Acute, subchronic, and mutagenicity studies with norbornene fluoroalcohol.
The object of this study was to evaluate the toxicity of norbornene fluoroalcohol (NBFOH), which is used as an intermediate in the production of fluorinated monomers and polymers. NBFOH was evaluated for acute oral, dermal, and inhalation toxicity, dermal sensitization using the Local Lymph Node Assay (LLNA), mutagenesis by the Ames assay, and subchronic toxicity in a 4-week inhalation rat study. NBFOH demonstrated slight acute toxicity in oral, dermal, and inhalation studies. Approximate lethal doses of 3400 and > 5000 mg/kg for the oral and dermal routes, respectively, and an approximate lethal concentration of 4300 mg/m(3) were determined. NBFOH demonstrated moderate skin irritation, was a severe eye irritant, produced dermal sensitization, but did not cause bacterial mutagenicity either in the presence or absence of S9 activation. Male and female rats were exposed nose only to airborne NBFOH at levels of 0, 410, 1400, and 1500 mg/m(3), 6 h/day, 5 days/week for 4 weeks with clinical and histopathology specimens collected 1 day after the final exposure. Due to the vapor pressure of NBFOH, the 1500 mg/m(3) atmosphere was 27% aerosol and 73% vapor; the 1400 mg/m(3) atmosphere was 5% aerosol and 95% vapor, and the 410 mg/m(3) level was only vapor. No test substance-related mortality or clinical signs of toxicity were observed over the course of the study, and male rats demonstrated significant weight loss and decreased food consumption at 1400 mg/m(3). Male rats from the 1500 mg/m(3) group demonstrated an 11% increase in prothrombin time that was significantly higher than the control value. Examination of fluoride in the urine did not demonstrate a concentration-response relationship, with minimal elevations observed in male rats at all exposure levels and sporadic increases in females. Both male and female rats exposed to 1400 mg/m(3) or greater had squamous metaplasia of the laryngeal mucosa and degeneration of the nasal olfactory and respiratory mucosa. Based on the above findings, NBFOH demonstrates the potential to produce allergic contact dermatitis, and subchronic inhalation studies indicate a no-observed-adverse-effect-level (NOAEL) of 410 mg/m(3).
DeLorme
Michael P
MP
E. I. DuPont de Nemours and Company, Haskell Laboratory for Health and Environmental Sciences, Newark, Delaware 19714-0050, USA. michael.p.delorme@usa.dupont.com
Ladics
Gregory S
GS
Donner
E Maria
EM
Wagner
Valentine O
VO
Finlay
Carol
C
Frame
Steven R
SR
Everds
Nancy E
NE
Loveless
Scott E
SE
D000818:Animals; D004487:Edema / Q000139:chemically induced; D004890:Erythema / Q000139:chemically induced; D005128:Eye Diseases / Q000139:chemically induced; D005260:Female; D005459:Fluorides / Q000652:urine; D005466:Fluorocarbons / Q000633:toxicity*; D023441:Local Lymph Node Assay; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D009152:Mutagenicity Tests; D019055:No-Observed-Adverse-Effect Level; D009636:Norbornanes / Q000633:toxicity*; D020005:Propanols / Q000633:toxicity*; D011517:Prothrombin Time; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley
D005466:Fluorocarbons; D009636:Norbornanes; D020005:Propanols; D005459:Fluorides