Inhalation Teratology and Reproduction Studies with 1, 1-Dichloro-2,2,2-Trifluoroethane(HCFC-123)

Abstract

HCFC 123 is one of the chemicals being developed as a replacement for CFC 11 in refrigerant and solvent applications. Supplementing earlier rat teratology studies, a rabbit inhalation teratology study was conducted. In addition, one-generation and twogeneration inhalation reproduction studies were conducted. In the teratology study, the pregnant rabbits were exposed to levels of 0 (control), 500, 1500, and 5000 ppm, 6 hr per day from Days 6 through 18 of gestation. Slight body weight losses and reduced food consumption were seen in does in all three exposure level groups. This response followed an exposure-related pattern. There were no other signs of maternal toxicity. There was also no evidence of treatment-related effects on the kits. A probe one-generation reproduction study was conducted. In this study four groups of 12 male and 12 female rats were exposed to vapors of HCFC 123 6 hr per day, 7 days per week from 4 weeks prior to mating through weaning of their offspring. The exposure levels for this study were 0 (control), 300, 1000, and 5000 ppm. There were no effects on mating and fertility, or on pup survival or birth weight. A two-generation study was subsequently conducted. In this study, five groups of 32 male and female rats were exposed to HCFC 123 from 6 weeks of age through weaning. From the offspring of these animals, groups of 28 males and females were selected for the F, generation. These animals were exposed to HCFC 123 from weaning (4 weeks of age) through weaning of the F, generation. All exposures were 6 hr per day, 7 days per week. The exposure levels for this study were 0 (control), 30, 100, 300, and 1000 ppm. There were no effects on any of the fertility or reproductive indices measured. As with prior studies, decreases in serum triglyceride levels were seen. Pup survival and birth weight were unaffected by treatment. Pup body weight gain was lower in all treatment groups during nursing, following an exposure-related pattern.

2,2‐Dichlor‐1,1,1‐trifluorethan [MAK Value Documentation in German language, 2000]

“…Bei F 1 -Tieren, nicht aber bei F 0 -Tieren, war ab 100 ml/m 3 die Progesteronkonzentration signifikant erniedrigt. Die Autoren sehen diese Veränderungen nicht als behandlungsbedingt an (Malinverno et al 1996;PAFT 1994 (Loizou et al 1994). Bei männlichen Fischer-344-Ratten, die in einer Expositionskammer initialen Konzentrationen von 100, 1000 oder 10 000 ml Dichlortrifluorethan/m 3 ausgesetzt waren, war die Konzentration an Trifluoressigsäure im Blut bei 10 000 ml/m 3 um mehr als 50% geringer als bei 1000 ml/m 3 .…”

“…Darüber hinaus waren ab der niedrigsten Konzentration biochemische Effekte zu beobachten: ab 30 ml/m 3 erhöhter Cholesteringehalt bei männlichen F 0 -und F 1 -Tieren, erniedrigte Werte an Lipoproteinen mit sehr niedriger Dichte (very low density lipoproteins, VLDL) und Chylomikron-Cholesterin bei weiblichen F 1 -Tieren; ab 100 ml/m 3 erniedrigter Cholesteringehalt bei weiblichen F 0 -Tieren, bei allen Tieren verringerte Serum-Triglyceride, bei männlichen F 1 -Tieren erniedrigter Progesterongehalt; ab 300 ml/m 3 erniedrigte Konzentration an LH bei männlichen F 0 -Tieren. Die Autoren diskutieren als mögliche Ursache für die verringerte Körpergewichtszunahme der Nachkommen die verminderten Konzentrationen an Serum-Triglyceriden (Malinverno et al 1996;PAFT 1994 (Buschmann et al 1996). Die verringerten Körpergewichtszunahmen bei säu-genden Rattenjungen, deren Mütter gegenüber Dichlortrifluorethan exponiert waren, sind offensichtlich auf die Beeinträchtigung des Fettstoffwechsels der Jungtiere durch Aufnahme von Trifluoressigsäure über die Muttermilch zurückzuführen (siehe auch Cook et al 1999).…”