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crease in the incidence of Leydig cell hyperplasia. These toxicity findings are assumed to be relevant for the prediction of human risk.

Quantitative Evaluation

Reproductiveand Developmental Toxicity

There are no human data from which to develop a quantitative evaluation. Laboratory studies in rats identified a NOAEL of 50,000 ppm for reproductive and developmental effects for a less than chronic exposure. The NOAEL of 50,000 ppm was adjusted to convert from a 1hr/d exposure to a 6hr/d exposure; the adjusted NOAEL is 8,300 ppm. Dividing the adjusted NOAEL by an aggregate uncertainty factor of 300 (3 for interspecies extrapolation, 10 for intraindividual differences, and 10 for an incomplete database), the UEL for reproductive and developmental toxicity for less than a chronic exposure is 28 ppm.

A similar UEL is calculated for chronic exposures. Laboratory studies in rats identified a NOAEL of 10,000 ppm based on a significant increase in the incidence of Leydig cell hyperplasia. Applying an aggregate uncertainty factor of 300 (3 for interspecies extrapolation, 10 for intraindividual differences, and 10 for an incomplete database), the UEL for reproductive and developmental toxicity for a chronic exposure is 33.3 ppm.

Certainty of Judgment and Data Needs

Data on the toxicity and disposition of HFC-134a suggest that it is a compound with little or no reproductive or developmental toxicity except at very high exposure concentrations that induce narcosis. However, data are needed from postnatal evaluations and from a multigeneration study with 6 hr/d exposure. The similarities in pharmacokinetics between humans and laboratory animals provide confidence that the data are relevant for predicting human risk.



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