Document ID: EPA-HQ-OPPT-2008-0918-0100
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2013-05-31T04:00Z

Reviewer:

Ernest V. Falke

April 18, 2011

Reference/Report:

HFO-1234yf: A 2-PHASE INHALATION SCREENING STUDY AND SINGLE EXPOSURE
STUDY IN RABBITS VIA WHOLE-BODY INHALATION EXPOSURE (GLP)

Study Type:

	One hour inhalation study in pregnant rabbits.

Study Date:

	February 28, 2011

Test Material:

	Name:

		HFO-1234yf (2,3,3,3 – Tetrafluoropropene)

	CAS No:

		754-12-1

	Structure:

Test Material Composition:

	HFO-1234yf was administered as a gas and was 99.99% pure.

Sponsor:

Honeywell

101 Columbia Road

PO Box 2245R

Morristown, New Jersey 07962-1057

Test Lab:

Huntingdon Life Sciences

100 Mettlers Road

East Millstone, New Jersey 08875-2360

Materials Methods/Results

	In earlier developmental toxicity studies in rabbits, lethality of the
dams was observed after multiple exposures.  While deemed unlikely, the
outcome of lethality from a single exposure was not known.  This
experiment was designed to address that question.

	New Zealand White rabbits were exposed to target concentrations of 0;
50,000; and 100,000 ppm for 1 hour and observed for 14 days post
exposure.  Analytical concentrations for male/female were 0/0;
45,000/47,000; and 100,000/102,000 respectively.  Five males and 6
pregnant females were exposed at each dose.  Five non-pregnant females
were exposed at 0 and 100,000 ppm.

	No mortality was observed for any condition of the experiment.  No
differences in body weight over the experiment, gross pathology, and
histopathology (control and high dose) of heart, kidney, liver and lung
were observed.

	Metabolites were analyzed from urine samples taken at 12 hour intervals
after exposure up to 48 hours post-exposure.  Metabolite patterns were
similar in all exposed groups except an unidentified metabolite
approximately twice as much in females (both groups) as males.

	In conclusion, a single exposure of pregnant rabbits to high levels of
HFO-1234yf (100,000 ppm) will not cause lethality, changes in body
weight, or pathology and histopathology of major organs .  The cause of
lethality in dams exposed multiple time in developmental toxicity
studies remains unknown.

EPA Review of HFO-1234yf: A 2-Phase Inhalation Screening Study and
Single Exposure Study in Rabbits via Whole-Body Inhalation Exposure
(GLP)