Inhalation toxicity study

Health and Safety Factors. Boron trifluoride is primarily a pulmonary irritant. The toxicity of the gas to humans has not been reported (58), but laboratory tests on animals gave results ranging from an increased pneumonitis to death. The TLV is 1 ppm (59,60). Inhalation toxicity studies in rats have shown that exposure to BF at 17 mg/m resulted in renal toxicity, whereas exposure at 6 mg/m did not result in a toxic response (61). Prolonged inhalation produced dental fluorosis (62). High concentrations bum the skin similarly to acids such as HBF and, if the skin is subject to prolonged exposure, the treatment should be the same as for fluoride exposure and hypocalcemia. No chronic effects have been observed in workers exposed to small quantities of the gas at frequent intervals over a period of years. 

P. G. Watanabe, D. G. Pegg, J. D. Burek, H. O. Yakel, and L. W. Rampy, M 90-Day Bepeated Inhalation Toxicity Study of Cumene Hydroperoxide in Bats, Toxicology Research Laboratory, EPA Document No. 868600016, Eiche No. OTS0510168, Dow Chemical USA, Midland, Mich., 1979. 

M One-Year Inhalation Toxicity Study ofMntimonj Trioxide in the Rat (with a One-year Recovery Period), Bio /dynamics Incorporated, East Millstone, N.J. submitted to Antimony Oxide Industry Association (AOIA), Feb. 9, 1990. 

Polymers. Studies to determine possible exposure of workers to residual epichl orohydrin and ethylene oxide monomers in the polymers have been done. Tests of warehouse air where Hydrin H and Hydrin C are stored showed epichl orohydrin levels below 0.5 ppm. Air samples taken above laboratory mixing equipment (Banbury mixer and 6" x 12" mill) when compounds of Hydrin H or C were mixed gave epichl orohydrin levels below detectable limits, and ethylene oxide levels less than 0.2 ppm, well below permissible exposure limits (46). A subacute vapor inhalation toxicity study in which animals were exposed to emission products from compounded Parel 58 suggests that no significant health effects would be expected in workers periodically exposed to these vapors (47). 

Monsanto. 1987b. Three-month inhalation toxicity study of Skydrol 500B-4. 

CIIT. 1983a. 90-Day vapor inhalation toxicity study of hydrogen sulfide in B6C3Fj mice. Report to the Chemical Industry Institute of Toxicology, Research Triangle Park, NC, by ToxiGenics, Inc. CUT docket 42063. 

E.I.du Pont de Nemours. 1982b. Subacute Inhalation Toxicity Study of Aniline in Rats. OTS 84003A, Document 878220240. E.I.du Pont de Nemours and Co., Inc., Wilmington, DE. 

Craig, D.K., and J.Frye. 1988. Acute LC50 Nose Only Inhalation Toxicity Studies of Arsine in Rats [final report with cover letter to the Office of Pollution Prevention and Toxics, dated Feb. 21, 1992], Battelle, Columbus, OH. 

Keller, W.C., C.T.Olson, and K.C.Back. 1984. Teratogenic assessment of three methylated hydrazine derivatives in the rat. J. Toxicol. Environ. Health 13 125-131. Kinkead, E.R., C.C.Haun, E.H.Vemot, and J.D.MacEwen. 1985. A chronic inhalation toxicity study on monomethylhydrazine. AFAMRL-TR-85-025. Aerospace Medical Research Laboratory, Wright-Patterson AFB, OH. 

Mattie, D.R., et al., A 90-day continuous vapor inhalation toxicity study of JP-8 jet fuel followed by 20 or 21 months of recovery in Fischer 344 rats and C57BL/6 mice, Toxicol. Pathol., 19, 77, 1991. 

Gaworski, C.L., H.L.Leahy, W.J.Bashe, J.D.MacEwen, E.H.Vernot, C.C.Haun, R.H.Bruner, and LF.Wyman. 1985. A one-year inhalation toxicity study of Otto Fuel II. ADA 163 162 AAMRL-TR-85-071 NMRI-85-56, University of California, Irvine, California and Naval Medical Research Institute, Wright-Patterson Air Force Base, Ohio. 

Hext, P.M. 1989. 90-day inhalation toxicity study in the rat. ICI Report No. CTL/P/2466. Central Toxicology Laboratory, Imperial Chemical Industries, Alderley Park, Macclesfield, Cheshire, U.K. (Cited in NRC 1996). 

Hardy, J.C., G.C.Jackson, R.S.Rad, D.J.Lewis, and C.Gopinath. 1989b. Acute inhalation toxicity study in rats (PWT95/881676), Huntingdon Research Centre Ltd., Huntingdon, Cambridgeshire, England (Cited in ECETOC 1994). 

Hino, Y, K.Yamasaki, and K.Schiraishi. 1992. Twenty-eight-day repeated inhalation toxicity study of HCFC 141b in rats. Report B 18-0005, Hita Research Laboratory Chemical Biotesting Center, Chemicals Inspection and Testing Institute, Japan. 

Bio/Dynamics Inc. 1978. 26 Week inhalation toxicity study of w-hexane in the rat. Unpublished report prepared for the American Petroleum Institute, Washington, DC. EPA -FYI-AX-1081-0137. 

Many inhalation exposure techniques, such as the whole-body, nose-only, mouth-only, or head-only technique (Drew and Laskin, 1973 MacFarland, 1976 Leong et al., 1981 Phalen, 1984 Nelson, 1980), the intranasal exposure technique (Elliott and DeYoung, 1970 Smith et ah, 1981), the endotracheal nebulization technique (Leong et ah, 1985, 1988 Schreck et ah, 1986), and the body plethysmographic techniques (Alarie, 1966 Thome and Karol, 1989), have been developed for inhalation toxicity studies. Table 10.2 provides a summary of the advantages and disadvantages of each of the major inhalation exposure methodologies. 

Shiotsuka RN. 1989. Subchronic inhalation toxicity study of technical grade disulfoton (DI-SYSTON) in rats. Study No. 88-141-UA. Report No. 99648. Mobay Corporation, Corporate Toxicology Department, Stilwell, Kansas. 

Appeltnan, L.M., ten Berge, W.F., and Reuzel, P.G. Acute inhalation toxicity study of ammonia in rats with variable exposure periods, Am. Ind. Hyg. Assoc. J., 43(9) 662-665, 1982. 

Hoben, H.J., Ching, S.A., and Casarett. A study of inhalation of pentachlorophenol by rats Part III. Inhalation toxicity study. Bull Environ. Contam. Toxicol, 15(4) 463-465, 1976. 

Klonne, D.R., Dodd, D.E., Pritts, I.M., Nachreiner, D.J., Fowler. E.H.,Troup. C.M.. Homan. E.R., and Ballantyne, B. Dimeth-ylethanolamine acute, 2-week, and 13-week inhalation toxicity studies in rats. Fundam. Appl. Toxicol.,9 Z) 5l2-52l, 1987. Klonne, D.R., Ulrich, C.E., Weissmann, J., and Morgan, A.K. Acute inhalation toxicity of aliphatic (C1-C5) nitrites in rats. Fundam. Appl Tbxrco/., 8(1) 101-106, 1987a. 

Substances, which are skin or eye irritating or corrosive after single exposure (Section 4.5) should be suspected of inducing local effects upon repeated respiratory exposure to low concentrations. In contrast, local effects reported from skin sensitization studies as well as dermal repeated dose toxicity studies are not predictive of local effects on the respiratory tract. In addition, observations from irritation and/or sensitization studies as well as repeated dose inhalation toxicity studies are not predictive of local effects on the skin upon repeated dermal exposure (EC 2003). 

In practice, this means that no adjustment for difference in body size is needed for a NOAEC obtained for systemic effects in an inhalation toxicity study (van Genderen 1988, Feron et al. 1990, Vermeire et al. 1999, KEMI 2003). For example, a NOAEC of 50 mg/m observed for laboratory animals is also the equivalent human NOAEC (note that so far species-specific sensitivity has not been taken into account). 

Default Reference Values for Body Weights in Oral and Inhalation Toxicity Studies... 

Exposure Concentrations (ppm) Used in 3-Day (6 h/day) Inhalation Toxicity Studies in Male Rats with Nasal Toxicants... 

Warheit DB, Kelly DP, Carakostas MC, Singer AW A 90-day inhalation toxicity study with benomyl in rats. Fundam Appl Toxicol 12 333-345, 1989... 

Rusch GM, Hoffman GM, McConnell RF, et al Inhalation toxicity studies with horon trifluoride. Toxicol Appl Pharmacol 83 69-78, 1986... 

Inhalation toxicity studies with 1,3-butadiene two-year toxicity/carcinogenicity study in rats. Am Ind Hyg Assoc f 48 407-413, 1987... 

Reinhold RW, Hoffman GM, Bolte HF, et al Subchronic inhalation toxicity study of caprolactam (with a 4-week recovery) in the rat via whole-body exposures. Toxicol Sci 44(2) 197-205, 1998... 

Gaworski CL, Haun CC, MacEwen JD, et al A 90-day vapor inhalation toxicity study of decalin. Fundam Appl Toxicol 5 785-793, 1985... 

Trochimowicz HJ et al Ninety-day inhalation toxicity studies on two fluorocarbons. Toxicol Appl Pharmacol 41 299 (abst), 1977... 

Hurtt ME, Placke ME, Killinger JM, et al 13-Week inhalation toxicity study of dimethylformamide (DMF) in Cynomolgus monkeys. Eundam Appl Toxicol 18 596-601, 1992... 

Mobil Oil Corporation. TSCA sec. 8(e) Submission 8EHQ-0381-0366 Follow-up. 4 Four Week Inhalation Toxicity Study in the Rat. Prepared by Bio/dynamics, Inc, Washington, DC, Office of Toxic Substances, US Environmental Protection Agency, 1981... 

Landry TD, Yano BL Dipropylene glycol monomethyl ether A 13-week inhalation toxicity study in rats and rabbits. Fundam Appl Toxicol 4-.6U-6n, 1984... 

Landry TD, Ayres JA, Johnson KA, et al Ethyl chloride a two-week inhalation toxicity study and effects on liver non-protein sulfhydryl concentrations. Fundam Appl Toxicol 2 230-234, 1982... 

Landry TD, Johnson KA, Phillips JE, et ah Ethyl chloride 11-day continuous exposure inhalation toxicity study in B6C3F1 mice. Fundam Appl Toxicol 13 516-522, 1989... 

In a subacute inhalation toxicity study, rats of both sexes were exposed for 6 hours/day, 5 days/week for 4 weeks. Recovery groups were kept for an observation period of 14 days without treatment. At 891, 441, or 142 ppm hemolytic anemia was observed. Mild hemolytic anemia was found in female rats exposed to 100 ppm, but it had disappeared after the 14-day recovery period. 

Pavokv KL et ah Major findings in a twenty-four month inhalation toxicity study of methyl chloride in mice and rats. Toxicologist 2 161, 1982... 

Phillips RD, Moran EJ, Dodd DE, et al A 14-week vapor inhalation toxicity study of methyl isobutyl ketone. Eundam Appl Toxicol 9 380-388, 1987... 

Hamm TE Jr Ninety-Day Inhalation Toxicity Study of Nitrobenzene in F344 Rats, CD Rats, and B6C3F1 Mice Final Study Report. Research Triangle Park, NC, CRT, 1984... 

Lapin CA, Craig DK, Valerio MG, et al A subchronic inhalation toxicity study in rats exposed to silicon carbide whiskers. Fundam Appl Toxicol 16 128-146, 1991... 

Huntingdon Res Ctr Ltd Initial Submission Thioglycolic Acid Acute Inhalation Toxicity Study in Rats 4-Hour Exposure, with cover letter dated 09/15/94. EPA/OTS Doc 88-940000230... 

---