Review
Reproductive and developmental toxicity of hydrofluorocarbons used as refrigerants

https://doi.org/10.1016/j.reprotox.2009.11.005Get rights and content

Abstract

The present paper summarizes data on the reproductive and developmental toxicity of hydrofluorocarbons (HFCs), including pentafluoroethane (HFC-125), 1,1,1,2-tetrafluoroethane (HFC-134a), 1,1,1-trifluoroethane (HFC-143a), 1,1-difluoroethane (HFC-152a), difluoromethane (HFC-32) and 1,1,1,3,3-pentafluoropropane (HFC-245fa), used as refrigerants, published in openly available scientific literature. No developmental toxicity of HFC-125 was found even at 50,000 ppm in rats or rabbits. Although HFC-134a exhibited no dominant lethal effect or reproductive toxicity in rats, it caused low body weight in pre- and postnatal offspring and slightly retarded skeletal ossification in fetuses at 50,000 ppm in rats. No maternal or developmental toxicity was noted after exposure to HFC-143a even at 40,000 ppm in rats or rabbits or HFC-152a even at 50,000 ppm in rats. HFC-32 is slightly maternally and developmentally toxic at 50,000 ppm in rats, but not in rabbits. HFC-245fa caused decreases in maternal body weight and food consumption at 10,000 and 50,000 ppm and fetal weight at 50 000 ppm. No evidence of teratogenicity for these HFCs was noted in rats or rabbits. There is limited information about the reproductive toxicity of these HFCs. Animal studies remain necessary for risk assessments of chemicals because it is difficult to find alternative methods to determine the toxic effects of chemicals. It is required to reduce emissions of organic vapors containing HFCs to reduce the risk of exposure.

Introduction

In 1974, it was warned that the chlorofluoromethanes being added to the atmosphere might destroy atmospheric ozone [1]. This was the first startling claim that chemical compounds could damage the stratosphere and change the earth's environment. It is now recognized that the rate of destruction has been increased by harmful ozone-damaging agents like chlorofluorocarbons (CFCs), carbon tetrachloride, bromides, and halons present in coolants, fire extinguishers, foaming agents, solvents, and aerosol propellants [2]. The Montreal Protocol on Substances that Deplete the Ozone Layer was first established in 1987 and requested a phasing out of CFCs prior to the mid-1990s. New refrigerants must not contain chlorine, which was damaging the ozone layer. The new refrigerants must also be efficient in use because attention was turning to global warning: the new refrigerants themselves should have little direct impact on global warning upon their release [3]. Hydrochlorofluorocarbons (HCFCs) and hydrofluorocarbons (HFCs) were proposed as replacements for ozone-depleting CFCs. HCFCs still contain chlorine, but as their capacity to react with stratospheric ozone is limited, they can be considered environmentally safer than CFCs. The phasing out of HCFCs is scheduled by 2020 based on the updated Montreal Protocol. HFCs are recognized as acceptable alternatives to CFCs and HCFCs because of their low ozone-depleting potentials and global warnings [4]. HFCs possess many of the physical and thermochemical properties of HCFCs and CFCs, including high volatility, low thermal conductivity, low surface tension and low flammability [4]. Some HFCs released into the environment rapidly volatilize in the atmosphere, and are degraded to trifluoroacetic acid (TFA), formic acid (FA), hydrofluoric acid (HA), carbon dioxide (CO2) and carbon monoxide (CO) [5], [6], [7], [8], [9], [10], [11], [12]. Several products of the degradation of HFCs have reproductive and developmental effects [13].

Reproductive and developmental toxicity has increasingly become recognized as an important part of overall toxicology. In fact, adverse effects of environmental chemicals on the reproductive success of wildlife populations have been noted [14]. The possibility of chemicals entering biological systems is of great concern to the public with regard to possible reproductive and developmental toxicity. In this paper, we summarize the findings of studies into the reproductive and developmental toxicity of HFCs published in openly available scientific literature.

Section snippets

Reproductive and developmental toxicity of hydrofluorocarbons

Studies using inhalation, the most likely route of exposure in humans, are available on the reproductive and developmental toxicity of HFCs in rats and rabbits. Only statistically significant effects are summarized unless otherwise noted.

Conclusion

This paper examined the reproductive and developmental toxicity of HFCs used as a refrigerant. Although slight maternal and/or developmental toxicity was noted at high concentrations of HFC-125, HFC-134a, HFC-32 and HFC-245fa, these HFCs seem to have little potential to affect fetal development given the results of developmental toxicity studies performed in rats and rabbits and no significant risk is expected. There was no evidence to support the assumption of developmental toxicity in humans.

Conflict of interest

None.

Acknowledgement

This study was supported by grants from the New Energy and Industrial Technology Development Organization.

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    1,1,1,2-Tetrafluoroethane (HFC-134a) (CAS No. 811-97-2), Joint Assessment of Commodity Chemicals No. 50

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