A 13-week nose-only inhalation toxicity study for perfluoro-n-butyl iodide (PFBI) in rats with recommended occupational exposure levels

Abstract

A 13-week study was conducted to develop occupational exposure limits (OELs) for the solvent perfluoro-n-butyl iodide (PFBI). Fischer 344 rats (15 males & 10 females per group) were exposed for 6 h/day to 0 (air control), 500, 1500, or 5000 ppm PFBI vapor for 5 days/week for 13 consecutive weeks (at least 65 exposures) followed by a 4-week recovery period. Clinical observations, body weights, clinical pathology, organ weights, and histopathology as well as detailed evaluations of neurotoxicity and thyroid function parameters were conducted at the end of the treatment period for up to 10 animals/sex/group with 5 males/group held for a 4-week recovery period. Findings in the thyroid target tissue consisted of a minimal thyroid follicular cell hypertrophy occasionally accompanied by hyperplasia, but without an increase in thyroid weight in the 500, 1500, and 5000 ppm males. At ≥500 ppm, there was also increased thyroid stimulating hormone in females and increased T₃ and T₄ in animals of both sexes. These effects resolved following a 4-week recovery period in the males evaluated. Minor clinical pathology variations in all PFBI exposure groups were not considered biologically significant. A 9.4% reduction in absolute body weight in the 5000 ppm males was observed. Dosimetric adjustments for daily exposure time and uncertainty factors were selected to provide a basis for the proposed OELs. For acute (single event) exposures, a ceiling OEL of 3900 ppm, and for repeated exposures, an 8-h time-weighted average of 40 ppm PFBI were proposed.

Keywords::

• Inhalation toxicity
• 90-day study
• solvents
• CFC replacement
• hormones
• thyroid
• TSH
• male and female rats
• health hazard assessment
• occupational exposure limit

Acknowledgements

The authors would like to acknowledge the following for technical assistance: Sylvie J. Gosselin, D.V.M., Ph.D.; Nicholas Macri, D.V.M., Ph.D.; Lionel F. Rubin, V.M.D.; and Graham F. Healey of Huntingdon Life Sciences. Huntingdon Life Sciences, East Millstone, NJ, and AFRL/RHPB are fully accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC). Public clearance: AFMC-2010-0063.

Declaration of interest

Funding was provided by the Air Force through the Air Force Material Command and the Aeronautical Systems Center. The project was jointly conducted with Ed Snyder and Lois Gschwender, Air Force Research Laboratory, Materials Directorate.