Document e1xLj1jEKOoLyJBR9Yrj3z26M

AR226-3389 Genetic Toxicology of 8-2 Telomer B Alcohol G.L. KennedyJ R. Jung,2 H. Iwai,3 S. Shin-ya,4 S. Murphy,5 N. Drouot,5 C. Finlay,1 E.M. Donner,1 G.L. Erexson,6 and L.F. Stankowski, Jr.6 1. The DuPont Company, Haskell Laboratory fo r Health and Environmental Sciences, Newark, Delaware, USA 2. Clariant GmbH, Salzbach, Germany 3. Daikin Industries, Ltd., Osaka, Japan 4. Asahi Glass Company, Ltd., Tokyo, Japan 5. Atofina Chemicals, Philadelphia, Pennsylvania, USA, and Paris, France 6. Covance Laboratories, Vienna, Virginia, USA I K Abstract 8-2 Teiom er B Alcohol is a fluorinated chemical intermediate produced and used w orldw ide to m anufacture specialty polym ers and surfactants used to a) treat surfaces such as textiles to m ake them oil and w ater repellant and b) as a w etting and leveling agent in coatings and cleaning products, respectively. The global teiom er producers have initiated a scientific program to develop toxicity data for this chem ical. 8-2 Teiom er B A lcohol w as evaluated for b a cterial m utag en icity , in tw o independent experim ents, in S. typhim urium strains T A 98, T A 100, T A 1535, and T A 1537 and E. coli strain W P2vrA , at doses o f 33.3 to 5,000 ftg/plate w ith and without m etabolic activation (S9). Norm al grow th was observed in all strains and revertant frequencies for all doses o f 8-2 Teiom er B A lcohol, w ith and w ithout S9, approxim ated vehicle controls. In a m icro n u cleu s test, m ale rats w ere given a single oral (lim it) dose o f 2,000 mg/kg, and the bone marrow cells subsequently exam ined for the possible induction of m icronucleated polychrom atic erythrocytes (M N -PCE). A s in earlier studies, this lim it d ose elicited no clinical signs o f toxicity. N o signs of clinical or bone m arrow toxicity, and no statistically significant increases in M N -PC E frequencies w ere observed. U nder the conditions o f these tests, 8-2 T eiom er B A lcohol d id n o t induce a n increase in reverse m u tatio n s in S. typhim urium o r E. coli, o r a n increase in M N P C E s in ra t b o n e m a rro w . (Studies supported by the TRP* Toxicology Program .) * Teiom er Research Program I Purity o f Test Sample CF3-[CFjjrCH 2-CH2-OH* 99.3% CF3-[CF2)-CF=CH-CH2-OH 0.6% C F j-[CF2] Ii-CHs=CH2 0.1% P H Salmonella - E.coli Mammalian Microsome Reverse Mutation Assay Laboratory: Covance (Virginia) Dates of Conduct: October 23.2001 - December 10,2001 Director: LF. Stankowski, Jr. OECD Guidelines: 471, July 21. 1997 Tester Strains: TA98.TA 100, TA 1535, TA1537, WP2uwA Standard Conditions: with and without S9 mice Vehicle: DMSO Posidve Controls: S9 mix mb Benzo(a)pyrene TA98 ~ --------15 2-Nitrofluorene TA98 -1 2-Aininoanthracene TA100.TA1535, * 2.5-25 TA1537, WP2uvrA Sodium Azide TA100,TAt535 - 2 ICR-191 TA1537 -2 4-Nitroquinoline-N-oxide WP2uvrA -1 TA98 TA100 1S5 8-60 60-240 4-45 2-25 Assay considered positive if producing at least a 2x increase in mean reveitants per plate or at least 1 o f these tester strains over m ean revertants pe r plate o f appropriate vehicle control. T h is in crease h a d to be a ccom panied by a dose response to increasing concentrations o f th e test article. (TA98, TA100, W P2uvrA) [3x forT A 1535 andTA 1537] nyRat Micronucleus Assay Laboratory: Covance (Virginia) Dates of Conduct: October 18,2001 - November 19,2001 Director G.L. Erexson OECD Guidelines: 474, July 21,1997 Conditions: Rat, oral dose(2x) o f0,500,1000, or 2000 mg/kg Examined cells for nucrouuclcuB polychromatic erythrocytes at 24 and 48 hours post-dose The criteria for a positive response was the detection of a statistically significant increase in micronucleated PCEs for at least one dose level, Mid a statistically significant dose-related response. A test article that did not induce both of these responses was considered negative. Statistical significance was not the only determinant of a positive response; the Study Director also considered the biological relevance o f the results in the final evaluation. !liII3J3I1] I iiiiiiiiiiliiii i IlliUniiillli I * " "S' U II IS* I** ' '* ' M* " I K lSUinll i = r s r 8-2 Telom er B Alcohol M icronucleus Test in Bone M arrow Cells Summary Data - Male Rats m i Conclusions The results of the Salmonella - Escherichia coli I Mammalian-Microsome Reverse Mutation Assay indicate that under the conditions of this study, 8-2 Teiomer B Alcohol was not mutagenic in any of the tester strains in the presence o r absence o f an exogenous metabolic activation system containing induced hepatic microsomal enzymes from AroclorTM 1254-treatedrats. Conclusions The test article, 8-2 Teiomer B Alcohol, produced no signs o f clinical toxicity in male rats exposed to up to 2000 mg/kg, the regulatory limit dose for this assay. In addition, 8-2 Teiomer B Alcohol was not cytotoxic to the bone marrow at up to 2000 mg/kg. Note, if observed, a statistically significant decrease in PCE:NCE ration would be evidence of bone marrow cytotoxicity induced by the test article. In the micronucleus assay, 8-2 Teiomer B Alcohol did not induce a statistically significant increase in micronucleated PCEs at any o f the doses tested. Therefore, 8-2 Teiomer B Alcohol is considered negative in the rat bone marrow micronucleus assay under the conditions of this assay.