage side observations, food consumption/efficiency, body
weight, food consumption or opthalmoscopy.  In addition, no local
effects were noted.

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ctivity (acyl CoA-oxidase) related to peroxisomal proliferation,
predominantly in males at all exposure concentrations, but also in
females in the high-concentration group.   The liver effects were not
noted in recovery rats after 28 days post-exposure, with the exception
of the persistence of slight or very slight increased eosinophilic
granulation in 4/10 male rats at 3000 ppm.  The study authors identified
a NOEL of 1000 ppm for female rats, were unable to define a NOEL for
male rats, and identified a NOAEL/LOAEL of 300 ppm for male rats.

The subchronic study essentially validated the results of the previous
28-day inhalation study in rats using C6-perfluoroketone, which
indicated that peroxisomal proliferation resulted from rat exposure to
concentrations of 1000 ppm and higher. 

As stated in the 13-week study report, peroxisomal proliferation is a
liver response observed in rodents, predominantly male rats, in response
to exposure to certain compounds.  Responses in humans are poor or
absent following exposure to peroxisomal proliferators, due to genetic
differences in the elements necessary to respond to these compounds. 
For this reason, peroxisomal proliferation is considered to be a
species-specific response with more limited application to humans.  For
this reason, ICF has chosen the 1000 ppm exposure concentration in the
13-week study as the point of departure for developing the AEL for
C6-perfluoroketone.

A revised AEL has been developed as follows:

	1000 ppm x 6 hours (exposure of rats)/8 hours (workday) = 750 ppm (HEC)

750/3 (UF) = 250 ppm (AEL)

One uncertainty factor of 3 has been applied to account for interspecies
differences between rats and humans.  No other UFs have been applied. 
The database is comprehensive, including a one-generation reproductive
and developmental toxicity study in rats which showed no adverse effects
at any concentration tested up to 3000 ppm.  Therefore, the original UF
of 10 applied for database limitations in the initial AEL development
has been removed.  

We are aware that we have chosen as a point of departure an exposure
concentration that results in liver effects in the male rat (e.g., 
histopathological changes in the liver and increased relative liver
weight).  Studies show that rats and mice appear to be more sensitive
than humans to peroxisomal proliferators.  That is not to say that
humans are not responsive; they are responsive, for example, to a
certain class of pharmaceuticals known as hypolipidemic fibrates, such
as clofibrate, via activation of the peroxisome proliferator activated
receptor (PPAR).  There has been concern in the past with peroxisomal
proliferation in compounds that induce liver cancer in rodents and the
possibility that cancer induction is a concern with regard to humans
(e.g., DEHP, TCE, etc.; Melnick, 2001; Keshava and Caldwell, 2006). 
However, these compounds are much less potent as PPAR receptor agonists
than the hypolipidemic fibrates.  Further, these agents also induce
biological effects in animal models that appear to occur independently
of peroxisome proliferation.  It does not appear that C6-perfluoroketone
induces any other relevant toxicological effects in the rat other than
peroxisome proliferation in the liver and its associated effects. 
Therefore, we feel that establishing the AEL for C6-perfluoroketone at a
maximum of 250 ppm is appropriate and supported by the science.

Attachment 1 References

Keshava N and JC Caldwell (2006) Key issues in the role of peroxisome
proliferator-activated receptor agonism and cell signaling in
trichloroethylene toxicity.  Environ Health Perspect 114(9):1464-1470.

Melnick RL (2001) Is peroxisome proliferation an obligatory precursor
step in the carcinogenicity of di(2-ethylhexyl)phthalate (DEHP)? Environ
Health Perspect 109(5):437-442.

 This figure was calculated using expected annual production levels from
3M (2009a) and 2002 annual VOC emissions data from EPA (2008).

	     

Novec 649 Risk Screen

September 17, 2009

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Novec 649 Risk Screen – Heat Transfer End-Use 	       Attachment 1	   
 

Recommendation for an Acceptable Exposure Limit for C6- Perflouroketone

September 11, 2009

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