OECD SIDS 1,1-DIFLUOROETHANE (HFC-152A)

UNEP PUBLICATIONS 1 

## FOREWORD INTRODUCTION



# 1,1-DIFLUOROETHANE (HFC-152a)
CAS N°: 75-37-6OECD SIDS 1,1-DIFLUOROETHANE (HFC-152A)

UNEP PUBLICATIONS 2 

## SIDS Initial Assessment Report

For

SIAM 22

Paris, France, 18-21 April 2006

1. Chemical Name: 1,1-Difluoroethane (HFC-152a)

2. CAS Number: 75-37-6
3. Sponsor Country: Republic of Korea Contact Point: Hyun-Mi KIM, Ph. D. National Institute of Envi ronmental Research (NIER). Kyongseodong, Seogu, Incheon, 404-708, Korea Tel: +82-(0)32-560-7216 FAX: +82-(0)32-560-7256

4. Shared Partnership with:
5. Roles/Responsibilities of the Partners:

• Name of industry sponsor /consortium DuPont

• Process used Industry collect ed data and prepared the draft versions of the IUCLID dossier, SIAR, and SIAP.
6. Sponsorship History

• How was the chemical or category brought into the OECD HPV Chemicals Programme? This substance is sponsored by Korea under the ICCA Initiative and is submitted for the first discussion at SIAM 22.

7. Review Process Prior to the SIAM: NIER, Korea reviewed the documents and added the use volume and exposure information.
8. Quality check process: The quality of the existing data was reviewed against the OECD criteria as described in the Ma nual for Investigation of HPV Chemicals. 9. Date of Submission: 20 January, 2006
10. Date of last Update: 29 June 2006

11. Comments:OECD SIDS 1,1-DIFLUOROETHANE (HFC-152A)

UNEP PUBLICATIONS 3 SIDS INITIAL ASSESSMENT PROFILE

CAS No. 75-37-6

Chemical Name 1,1-Difluoroethane (HFC-152a)

Structural Formula F 2 – HC – CH 3

SUMMARY CONCLUSIONS OF THE SIAR

Human Health

No toxicokinetic data for HFC-152a were found.

HFC-152a has low acute inhalation toxicity, with a 4-hour rat approximate lethal concentration (ALC) of 383,000 ppm. No valid acute oral toxicity studies are available. Although no standard test results are available, the repeat dose studies show some potential for irritation. As with most HFCs, HFC-152a has the potential to produce cardiac sensitization in dogs challenged simultaneously with high exposure concentrations and high doses of exogenous epinephrine. Marked responses, which included a cardiac arrhythmia were observed in 3 of 12 dogs at 150,000 ppm. No response was observed at 50,000 ppm. No sensitization studies were available.

HFC-152a has low repeated dose toxicity. HFC-152a had anesthetic properties at a 100,000 ppm exposure level during a 2-week repeated dose inhalation study in rats. No other clinical, haematological, blood chemistry or histopathology effects were observed during the 2-week inhalation study. No adverse effects were observed in rats following a 3-month inhalation exposure to 25,000 ppm HFC-152a.

HFC-152a was not mutagenic in the in vitro bacterial reverse mutation test (Ames test) in Salmonella typhimurium and Escherichia coli strains. However, HFC-152a showed evidence of weak clastogenicity in an in vitro human lymphocyte chromosome aberration test. Further evaluation of the chromosome aberration potential using an in vivo micronucleus test produced negative results.

In a 2-year bioassay, HFC-152a was not carcinogenic to rats at inhalation exposure levels up to 25,000 ppm.

In a developmental study, female rats were exposed via inhalation up to 50,000 ppm during days 6 to 15 of pregnancy for 6 hours per day. No compound related maternal and developmental effects were observed at any of the concentrations tested, hence, the NOEL is 50,000 ppm. No histopathological or weight effects on reproductive organs were observed in male and female rats exposed up to 25,000 ppm HFC-152a for 6 hours per day, 5 days per week for 3, 12 or 24 months.

Environment

On the basis of its physical properties HFC-152a may be expected, when released to the environment, to partition almost exclusively into the atmosphere as it is a gas, with a vapor pressure at 25 o C of 6065.2 hPa, and it has a water solubility of 2.671 g/l at 25 o C. Any HFC-152a, which might be present in aqueous waste streamsdischarged directly into rivers or lakes would be expected, by analogy with similar compounds, to have a halflife with respect to volatilization of days or at the very most a few weeks. HFC-152a is expected to exist solely in the vapor-phase in the ambient atmosphere.

Vapor-phase HFC-152a is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals with a lifetime of 1.4 years. The atmospheric lifetime of this chemical suggests that it will mix throughout the troposphere with a globally averaged concentration in 2003 of about 2.6 ppt. Because of its IR absorption, it will contribute a very small amount to climate change with a global warming potential (GWP) relative to CO2 of 140 for a time horizon of 100 years.

In addition, some HFC-152a is expected to gradually diffuse into the stratosphere above the ozone layer where itOECD SIDS 1,1-DIFLUOROETHANE (HFC-152A)

UNEP PUBLICATIONS 4 will slowly degrade due to reaction with hydroxyl radicals and direct photolysis from UV-C radiation. The ozone depletion potential (ODP) of HFC-152a has been determined to be negligible.

HFC-152a is not expected to adsorb to sediment or particulate matter. Bioconcentration is expected to be low based on an estimated BCF value of approximately 2 using the measured n-octanol/water partition coefficient (log value is 0.75). A Mackay Level III fugacity mode l (EPIWIN v.3.05) predicts that HFC-152a will partition mainly to the air (99.9%), with very little going to water (0.111%), and virtually none going to soil or sediment (0.01 and <0.01%, respectively).

Based on the ECOSAR predictions (96-hour LC 50 in fish of 733 mg/L 48-hour EC 50 in daphnids of 720 mg/L, and 96-hour EC 50 in algae of 419 mg/L), actual toxicity test data for the analog chemical HFC-134a (96-hour LC 50 in fish of 450 mg/L and 48-hour EC 50 in daphnids of 980 mg/L), and the high Henry’s Law Constant for these compounds (0.02 atm-m3/mole for HFC-152a), the predicted toxicity of HFC-152a to aquatic organisms is low.

Exposure

The primary uses for HFC-152a are as an aerosol propellant and a foam expansion agent. Other potential uses include refrigeration blends and catalyst regeneration. Production capacities are confidential, but are in excess of 5000 metric tonnes per year. In Korea, it is also used in maintaining of a catalytic activity and estimated usage volume of 1,1-difluoroethane was 4.63, 4.85, and 3.14 tonnes/year in 2003, 2004, and 2005, respectively.

Emissions from HFC-152a manufacturing facilities are small. In the sponsor country, small amounts of HFC152a are used in a closed system. HFC-152a is treated with steam and emitted to wastewater plant. Fluorine is below the detection limit (1 mg/L) in discharged water. There are no reported natural sources of HFC-152a. HFC-152a used in propellant and foaming applications will be emitted to the atmosphere.

Industrial hygiene monitoring data during manufacture and industrial use show exposure to be well under acceptable exposure limits. The current AIHA WEEL (Workplace Environmental Exposure Limit) and DuPont AEL (Acceptable Exposure Limit) are 1000 ppm, 8-hour TWA (time-weighted average). Though consumer exposure has not been measured directly, modeling based on measurement of similar uses shows consumer exposure to be minimal during intended uses.

RECOMMENDATION AND RATIONALE FOR THE RECOMMENDATION AND NATURE OF FURTHER WORK RECOMMENDED

The chemical is currently of low priority for further work, due to its low hazard profile. Its global warming potential is acknowledged and is being addressed by other programs.OECD SIDS 1,1-DIFLUOROETHANE (HFC-152A)

UNEP PUBLICATIONS 5 

## SIDS Initial Assessment Report

1 IDENTITY

1.1 Identification of the Substance

CAS Number: 75-37-6 IUPAC Name: 1,1-Difluoroethane Molecular Formula: C 2 H 4 F 2 Structural Formula: F 2 – HC – CH 3 Molecular Weight: 66.1Synonyms: Ethane, 1,1-difluoroHFC-152a (name to be used throughout dossier) Freon  152a Ethylidene fluoride Genetron  152a Algofrene 67 Dymel 152 Dymel 152a F152A FC152a FKW 152a HFA 152a R 152a Ethylene fluoride Ethylidene difluoride Genetron 100 (CHEMLIST, 1999; HSDB; 2000).

Since solubility and physical char acteristics are similar, data fo r analogous chemicals, 1,1,1,2,2- pentafluoroethane (HFC-125) and 1,1,1,2-tetrafluoroethane (HFC- 134a), are used where data are lacking for 1,1-difluoroethan e (HFC-152a) (DuPont, 2002a; 2003).

1.2 Purity/Impurities/Additives
Purity: > 99.9 %
Impurities/Additives: Typical impurities in HFC-152a includ e low level (ppm) water, low level (ppb) residual HCl and/or HF acids (DuPont Co., 2006).OECD SIDS 1,1-DIFLUOROETHANE (HFC-152A)

UNEP PUBLICATIONS 6 1.3 Physico-Chemical Properties

Table 1 Summary of Physico-Chemical Properties

Property Value Physical state Gas Melting point -117 ° C Lewis, 1993 Boiling point -24.7 ° C Lewis, 1993 Density 0.91 g/mL @ 21 ° C Kirk-Othmer, 1991
Vapour pressure 4,550 mmHg (6,065.2 hPa) @ 25 ° C Daubert and Danner, 1989a Water solubility (calculated) 2.671 g/L @ 25 ° C Meylan and Howard, 1996

Partition coefficient n-octanol/water (log value) (measured) 0.75 Jow and Hansch, n.d.

Henry’s law constant (calculated) 0.02 atm-m 3 /mole (2,026.5 Pa-m 3 /mole) Daubert and Danner, 1989b Ruelle and Kesselring, 1997 SRC, n.d. Flammability limits 3.7 % - 18 % (in air) Sax and Lewis, 1987



### 2 GENERAL INFORMATION ON EXPOSURE

2.1 Production Volumes and Use Pattern
HFC-152a is produced in a closed system by catalyt ic reaction of vinyl chloride with hydrofluoric acid and is purified based on market specification. Production capacities are confidential, but are in excess of 5,000 metric tonne (10 million pounds) pe r year. In Korea, estimated usage volume of 1,1-difluoroethane was 4.63, 4.85, and 3.14 tonn es/year in 2003, 2004, and 2005, respectively (NIER, 2005).

Approximately 80 % of HFC-152a is used as an ae rosol propellant and approximately 15 % is used as a foam expansion agent. The remaining 5 % of the HFC-152a is for other potential uses, which include refrigeration blends and cata lyst regeneration. In Korea, it is also used in maintaining of a catalytic activity (NIER, 2005).

Because of its low vapor pressu re, HFC-152a is handled as a li quefied gas during manufacture and shipping. Therefore, HFC-152a is handled in closed pressurize systems so that exposure typically does not occur in the manufacturing, except fo r during maintenance or an abnormal process situation, such as a leak (DuPont, 2004).

HFC-152a is used in aerosol cons umer personal care and household products and is dispensed with the product during use. Typically there is no HFC-152a left in the container when it is disposed (DuPont, n.d.).

HFC-152a used to manufacture foam is contained within the foam, and remains in the foam for a long period of time. The HFC-152a will be disposed with the foam (DuPont, 2002b).

HFC-152a used in refrigerants is contained in th e refrigeration system until such time as it is collected for recycle or disposal (DuPont, 2005).OECD SIDS 1,1-DIFLUOROETHANE (HFC-152A)

UNEP PUBLICATIONS 7 2.2 Environmental Exposure and Fate
On the basis of its physical properties, HFC- 152a may be expected, when released to the environment, to partition almost exclusively into the atmosphere as:

• it is a gas, with a vapour pressure at 25 °C of 4,550 mmHg.

• it has a limited water solubility of 2.7 g/L at 25 °C.
Any HFC-152a that might be present in aqueous wa ste streams discharged directly into rivers or lakes would be expected, by anal ogy with similar compounds, to have a half-life with respect to volatilisation of days or at the very most a fe w weeks. In the sponsor country, small amounts of HFC-152a are used in a closed system. HFC-152a is treated with steam and emitted to wastewater plant. Fluorine is below the detection limit in discharged water (NIER, 2005).

2.2.1 Sources of Environmental Exposure
There are no reported natural s ources of HFC-152a. HFC-152a us ed in propellant and foaming applications will be emitted to the atmosphere.

2.2.2 Photodegradation
1,1-Difluoroethane (HFC-152a) is expected to exist solely in the vapor-phase in the ambient atmosphere. Vapor-phase HFC-152a is degrad ed in the atmosphere by reaction with photochemically-produced hydroxyl radicals with an atmospheric lifetime of 1.4 years. The atmospheric lifetime of this chemical suggests that some HFC-152a is expected to gradually diffuse into the stratosphere above the ozone layer where it will degrade due to direct photolysis from UVC radiation (Nimitz and Skaggs, 1992; SRC, n.d.).

The molecular breakdown to give CO, CO 2 , H 2 O, and C(O)F 2 proceeds via various free-radical intermediates. C(O)F 2 is incorporated into rain, cloud, or fog water and is hydrolyzed to form HF and CO 2 (AFEAS, 1989).

2.2.3 Stability in Water
HFC-152a is predicted to be stable in wate r under environmentally relevant conditions, and hydrolysis is not expected to occur, as indicated by HydroWin calculations.

2.2.4 Transport between Enviro nmental Compartments
Mackay Level III fugacity model (EPIWIN v.3.05) predicts that HFC-152a will partition mainly to the air (99.9 %), with very little going to wate r (0.111 %), and virtually none going to soil or sediment (0.01 and < 0.01 %, respectively). The fo llowing input parameters were used: Molecular Weight: 66.05; Henry’s Law Constant: 0.0203 atm-m 3 /mole; Vapor Pressure: 3.86 x 10 3 ; log Kow: 0.75; Soil Koc: 2.31.
If released to water, HFC-152a is not expected to adsorb to sediment or particulate matter based upon the estimated Koc of 60 (SRC, n.d.). HFC-152a is expected to volatilize rapidly from water surfaces based upon this compound’s estimated Henr y’s Law constant. Estimated half-lives for a model river and model lake are 2 and 77 hours, resp ectively (Lyman et al., 1990; SRC, n.d.).OECD SIDS 1,1-DIFLUOROETHANE (HFC-152A)

UNEP PUBLICATIONS 8 2.2.5 Biodegradation
Modeling of several physical-chemic al parameters and fate proces ses (Table 2) was conducted to help provide insight into the behavior in the en vironment of a homologous series of 4 fluorocarbon compounds (HFC-152a, HF C-134a, and HFC-125).

Syracuse Research Corporation models for esti mating physical-chemica l properties and fate processes were used to estimate log 10 Kow (Meylan and Howard, 1995 ), water solubility at 25  ̊ C (Meylan and Howard, 1996), Henry’s Law Consta nt (Meylan and Howard, 1991), and ultimate biodegradation (Boethling et al., 1994). The dominant fate process co ntrolling distribution of these compounds in the environment is volatilisation (Mackay et al., 1996).

Table 2 Environmental Fate Parameters

Compound log 10 Kow (Estimated) Water Solubility (Estimated) Henry’s Law Constant (Estimated) Ultimate Degradation (Estimated)

HFC-152a (1,1-Difluoroethane) (C 2 H 4 F 2 ) 1.13 2,671 mg/L 0.38 atm-m 3 /mole Weeks

HFC-134a (1,1,1,2-Tetrafluoroethane) (C 2 H 2 F 4 ) 1.68 768 mg/L 1.5 atm-m 3 /mole Weeks-months

HFC-125 (1,1,1,2,2-Penta fluoroethane) (C 2 HF 5 ) 1.55 867 mg/L 3.1 atm-m 3 /mole Weeks-months

Highly chlorinated/fluorinated compounds are not e xpected to biodegrade rapidly (Boethling et al., 1994). Based on the expected lack of sorption to soil , sediment, or particulate matter from fugacity modeling and its high vapour pressure, biodegra dation is not expected to be an important environmental fate process for HFC-152a (HSDB, 2000). In additi on, biodegradation testing with similar compounds, e.g. difluorom ethane (HFC-32), which was degr aded 8 % after 28 days, and 1,1,1,2-tetrafluoroethane (HFC-134a), which was degraded 4 % after 28 days, has indicated that these types of compounds are not readil y biodegradable (Tobeta 1989; 1992).

2.2.6 Bioaccumulation
Bioconcentration is expect ed to be low based upon an estimated BCF value of 2 (SRC, n.d.).

2.2.7 Other Information on Environmental Fate

Due to the absence of chlorine and bromine at oms in the molecule, and the ozone depletion potential of other hydrofluorocar bons (HFC’s), the contribution of HFC-152a to atmospheric ozone depletion can be considered negligible. Global Warming potential (GWP) valu es of 410, 120, and 37 relative to carbon dioxide (GWP = 1) were calculated for integration time horizons of 20, 100, and 500 years, respectively (IPCC TAR, 2001). An official value of 140 wa s adopted by the Kyoto Protocol (IPCC AAR, 1996) for at time horizon of 100 years, indicating a potent ial contribution to global warming.OECD SIDS 1,1-DIFLUOROETHANE (HFC-152A)

UNEP PUBLICATIONS 9 The Advanced Global Atmospheric Gasses Expe riment observed the tropospheric abundance of HFC-152a to be 2.6 ppt in 2003 (IPCC/TEAP, 2005).

2.3 Human Exposure
HFC-152a is a gas at room temperature. Theref ore, the main route of human exposure is via inhalation. On the basis of its physico-chemical pr operties, if released into the environment HFC152a will partition mostly into the atmosphere.

2.3.1 Occupational Exposure

Emissions from DuPont HFC-152a manufacturi ng facilities are small and industrial hygiene monitoring data during manufactur e and industrial use show exposur e to be well under acceptable exposure limits. In the sponsor country, HFC-152a is handled in a closed system. Workers typically do not have a potential exposure to HFC-152a ex cept for during maintenance or a leak. No industrial hygiene monitoring data were available (NIER, 2005).
The current AIHA WEEL (Workplace Envir onmental Exposure Limit) and DuPont AEL (Acceptable Exposure Limit) are 1000 ppm, 8-hour TWA (time-weighted average) (AIHA, 1994; DuPont Co., 1998).

2.3.2 Consumer Exposure
HFC-152a consumer exposures have been modeled based on similar use scenarios. The predicted aggregate exposure of the general public while us ing key products is minimal (DuPont, 2001a).



### 3 HUMAN HEALTH HAZARDS

3.1 Effects on Human Health

3.1.1 Toxicokinetics, Metabolism and Distribution
No kinetic, metabolism, and distribution studie s in animals or humans were identified.

3.1.2 Acute Toxicity

Studies in Animals

Inhalation
The 4-hour inhalation ALC (approxi mate lethal concentration) in male rats was 383,000 ppm. Labored breathing, lethargy, and unresponsiveness to sound were observed during exposure, but no clinical signs were noted foll owing exposure. No compound-relate d gross pathology changes were observed (DuPont Co., 1975). Ac ute inhalation studies ar e summarized in Table 3:OECD SIDS 1,1-DIFLUOROETHANE (HFC-152A)

UNEP PUBLICATIONS 10 Table 3 Acute Inhalation Studies in Animals

Species Duration of Exposure Concentration (ppm) Effect Reference

Rat (ChR-CD®) 4 hours 66,400 175,200 319,000 383,000 437,500 ALC = 383,000 ppm DuPont Co., 1975

Rat (strain not reported) 30 minutes 100,000 - 550,000 No postural reflex (200,000 ppm); no righting reflex (250,000 ppm); no corneal reflex (450,000 ppm); acute irritation of lungs ( ≥ 400,000 ppm); lethality ( ≥ 500,000 ppm) Lester and Greenberg, 1950

Rat (strain not reported) 2 hours 74,000 100,000 200,000 Occasional trembling and incoordination DuPont Co., 1951

Rat (ChR-CD) 15 minutes 1100 °C 1200 °C 1300 °C (pyrolysis products) Ptosis ( ≥ 1100 °C); apnea( ≥ 1100 °C); pale ears ( ≥ 1100 °C); hyperemia ( ≥ 1100 °C); dyspnea ( ≥ 1100 °C); irregular respiration ( ≥ 1100 °C); lacrimation ( ≥ 1100 °C); chromodacryorrhea ( ≥ 1100 °C); salivation ( ≥ 1100 °C); gasping (1300 °C); convulsions (1300°C) DuPont Co., 1966

Dog (Beagle) Not Reported 500,000 Light surgical anesthesia; no change in EKG Van Poznak and Artusio (1960).

Dermal

No acute dermal studies in animals were identified.

Oral
There was no reliable acute oral study.

Other Available Data
Cardiotoxicity studies in rats and dogs performe d at levels up to 40 % HFC-152a showed varying effects listed in Table 4 below (Simaan and Av iado, 1975; Aviado and Belej, 1975). Male beagle dogs were exposed to 50,000 or 150,000 ppm HFC- 152a in a cardiac sens itisation study. Marked responses, which included a cardiac arrhythmia that was considered to pose a serious threat to life, were observed in 3 of 12 dogs at 150,000 ppm. No response was observed at 50,000 ppm (DuPont Co., 1969; Reinhardt et al., 1971).OECD SIDS 1,1-DIFLUOROETHANE (HFC-152A)

UNEP PUBLICATIONS 11 Table 4 Cardiotoxicity Studies in Animals

Species Concentration (ppm) Effect Reference Dog (Mongrel) 200,000 Decrease in mean pulmonary arterial flow Simaan and Aviado, 1975

Dog (strain not reported) 25,000 - 200,000 Depression of force of contraction ( ≥ 100,000 ppm); displacement of ventricular function curve ( ≥ 100,000 ppm) Aviado and Belej, 1975

Studies in Humans

Inhalation

No reliable inhalation studies in humans were identified.

Dermal

No dermal studies in humans were identified.

Oral

No oral studies in humans were identified.
Other Routes of Exposure

No additional studies were identified.

Conclusion
Although there is no standard studies available, information from a lim ited study indicates that HFC-152a is of low acute oral toxicity. HFC-152a has low acute inhalation toxicity, with a 4-hour rat ALC of 383,000 ppm. As with most HFCs, HFC- 152a has the potential to produce cardiac sensitisation in dogs challenged simultaneously with high exposure concentrations (150,000 ppm) and high doses of exogenous epinephrine.

3.1.3 Irritation

In an acute- inhalation study in rats, there was considerab le effusion of fluid from the respiratory tract, indicative of acute irritati on of the lungs, at concentrations ≥ 400,000 ppm. When exposed at 100,000 ppm for 16 hours/day for 2 months, a mild di ffuse infiltration of r ound cells (suggestive of mild chronic irritation) was th e only finding noted (Lester and Greenberg, 1950). In a 2-year carcinogenicity study, nasal discharge in rats was reported (DuPont Co ., 1982; 1992), suggesting that chronic low level nasal irritation occurred.

3.1.4 Sensitisation
No skin or respiratory tract sensitisation studies in animals or humans were identified.OECD SIDS 1,1-DIFLUOROETHANE (HFC-152A)

UNEP PUBLICATIONS 12 3.1.5 Repeated Dose Toxicity

Studies in Animals

Inhalation
ChR-CD rats exposed to 100,000 ppm HFC-152a for 6 hours/day, 5 days/week for 2 weeks appeared to be anesthetized during exposure. Al though there was a slight increase in urinary fluoride following the last exposur e, no other effects were observe d in clinical, haematological, blood chemistry, or histopathology endpoints (DuPont Co., 1976). When exposed at 100,000 ppm for 16 hours/day for 2 months, a mi ld diffuse infiltration of round cells in the lung (suggestive of mild chronic irritation) was the only finding note d (Lester and Greenberg, 1950). During a 2-year inhalation study in Crl:CD ® Br rats, no adverse effects were observed at the 3-month interim evaluation point. The NOAEL was 25,000 ppm (67,500 mg/m 3 ) (DuPont Co., 1982; 1992). Additional results of the 2-year inhalation study ar e detailed in section 3.1.7 Carcinogenicity – in vivo studies in animals.

Dermal
No dermal repeated dose studies in animals were identified.

Oral
No oral repeated dose studies in animals were identified.

Studies in Humans
No repeated dose inhalation, dermal, or oral studies in humans were identified.

Conclusion
HFC-152a has low repeated dose toxi city. Indications of respirator y tract irritation were observed acutely at concentrations ≥ 400,000 ppm and after repeated concentrations of 100,000 ppm. HFC-152a had anaesthetic properties at a 100,000- ppm exposure level during a 2-week repeated dose inhalation study in rats . No other clinical, haematological, blood chemistry, or histopathology effects were observe d. No adverse effects were observed in rats following a 3-month inhalation exposure to 25,000 ppm HFC-152a.

3.1.6 Mutagenicity

Studies in Animals

In vitro Studies
HFC-152a was not mutagenic in the in vitro bacterial reverse mutation te st (Ames test), following OECD Guideline 471, in Salmonella typhimurium and Escherichia coli strains, when tested with or without metabolic activation (DuPont Co., 2000a).

In vivo Studies
HFC-152a was negative in a rat in vivo micronucleus assay following OECD Guideline 474 (DuPont Co., 2001b), but was positive in the Drosophila SLRL test (Garrett and Fuerst, 1974).OECD SIDS 1,1-DIFLUOROETHANE (HFC-152A)

UNEP PUBLICATIONS 13 Studies in Humans
HFC-152a showed evidence of weak clastogenicity, on ly in the absence of metabolic activation, in

an in vitro human lymphocyte chromosome aberration test following OECD Guideline 473 (DuPont, 2000b).

Conclusion
HFC-152a was not mutagenic in the in vitro bacterial reverse mutation test (Ames test) in Salmonella typhimurium and Escherichia coli strains. However, HFC-152a showed evidence of weak clastogenicity in an in vitro human lymphocyte chromosome aberration test. Further evaluation of the chromosome aberration potential using an in vivo micronucleus test produced negative results.

3.1.7 Carcinogenicity

In vitro Studies

No in vitro carcinogenicity studies were identified.

In vivo Studies in Animals

Inhalation
Male and female rats were exposed to 0, 2, 000, 10,000, or 25,000 ppm HFC-152a for 6 hours per day, 5 days per week for 2 years. During the cour se of the study, no differe nces in body weights or body weight gains were observed. Clinical signs observed incl uded ocular/nasal discharge, wet/stained perinea, stained body/face, and/or swollen ears.
Clinical chemistry effects noted throughout th e study included increased mean corpuscular volumes, increased serum bilirubin, increased hemato crits, and/or increased urobilinogin. In the absence of any abnormalities in hematopoietic tissues or red blood cells or changes in serum bilirubin, these observations, which would be c onsistent with a haemol ytic effect, provide inconclusive evidence of such a condition. A decrease in eosinophils and/or monocytes was observed. A dose-dependent increas e in urinary fluoride concentration, but no fluorosis was observed. An increase in serum creatinine and ur ine volume, and a decrease in urine osmolality were observed in female rats.
At the end of the 2-year study, no treatment-related differences in organ weights were observed in male rats, but significant organ we ight changes were observed in fema le rats at all concentrations with unclear biological significance . No treatment-related tumors were observed in male and female rats. Therefore, HFC-152a was not carcinogenic and did not produ ce life-shortening toxic effects (DuPont Co., 1982; 1992).

Dermal
No dermal carcinogenicity studies in animals were identified.

Oral
No oral carcinogenicity studies in animals were identified.

Studies in Humans
No carcinogenicity studies in humans were identified.OECD SIDS 1,1-DIFLUOROETHANE (HFC-152A)

UNEP PUBLICATIONS 14 Conclusion
HFC-152a was not carcinogenic to rats.

3.1.8 Toxicity for Reproduction

Studies in Animals
Effects on Fertility
Although no specific reproduction studi es have been performed with HFC-152a, histopathology of reproductive organs was examined in a 2- year chronic and carcinogenicity study. No histopathological or weight effect s on reproductive organs were obser ved in male and female rats exposed to HFC-152a via inhalatio n for 6 hours per day, 5 days per week for 2 years. The NOAEL was 25,000 ppm (DuPont Co., 1982).
Developmental Toxicity
Pregnant female rats were exposed to 0, 5,000, or 50,000 ppm HFC-152a for 6 hours per day on gestation days 6 - 15. No maternal or developmen tal toxicity was observed. The NOEL for maternal and developmental toxicity was 50,000 ppm, the highest level tested (DuPont Co., 1979).

Studies in Humans
Effects on Fertility
No reproduction studies in humans were identified.
Developmental Toxicity
No developmental toxicity studie s in humans were identified.

Conclusion
HFC-152a was not a developmenta l toxin in rats. No histopat hological or weight effects on reproductive organs were observed in male and female rats exposed to HFC-152a for 6 hours per day, 5 days per week for 2 years.

3.2 Initial Assessment for Human Health
HFC-152a has a very low potential for producing adve rse health effects in workers or the general population. HFC-152a has low acut e inhalation toxicity, with a rat 4-hour approximate lethal concentration of 383,000 ppm. Male beagle dogs treated with exogenous epinephrine were exposed to 50,000 or 150,000 ppm HFC-152a in a cardiac se nsitisation study. Marked responses, which included a cardiac arrhythmia, were observed in 3 of 12 dogs at 150,000 ppm. No response was observed at 50,000 ppm. Although significant orga n weight changes were observed at all concentrations tested after 90 days of exposure, the biological significance is unc lear. The NOAEL for developmental toxicity was 50,000 ppm (the highest dose tested), a nd no adverse effects on reproductive organ weight were observed following 3 months of exposure to 25,000 ppm. HFC152a was not mutagenic in the in vitro bact erial reverse mutation test (Ames test) in Salmonella typhimurium and Escherichia coli strains. However, HFC-152a showed evidence of weak clastogenicity in an in vitro human lymphocyte chromosome aberration test . Further evaluation of the chromosome aberration potential using an in vivo micronucleus test produced negative results. As no significant increase in tumors were obse rved, HFC-152a was not carcinogenic and did not produce life-shortening toxic effects at doses ranging from 2,000 to 25,000 ppm.OECD SIDS 1,1-DIFLUOROETHANE (HFC-152A)

UNEP PUBLICATIONS 15 

### 4 HAZARDS TO THE ENVIRONMENT

4.1 Aquatic Effects
Acute Toxicity Test Results
No ecotoxicological stud ies have been conducted with HFC-152a and there is very little or no ecotoxicology data for similar non-chlorinated, fluorocarbon compounds. The related compounds HFC-134a (1,1,1,2-tetrafluoroethane) and HFC-12 5 (1,1,1,2,2-pentafluoroethane) have been included here for comparison with HFC-152a as th ey are both fluorinated ethane substances, and test data for HFC134a are available. ECOSAR was used to predict the aquatic toxicity of these fluorocarbons to green algae, daphnids (planktoni c freshwater crustaceans), and fish (Table 5). ECOSAR predictions are based on actual toxicity te st data for classes of compounds with similar modes of action, i.e., narcosis in th e case of fluorocarbons. Predicted log 10 Kow values were used as input for the ECOSAR model. To help gauge the se nsitivity of the prediction to this parameter, ECOSAR predictions were made using 2 Kow va lues. The initial Kow value was based on the estimated value from the Syracuse Research Cor poration model except for the measured value of 0.75 for HFC-152a (Jow and Hansch, n.d.). The s econd Kow value was empiri cally selected to be approximately log 10 0.5 greater than the initial measured or estimated value.

Table 5 Aquatic Toxicity Values

Compound log 10 Kow (Estimated) Algae, 96-hr EC 50 (Estimated) (mg/L) Daphnid, 48-hr EC 50 (Estimated) (mg/L) Fish, 96-hr LC 50 (Estimated) (mg/L)

HFC-152a (1,1-Difluoroethane) (C 2 H 4 F 2 ) 0.75*
1.5 419
91 720
150 733
145

HFC-134a (1,1,1,2-Tetrafluoroethane) (C 2 H 2 F 4 ) 1.5
2.0 140
51 231
81 223
76

HFC-125 (1,1,1,2,2-Penta fluoroethane) (C 2 HF 5 ) 1.5
2.0 165
60 272
95 263
89

* measured value

The only test data available ar e for HFC-134a. Results of aqua tic testing of HFC-134a with daphnids and fish indicated that the daphnid 48-hour EC 50 was 980 mg/L and the 96-hour fish LC 50 was 450 mg/L (Stewart and Thompson, 1991; Thom pson, 1991). The lower measured log Kow of 0.75 would lead to estimated toxici ty values that would be even closer to the actual data. Based on the ECOSAR predictions, the actual toxicity test data, and the high Henry’s Law Constant for these compounds, HFC-152a is considered a lo w hazard to aquatic organisms.

Chronic Toxicity Test Results
No chronic toxicity studies were identified.
Toxicity to Microorganisms
No toxicity studies to microorganisms were identified.OECD SIDS 1,1-DIFLUOROETHANE (HFC-152A)

UNEP PUBLICATIONS 16 4.2 Terrestrial Effects
Acute Toxicity Test Results
No acute toxicity studies were identified.
Chronic Toxicity Test Results
No chronic toxicity studies were identified.

4.3 Other Environmental Effects

No additional data were identified.

4.4 Initial Assessment for the Environment
HFC-152a is expected to exist solely in the vapo ur-phase in the ambient atmosphere. Vapour-phase HFC-152a is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals with an atmospheric ha lf-life of about 472 days. The long atmospheric lifetime of this chemical suggests that some HFC-152a is expected to gradually diffuse into the stratosphere above the ozone layer, where it will sl owly degrade due to direct photol ysis from UV-C radiation (Nimitz and Skaggs, 1992; SRC, n.d.). HFC-152a is not exp ected to adsorb to sediment or particulate matter. Bioconcentration is expected to be low based on an estimated BCF value of approximately 2. The predicted toxicity of HFC-152a to aquatic organisms is low.



### 5 RECOMMENDATIONS
The chemical is currently of low priority for furthe r work, due to its low hazard profile. Its global warming potential is ackn owledged and is being addr essed by other programmes.OECD SIDS 1,1-DIFLUOROETHANE (HFC-152A)

UNEP PUBLICATIONS 17 

### 6 REFERENCES
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AIHA (1994). Workplace Environmental Exposure Level Guide , “1,1-Difluoroethane,” American Industrial Hygiene Associ ation, Fairfax, VA.
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CHEMLIST (1999). STN Regulatory Database.
Daubert TE and Danner RP (1989) . Physical and Thermodynamic Properties of Pure Chemicals Data Compilation, Taylor and Francis, Washington, DC (HSDB/5205).
Daubert, T. E. and R. P. Danner (1989b). Phys ical and Thermodynamic Properties of Pure Chemicals Data Compilation , Amer. Inst. Chem. Eng., Hemisphere Pub. Corp., New York (HSDB/5205).
DuPont (n.d.). Technical Informat ion Bulletin, DuPont Dymel® 152a.

DuPont Co. (1951). Unpublished Data, Haskell La boratory Report No. 2 - 52, “Inhalation Toxicity Studies of Various Freon Compounds” (December 26).
DuPont Co. (1966). Unpublished Data, “Acute I nhalation Toxicity of Fluorocarbon Pyrolysis Products” (November 2).
DuPont Co. (1969). Unpublished Data, Haskell Laboratory Report No. 354 - 69, “Cardiac Sensitization” (November 7).
DuPont Co. (1975). Unpublished Data, Haskell La boratory Report No. 699 - 75, “Acute Inhalation Toxicity” (November 18).
DuPont Co. (1976). Unpublished Data, Haskell Laboratory Report No. 158 - 76, “Subacute Two-Week Inhalation Toxicity” (March 2).
DuPont Co. (1979). Unpublished Data, Haskell Laboratory Report No. 437 - 79, “Embryotoxicity and Teratogenicity Studies in Ra ts with HFC-152a” (March 10).
DuPont Co. (1982). Unpublished Data, Haskell Laboratory Report No. 8 - 82, “Two-Year Inhalation Study with HFC-152a in Rats” (Novemb er 30) (also cited in TSCA Fiche OTS0520846 ).
DuPont Co. (1990). Unpublished Data, Haske ll Laboratory Report No. 524 - 90, “Approximate Lethal Dose (ALD) of HFC-152a in Rats” (September 26) (also cited in TSCA fiche OTS0530083 ).OECD SIDS 1,1-DIFLUOROETHANE (HFC-152A)

UNEP PUBLICATIONS 18 DuPont Co. (1992). Pathology Associates Inc., “Pat hology Peer Review of a Two-Year Inhalation Study of HFC-152a in CD Rats” (May 19).
DuPont Co. (1998). Materi al Safety Data Sheet No. DU001260 (November 4).
DuPont Co. (2000a). Unpublished Data, Haskell Laboratory Report No. DuPont-4032, “Bacterial Reverse Mutation Test: Plate Incorporati on Assay with a Gas” (September 15).
DuPont Co. (2000b). Unpublishe d Data, Haskell Laboratory Report No. DuPont-4016, “ In vitro Mammalian Chromosome Aberration Test in Human Lymphocytes” (August 25).
DuPont Co. (2001a). Initial Human Health and E nvironmental Screening Assessment for Dimethyl Ether (DME) Technical Summary (revised August 29).
DuPont Co. (2001b). Unpublished Data, Hask ell Laboratory Report No. DuPont-5426, “Rat Micronucleus Test” (May 18).
DuPont Co. (2002a). Material Safety Da ta Sheet 2187FR, SUVA 134a (November 4).
DuPont Co. (2002b). DuPont Product Literature, DuPont Formacel ® Z-2.

DuPont Co. (2003). Material Safety Data Sheet 6016FR, HFC-125 Sterilant (March 10).
DuPont Co. (2004). Material Sa fety Data Sheet 3024FR, Formace l Z-2 Blowing Agent (September 15).
DuPont Co. (2005). Refrigera nts Product Literature - Safety of DuPont SUVA ® and ISCEON ® 9 Series Refrigerants (AS-1).

DuPont Co. (2006). Unpublish ed Data, DSPEC database.

ECOSAR v0.99h.
Garrett S and Fuerst R (1974) . Sex-linked mutations in Drosophila after exposure to various mixtures of gas atmospheres. Environ. Res. , 7(3):286 - 293.
HSDB (2000). Hazardous Substa nce Data Bank (HSDB/5205).
IPCC SAR (1996). Climate Change 1995. The Science of Climate Change , Cambridge University Press, Great Britain.
IPCC/TAR (2001). Climat e Change 2001: The Scientific Basis , Cambridge University Press, New York, NY.
IPCC/TEAP (2005). Safeguard ing the Ozone Layer and the Global Climate System. Issues Related to Hydrofluorocarbons and Perfluorocarbons , Cambridge University Press, New York, NY.
Jow, P. and Hansch, C. (n.d.). Pomona College, unpublished analysis (cited in Hansch, C. and A. Leo (1995). Exploring QSAR Fundamentals a nd Applications in Chemistry and Biology , Amer. Chem. Soc., Washington, DC).
Kirk-Othmer Encyclopedia of Chemical Technology (1991). Volume 1, p. 677, John Wiley and Sons, New York.
Ko MKW and Sze ND (1997). Final Report on M odeling Studies to Asse ss the Environmental Effects of Alternative CFCs (TSCA Fiche OTS0558956 ).OECD SIDS 1,1-DIFLUOROETHANE (HFC-152A)

UNEP PUBLICATIONS 19 Lester D and Greenberg LA (1950). Acute and chronic toxicity of so me halogenated derivatives of methane and ethane. Arch. Ind. Hyg. Occup. Med. , 2:335 - 344.
Lewis, R. J., Sr. (1993). Hawley’s Condensed Chemical Dictionary , 12 th ed., p. 399, Van Nostrand Reinhold Co., New York.
Life Sciences Research (1992a). Unpublished Data, Report 91/0935, “HCFC-123: Determination of its EC 50 to Selenastrum capricornutum ” (April 22).
Life Sciences Research (1992b) . Unpublished Data, Report 91/0972, “HCFC-123: Acute Toxicity
to Daphnia magna ” (April 22).
Life Sciences Research (1992c). Unpublished Data, Report 91/0939, “HCFC-123: Acute Toxicity to Rainbow Trout” (April 22).
Life Sciences Research ( 1992d). Unpublished Data, Report 91/ PFE008/0477, “HCFC 123 (Liquid): Biotic Degradation Closed Bottle Test” (A pril 22) (cited in TSCA Fiche OTS0546420 ).
Lyman, W. J. et al. (1990). Handbook of Chemical Property Estimation Methods , pp. 4 - 9, 5 - 4, 5 - 10, 15 - 1 to 15 - 29, Amer. Chem. Soc., Washington, DC (HSDB/5205).
Mackay D, Di Guardo A, Paterson S, and Cowan CE (1996). Evaluating the environmental fate of a variety of types of chemicals using th e EQC model. Environ. Toxicol. Chem. , 15(9):1627 - 1637.

Meylan, W. M. and P. H. Howard (1991). Bond contribution method for estimating Henry’s Law constants. Environ. Toxicol. Chem. , 10:1283 - 1293 (HENRYWIN Software available from Syracuse Research corp., Environmenta l Science Center, Syracuse, NY 13210).

Meylan WM and Howard PH (1995). Atom/fragm ent contribution method for estimating octanolwater partition coefficients. J. Pharm. Sci. , 84:83 - 92.
Meylan WM and Howard PH (1996). Improved method for estimating water solubility from octanol/water partitio n coefficient. Environ. Toxicol. Chem. , 15:100 - 106.
NIER (2005). Survey on circulation volume and use pattern of 1,1-difluoroethane in Korea, 2005, National Institute of Enviro nmental Research, Korea.
Nimitz, J. S. and S. R. Skaggs (1992). Esti mating tropospheric lifetimes and ozone-depletion potentials of one- and two-carbon hydrofluorocarbons and hydrochlorofluoro carbons. Environ Sci. Technol. , 26:739 - 744 (HSDB/5205).
Reinhardt CF, Azar A, Maxfield ME, Smithe PE, Jr., and Mullin LS (1971). Cardiac arrhythmias and aerosol “sniffing.” Arch. Environ. Health , 22:265 - 279.
Ruelle, P. and U. W. Kesselring (1997). Aqueous so lubility prediction of environmentally important chemicals from the mobile order thermodynamics. Chemosphere , 34:275 - 298 (HSDB/5205).
Sax, N. I. and R. J. Lewis, Sr. (1987) . Hawley’s Condensed Chemical Dictionary , 11 th ed., p. 397, Van Nostrand Reinhold Co., New York.
Simaan JA and Aviado DM (1975). Hemodynamic effects of aerosol pr opellants. I. Cardiac depression in the dog. Toxicology , 5:127 - 138.
SRC (Syracuse Research Corpor ation) (n.d.). (HSDB/5205).OECD SIDS 1,1-DIFLUOROETHANE (HFC-152A)

UNEP PUBLICATIONS 20 Stewart, K. M. and R. S. Thompson (1991) . ICI Group Environmental Laboratory Report No. BL3908/B, ICI, UK (cited in Berends, A. G. et al. (1999). Arch. Environ. Contam. Toxicol.
, 36(2):146 - 151).
Thompson, R. S. (1991). ICI Group Environmen tal Laboratory Report No. BL4035/B, ICI, UK (cited in Berends, A. G. et al. ( 1999). Arch Environ. Contam. Toxicol. , 36(2):146 - 151).
Tobeta Y (1989). Test on biodegradability of HFC-134 a by microorganisms, Kurume Research Laboratories, Fukuoka, Japan (cited in Berends AG, de Rooij CG, Shin-ya S, and Thompson RS (1999). Biodegradation and ecotoxicity of HFCs and HCFCs. Arch. Environ. Contam. Toxicol.
, 36(2):146 - 151).
Tobeta Y (1992). Test on biodegr adability of HFC-32 a by microorg anisms (closed bottle test), Kurume Research Laboratories Report No. 12121, Fukuoka, Japan (cited in Berends AG, de Rooij CG, Shin-ya S, and Thompson RS (1999). Biodegrad ation and ecotoxicity of HFCs and HCFCs. Arch. Environ. Contam. Toxicol. , 36(2):146 - 151).
Van Poznak A and Artusio JF, Jr. (1960). Anesth etic properties of a se ries of fluorinated compounds. I. Fluorinated hydrocarb ons. Toxicol. Appl. Pharmacol. , 2:363 - 373.OECD SIDS 1,1-DIFLUOROETHANE (HFC-152A)

UNEP PUBLICATIONS 21 

# S I D S

Dossier

Existing Chemical : ID: 75-37-6 CAS No. : 75-37-6 Substance name : Ethane, 1,1-difluoro Synonym : HFC-152a

Producer related part Company : E. I. du Pont de Nemours and Company Creation date : 15.01.2003

Substance related part Company : E. I. du Pont de Nemours and Company Creation date : 15.01.2003

Status : Memo :

Printing date : 29.06.2006 Revision date : Date of last update : 29.06.2006

Number of pages : 80

Chapter (profile) : Chapter: 1, 2, 3, 4, 5, 6, 7, 8, 10 Reliability (profile) : Reliability: without reli ability, 1, 2, 3, 4 Flags (profile) : Flags: without flag, confidential, non confidential, WGK (DE), TALuft (DE), Material Safety Dataset, Risk Assessment, Directive 67/548/EEC, SIDSOECD SIDS 1,1-DIFLUOROETHANE (HFC-152A) 1. GENERAL INFORMATION ID: 75-37-6 DATE: 29.06.2006

UNEP PUBLICATIONS 22 1.0.1 APPLICANT AND COMPANY INFORMATION

Type : manufacturer Name : E. I. du Pont de Nemours and Company Contact person : Date : Street : 1007 Market Street Town : 19898 Wilmington, Delaware Country : United States Phone : Telefax : Telex : Cedex : Email : Homepage : 22.09.2005

1.0.2 LOCATION OF PRODUCTION SITE, IMPORTER OR FORMULATOR

Type : manufacturer Name of plant : DuPont- Corpus Christi Street : Town : Corpus Christi Country : United States Phone : Telefax : Telex : Cedex : Email : Homepage : 22.09.2005

1.0.3 IDENTITY OF RECIPIENTS

1.0.4 DETAILS ON CATEGORY/TEMPLATE

1.1.0 SUBSTANCE IDENTIFICATION

IUPAC Name : 1,1-Difluoroethane Smiles Code : FC(F)C Molecular formula : C 2 H 4 F 2 Molecular weight : 66.05 Petrol class : 29.06.2006 (10) (41)OECD SIDS 1,1-DIFLUOROETHANE (HFC-152A) 1. GENERAL INFORMATION ID: 75-37-6 DATE: 29.06.2006

UNEP PUBLICATIONS 23 1.1.1 GENERAL SUBSTANCE INFORMATION

Purity type : typical for marketed substance Substance type : organic Physical status : gaseous Purity : > 99.9 % w/w Colour : Clear, colorless Odour : Slight ethereal odor

Attached document : HFC-152a structure.bmp

31.03.2006 (26)

1.1.2 SPECTRA

Type of spectra : other Attached document : spectra.bmp

1.2 SYNONYMS AND TRADENAMES

Algofrene 67 15.01.2003

Dymel 152 15.01.2003

Dymel 152aOECD SIDS 1,1-DIFLUOROETHANE (HFC-152A) 1. GENERAL INFORMATION ID: 75-37-6 DATE: 29.06.2006

UNEP PUBLICATIONS 24 15.01.2003

Ethylene fluoride 15.01.2003

Ethylidene difluoride 15.01.2003

Ethylidene fluoride 15.01.2003

F152A 15.01.2003

FC152a 15.01.2003

FKW 152a 15.01.2003

Freon(R) 152a 15.01.2003

Genetron 100 15.01.2003

Genetron(R) 152a 15.01.2003

HFA 152a 15.01.2003

HFC-152a (name to be used throughout dossier) 23.03.2006

R 152a 30.05.2006 (10) (41)

1.3 IMPURITIES

Remark : Typical impurities in HFC-152a in clude low level (ppm) water, low level (ppb) residual HCl and/or HF acids. 29.06.2006 (33)

1.4 ADDITIVES

Remark : None.OECD SIDS 1,1-DIFLUOROETHANE (HFC-152A) 1. GENERAL INFORMATION ID: 75-37-6 DATE: 29.06.2006

UNEP PUBLICATIONS 25 14.06.2005

1.5 TOTAL QUANTITY

Remark : Production capacities are confidenti al, but are in excess of 5,000 metric tones (10 million pounds) per year. 29.06.2006 (34)

Remark : In Korea, estimated usage volume of 1,1-difluoroethane was 4.63, 4.85, and 3.14 tonnes/year in 2003, 2004, and 2005, respectively. 30.05.2006 (55)

1.6.1 LABELLING

Remark : Flammable gas. 30.05.2006 (25) (26)

1.6.2 CLASSIFICATION

1.6.3 PACKAGING

Memo : HFC-152a is sold in small packages (steel reusable cylinders ranging from 95 lbs to 2,000 lbs), and in bulk containers (ISO tanks, tank trailers, and rail cars). 29.06.2006 (31)

1.7 USE PATTERN

Remark : Approximately 80 % of HFC-152a is used as a propellant in aerosol products. It is present in the aerosol container, liquified under pressure as part of the aerosol form ulation. The vapor pressure of the 152a provides the driving force for dispensing the product.

Approximately 15 % of HFC-152a is used as a foam expansion agent. In foam manufacture HFC-152a is th e formulation ingredient used to foam the polymer. It is stored as an ingredient and feed to the foaming process directly. The HFC-152a is contained in process equipment and the closed-cell foam product, so that exposure to workers and consumer is negligible.

Approximately 5 % of HFC-152a is used for other potential uses, which include catalyst regeneratio n, as well as HFC-152a being blended with other fluorocarbons for use as in refrigeration systems.OECD SIDS 1,1-DIFLUOROETHANE (HFC-152A) 1. GENERAL INFORMATION ID: 75-37-6 DATE: 29.06.2006

UNEP PUBLICATIONS 26 The refrigerant blends are contained in closed pressurized containers and refrigeration systems. Poten tial for exposures would occur only during servicing or an abnormal situation such as a leak. 29.06.2006 (14) (30) (31)

Remark : In Korea, it is used in maintaining of a catalytic activity. 10.03.2006 (55)

1.7.1 DETAILED USE PATTERN

1.7.2 METHODS OF MANUFACTURE

Origin of substance : other Type : Remark : HFC-152a is produced by catalytic reaction of vinyl chloride with hydrofluoric acid. 30.05.2006 (54)

1.8 REGULATORY MEASURES

1.8.1 OCCUPATIONAL EXPOSURE LIMIT VALUES

Type of limit : other: AIHA WEEL 8-hour TWA Limit value : 1,000 other: ppm 30.05.2006 (1)

Type of limit : other: DuPont Acceptable Exposure Limit (AEL) 8-hour TWA Limit value : 1,000 other: ppm 30.05.2006 (25) (26)

1.8.2 ACCEPTABLE RESIDUES LEVELS

Proposed residues level : HFC-152a is volatile and generally leaves no residue.

Maximum residue level : mg/kg

29.06.2006 (41)

1.8.3 WATER POLLUTION

Remark : None. 14.06.2005OECD SIDS 1,1-DIFLUOROETHANE (HFC-152A) 1. GENERAL INFORMATION ID: 75-37-6 DATE: 29.06.2006

UNEP PUBLICATIONS 27 1.8.4 MAJOR ACCIDENT HAZARDS

Remark : Hazards include pressure, flammability, and potential for liquid exposure to cause frostbite. 30.05.2006 (25) (26)

1.8.5 AIR POLLUTION

Remark : HFC-152a has no ozone depletion potential, low global warming potential, and is not regulated as a volatile organic compound. 29.06.2006 (14)

1.8.6 LISTINGS E.G. CHEMICAL INVENTORIES

Type : EINECS Additional information : EINECS Inventory CAS RN: 75-37-6 Name: 1,1-Difluoroethane EINECS Inventory Number: 200-866-1 30.05.2006 (10)

1.9.1 DEGRADATION/TRANSFORMATION PRODUCTS

Remark : Hydrogen Fluoride. 23.03.2006 (25) (26)

Remark : The atmospheric degradation of hydrofluorocarbons (HFCs) have been extensively studied through di fferent research programmes from industry (AFEAS) and from EU (S tep halocside project (STEPHALOCSIDE/AFEAS, 1993) and were reported in the different WMO-UNEP scientific assessment s on stratospheric ozone (WMO, 1989; 1991; 1994) 30.05.2006 (67) (68)

1.9.2 COMPONENTS

1.10 SOURCE OF EXPOSURE

Source of exposure : Human: exposure by production Exposure to the : Remark : As a liquefied gas HFC-152a has to be handled in closed pressurizeOECD SIDS 1,1-DIFLUOROETHANE (HFC-152A) 1. GENERAL INFORMATION ID: 75-37-6 DATE: 29.06.2006

UNEP PUBLICATIONS 28 systems so that exposure typically does not occur in the manufacturing, except for during maintenance or an abnormal process situations, such as a leak. 29.06.2006 (31)

Source of exposure : Human: exposure by production Exposure to the : Remark : HFC-152a used to manufacture foam is contained within the foam, and remains in the foam for a long period of time. The HFC-152a will be disposed with the foam. 29.06.2006 (30)

Source of exposure : Human: exposure of the consumer/bystander Exposure to the : Remark : HFC-152a is used in aerosol cons umer personal care and household products and is dispensed with the product during use. Typically there is no 152a left in the container when it is disposed. 29.06.2006 (14)

Source of exposure : other Exposure to the : Remark : HFC-152a used in refrigerants is c ontained in the refrigeration system until such time as it is coll ected for recycle or disposal. 29.06.2006 (32)

1.11 ADDITIONAL REMARKS

1.12 LAST LITERATURE SEARCH

1.13 REVIEWSOECD SIDS 1,1-DIFLUOROETHANE (HFC-152A) 2. PHYSICO-CHEMICAL DATA ID: 75-37-6 DATE: 29.06.2006

UNEP PUBLICATIONS 29 2.1 MELTING POINT

Value : -117 °C Decomposition : no, at °C Sublimation : Method : Year : 1993 GLP : no data Test substance : as prescribed by 1.1 - 1.4 Reliability : (2) valid with restrictions 2g. Data from handbook or collection of data. Flag : Critical study for SIDS endpoint 14.06.2005 (47)

2.2 BOILING POINT

Value : -24.7 °C at Decomposition : Method : Year : 1993 GLP : no data Test substance : as prescribed by 1.1 - 1.4 Reliability : (2) valid with restrictions 2g. Data from handbook or collection of data. Flag : Critical study for SIDS endpoint 14.06.2005 (47)

Value : -25 °C at Decomposition : Method : Year : GLP : Test substance : as prescribed by 1.1 - 1.4 Reliability : (4) not assignable 4b. Secondary literature. 24.03.2006 (26)

2.3 DENSITY

Type : Value : .91 at 21 °C Method : Year : 1991 GLP : no data Test substance : as prescribed by 1.1 - 1.4 Result : Density is 0.91 g/mL at 21°C. Reliability : (2) valid with restrictionsOECD SIDS 1,1-DIFLUOROETHANE (HFC-152A) 2. PHYSICO-CHEMICAL DATA ID: 75-37-6 DATE: 29.06.2006

UNEP PUBLICATIONS 30 2g. Data from handbook or collection of data.

Flag : Critical study for SIDS endpoint 24.03.2006 (44)

Type : Value : .9 at 25 °C Method : Year : 1998 GLP : no data Test substance : as prescribed by 1.1 - 1.4

Remark : Density was determined for liqui d density, units are in mg/L. Reliability : (4) not assignable 4b. Secondary literature. 24.03.2006 (25)

2.3.1 GRANULOMETRY

2.4 VAPOUR PRESSURE

Value : 6,065.2 hPa at 25 °C Decomposition : Method : other (measured) Year : 1989 GLP : no data Test substance : as prescribed by 1.1 - 1.4 Reliability : (2) valid with restrictions 2g. Data from handbook or collection of data. Flag : Critical study for SIDS endpoint 31.03.2006 (12)

Value : 5,998.5 hPa at 25 °C Decomposition : Method : Year : GLP : Test substance : as prescribed by 1.1 - 1.4 Remark : Vapor pressure was repor ted as 87 psia at 25°C Reliability : (4) not assignable 4b. Secondary literature. 09.01.2006 (26)

Value : 4,343.7 hPa at 20 °C Decomposition : Method : Year : 1975 GLP : no dataOECD SIDS 1,1-DIFLUOROETHANE (HFC-152A) 2. PHYSICO-CHEMICAL DATA ID: 75-37-6 DATE: 29.06.2006

UNEP PUBLICATIONS 31 Test substance : as prescribed by 1.1 - 1.4 Remark : Vapor pressure was listed as 63 psig. Reliability : (4) not assignable 4e. Documentation insufficient for assessment. 23.03.2006 (5)

Value : 5,146.2 hPa at 25 °C Decomposition : Method : other (calculated) Year : GLP : no Test substance : as prescribed by 1.1 - 1.4 Reliability : (2) valid with restrictions 2f. Accepted calculation method. 30.03.2006 (37)

2.5 PARTITION COEFFICIENT

Partition coefficient : octanol-water Log pow : .75 at °C pH value : Method : other (measured) Year : GLP : no data Test substance : as prescribed by 1.1 - 1.4 Reliability : (2) valid with restrictions 2g. Data from handbook or collection of data. Flag : Critical study for SIDS endpoint 23.03.2006 (43)

Partition coefficient : octanol-water Log pow : 1.13 at °C pH value : Method : other (calculated) Year : 1995 GLP : no data Test substance : as prescribed by 1.1 - 1.4 Reliability : (2) valid with restrictions 2f. Accepted calculation method. 24.03.2006 (52)

2.6.1 SOLUBILITY IN DIFFERENT MEDIA

Solubility in : Value : 2,671 mg/l at 25 °C pH value : concentration : at °COECD SIDS 1,1-DIFLUOROETHANE (HFC-152A) 2. PHYSICO-CHEMICAL DATA ID: 75-37-6 DATE: 29.06.2006

UNEP PUBLICATIONS 32 Temperature effects :

Examine different pol. :

pKa : at 25 °C Description : Stable : Deg. product : Method : other: Estimated Year : 1996 GLP : no data Test substance : as prescribed by 1.1 - 1.4 Method : The method used is a new mew calculation method that outperformed other widely used general-purpose equations based on log Kow.

The program uses the following equation if a melting point is available:

log S = 0.693 - 0.96 log Kow - 0.0092(Tm-25) - 0.00314(MW) + summation of f1

The program uses the following equation if no melting point is available:

log S = 0.796 - 0.854 log Kow - 0.00728(MW) + summation of f1

where:

S= water solubility in moles/L Kow = n-octanol:water partition coefficient Tm = melting temperature in °C Summation of f1 = summation of all correction factors applicable to a given compound Reliability : (2) valid with restrictions 2f. Accepted calculation method. Flag : Critical study for SIDS endpoint 24.03.2006 (53)

Solubility in : Water Value : 17.8 g/l at 25 °C pH value : concentration : at °C Temperature effects : Examine different pol. :

pKa : at 25 °C Description : Stable : Deg. product : Method : Year : 1997OECD SIDS 1,1-DIFLUOROETHANE (HFC-152A) 2. PHYSICO-CHEMICAL DATA ID: 75-37-6 DATE: 29.06.2006

UNEP PUBLICATIONS 33 GLP : no data Test substance : as prescribed by 1.1 - 1.4 Reliability : (2) valid with restrictions 2f. Accepted calculation method. 11.01.2006 (57)

Solubility in : Water Value : 2.8 g/l at 25 °C pH value : concentration : at °C Temperature effects : Examine different pol. :

pKa : at 25 °C Description : Stable : Deg. product : Method : Year : 1998 GLP : no data Test substance : as prescribed by 1.1 - 1.4 Reliability : (4) not assignable 4b. Secondary literature. 09.01.2006 (25)

Solubility in : Water Value : 3,200 mg/l at 20 °C pH value : concentration : at °C Temperature effects : Examine different pol. :

pKa : at 25 °C Description : Stable : Deg. product : Method : other: experimental Year : 1982 GLP : no data Test substance : as prescribed by 1.1 - 1.4

Test substance : HFC-152a, purity not reported Reliability : (4) not assignable 4b. Secondary literature. 30.03.2006 (40)

2.6.2 SURFACE TENSIONOECD SIDS 1,1-DIFLUOROETHANE (HFC-152A) 2. PHYSICO-CHEMICAL DATA ID: 75-37-6 DATE: 29.06.2006

UNEP PUBLICATIONS 34 2.7 FLASH POINT

Value : < -50 °C Type : open cup Method : Year : 1998 GLP : no data Test substance : as prescribed by 1.1 - 1.4 Reliability : (4) not assignable 4b. Secondary literature. 09.01.2006 (25)

2.8 AUTO FLAMMABILITY

2.9 FLAMMABILITY

Result : other: 3.7 % - 18 % (in air) Method : Year : 1987 GLP : no data Test substance : as prescribed by 1.1 - 1.4 Reliability : (2) valid with restrictions 2g. Data from handbook or collection of data. 14.06.2005 (58)

Result : other: 3.9 % - 16.9 % (in air) Method : Year : 1998 GLP : no data Test substance : as prescribed by 1.1 - 1.4 Reliability : (4) not assignable 4b. Secondary literature. 09.01.2006 (25)

2.10 EXPLOSIVE PROPERTIES

2.11 OXIDIZING PROPERTIES

2.12 DISSOCIATION CONSTANT

2.13 VISCOSITY

2.14 ADDITIONAL REMARKSOECD SIDS 1,1-DIFLUOROETHANE (HFC-152A) 3. ENVIRONMENTAL FATE A ND PATHWAYS ID: 75-37-6 DATE: 29.06.2006

UNEP PUBLICATIONS 35 3.1.1 PHOTODEGRADATION

Type : other: modeled Light source : Light spectrum : nm Relative intensity : based on intensity of sunlight Deg. product : Method : other (calculated) Year : GLP : Test substance : as prescribed by 1.1 - 1.4 Method : According to a model of gas/particle partitioning of semivolatile organic compounds in the atmo sphere (Bidleman TF (1988). Atmospheric processes. Envir on. Sci. Technol., 22:361 - 367 (HSDB/5205), 1,1-difluoroethane is expected to exist solely as a vapor in the ambient atmosphere. Result : The rate constant of 3.4E+14 cm 3 /molecule-sec corresponds to an atmospheric half-life of about 472 days at an atmospheric concentration of 5E+5 hydroxyl radicals per cm 3 Atkinson R (1989). J. Phys. and Chem. Reference Data (HSDB/5205).

The long atmospheric lifetime of this chemical suggests some 1,1- difluoroethane is expected to gra dually diffuse into the stratosphere above the ozone layer where it will slowly degrade due to direct photolysis from UV-radi ation (Nimitz JS and Skaggs SR (1992). Estimating tropospheric lifetimes and ozone-depleti on potentials of one- and two-carbon hydrofluorocarbons and hydrochlorofluorocarbons. Envi ron Sci. Technol., 26:739 - 44 (HSDB/5205); SRC (Syracuse Res earch Corporation) (n.d.). (HSDB/5205).

1,1-Difluoroethane is not expected to undergo hydrolysis or direct photolysis in the troposphere due to the lack of functional groups to hydrolyze or absorb UV light at environmentally significant wavelengths (SRC (Syracuse Rese arch Corporation) (n.d.). (HSDB/5205). Reliability : (2) valid with restrictions 2g. Data from handbook or collection of data. Flag : Critical study for SIDS endpoint 04.04.2006 (41)

Deg. product : Method : other (calculated) Year : 1997 GLP : Test substance : as prescribed by 1.1 - 1.4 Remark : Using the AER (Atmospheric and Environmental Research) model, the lifetime global warming pot ential value for HFC-152a was calculated to be 1.5 years.OECD SIDS 1,1-DIFLUOROETHANE (HFC-152A) 3. ENVIRONMENTAL FATE A ND PATHWAYS ID: 75-37-6 DATE: 29.06.2006

UNEP PUBLICATIONS 36 Reliability : (2) valid with restrictions 2f. Accepted calculation method. 11.01.2006 (45)

Type : air Light source : Light spectrum : nm Relative intensity : based on intensity of sunlight Deg. product : Method : Year : 1992 GLP : no data Test substance : as prescribed by 1.1 - 1.4

Remark : Reaction of several HFCs and HCFCs with Cl radicals were studied. concentration of reagents and pr oducts were monitored by a FT-IR absorption spectrometer. Chlorine radicals were used in order to study the degradation pathways, as a surrogate of OH radicals.

RESULTS: Reaction of HFC-152a with Cl 2 for 20 minutes gave C(O)F 2 as product, with a yield of 100 %.

The proposed mechanism was:

Cl + CHF 2 CH 3 -> HCl + CHF 2 CH 2 CHF 2 CH 2 + O 2 -> CHF 2 CH 2 O 2 2CHF 2 CH 2 O 2 -> 2CHF 2 CH 2 O + O 2 CHF 2 CH 2 O -> HCH(O) +CHF 2 CHF 2 + O 2 -> CHF 2 O 2 2CHF 2 O 2 -> 2CHF 2 O + O 2 2CHF 2 O + O 2 -> C(O)F 2 + HO 2 Reliability : (2) valid with restrictions 2e. Study well documented, meets generally accepte d scientific principles, acceptable for assessment. Flag : Critical study for SIDS endpoint 31.03.2006 (36)

Deg. product : Method : other (calculated): AOPWIN v1.91 Year : GLP : no Test substance : as prescribed by 1.1 - 1.4 Result : Overall OH Rate Constant = 0.0348E-12 cm 3 /molecule-sec

Half-life = 307.163 days (12-hour day; 1.56E+6 OH/cm 3 ). Reliability : (2) valid with restrictions 2f. Accepted calculation method. 23.03.2006 (37)OECD SIDS 1,1-DIFLUOROETHANE (HFC-152A) 3. ENVIRONMENTAL FATE A ND PATHWAYS ID: 75-37-6 DATE: 29.06.2006

UNEP PUBLICATIONS 37 3.1.2 STABILITY IN WATER

Deg. product : Method : other (calculated): HYDROWIN v1.67 Year : GLP : no Test substance : as prescribed by 1.1 - 1.4 Result : R2 | R1-C-H | R3

X: -F (leaving halogen in R1) R1: -CH-F2 R2: -H R3: -H

Kb hydrolysis at atom #4: 1.157E-13 L/mol-sec

Total Kb for pH > 8 at 25 °C: 1.157E-13 L/mol-sec Kb half-Life at pH 8: 1.898E+11 years Kb Half-Life at pH 7: 1.898E+12 years

The rate constant estimated for the Alkyl Halide DOES NOT include the neutral hydrolysis rate consta nt! For some alkyl halides, the neutral rate constant is the dominan t hydrolysis rate at environmental pHs. If the neutral ra te constant is important, the HYDRO estimated rate will under estimate the actual rate. Reliability : (2) valid with restrictions 2f. Accepted calculation method. Flag : Critical study for SIDS endpoint 08.03.2006 (37)

3.1.3 STABILITY IN SOIL

3.2.1 MONITORING DATA

3.2.2 FIELD STUDIES

3.3.1 TRANSPORT BETWEEN ENVIRONMENTAL COMPARTMENTS

Type : fugacity model level IIIOECD SIDS 1,1-DIFLUOROETHANE (HFC-152A) 3. ENVIRONMENTAL FATE A ND PATHWAYS ID: 75-37-6 DATE: 29.06.2006

UNEP PUBLICATIONS 38 Media : other: air-water-soil-sediment

Air : % (Fugacity Model Level I) Water : % (Fugacity Model Level I) Soil : % (Fugacity Model Level I) Biota : % (Fugacity Model Level II/III) Soil : % (Fugacity Model Level II/III) Method : other: Mackay, Level III Fugacity Model Year : Method : Calculated according to Mackay, Level III, Syracuse Research Corporation Epiwin Version 3.05 Em issions to Air (1,000 kg/hr) EPA Model Defaults.

Data Used: Molecular Weight: 66.05 Henry's Law Constant: 0.0203 atm-m 3 /mole (Henry database) Vapor Pressure: 4,550 mmHg at 25 °C (user entered) Log Kow: 0.75 (Jow and Hansch, n.d.) Soil Koc: 2.31 (calculated by model) Result : Distributions: Air 99.9 % Water 0.111 % Soil 0.0113 % Sediment 0.000214 % Reliability : (2) valid with restrictions 2f. Accepted calculation method. 30.03.2006 (43) (49) (50) (51)

Type : Media : Air : % (Fugacity Model Level I) Water : % (Fugacity Model Level I) Soil : % (Fugacity Model Level I) Biota : % (Fugacity Model Level II/III) Soil : % (Fugacity Model Level II/III) Method : other: modeled Year :

Result : Estimated half-lives for a model ri ver (1 m deep, flowing 1 m/sec, wind velocity of 3 m/sec) and m odel lake (1 m deep, flowing 0.05 m/sec, wind velocity of 0.5 m/sec) are 2 and 77 hours, respectively (Lyman et al., 1990; SRC, n.d.). Based on a recommended classification scheme (Swann et al ., 1983), an estimated Koc value of 60 (SRC, n.d.), determined from a measured log Kow of 0.75 (Jow and Hansch, n.d.) and a recommen ded regression-derived equation (Lyman et al., 1990), 1,1-difluoroethane is not expected to adsorb to suspended solids and sediment in water (SRC, n.d.). 1,1- Difluoroethane is expected to volatilize rapidly from water surfaces (Lyman et al., 1990; SRC, n.d.) based on an estimated Henry's Law constant of 0.02 atm-m 3 /mole (Daubert and Danner, 1989); Ruelle and Kesselring, 1997; SRC, n.d.).OECD SIDS 1,1-DIFLUOROETHANE (HFC-152A) 3. ENVIRONMENTAL FATE A ND PATHWAYS ID: 75-37-6 DATE: 29.06.2006

UNEP PUBLICATIONS 39 References for modeling:

Lyman WJ, Reehl WF, and Rosenblatt DH (1990). Handbook of Chemical Property Estimation Methods, pp. 4 - 9, 5 - 4, 5 - 10, 15 - 1 to 15 - 29, Amer. Chem. Soc., Washington, DC (HSDB/5205)

SRC (Syracuse Research Corpor ation) (n.d.). (HSDB/5205).

Swann RL, Laskowski DA, McCall PJ, Vander Kuy K, and Dishburger HJ (1983). A rapid me thod for the estimation of the environmental parameters octanol/w ater partition coefficient, soil sorption constant, water to air ratio, and water solubility. Res. Rev., 85:23 (HSDB/5205).

Jow P and Hansch C (n.d.). Pomo na College, unpublished analysis (cited in Hansch C and Leo A (1995). Exploring QSAR Fundamentals and Applications in Chemistry and Biology, Amer. Chem. Soc., Washington, DC (HSDB/5205).

Daubert TE and Danner RP (1989). Physical and Thermodynamic Properties of Pure Chemicals Data Compilation, Amer. Inst. Chem. Eng., Hemisphere Pub. Corp., New York (HSDB/5205).

Ruelle P and Kesselring UW (1997). Aqueous solubility prediction of environmentally important chemicals from the mobile order thermodynamics. Chemosphere, 34:275 - 298 (also cited in HSDB/5205). Reliability : (2) valid with restrictions 2f. Accepted calculation method. 30.03.2006 (41)

3.3.2 DISTRIBUTION

Method : Determined from a measured log Kow of 0.75. Remark : Estimated Koc = 60 Reliability : (2) valid with restrictions 2f. Accepted calculation method. 11.01.2006 (60)

Remark : Estimated Henry's Law constant = 0.02 atm-m 3 /mole (2026.5 Pam 3 /mol), determined from a vapor pressure of 4,550 mmHg and water solubility of 17,800 mg/L. Reliability : (2) valid with restrictions 2f. Accepted calculation method. 04.04.2006 (11) (57) (60)

Method : PCKOC v1.66OECD SIDS 1,1-DIFLUOROETHANE (HFC-152A) 3. ENVIRONMENTAL FATE A ND PATHWAYS ID: 75-37-6 DATE: 29.06.2006

UNEP PUBLICATIONS 40 Remark : Estimated Koc = 35 Reliability : (2) valid with restrictions 2f. Accepted calculation method. 30.03.2006 (37)

3.4 MODE OF DEGRADATION IN ACTUAL USE

3.5 BIODEGRADATION

Type : aerobic Inoculum : other: filtered sample of seconda ry effluent from a sewage plant Contact time : Degradation : 4 (±) % after 28 day(s) Result : other: not readily biodegradable Deg. product : Method : OECD Guide-line 301 D "Ready Biode gradability: Closed Bottle Test" Year : 1989 GLP : no data Test substance : other TS Method : The test was performed in accor dance with OECD guideline 301D and EEC guideline C.6. A solution of the test substance in mineral medium was inoculated with a filte red sample of secondary effluent from a sewage plant. The initia l test substance concentration was 1.44 mg/L. Bottles were completely filled, closed, and incubated in the dark for a period of 28 days at 20 ± 1 °C. The decrease of the oxygen content in the medium over a period of 28 days was used to calculate the percentage of aerobic biodegradation. To correct for the endogenous oxygen consumption of the inoculum, blanks with secondary effluent but without test substance were included in the
test.

The biodegradation was also based on the gas chromatgraphic analysis of the test substance in th e solutions at the end of the study. Measured concentrations in bottle s with mineral medium and test substance were compared with concen trations in bottles with mineral medium, test substance, and in oculum. The biodegradation was determined using the difference in the measured concentration. To verify the procedures used, the biodegradability of a reference compound (sodium n-dodecylsulfate) was measured. Result : The TOD (based on biomass integral) was 0.7. The measured decrease of oxygen content was 0.03 mg/L. Test substance : other TS: HFC-134a (1,1,1,2-tetrafl uoroethane), purity not specified Reliability : (1) valid without restriction 1a. GLP guideline study. 30.03.2006 (63)OECD SIDS 1,1-DIFLUOROETHANE (HFC-152A) 3. ENVIRONMENTAL FATE A ND PATHWAYS ID: 75-37-6 DATE: 29.06.2006

UNEP PUBLICATIONS 41 Type : aerobic Inoculum : other: filtered sample of seconda ry effluent from a sewage plant Contact time : Degradation : 8 (±) % after 28 day(s) Result : other: not readily biodegradable Deg. product : Method : OECD Guide-line 301 D "Ready Biode gradability: Closed Bottle Test" Year : 1992 GLP : no data Test substance : other TS Method : The test was performed in accor dance with OECD guideline 301D and EEC guideline C.6. A solution of the test substance in mineral medium was inoculated with a filte red sample of secondary effluent from a sewage plant. The initia l test substance concentration was 3.38 mg/L. Bottles were completely filled, closed, and incubated in the dark for a period of 28 days at 20 ± 1 °C. The decrease of the oxygen content in the medium over a period of 28 days was used to calculate the percentage of aerobic biodegradation. To correct for the endogenous oxygen consumption of the inoculum, blanks with secondary effluent but without test substance were included in the
test.

The biodegradation was also base d on the gas chromatgraphic analysis of the test substance in th e solutions at the end of the study. Measured concentrations in bottle s with mineral medium and test substance were compared with concen trations in bottles with mineral medium, test substance, and in oculum. The biodegradation was determined using the difference in the measured concentration. To verify the procedures used, the biodegradability of a reference compound (sodium n-dodecylsulfate) was measured. Result : The TOD (based on biomass inte gral) was 2.1. The measured decrease of oxygen content was 0.16 mg/L. Test substance : other TS: HFC-32 (difluoromet hane), purity not specified Reliability : (1) valid without restriction 1a. GLP guideline study. 30.03.2006 (64)

3.6 BOD5, COD OR BOD5/COD RATIO

3.7 BIOACCUMULATION

BCF : 2 Elimination : Method : other: Modeled Year : GLP :OECD SIDS 1,1-DIFLUOROETHANE (HFC-152A) 3. ENVIRONMENTAL FATE A ND PATHWAYS ID: 75-37-6 DATE: 29.06.2006

UNEP PUBLICATIONS 42 Test substance : as prescribed by 1.1 - 1.4 Method : BCF was determined using a measured log Kow of 0.75 (Jow P and Hansch C (n.d.). Pomona College, unpublished analysis (cited in Hansch C and Leo A (1995). Expl oring QSAR Fundamentals and Applications in Chemistry and Biology, Amer. Chem. Soc., Washington, DC)) and a recommen ded regression-derived equation (Lyman WJ, Reehl WF, and Rosenblatt DH (1990). Handbook of Chemical Property Estimation Methods, pp. 4 - 9, 5 - 4, 5 - 10, 15 - 1 to 15 - 29, Amer. Chem. Soc., Washington, DC (HSDB/5205)).

Result : According to a classification sche me (Franke C, Studinger G, Berger G, Böhling S, Bruckmann U, C ohors-Fresenborg U, and Jöhncke U (1994). The assessment of bio accumulation. Chemosphere, 29:1501- 1514 (HSDB/5205)), the estimated BC F value of 2 suggests that bioconcentration in aquatic or ganisms is low SRC (Syracuse Research Corporation) (n.d.). (HSDB/5205)). Reliability : (2) valid with restrictions 2f. Accepted calculation method. 09.01.2006 (41)

3.8 ADDITIONAL REMARKSOECD SIDS 1,1-DIFLUOROETHANE (HFC-152A) 4. ECOTOXICITY ID: 75-37-6 DATE: 29.06.2006

UNEP PUBLICATIONS 43 4.1 ACUTE/PROLONGED TOXICITY TO FISH

Type : other: Modeled Species : other: Fish Exposure period : 96 hour(s) Unit : mg/l LC 50 : 733 Method : other: calculated ECOSAR v0.99h Year : GLP : Test substance : as prescribed by 1.1 - 1.4 Remark : log 10 Kow of 0.75 Reliability : (2) valid with restrictions 2f. Accepted calculation method. Flag : Critical study for SIDS endpoint 09.01.2006 (35)

Type : semistatic Species : Oncorhynchus mykiss (Fish, fresh water) Exposure period : 96 hour(s) Unit : mg/l LC 50 : 450 Limit test : Analytical monitoring : yes Method : Directive 84/449/EEC, C.1 "A cute toxicity for fish" Year : 1991 GLP : yes Test substance : other TS Method : To prevent loss of the substance from the solutions, closed vessels were used. The test was conducted under semistatic conditions with daily renewal of the test solutions . Chemical analyses of the test solutions were performed to check the exposure of the organisms to the test chemical. If the diffe rence between nominal and mean measured concentrations was more th an 20 %, the endpoint of the test was based on mean measured concentrations.

Saturated solutions were prepared. HFC-134a was bubbled for 60 minutes through medium via a sintered glass diffuser. This solution was diluted with oxygen saturated solutions to restore the amount of oxygen in the test solutions.

The EC 50 value was determined using the method of Stephan, 1977 (Stephan, C. E. (1977). Methods for calculating an LC 50 . Proceedings first annual symposium on aquatic toxi cology. In: Mayer, F. L. and J. L. Hamelink (eds). Aquatic toxico logy and hazard evaluation, ASTM STP 634:65-84). Remark : Data provided on analog chemi cal (similar non-chlorinated fluorocarbon) to strengthen the us e of ECOSAR to characterize the toxicity of HFC-152a.OECD SIDS 1,1-DIFLUOROETHANE (HFC-152A) 4. ECOTOXICITY ID: 75-37-6 DATE: 29.06.2006

UNEP PUBLICATIONS 44 Result : No mortality was found after 96 hours of exposure at mean measured concentrations of 180 and 300 mg/L, but symptoms of toxicity were observed at these concentrations (d ark discoloration, quiescence, and sounding behavior). No symptoms of toxicity occurred at a mean measured concentration of 87 mg/L. Test substance : other TS: HFC-134a (1,1,1,2-tetrafl uoroethane), purity not specified Reliability : (2) valid with restrictions 2a. Guideline study without detailed documentation. Flag : Critical study for SIDS endpoint 04.04.2006 (62)

4.2 ACUTE TOXICITY TO AQUATIC INVERTEBRATES

Type : other: Modeled Species : other: Daphnid Exposure period : 48 hour(s) Unit : mg/l EC 50 : 720 Method : other: calculated ECOSAR v0.99h Year : GLP : Test substance : as prescribed by 1.1 - 1.4 Remark : log10 Kow of 0.75 Reliability : (2) valid with restrictions 2f. Accepted calculation method. Flag : Critical study for SIDS endpoint 23.03.2006 (35)

Type : static Species : Daphnia magna (Crustacea) Exposure period : 48 hour(s) Unit : mg/l EC 50 : 980 Analytical monitoring : yes Method : Directive 84/449/EEC, C.2 "A cute toxicity for Daphnia" Year : 1991 GLP : yes Test substance : other TS Method : To prevent loss of the substance from the solutions, closed vessels were used. The test was conducted under static conditions. Chemical analyses of the test solutions were performed to check the exposure of the organisms to the test ch emical. If the difference between nominal and mean measured concentrations was more than 20 %, the endpoint of the test was based on mean measured concentrations.

Saturated solutions were prepared. HFC-134a was bubbled for 60 minutes through medium via a sintered glass diffuser. This solution was diluted with oxygen saturated solutions to restore the amount ofOECD SIDS 1,1-DIFLUOROETHANE (HFC-152A) 4. ECOTOXICITY ID: 75-37-6 DATE: 29.06.2006

UNEP PUBLICATIONS 45 oxygen in the test solutions.

The EC 50 value was determined using the method of Stephan, 1977 (Stephan, C. E. (1977). Methods for calculating an LC 50 . Proceedings first annual symposium on aquatic toxi cology. In: Mayer, F. L. and J. L. Hamelink (eds). Aquatic toxico logy and hazard evaluation, ASTM STP 634:65 - 84). Remark : Data provided on analog chemic al (similar non-chlorinated fluorocarbon) to strengthen the use of ECOSAR to characterize the toxicity of HFC-152a. Result : The acute test with Daphnia magn a showed a steep concentrationimmobility curve. At mean measured concentrations of 870 and 1,100 mg/L the immobility after 48 hours was 0 and 100 %, respectively. Test substance : other TS: HFC-134a (1,1,1,2-tetrafl uoroethane), purity not specified Reliability : (2) valid with restrictions 2a. Guideline study without detailed documentation. Flag : Critical study for SIDS endpoint 04.04.2006 (61)

4.3 TOXICITY TO AQUATIC PLANTS E.G. ALGAE

Species : other algae Endpoint : other: Modeled: Inhibition of gr owth measured as number of cells Exposure period : 96 hour(s) Unit : mg/l EC 50 : 419 Method : other: calculated ECOSAR v0.99h Year : GLP : Test substance : as prescribed by 1.1 - 1.4 Remark : log 10 Kow of 0.75 Reliability : (2) valid with restrictions 2f. Accepted calculation method. Flag : Critical study for SIDS endpoint 09.01.2006 (35)

4.4 TOXICITY TO MICROORGANISMS E.G. BACTERIA

4.5.1 CHRONIC TOXI CITY TO FISH

4.5.2 CHRONIC TOXICITY TO AQUATIC INVERTEBRATESOECD SIDS 1,1-DIFLUOROETHANE (HFC-152A) 4. ECOTOXICITY ID: 75-37-6 DATE: 29.06.2006

UNEP PUBLICATIONS 46 4.6.1 TOXICITY TO SEDIMENT DWELLING ORGANISMS

4.6.2 TOXICITY TO TERRESTRIAL PLANTS

4.6.3 TOXICITY TO SOIL DWELLING ORGANISMS

4.6.4 TOX. TO OTHER NON MAMM. TERR. SPECIES

4.7 BIOLOGICAL EFFECTS MONITORING

4.8 BIOTRANSFORMATION AND KINETICS

4.9 ADDITIONAL REMARKSOECD SIDS 1,1-DIFLUOROETHANE (HFC-152A) 5. TOXICITY ID: 75-37-6 DATE: 29.06.2006

UNEP PUBLICATIONS 47 5.0 TOXICOKINETICS, METABOLISM AND DISTRIBUTION

5.1.1 ACUTE ORAL TOXICITY

Type : other: Approximate Lethal Dose (ALD) Value : > 1,500 mg/kg bw Species : rat Strain : other: Crl:CD(R)BR Sex : male Number of animals : 6 Vehicle : other: corn oil Doses : 200, 300, 450, 670, 1,000, 1,500 mg/kg Method : other Year : 1990 GLP : yes Test substance : as prescribed by 1.1 - 1.4 Method : Food and water were available to the rats ad libitum. Rats were approximately 7 weeks old upon arri val. HFC-152a was dissolved in corn oil (23 or 46 mg/mL) and kept under pressure in aerosol cans that were maintained in an ice bath. The cans were fitted with a septum from which the dosing so lution was withdrawn. One rat per dose group was administered the compound by gavage. Dose levels were 200, 300, 450, 670, 1,000, or 1,500 mg/kg. Doses of 450 mg/kg and above were administered in 2 portions about 15 minutes apart. A dose of 1,500 mg/kg was the maximum feasible dose. Rats were observed for mortality, clinical signs, and body weight over a 14-day period. Result : No mortality occurred at any dose level. Immediately after dosing, abdominal distention rela ted to gas evolution was evident in all rats. Lethargy was observed at 1,000 and 1,500 mg/kg. High carriage, wet and yellow stained perineum, and dia rrhea were observed in all rats 1 to 2 days post-dosing. No other toxicologically significant effects occurred. Test substance : HFC-152a, purity 99.9 % Reliability : (3) invalid 3c. Unsuitable test system. 09.01.2006 (23)

5.1.2 ACUTE INHALATION TOXICITY

Type : other: Approximate Lethal Concentration (ALC) Value : 383,000 ppm Species : rat Strain : other: ChR-CD(R) Sex : male Number of animals : 30 Vehicle :OECD SIDS 1,1-DIFLUOROETHANE (HFC-152A) 5. TOXICITY ID: 75-37-6 DATE: 29.06.2006

UNEP PUBLICATIONS 48 Doses : 66,400, 175,200, 319,000, 383,000, 437,500 ppm Exposure time : 4 hour(s) Method : other Year : 1975 GLP : no Test substance : as prescribed by 1.1 - 1.4 Method : Groups of 6 rats were exposed whole-body to 66,400, 175,200, 319,000, 383,000, and 437,500 ppm. The age of the rats was not specified, however, the initial body weight of the rats was 240 - 297 grams. The gas was regulated through a calibrated flowmeter into a mixing chamber. Regulated flows of air and/or oxygen were used as the carrier gas from the mixing chamber to the exposure chamber. At the 66,400 ppm level, air was used as the carrier gas. At 175,200 ppm, chamber concentrations were 16 – 17 %. Oxygen level was maintained at about 20 % for the exposure concentrations at or above 319,000 ppm. Chamber atmospheres were sampled at 30-minute intervals and analyzed by thermal conductivity gas chromatography.Clinical observations were recorded during the exposure and postexposure. Gross pathology was perf ormed on surviving rats after a 14-day observation period. Remark : Reliability: High because a scientifically defensible or guidelined method was used. Result : Mortality ratio of 1/6 occurred at 383,000 ppm and 2/6 occurred at 437,500 ppm. Labored breathing, lethargy, and unresponsiveness to sound were observed during exposure. No clinical signs were noted following exposure. No compound-related gross pathology changes were observed. Test substance : HFC-152a, purity 99.9 % Reliability : (1) valid without restriction 1d. Test procedure in accordance with generally accepted scientific standards and described in sufficient detail. Flag : Critical study for SIDS endpoint 09.01.2006 (18)

Type : other: Cardiac Sensitization Value : 150,000 ppm Species : dog Strain : Beagle Sex : male Number of animals : 24 Vehicle : Doses : 50,000, 150,000 ppm Exposure time : 5 minute(s) Method : other Year : 1969 GLP : no Test substance : as prescribed by 1.1 - 1.4 Method : Beagle dogs (12/group) were exposed to 50,000 or 150,000 ppm for 5 minutes. The age of the dogs was not specified. The dogs received a control injection of epinephrine (0.008 mg/kg) intravenously, prior toOECD SIDS 1,1-DIFLUOROETHANE (HFC-152A) 5. TOXICITY ID: 75-37-6 DATE: 29.06.2006

UNEP PUBLICATIONS 49 exposure and a challenge injection (same dosage) after breathing the test material for 5 minutes. The desired concentrations (calculated) were achieved by delivering a mete red volume of the vapor or gas from the pressured cylinder containi ng the test substance and diluting it with a known volume of air. The flow meter used for monitoring the test compound had been previ ously calibrated with the compound by a dry gas test meter.

The dogs were trained to maintain a standing position while lightly supported by a cloth sling with a hole for each leg, to wear a mask over their snout, and to accept a venupuncture. An electrocardiogram was recorded continuously during the experimental procedure. Result : Marked responses (a cardiac arrhythmia which was considered to pose a serious threat to life) were ob served in 3 of the 12 dogs at the 150,000 ppm level. No response was seen at the 50,000 ppm level. Test substance : HFC-152a, purity 99.99 % Reliability : (2) valid with restrictions 2e. Study well documented, meets generally accepte d scientific principles, acceptable for assessment. Flag : Critical study for SIDS endpoint 24.03.2006 (17) (56)

Type : other Value : Species : rat Strain : other: albino Sex : no data Number of animals : Vehicle : Doses : ranged from 100,000 to 550,000 ppm Exposure time : 30 minute(s) Method : other Year : 1950 GLP : no Test substance : as prescribed by 1.1 - 1.4 Method : Rats were exposed for a maximum of 30 minutes to concentrations ranging from 100,000 to 550,000 ppm. Result : The postural reflex was lost at 200,000 ppm, righting reflex was lost at 250,000 ppm, and the corneal reflex was lost at 450,000 ppm. Exposure to concentrations > 500,000 ppm was lethal in 10 - 25 minutes. At concentrations of 400,000 ppm or higher, there was considerable effusion of fluid from th e respiratory tract, indicative of acute irritation of the lungs. Test substance : HFC-152a, purity not reported Reliability : (2) valid with restrictions 2e. Study well documented, meets generally accepte d scientific principles, acceptable for assessment. 04.04.2006 (46)

Type : otherOECD SIDS 1,1-DIFLUOROETHANE (HFC-152A) 5. TOXICITY ID: 75-37-6 DATE: 29.06.2006

UNEP PUBLICATIONS 50 Value : Species : rat Strain : no data Sex : no data Number of animals : 2 Vehicle : Doses : 74,000, 100,000, or 200,000 ppm Exposure time : 2 hour(s) Method : other Year : 1952 GLP : no Test substance : as prescribed by 1.1 - 1.4 Result : Occasional trembling and incoordina tion were observed during the exposure. No gross or pathological changes were found in the rats 4 – 7 days post-exposure. Test substance : HFC-152, purity not specified Reliability : (2) valid with restrictions 2e. Study well documented, meets generally accepte d scientific principles, acceptable for assessment. 11.01.2006 (15)

Type : other: Approximate Lethal Concentra tion (ALC) (Lethality in 2 - 4 of 6 rats) Value : 64,000 ppm Species : rat Strain : Sherman Sex : male/female Number of animals : 6 Vehicle : Doses : Exposure time : 4 hour(s) Method : other Year : 1949 GLP : no Test substance : as prescribed by 1.1 – 1.4 Result : Inhalation of 64,000 ppm HFC-152a fo r 4 hours killed 2/6, 3/6, or 4/6
rats. Test substance : HFC-152a, purity not reported Reliability : (2) valid with restrictions 3a. Documentation insufficient for assessment. 04.04.2006 (9)

Type : LC 50 Value : 977,200 ppm Species : mouse Strain : no data Sex : no data Number of animals : Vehicle : Doses :OECD SIDS 1,1-DIFLUOROETHANE (HFC-152A) 5. TOXICITY ID: 75-37-6 DATE: 29.06.2006

UNEP PUBLICATIONS 51 Exposure time : 2 hour(s) Method : other Year : 1982 GLP : no data Test substance : as prescribed by 1.1 - 1.4 Result : The LC 50 was 977,200 ppm (896,000 - 1,065,000 ppm). Narcotic effects were observed at the LC 50
. Test substance : HFC-152a, purity not reported Reliability : (4) not assignable 4b. Secondary literature. 24.03.2006 (42)

Type : other Value : Species : dog Strain : no data Sex : no data Number of animals : 3 Vehicle : Doses : 500,000 ppm Exposure time : Method : other Year : 1960 GLP : no Test substance : as prescribed by 1.1 - 1.4 Method : Three dogs inhaled HFC-152a at a concentration of 500,000 ppm. Two dogs also received atropine an d succinylcholine intravenously. Result : Light surgical anesthesia, with no change in EKG, resulted. Test substance : HFC-152a, purity not reported Reliability : (2) valid with restrictions 2e. Study well documented, meets generally accepte d scientific principles, acceptable for assessment. 11.01.2006 (65)

Type : other Value : Species : human Strain : Sex : Number of animals : Vehicle : Doses : 50,000 ppm Exposure time : Method : other Year : 1960 GLP : no data Test substance : as prescribed by 1.1 – 1.4 Result : HFC-152a was inhaled br iefly by several volunteers, who noted good analgesia and impending loss of consciousness. Test substance : HFC-152a, purity not reportedOECD SIDS 1,1-DIFLUOROETHANE (HFC-152A) 5. TOXICITY ID: 75-37-6 DATE: 29.06.2006

UNEP PUBLICATIONS 52 Reliability : (3) invalid 3a. Documentation insufficient for assessment. 11.01.2006 (65)

Type : other: Acute Inhalation Toxi city of Pyrolysis Products Value : Species : rat Strain : other: CHR-CD Sex : male Number of animals : Vehicle : Doses : various temperatures (1,100, 1,200, and 1,300 °C) Exposure time : 15 minute(s) Method : Year : 1966 GLP : no Test substance : as prescribed by 1.1 - 1.4 Method : Rats were exposed for 15 minutes to vapors produced by heating HFC-152a to various temperatures (1,100, 1,200, and 1,300 °C). Result : No mortality was observed in the st udy. Clinical signs observed at all three temperatures included ptosis, apnea, pale ears followed by hyperemia, marked dyspnea followed by rapid irregular respiration, lacrimation, chromodacryorrhea , salivation, and moderate responsiveness. Rats exposed at 1, 300 °C also exhibited gasping and mild convulsions. Test substance : HFC-152a, purity not reported Reliability : (2) valid with restrictions 2e. Study well documented, meets generally accepte d scientific principles, acceptable for assessment. 11.01.2006 (16)

Type : other: Cardiac Sensitization Value : Species : rat Strain : Wistar Sex : female Number of animals : 50 Vehicle : Doses : 25,000, 50,000, 100,000, 200,000, 400,000 ppm Exposure time : Method : other Year : 1975 GLP : no data Test substance : as prescribed by 1.1 - 1.4 Method : Female rats were anesthetized. Result : Administration of 100,000 ppm HFC-152a caused slowing of the heart rate whereas 50,000 ppm provoked abnormalities of the electrocardiographic patterns (p rolongation of the P-R interval, elevation of the S-T segment, and widening of the T-wave). Test substance : HFC-152a, purity not reportedOECD SIDS 1,1-DIFLUOROETHANE (HFC-152A) 5. TOXICITY ID: 75-37-6 DATE: 29.06.2006

UNEP PUBLICATIONS 53 Reliability : (3) invalid 3b. Significant methodological deficiencies. 24.03.2006 (13)

Type : other: Cardiac Sensitization Value : Species : mouse Strain : Swiss Sex : male Number of animals : Vehicle : Doses : 200,000, 400,000 ppm Exposure time : 6 minute(s) Method : other Year : 1974 GLP : no data Test substance : as prescribed by 1.1 - 1.4 Method : Exposure was to anesthetized mice Result : Exposure did not sensitize the heart to epinephrine. No cardiac arrythmias were observed. Test substance : HFC-152a, purity not reported Reliability : (3) invalid 3b. Significant methodological deficiencies. 11.01.2006 (3)

Type : other: Cardiac Sensitization Value : Species : mouse Strain : Swiss Sex : male Number of animals : Vehicle : Doses : up to 400,000 ppm Exposure time : 4 minute(s) Method : other Year : 1974 GLP : no data Test substance : as prescribed by 1.1 - 1.4 Method : Male mice were anesthetized. Result : Mice exhibited reduction in respirat ory rate, tidal volume, respiratory minute volume, decreased pulmona ry compliance, and increased pulmonary resistance. HFC-152a did not produce arrhythmias nor did it sensitize the heart to epinephr ine. Inhalation of HFC-152a caused sensitization of the heart to epinephrine in mice that had experimentally induced bronc hopulmonary lesions following intratracheal injection of papain. Test substance : HFC-152a, purity not reported Reliability : (3) invalid 3b. Significant methodological deficiencies. 11.01.2006 (8)OECD SIDS 1,1-DIFLUOROETHANE (HFC-152A) 5. TOXICITY ID: 75-37-6 DATE: 29.06.2006

UNEP PUBLICATIONS 54 Type : other: Cardiotoxicity

Value : Species : rat Strain : Wistar Sex : male Number of animals : Vehicle : Doses : 2.5, 5, 10, 20, 40 % Exposure time : Method : other Year : 1975 GLP : no data Test substance : as prescribed by 1.1 – 1.4 Result : There were no observations relating to the effect of HFC-152a on the respiratory system. In anesthetized rat, abnormalities in the electrocardiogram were produced at 40 % HFC-152a. Test substance : HFC-152a, purity not specified Reliability : (3) invalid 3b. Significant methodological deficiencies. 24.03.2006 (66)

Type : other: Cardiotoxicity Value : Species : dog Strain : other: Mongrel Sex : male/female Number of animals : 13 Vehicle : Doses : 20 % Exposure time : 5 minute(s) Method : other Year : 1975 GLP : no data Test substance : as prescribed by 1.1 - 1.4 Method : Hemodyanamic effects of fluorocarbon propellants on the systemic and pulmonary components of the cardiovascular system were studied, with special attention to ef fects on cardiac output as reflected by mean pulmonary arterial flow, to tal systemic vascular resistance, and pulmonary vascular resistance. Result : HFC-152a administered at a maximal concentration of 20 %, except for a decrease in mean pulmonary arterial flow of 7 %, was without effect on the studied parameters. Test substance : HFC-152a, purity not specified Reliability : (2) valid with restrictions 2e. Study well documented, meets generally accepte d scientific principles, acceptable for assessment. 24.03.2006 (59)

Type : other: CardiotoxicityOECD SIDS 1,1-DIFLUOROETHANE (HFC-152A) 5. TOXICITY ID: 75-37-6 DATE: 29.06.2006

UNEP PUBLICATIONS 55 Value : Species : dog Strain : Sex : Number of animals : Vehicle : Doses : 2.5, 5, 10, 20 % Exposure time : Method : other Year : 1975 GLP : no data Test substance : as prescribed by 1.1 – 1.4 Result : HFC-152a administered in 10 or 20 % concentration caused depression of the force of contraction and a displacement of the ventricular function curve. Test substance : HFC-152a, purity not specified Reliability : (2) valid with restrictions 2e. Study well documented, meets generally accepte d scientific principles, acceptable for assessment. 24.03.2006 (4)

Type : other: Cardiotoxicity Value : Species : dog Strain : other: Mogrel Sex : Number of animals : Vehicle : Doses : up to 20 % Exposure time : 5 minute(s) Method : other Year : 1975 GLP : no data Test substance : as prescribed by 1.1 - 1.4 Result : HFC-152a did not influence the card iovascular system when inhaled at a concentration of 20 %. However, at a concentration of 10 %, there was a stimulation of respirat ion and an increase in pulmonary resistance. Test substance : HFC-152a, purity not specified Reliability : (3) invalid 3b. Significant methodological deficiencies. 24.03.2006 (6)

Type : other: Cardiotoxicity Value : Species : monkey Strain : other: Macaca mulatta Sex : Number of animals : 30 Vehicle :OECD SIDS 1,1-DIFLUOROETHANE (HFC-152A) 5. TOXICITY ID: 75-37-6 DATE: 29.06.2006

UNEP PUBLICATIONS 56 Doses : 2.5, 5, 10, 20 %

Exposure time : 5 minute(s) Method : other Year : 1974 GLP : no data Test substance : as prescribed by 1.1 - 1.4 Result : HFC-152a did not influenc e cardiac rhythm, heart rate, contracility, aortic blood pressure, le ft atrial pressure, or pulmonary arterial pressure. In concentrations as high as 20 %, HFC-152a can be regarded as inactive in the cardiovascular system. Test substance : HFC-152a, purity not specified Reliability : (3) invalid 3b. Significant methodological deficiencies. 24.03.2006 (7)

Type : other: Cardiotoxicity Value : Species : monkey Strain : other: Rhesus Sex : Number of animals : Vehicle : Doses : up to 20 % Exposure time : Method : other Year : 1975 GLP : no data Test substance : as prescribed by 1.1 - 1.4 Result : HFC-152a did not influence respirat ion or circulation, even when inhaled in levels up to 20 % concentration. Test substance : HFC-152a, purity not specified Reliability : (3) invalid 3b. Significant methodological deficiencies. 24.03.2006 (5)

5.1.3 ACUTE DERMAL TOXICITY

5.1.4 ACUTE TOXICITY, OTHER ROUTES

5.2.1 SKIN IRRITATION

5.2.2 EYE IRRITATIONOECD SIDS 1,1-DIFLUOROETHANE (HFC-152A) 5. TOXICITY ID: 75-37-6 DATE: 29.06.2006

UNEP PUBLICATIONS 57 5.3 SENSITIZATION

5.4 REPEATED DOSE TOXICITY

Type : Sub-acute Species : rat Sex : male Strain : other: ChR-CD Route of admin. : inhalation Exposure period : 2 weeks Frequency of treatm. : 6 hours/day, 5 days/week Post exposure period : 14-day recovery period Doses : 100,000 ppm Control group : yes Method : other Year : 1976 GLP : no Test substance : as prescribed by 1.1 - 1.4 Method : Ten rats/concentration were expose d. Control animals were exposed to house-line air. Five rats/group were sacrificed for gross and histopathologic examination after the last exposure. The remaining rats were sacrificed after a 14-day recovery period. At both sacrifice intervals, hematological, urine analytical, and biochemical indices were also measured in all rats. Result : No clinical, hematological, blood chemistry or histopathological evidence of effect was seen. There was a slight increase in urinary fluoride following the last exposur e. During the exposure the rats appeared to be anesthetized as indicated by sleeping and unresponsiveness to sound. Test substance : HFC-152a, purity 99.9+% Reliability : (2) valid with restrictions 2e. Study well documented, meets generally accepte d scientific principles, acceptable for assessment. 04.04.2006 (19)

Type : Species : rat Sex : no data Strain : other: albino Route of admin. : inhalation Exposure period : 2 months Frequency of treatm. : 16 hours/day Post exposure period : Doses : 100,000 ppm Control group : Method : other Year : 1950 GLP : no data Test substance : as prescribed by 1.1 - 1.4OECD SIDS 1,1-DIFLUOROETHANE (HFC-152A) 5. TOXICITY ID: 75-37-6 DATE: 29.06.2006

UNEP PUBLICATIONS 58 Method : Eight rats were exposed to 10 % HFC-152a for 16 hours per day for 2 months. At the conclusion of th e repeated exposures, surviving animals were sacrificed and examined for gross pathological changes. Sections of lung and liver we re examined microscopically. Result : No signs of ill health were apparent at any time. Gross examination at autopsy revealed no changes. Microscopic examination revealed a mild diffuse infiltration of small and large round cells in the lung suggestive of mild chronic irritation. Test substance : HFC-152a, purity not reported Reliability : (2) valid with restrictions 2e. Study well documented, meets generally accepte d scientific principles, acceptable for assessment. 04.04.2006 (46)

5.5 GENETIC TOXICITY ‘IN VITRO‘

Type : Bacterial reverse mutation assay System of testing : Salmonella typhimurium strains TA97a, TA98, TA100, and TA1535 and Escherichia coli strain WP2uvrA (pKM101) Test concentration : 0, 20, 30, 40, 50, 75 % Cycotoxic concentr. : Metabolic activation : with and without Result : negative Method : OECD Guide-line 471 Year : 2000 GLP : yes Test substance : as prescribed by 1.1 - 1.4 Method : This study also followed the U.S. EP A Health Effects Test Guideline OPPTS 799.9510 (1989) and Commis sion Directive 92/69/EEC, EEC Method B.12.

The study consisted of 2 independe nt trials with and without a metabolic activation system (Arocl or®-induced rat liver S-9). Three replicates were plated for each tester strain, test concentration, and condition. Positive and negative cont rols were included in all assays. The reaction mixture (S-9 mix) contained glucos e 6-phosphate, NADP, NaH 2 PO 4 , KCl, MgCl 2 , distilled water, and S-9. Treatments with activation were conducted by a dding 0.5 mL of S-9 mix, and 0.1 mL of an overnight culture to 2 mL of top agar. These components were briefly mixed and poured onto a minimal glucose agar plate. Treatments in the absence of the metabolic activation system were identical to those with activation wi th the exception that 0.5 mL of sterile buffer was used as a replacement for the S-9.

Plates were exposed to dilutions of the test gas in 6-L glass chambers. The test substance and filtered air flows were regulated using individual rotameters, and mixed prior to entry into the chambers. Chambers were placed into an incubator at 37 oC for approximately 48 hours. Gas chromatographic analysis was used to confirm theOECD SIDS 1,1-DIFLUOROETHANE (HFC-152A) 5. TOXICITY ID: 75-37-6 DATE: 29.06.2006

UNEP PUBLICATIONS 59 concentration of test atmospheres.

Bacterial background lawns were ev aluated for evidence of test substance toxicity and precipitation. Revertant colonies for a given tester strain and condition were counted by an automated colony
counter.

Positive control substances tested in this study included 2- nitrofluorene, N-ethyl-N-nitro-N-ni troguanidine, sodium azide, ICR 191 acridine mutagen, 9,10-dimethyl-1,2-benzanthracene, and 2- aminoanthracene.

Filtered house-line air was the test substance diluent and negative control.

A test substance was classified as positive if the mean number of revertants in any strain (excep t S. typhimurium TA1535) at any concentration was at least 2 times greater than the mean number of revertants of the concurrent negative control, and there was a concentration-related in crease in the mean number of revertants per plate in that same strain. For S. typhimurium TA1535, there must be no test substance concentration with a mean number of revertants that is at least 3 times greater than the mean number of revertants of its concurrent negative control and a concentration-related increase in the mean number of revertants pe r plate. A test substance was classified as negative if all pos itive classification criteria for all strains were not met.

Data for each tester strain were evaluated independently. For each tester strain, the mean number of revertants and the standard deviation at each concentration in the presence and absence of the exogenous metabolic system were calculated. Result : The actual concentrations for the firs t trial were 0, 20.4, 33.5, 42.0, 55.5, and 82.7 % in the absence of S-9 and 0, 21.7, 33.4, 43.6, 56.1, and 84.4 % in the presence of S- 9. No test substance-related precipitate was observed at any con centration level. Test substancerelated toxicity, evidenced by the concentration-dependent reduction in the mean number of revertants per plate, was observed in the first trial in S. typhimurium strains TA97a (-S-9) and TA1535 (+S-9), and in the E. coli strain (+S-9, -S-9).

The actual concentrations for the sec ond trial were 0, 20.5, 30.9, 41.4, 53.9, and 85.1 % in the absence of S-9 and 0, 20.8, 31.7, 41.9, 55.3, and 81.4 % in the presence of S-9. Test substance-related toxicity, evidenced by the concentration-dependent reduction in the mean number of revertants per plate, was observed in the first second in S. typhimurium strains TA97a (-S-9) and TA98 (+S-9, -S-9), and in the E. coli strain (+S-9, -S-9).

All acceptability criteria were met in this test. All tester strainsOECD SIDS 1,1-DIFLUOROETHANE (HFC-152A) 5. TOXICITY ID: 75-37-6 DATE: 29.06.2006

UNEP PUBLICATIONS 60 exhibited appropriate phenotypic char acteristics. No test substancerelated precipitate was observed. Th e mean number of revertants in the negative control for each strain was within the prescribed acceptable historical control range. Mean positive control values for the tester strains exhibited greater than a 3-fold increase over the means of the respective negative controls in both trials. Differences between targeted and actual doses in both analyses were acceptable for the purposes of this assay and in no way impacted the integrity or validity of this study. Test substance : HFC-152a, purity 99.99 % Reliability : (1) valid without restriction 1a. GLP guideline study. Flag : Critical study for SIDS endpoint 09.01.2006 (28)

Type : Chromosomal aberration test System of testing : Human lymphocytes Test concentration : Test 1 (3-hour exposure with and without S-9): 0, 35, 50, 70 % Test 2 (3-hour exposure with S-9): 0, 35, 50, 70 % Test 2 (19-hour exposure without S-9): 0, 35, 50, 70 % Test 3 (19-hour exposure without S-9): 0, 50, 60, 70 % Cycotoxic concentr. : Metabolic activation : with and without Result : Method : OECD Guide-line 473 Year : 2000 GLP : yes Test substance : as prescribed by 1.1 - 1.4 Method : This study also followed the U.S. EPA Health Effects Test Guidelines OPPTS 870.5375 (1998).

Human lymphocytes, in whole blood culture, were stimulated to divide by addition of phytohaema gglutinin, and duplicate cultures were exposed to the test substance. Treatment atmospheres of the test substance were prepared in steril e glass bottles with septum caps. Negative and positive control cultures were also prepared. Mitomycin C and cyclophosphamide were used as positive control substances. Air was used as the negative control substance.

The test substance was sampled from the cylinder into a gas-sampling bag. Air was withdrawn from each pre-warmed (37 °C) bottle and then an appropriate volume of test substance gas was introduced from the sampling bag, inserted through the septum cap, and the atmosphere was equilibrated at 37 °C. After injection of the lymphocyte culture, air was allowed to enter each bottle through a hollow needle to produce the requi red concentration at atmospheric pressure. After approximately 48 hours, the cultures in duplicate were injected into the sterile glass bottles. The culture bottles were incubated on their sides at 37 °C in a roller apparatus which rotated the bottles once every 8 minutes.OECD SIDS 1,1-DIFLUOROETHANE (HFC-152A) 5. TOXICITY ID: 75-37-6 DATE: 29.06.2006

UNEP PUBLICATIONS 61 Test 1 included a 3-hour treatment with and without S-9 mix and 16 hours of recovery. Test 2 included a 3-hour treatment with S-9 mix and 16 hours of recovery, and a 19-ho ur continuous treatment without S-9.

Following the results of the second te st, a third test was performed for a continuous treatment time, in the absence of S-9 only, to demonstrate reproducibility.

Two hours before the end of the in cubation period, cell division was arrested using Colcemid(R), the cells harvested and slides prepared, so that metaphase cells could be examined for numerical (polyploidy) and structural chromosomal damage.

In order to assess the toxicity to cultured lymphocytes, the mitotic index was calculated for all cultures treated with the test substance and the negative control. The highest dose level scored for chromosomal damage was, whenever possible, selected as the dose level causing a relative depression in mitotic index of at least 50 %.

The test substance was considered to cause a positive response if the following conditions were met:

Statistically significant increases (p < 0.01) in the frequency of metaphases with aberrant chro mosomes (excluding gaps) were observed at one or more test concentration.

The increases exceeded the negative control range of this laboratory, taken at the 99 % confidence limit.

The increases were reproducible between replicate cultures.

The increases were not associated with large changes in osmolality of the treatment medium or extreme toxicity.

Evidence of a dose-relationship was considered to support the conclusion.

A negative response was claimed if no statistically significant increases in the number of aberra nt cells above concurrent control frequencies were observed, at any dose level.

The numbers of aberrant and poly ploid metaphase figures in each treatment group were compared with the negative control value using a one-tailed Fisher's test. Result : No substantial toxicity (greater than or equal to 50 % mitotic inhibition) was observed at any dose level under any testing condition.OECD SIDS 1,1-DIFLUOROETHANE (HFC-152A) 5. TOXICITY ID: 75-37-6 DATE: 29.06.2006

UNEP PUBLICATIONS 62 In the first test, after 3-hour exposure in the absence or presence of S9, the test substance caused no bi ologically relevant statistically significant increases in the propor tion of cells with chromosomal aberrations at any dose level.

In the second test, after 19-hour expo sure in the absence of S-9, the test substance caused statistically significant increases in the proportion of metaphase figures co ntaining chromosomal aberrations at the 70 % dose levels both including and excluding gap-type aberrations. A trend test analysis also recorded a statistically significant dose-response. The observed increased chromosome aberration frequencies were outside the upper 99 % confidence limits of the historical control range. In the presence of S-9, the test substance caused no statistically si gnificant increase in the proportion of metaphase figures containing ch romosomal aberrations at any dose level.

In the third test, after a confirma tory 19-hour exposure in the absence of S-9, the test substance caused a statistically significant increase in the proportion of cells with chromo somal aberrations only at the 60 % dose level, excluding gap-type aberrations only. There was, however, no recording of a statis tically significant dose-response. Cultures treated with the test subs tance at 50 and 70 % did not show any statistically significant ch romosome aberration increases.

A quantitative analysis for polyploidy was made in cultures treated with the negative control and highest dose level. No increases in the proportion of polyploid cells were seen in any test.

All positive control compounds caused large, statisti cally significant increases in the proportion of aberrant cells, demonstrating the sensitivity of the test system and the efficacy of the S-9 mix.

It was concluded that the test substance showed statistically significant evidence of clastogenic activity in this test system only after continuous 19-hour treatment in the absence of S-9. However, the observed positive responses were weak and considered to be of marginal biological relevance. Test substance : HFC-152a, purity 99.99 % Conclusion : Weakly positive Reliability : (1) valid without restriction 1a. GLP guideline study. Flag : Critical study for SIDS endpoint 09.01.2006 (27)

Type : Bacterial reverse mutation assay System of testing : Salmonella typhimurium strain s TA98, TA97, TA100, and TA1537 or in Escherichia coli WP2 uvrA Test concentration : Cycotoxic concentr. :OECD SIDS 1,1-DIFLUOROETHANE (HFC-152A) 5. TOXICITY ID: 75-37-6 DATE: 29.06.2006

UNEP PUBLICATIONS 63 Metabolic activation : with and without Result : negative Method : other Year : 1994 GLP : no data Test substance : as prescribed by 1.1 - 1.4 Test substance : HFC-152a, purity not reported Reliability : (4) not assignable 4a. Abstract. 23.03.2006 (2)

Type : Bacterial reverse mutation assay System of testing : Salmonella typhimurium strains TA1535, TA1537, TA98, and TA100 Test concentration : 0, 20, 35, 50 % Cycotoxic concentr. : Metabolic activation : with and without Result : negative Method : other Year : 1977 GLP : no Test substance : as prescribed by 1.1 - 1.4 Test substance : HFC-152a, purity 99.9+% Reliability : (4) not assignable 4a. Abstract. 09.01.2006 (20)

Type : Bacterial reverse mutation assay System of testing : Salmonella typhimurium strains TA1535 and TA100 Test concentration : Cycotoxic concentr. : Metabolic activation : with Result : negative Method : other Year : 1984 GLP : no data Test substance : as prescribed by 1.1 - 1.4 Test substance : HFC-152a, purity not reported Reliability : (4) not assignable 4a. Abstract. 09.01.2006 (48)

5.6 GENETIC TOXICITY ‘IN VIVO‘

Type : Micronucleus assay Species : rat Sex : male/female Strain : Sprague-Dawley Route of admin. : inhalationOECD SIDS 1,1-DIFLUOROETHANE (HFC-152A) 5. TOXICITY ID: 75-37-6 DATE: 29.06.2006

UNEP PUBLICATIONS 64 Exposure period : 6 hours

Doses : 0, 4875, 9750, 19,500 ppm Result : negative Method : OECD Guide-line 474 "Genetic Toxicology: Micronucleus Test" Year : 2001 GLP : yes Test substance : as prescribed by 1.1 - 1.4 Method : The procedures used in the test were also based on the recommendations of the EC Co mmission Directive 2000/32/EC Annex 4C - B.12. Mutagenicity - In vivo mammalian erythrocyte micronucleus test. No. L 136/50 and US EPA (1998) Health Effects Test Guidelines; OPPTS 870. 5395 Mammalian erythrocyte micronucleus test. EPA 712-C-98-226.

Animals were treated for a single 6-hour period of whole body inhalation exposure to nominal co ncentrations of 4,875, 9,750, and 19,500 ppm. The negative control group received clean air only. The positive control group was dosed, orally, by gastric intubation, with cyclophosphamide at 20 mg/kg body weight. Rats we ighed between 140 and 149 grams on dispatch from the supplier. Each group of animals was kept, with sexes separa te, in cages and maintained in a controlled environment. Temperatures recorded throughout the test were in the range 21 ± 2 °C. Relative humidity was recorded in the range 34 - 56 %. Although the lower limit was outside the normal range for this species (55 ± 10 %), no adverse effects were recorded for any animal throughout the test and was not considered to have any affect on the integrity of the st udy. The room was illuminated by artificial light for 12 hours per day. Animals were provided with food and tap water ad libitum except during the period of inhalation
exposure.
Animals were exposed in whole- body exposure chambers constructed from stainless steel and glass. The internal volume of each chamber was approximately 750 litres. Air was introduced into each exposure chamber at a total rate of 150 lit res per minute. The flow through each chamber was approximately 12 air changes an hour; normally sufficient to maintain oxygen concentration above 19 % v/v, temperature approximately 22 (± 1) °C and relative humidity between 40 – 60 %. The exposure chamber was maintained 1 - 10 mm H 2 O below ambient pressure. Animals were housed singly in stainless steel mesh compartments during exposure.

The test atmosphere was produced by diluting the gaseous test substance with air. Adjustments were made to the gaseous test substance supply to each chamber during exposures in order to maintain the desired concentrations . The dilutions of gaseous test substance with air were determin ed during preliminary generation trials. During exposure the chambe r atmosphere was sampled to determine the concentration of test vapor on at least six occasions during each exposure. The nominal concentration of test substanceOECD SIDS 1,1-DIFLUOROETHANE (HFC-152A) 5. TOXICITY ID: 75-37-6 DATE: 29.06.2006

UNEP PUBLICATIONS 65 was calculated by recording the amount of test substance delivered to the generation system during the exposure. The usage over the six hours exposure was divided by the tota l airflow through the chamber. Any losses during the generatio n process were quantified and included in the calculation of the nominal concentration. Airflow, chamber temperature, and humidity were monitored continuously and recorded at approximately 30-minute intervals.

Following dosing, the animals were examined regularly and any observed mortality or adverse clin ical signs were recorded. Five males and five females we re sacrificed from the negative control and each of the test substance groups 24 hours after completion of the exposure period and from the positive control group 24 hours after dosing. In addition 5 male and 5 fema le animals were sacrificed from the negative control and high level treatment groups 48 hours after completion of the exposure period.

The animals were killed by cervical dislocation following carbon dioxide inhalation and both femurs dissected out from each animal. The femurs were cleared of ti ssue and the proximal epiphysis removed from each bone. The bone ma rrow of both femurs from each animal was flushed out and pooled in a total volume of 10 mL Hanks' balanced salts solution by aspiration. The resulting cell suspensions were centrifuged at 1,000 rpm (1 50 x g) for 5 minutes and the supernatant discarded. Each resulting cell pellet was resuspended in 2 mL of filtered foetal calf se rum before being sedimented by centrifugation. The supernatant was discarded and the final cell pellet was resuspended in a small volume of foetal calf serum to facilitate smearing in the conventional manner on glass microscope slides. Several smears were prepared from each femur.

Due to the presence of mast cell granules in rat bone smears, which appear identical to micronuclei wh en stained using the Romanowsky methods, a modified Feulgen stai ning method was employed. This method specifically stains DNA-containing bodies deep purple while leaving mast cell granules unsta ined. The method also allows reasonable differentiation of mature and immature erythrocytes and produces permanent preparations. The stained smears were examined (under code) by light microscopy to determine the incidence of micronucleated cells per 2000 immature erythrocytes (polychromatic erythrocytes, PCE) per animal. Th e proportion of PCEs was assessed by examination of at least 1000 erythrocytes from each animal.

The results for each treatment group were compared with the results for the concurrent control group us ing non-parametric statistics. For incidences of micronucleated imma ture erythrocytes, exact one-sided P-values were calculated by permutation. Comparison of several dose levels was made with the concurre nt control using the Linear by Linear Association test for tren d, in a step-down fashion if significance was detected. For individual inter-group comparisonsOECD SIDS 1,1-DIFLUOROETHANE (HFC-152A) 5. TOXICITY ID: 75-37-6 DATE: 29.06.2006

UNEP PUBLICATIONS 66 (i.e. the positive control group), this procedure simplified to a straightforward permutation test. For assessment of effects on the proportion of immature erythrocytes , equivalent permutation tests based on rank scores were used, i. e. exact versions of Wilcoxon's sum of ranks test and Jonckheere's test for trend. Result : The exposure mean concentrations of the test material were 5,031, 9,413, and 19,030 ppm compared with target levels of 4,875, 9,750, and 19,500 ppm, respectively, expres sed in terms of volume of test substance vapour per unit volume of atmosphere.

Neither mortality nor adverse clinical signs was observed in the micronucleus test for any animal in any dose group over the duration of the test.

No statistically significant in creases in the frequency of micronucleated PCEs and no substan tial decrease in the proportion of PCEs were observed in rats treated with the test substance and killed 24 or 48 hours, compared to negative control values.

The positive control compound, cyclophosphamide, produced large, highly significant increases in th e frequency of micronucleated PCEs and a decrease in the proportion of PCEs.

It was concluded that the test substance did not show any evidence of causing chromosome damage or bone marrow cell toxicity when administered by whole body inhalation exposure in this in vivo test procedure. Test substance : HFC-152a, purity 99.99 % Reliability : (1) valid without restriction 1a. GLP guideline study. Flag : Critical study for SIDS endpoint 09.01.2006 (29)

Type : Drosophila SLRL test Species : Drosophila melanogaster Sex : male/female Strain : other: Canton-S Route of admin. : Exposure period : 5 minutes Doses : 100 %; flow rate of 10 mL/min Result : positive Method : other Year : 1974 GLP : no Test substance : as prescribed by 1.1 - 1.4 Method : The Canton-Special (Canton-S) strain was obtained from the laboratory of Dr. Luolin Browning of Houston Texas. The cultures were kept under standard laboratory conditions in an air conditioned room at approximately 22 °C. Ne wly hatched (< 12 hours old) unetherized virgin flies were used.OECD SIDS 1,1-DIFLUOROETHANE (HFC-152A) 5. TOXICITY ID: 75-37-6 DATE: 29.06.2006

UNEP PUBLICATIONS 67 A Turner bulb apparatus was us ed. The gas was passed through a cotton trap and from there into a dry gassing chamber that contained the flies. From this Turner bulb, tubing connected with the inlet of a second Turner bulb, which contained 15 mL of water, into which the gas was bubbled. In this way, 100 ± 5 bubbles per minute could easily be counted. The rate of gas flow in mL/min, as determined by bubble count, was also measured by water displacement. The gassing time was 5 minutes with a flow rate of 10 mL/min, with the flies remaining in the gaseous atmosphere another 5 minutes. The treated flies were then placed in a cl ean container and observed. Upon recovery, the flies were lightly etherized and the males placed in 1/2 pint culture bottles. The females were discarded. Using the Basc technique, untreated Muller-5 virg in females were placed with Canton-S treated males. The Basc technique was used for scoring sex-linked recessive lethal mutations that arose in the germ line of the treated paternal male. The protocol for scoring semilethal (mosaic lethal) recessive mutations was to fu rther test any F2 culture having a ratio of at least 10 heterozygous females, or 11 Basc males, to 1 normal male, and if this ratio continued in the F3 generation, to score the culture as a semilethal mutation.

The significance of the mutation rate induced was determined by ttest comparison to the control rate. Result : Individual lethal tests of 276 F1 females gave 1 lethal and 8 semilethal, each scored as 0.5 lethal , giving a lethal count of 5/276 chromosomes. A lethal mutation fr equency of 1.5 % was calculated; this value was corrected for a s pontaneous frequency of 0.23 %. A number of developmental type ab normalities were noted among F2 progeny. One heterozygous female had ocelli in place of proboscis and no proboscis was present. Eye color mutants transmitted were white, apricot, and a deep orange. Test substance : HFC-152a, purity > 98 % Reliability : (4) not assignable 4e. Documentation insufficient for assessment. 09.01.2006 (38)

Type : Drosophila SLRL test Species : Drosophila melanogaster Sex : Strain : other: Canton-S and Muller-5 Route of admin. : Exposure period : 6 minutes Doses : Result : positive Method : other Year : 1974 GLP : no data Test substance : as prescribed by 1.1 - 1.4 Result : HFC-152a was mutagenic to Drosophila melanogaster as determinedOECD SIDS 1,1-DIFLUOROETHANE (HFC-152A) 5. TOXICITY ID: 75-37-6 DATE: 29.06.2006

UNEP PUBLICATIONS 68 by the Basc technique for the detect ion of sex-linked lethal recessive mutations. Treatment with HFC-152a produced a mutation rate of 1.31 ± 0.05. Test substance : HFC-152a, purity 99.5 - 99.9 % Reliability : (2) valid with restrictions 2d. Test procedure in accordance wi th national standard methods with acceptable restrictions. 09.01.2006 (39)

5.7 CARCINOGENICITY

Species : rat Sex : male/female Strain : other:Crl:CD(R)Br Route of admin. : inhalation Exposure period : 2 years Frequency of treatm. : 6 hours/day, 5 days/week (excluding holidays) Post exposure period : Doses : 0, 2,000, 10,000, 25,000 ppm Result : negative Control group : yes Method : other Year : 1982 GLP : yes Test substance : as prescribed by 1.1 - 1.4 Method : Food and water were available to the rats ad libitum except during exposures. Thirty rats per sex per concentration (54 days of age at the time of the first exposure) we re exposed whole-body to the vapor. During exposures, chamber temperature and relative humidity were maintained at approximately 24 ± 5 °C and 50 ± 10 %, respectively. Chamber atmospheres were genera ted by metering HFC-152a vapors from 1-ton cylinders of liquid HFC-152a, maintained at room temperature, through rotometers into the chamber air flow. The control chamber received diluti on air only. Chamber atmospheres were quantitatively analyzed for HFC-152a by gas chromotography.

Body weights were recorded twice monthly for the first 14 weeks, and then once monthly for the rema inder of the study. All animals were observed for abnormal behavior and clinical signs of toxicity twice daily during the work week. On weekends and holidays, all cages were observed daily for animals that had died.

Ten rats/sex/group were subjected to clinical pathol ogy evaluation at 1, 3, 6, 12, 18, and 24 months on test. Twelve hematological and 8 clinical chemistry parameters were measured or calculated. On the day prior to each bleeding time, an overnight urine specimen was collected and 12 urine parameters were measured or calculated.

Ten rats/sex/group were sacrificed and necropsied at 3 and 12OECD SIDS 1,1-DIFLUOROETHANE (HFC-152A) 5. TOXICITY ID: 75-37-6 DATE: 29.06.2006

UNEP PUBLICATIONS 69 months. All surviving rats at 24 months were sacrificed and necropsied. Gross examinations we re conducted on all rats and 38 tissues were saved for microscopic examination. Organ weights were recorded for 10 of the organs. Hi stopathological examinations were conducted on the control and high-exposure groups and on any animals that died or were sacrificed in extremis. In addition, kidneys and nasal tissues at the 3-mont h and 24-month final sacrifices, respectively, from all intermediate - and low-exposure rats received histological evaluation.

Clinical measurements were subjec ted to partially-nested and crossed analysis of variance. Organ weight and final body we ight data were subjected to one-way analysis of variance and Dunnett's test. The least significant differences from control values were calculated whenever the ratio of variances indicated that differences existedamong the study groups. Body weight data were subjected to oneway analysis of variance. Significa nce was judged at the p = 0.05 level of significance. The results of histopathologic examination were analyzed by the Fisher's Exact Test for differences between control and exposed groups and by the Ma ntel-Haenszel Test for a doserelated trend. Result : Overall means and standard deviations of the weekly average exposure concentrations were 2,000 ± 100, 10,000 ± 500, and 25,000 ± 600 ppm HFC-152a.

Mean body weights and body weight ga ins of male and female rats were comparable or superior to their respective controls. Ocular/nasal discharges (25,000 ppm males a nd females), wet/ stained perinea (25,000 ppm males and females), and stained body/face (25,000 females) were observed. Dose-resp onse trends were apparent for the latter two signs. Swollen ears were significantly elevated in the 2000 ppm male and the 25,000 ppm males and females with a dose-related trend apparent in the females. Incidence of the clinical signs noted above are presented in the table below:

Exposure (ppm) 0 2,000 10,000 25,000

Males Ocular/nasal discharges 19a 27 21 31 Wet/stained perineum 10 4 12 25 Swollen ears 11 30 16 31

Females Ocular/nasal discharges 13 16 15 24 Wet/stained perineum 30 18 36 50 Stained body/face 3 6 9 21 Swollen ears 4 5 4 16

a Incidence is the total number of rats affected throughout the study.OECD SIDS 1,1-DIFLUOROETHANE (HFC-152A) 5. TOXICITY ID: 75-37-6 DATE: 29.06.2006

UNEP PUBLICATIONS 70 At the time of final sacrifice, mortality ratios of male rats were 48/100, 51/100, 49/100, and 51/100 in the 0, 2,000, 10,000 and 25,000 ppm groups, respectively. Mortality ratios in female rats were 54/100, 61/100, 47/100, and 47/100 in the 0, 2,000, 10,000 and 25,000 ppm groups, respectively.

Over the duration of the study, female rats exhibited increased mean corpuscular volumes (10,000 and 25,000 ppm) and increased serum bilirubin (all treatment groups), while male rats exhibited increased hematocrits (10,000 and 25,000 ppm), increased mean corpuscular volumes (10,000 and 25,000 ppm), and increased urobilinogin (25,000 ppm). In the absence of a ny abnormalities in hematopoietic tissues or red blood cell counts among either males or females or of changes in serum bilirubin in males, the above observations, which would be consistent with a hemoly tic effect, provide inconclusive evidence of such a condition. While significantly lower than control values for all treated female groups when analyzed as relative numbers, eosinophils were signifi cantly low only for the 10,000 ppm female group when analyzed as absolute numbers. Monocytes were significantly lower than control values for all treated male groups when analyzed as either relative or absolute numbers. The depression in monocytes, however, is of unknown clinical or biological significance.

A dose-related increase in urinary fluoride concentration and excretion was observed in the 10,000 and 25,000 ppm male and female rats and in the 2,000 ppm males when evaluated over the entire study. Urine fluoride concentrati ons (μg) are listed in the tables below.

Months on Test (males) 1 3 6 12 18 24

Concentration (ppm) Urine Fluoride (ppm) 0 1.7 1.4 3.7 3.4 10.9 2.5 2,000 2.9 1.9 6.9 7.1 38.9 4.2 10,000 6.5 5.6 13.7 16.4 44.8 8.5 25,000 8.1 11.8 19.2 30.9 88.4 13.0

Months on Test (females): 1 3 6 12 18 24

Concentration (ppm) Urine Fluoride (ppm) 0 4.2 2.3 3.5 2.8 10.8 2.2 2,000 5.3 2.4 5.3 4.5 17.0 4.1 10,000 9.4 4.9 11.8 12.5 32.0 13.5 25,000 9.6 5.3 14.2 14.6 42.8 10.5

Serum creatinine was significantly elevated in both the 10,000 and 25,000 ppm female groups. The latter also exhibited increased urine volume and a decrease in urine osmolality.OECD SIDS 1,1-DIFLUOROETHANE (HFC-152A) 5. TOXICITY ID: 75-37-6 DATE: 29.06.2006

UNEP PUBLICATIONS 71 At the 3-month sacrifice, statistical ly significant differences in the following organ weights were noted: increased absolute heart, stomach, and adrenal weights (2000 ppm males); decreased absolute liver and spleen weights (25,000 ppm males); decreased relative liver and spleen weights (10,000 and 25,000 ppm males); decreased relative lung weights (2,000 and 25,000 ppm males); decreased relative testes weights (10,000 ppm males); decreased relative pituitary weights (2,000 ppm male s); increased ab solute stomach weights (2,000 ppm females); incr eased adrenal weights (2,000 and 10,000 ppm females); decreased absolute brain weights (25,000 females); decreased relative br ain weights (2,000 and 25,000 ppm females); decreased absolute heart weight (25,000 females); decreased relative heart weight s (all treated female groups); decreased absolute lung weights (10,000 and 25,000 ppm females); decreased absolute spleen weight s (25,000 ppm females); decreased relative spleen weights (all treated females); increased absolute pituitary weights (all treated females); increased relative pituitary weights (10,000 and 25,000 ppm females); and decreased relative liver weights (25,000 ppm females). Renal tubular changes were noted in females at the 3-month s acrifice. The changes consisted of slight cytoplasmic vacuolation, lu minal dilation, and presence of occasional vesiculated nuclei in 4/10 males and 7/10 females in the 25,000 ppm group. Similar lesions were not seen in rats from the 2,000 or 10,000 ppm groups. A pathological peer review of the study by Pathology Associates revealed no distinct evidence of HFC-152ainduced toxicity or carcinogeni city in any tissue examined. Preparation of additiona l kidney sections indica ted that renal tubular changes recorded by the original pat hologist in female rats sacrificed after 3 months exposure were the re sult of tissue processing artifact rather than treatment-related nephrotoxicity.

At the 12-month sacrifice, no differ ences in macroscopic lesions weredetected between the treated and control groups. No compoundrelated neoplastic or non-neoplas tic lesions were observed. Differences in mean absolute and relative organ weights of animals sacrificed at 12 months consisted of: increased absolute lung weights (10,000 ppm males); decreased absolute thymus weights (2,000 ppm males); decreased relative thym us weights (2,000 and 10,000 ppm males); increased relative heart and stomach weights (25,000 ppm males); decreased absolute pituitary weights (2,000 and 10,000 ppm females); decreased relative pituit ary weights (all treated females); and decreased relative liver weights (25,000 ppm females).

No statistically significant difference in mean absolute or relative organ weights were noted between treated and control male rats sacrificed at 24 months. However, treated female rats presented the following differences from contro l in organ weights: increased absolute and relative lung weights (2,000 and 10,000 ppm), increased absolute stomach weight (25,000 pp m), increased relative stomachOECD SIDS 1,1-DIFLUOROETHANE (HFC-152A) 5. TOXICITY ID: 75-37-6 DATE: 29.06.2006

UNEP PUBLICATIONS 72 weight (all treated fe males), increased relative heart weight (2000 ppm), and increased relative liver weight (25,000 ppm).

Female Exposure (ppm) 0 2,000 10,000 25,000

Absolute lung weight (g) 1.9939 2.1244 2.1166 2.0562 Relative lung weight (g) 0.3870 0.4447 0.4415 0.4115 Absolute stomach weight (g) 2.5302 2.6428 2.6200 2.7792 Relative stomach weight (g) 0.4857 0.5494 0.5446 0.5448 Relative heart weight (g) 0.2570 0.3176 0.2966 0.2917 Relative liver weight (g) 3.3324 3.4723 3.6701 3.8151

Atrophy of the nasal olfactory epit helium was noted at the 2-year sacrifice in some rats from all but the intermediate-exposure females. Incidences of the lesions are provided in the table below. The incidence of focal mucosal metapl asia in all treated groups were clearly not dose-related. The incr eased incidence of mucosal atrophy was statistically significant in the 2,000 and 25,000 ppm male and female groups, although an analys is for dose-related trend was significant only in the males.

Exposure (ppm) 0 2,000 10,000 25,000

Males No. of nasal

tissues examined 97 87 92 89 Focal mucosal metaplasia 57 21 21 21 Mucosal atrophy 0 5 2 8

Females

No. of nasal tissues examined 95 88 91 95 Focal mucosal metaplasia 22 17 6 23 Mucosal atrophy 0 9 0 17

Atrophy of the olfactory epithelium was confirmed by the peer review to be present in small numb ers of females exposed for 2 years. These nasal changes, however, usuall y were unilateral in distribution and were entirely consistent with olfactory lesions, which have been described as spontaneous alterations in aging rats. Further, group incidence trends for olfactory atrophy were inconsistent with exposure concentration gradients. Ol factory changes, therefore, were not regarded as treatment related.

A nasal adenoma in 1 male and 1 female from the 25,000 ppm groups and osteomas originating from the skull in 3 males from the 25,000OECD SIDS 1,1-DIFLUOROETHANE (HFC-152A) 5. TOXICITY ID: 75-37-6 DATE: 29.06.2006

UNEP PUBLICATIONS 73 ppm group were observed at the final sacrifice. These tumor types did not occur in the concurrent contro ls. The incidence of neither tumor was statistically significant and each was considered to be of unclear biological significance.

FC-152a was not carcinogenic and pr oduced no life-shortening toxic effects. Test substance : HFC-152a, purity > 99.9 % Reliability : (1) valid without restriction 1b. Comparable to guideline study. Flag : Critical study for SIDS endpoint 04.04.2006 (22) (24)

5.8.1 TOXICITY TO FERTILITY

5.8.2 DEVELOPMENTAL TOXICITY/TERATOGENICITY

Species : rat Sex : female Strain : other: Charles River CD(R) Route of admin. : inhalation Exposure period : Days 6 - 15 of gestation Frequency of treatm. : Daily Duration of test : 6 hours/day Doses : 0, 5,000, 50,000 ppm Control group : yes, concurrent vehicle NOAEL maternal tox. : 50.000 ppm

NOAEL teratogen. : 50.000 ppm Method : other Year : 1979 GLP : no Test substance : as prescribed by 1.1 - 1.4 Method : The rats were bred by the supplier (Charles River). The morning when sperm were found in the vaginal smear was counted as Day 1 of gestation. Animals (young adults weighing approximately 185 grams) were delivered at either 4 or 2 days pregnant. F ood and water were available ad libitum except during inhalation exposures.

Pregnant female rats (27 rats/g roup) were exposed to nominal concentrations of 0, 5,000, or 50,000 ppm HFC-152a for 6 hours per day on days 6 - 15 of gestation. De sired exposure conc entrations were generated by metering the vapors of HFC-152a from the cylinder into 1.4 m 3 stainless steel and glass ch ambers operating under dynamic airflow conditions. Chamber atmo spheres were monitored every 30 minutes via gas chromatograph (GC) . The GC was calibrated daily with gaseous standards. Control anim als were exposed to room air inOECD SIDS 1,1-DIFLUOROETHANE (HFC-152A) 5. TOXICITY ID: 75-37-6 DATE: 29.06.2006

UNEP PUBLICATIONS 74 identical chambers. Animals were obs erved daily for signs of toxicity and weighed periodically thr oughout the study. Dams were euthanized on Day 21 and organs of the thoracic and abdominal cavities were examined and the uterine weight was recorded. Corpora lutea, implantation sites, live and dead fetuses, resorptions, fetal weight, crown-rump length of live fe tuses, and a gross external fetal examination were recorded. Half of the fetuses from each litter were examined for skeletal abnormalitie s. The remaining fetuses were examined for visceral and neural anomalies (via the Wilson method with modification describe d by Barrow and Taylor).

For statistical evaluation of the data, the litter was considered the experimental unit of treatment an d observation. The Fisher Exact probability test was used to evalua te the incidence of resorptions and abnormalities among litters. Mate rnal and fetal body weights and fetal crown-rump measurements were treated statistically by analysis of variance and least significant difference (LSD) tests. The number of corpora lutea, implantations, an d live fetuses per litter were analyzed by the Wilcoxon rank sum test. In all cases, two-tailed significance tests were performed and significance wa s judged at the 0.05 probability level. Result : The daily average analytical expos ure levels during the entire 10-day exposure period were 5,300 ± 1,200 and 45,300 ± 4,900 ppm.

No compound-related clinical signs of maternal toxicity or body weight changes were observed. No gross pathological abnormalities were observed in ovaries, uterine ho rns, vital organs, or tissues of treated animals.

Pregnancy ratios were 22/27, 21/27, and 19/27 at 0, 5,000, and 50,000 ppm, respectively. A summ ary of other reproductive outcomes (means/litter) are provided in the table below:

Concentration (ppm) 0 5000 50,000

Corpora lutea: 11.6 11.3 12.2 Implantations: 10.0 9.4 10.5 No. of Resorptions: 1.5 1.4 1.2 Total No. of Fetuses: 9.3 8.8 9.9 Total No. of Live Fetuses: 9.3 8.8 9.9 Mean Fetal Weight (g): 4.3 4.4 4.3 Sex Ratio: NR NR NR NR = Fetal sex was not recorded; therefore, sex ratios could not be calculated.

The number of corpora lutea, implantation sites, and live fetuses per litter were similar in all groups . The post-implantation death ofOECD SIDS 1,1-DIFLUOROETHANE (HFC-152A) 5. TOXICITY ID: 75-37-6 DATE: 29.06.2006

UNEP PUBLICATIONS 75 fertilized ova in exposed female s indicated by early and late resorptions and dead fetuses was not different from that of the control group. Fetal body measurements, i.e. mean weight and crown-rump length in groups were not di fferent from controls.

The HFC-152a treatment did not a ffect embryonal development as measured by gross external, visc eral, and skeletal examinations. Petechial hemorrhages and small subcutaneous hematomas on various parts of the body and the number of runts among litters and fetuses were similar in all gr oups. Apparent hydronephrosis, transposition of the viscera, live r peliosis, and internal hemorrhage were detected; however, none of thes e findings were considered to be treatment-related. No statistically significant differences in the frequency of minor skeletal anomal ies or variants were observed.

A summary of gross, soft tissue, and skeletal anomalies are provided in the table below. Data are presen ted as number of litters (fetuses) affected.

Concentration (ppm) 0 5,000 50,000

Gross External, Number examined: 22(205) 20(184) 19(188) Petechial hemorrhages 4(4) 5(5) 3(5) Hematoma 10(12) 6(7) 8(14) Runts 2(2) 1(1) 1(1)

Soft Tissue, Number examined: 22(105) 20(93) 19(90) Hydronephrosis (apparent) 1(1) 3(4) 2(2) Situs inversus 0 0 1(1) Liver peliosis 0 0 3(3) Internal hemorrhage 1(1) 0 0

Skeletal, Number examined: 22(100) 20(91) 19(98) 14th rudimentary rib 16(51) 16(53) 19(69) Wavy ribs 8(17) 6(8) 5(7) Sternebrae unossified 10(14) 9(16) 12(23) Bipartite centra 3(3) 0 2(2) Hyoid unossified 2(3) 0 4(6)

The NOEL for maternal and develo pmental toxicity was 50,000 ppm, the highest level tested. Test substance : HFC-152a, purity > 99.9 % Reliability : (2) valid with restrictions 2e. Study well documented, meets generally accepte d scientificOECD SIDS 1,1-DIFLUOROETHANE (HFC-152A) 5. TOXICITY ID: 75-37-6 DATE: 29.06.2006

UNEP PUBLICATIONS 76 principles, acceptable for assessment.

Flag : Critical study for SIDS endpoint 30.05.2006 (21)

5.8.3 TOXICITY TO REPRODUCTION, OTHER STUDIES

Type : other: 2-year Chronic and Carcinogenicity Study In vitro/in vivo : In vivo Species : rat Sex : male/female Strain : other: Rats/Crl:CD(R)BR Route of admin. : inhalation Exposure period : 2 years Frequency of treatm. : 6 hours/day, 5 days/week (excluding holidays) Duration of test : Doses : 0, 2,000, 10,000, 25,000 ppm Control group : yes, concurrent vehicle Result : No histopathological or weight effects on reproductive organs of either male or female rats were observed. Method : other Year : 1982 GLP : yes Test substance : as prescribed by 1.1 - 1.4 Method : Refer to 2-year carcinogenicity study in Section 5.7 for methods. Result : Additional information can be found in the Carcinogenicity Section (Section 5.7). Test substance : HFC-152a, purity > 99.9 % Reliability : (2) valid with restrictions 2e. Study well documented, meets generally accepte d scientific principles, acceptable for assessment. Flag : Critical study for SIDS endpoint 09.01.2006 (22)

5.9 SPECIFIC INVESTIGATIONS

5.10 EXPOSURE EXPERIENCE

5.11 ADDITIONAL REMARKSOECD SIDS 1,1-DIFLUOROETHANE (HFC-152A) 6. REFERENCES ID: 75-37-6 DATE: 29.06.2006

UNEP PUBLICATIONS 77 (1) AIHA (2005). 1,1-Difluoroethane. Wor kplace Environmental Exposure Level Guide, American Industrial Hygiene Association, Fairfax, VA.
(2) Araki A, Noguchi T, Kato F, and Matsushima T (1994). Improved method for mutagenicity testing of ga seous compounds by using a gas sampling bag. Mutat. Res., 307(1):335 - 344.
(3) Aviado DM and Belej MA (1974). Toxicity of aerosol propellants on the respiratory and circulatory systems. I. Cardiac arrhythmia in the mouse. Toxicology, 2:31 - 42.
(4) Aviado DM and Belej MA (1975). Toxicity of aerosol propellants in the respiratory and circulatory systems. V. Ventricular func tion in the dog. Toxicology, 3:79 - 86.
(5) Aviado DM and Smith DG (1975). Toxicity of aerosol propellants in the respiratory and circulatory systems. VIII. Respiration and ci rculation in primates. Toxicology, 3:241 - 252.
(6) Belej MA and Aviado DM (1975). Cardiopulmona ry toxicity of propellants for aerosols. J. Clin. Pharmacol., 15(1):105 - 115.
(7) Belej MA, Smith DJ, and Aviado DM (1974) . Toxicity of aerosol propellants in the respiratory and circulatory sy stems. IV. Cardiotoxicity in the monkey. Toxicology, 2:381 - 395.
(8) Brody RS, Watanabe T, and Aviado DM ( 1974). Toxicity of aerosol propellants on the respiratory and circulatory systems. III. Influence of bronchopulmonary lesion on cardiopulmonary toxicity in the mouse. Toxicology, 2:173 - 184.

(9) Carpenter CP, Smyth HF, Jr., and Pozzani UC (1949). The assay of acute vapor toxicity, and the grading and interpreta tion of results on 96 chemical compounds. J. Ind. Hyg. Toxicol., 31:343 - 346.

(10) CHEMLIST (1999). ST N Regulatory Database.

(11) Daubert TE and Danner RP (1989). P hysical and Thermodynamic Properties of Pure Chemicals Data Compilation, Amer. Inst. Chem . Eng., Hemisphere Pub. Corp., New York (HSDB/5205).

(12) Daubert TE and Danner RP (1989). P hysical and Thermodynamic Properties of Pure Chemicals Data Compilation, Taylor a nd Francis, Washington, DC (HSDB/5205).
(13) Doherty RE and Aviado DM (1 975). Toxicity of aerosol propellants in the respiratory and circulatory systems. VI . Influence of cardiac and pulmonary vascular lesions in the rat. Toxicology, 3:213 - 224.

(14) DuPont (n.d.). Technical Inform ation Bulletin, DuPont Dymel® 152a.

(15) DuPont Co. (1951). Unpublis hed Data, Haskell Laboratory Report No. 2 - 52, "Inhalation Toxicity Studies of Various Freon Compounds."OECD SIDS 1,1-DIFLUOROETHANE (HFC-152A) 6. REFERENCES ID: 75-37-6 DATE: 29.06.2006

UNEP PUBLICATIONS 78 (16) DuPont Co. (1966). Unpublished Data, "Acute Inhalation Toxicity of Fluorocarbon Pyrolysis Products."

(17) DuPont Co. (1969). Unpubl ished Data, Haskell Laboratory Report No. 354 - 69, "Cardiac Sensitization" (November 7).

(18) DuPont Co. (1975). Unpubl ished Data, Haskell Laboratory Report No. 699 - 75, "Acute Inhalation Toxicity" (November 18).

(19) DuPont Co. (1976). Unpublished Data, Hask ell Laboratory Report No. 158 - 76, "Subacute Two-Week Inhalation Toxicity" (March 2).

(20) DuPont Co. (1977). Unpublished Da ta, Haskell Laboratory Report No. 731 - 77, "Mutagenic Activity in the Salmonell a/Microsome Assay" (September 16).

(21) DuPont Co. (1979). Unpublished Da ta, Haskell Laboratory Report No. 437 - 79, "Embryotoxicity and Terat ogenicity Studies in Rats with HFC-152a" (March 10).

(22) DuPont Co. (1982). Unpublished Data, Ha skell Laboratory Report No. 8 - 82, "Two-year Inhalation Study with HFC-152a in Rats" (November 30) (also cited in TSCA Fiche OTS0520846).

(23) DuPont Co. (1990). Unpublished Data , Haskell Laboratory Report No. 524-90, "Approximate Lethal Dose (ALD) of HFC-152 a in Rats" (September 26) (also cited in TSCA fiche OTS0530083).
(24) DuPont Co. (1992). Pathology Associates, Inc., "Pathology Peer Review of a Two-Year Inhalation Study of HFC-152a in CD Rats" (May 19).
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