Butyl Benzyl Phthalate (BBP) is an aromatic ester that is used as a plasticizer at concentrations below 1.0%.
After oral and intravenous (iv) administration, BBP was rapidly excreted. The oral LD50 was: 2.3 g/kg for F344/N rats, and 4.2-6.2 g/kg for B6C3F1 mice. Rats and mice exposed to high concentrations of BBP lost weight, had testicular atrophy, hemorrhages, and hepatomegaly. No toxicity was reported in an oral subchronic toxicity study using dogs.
BBP was not a reproductive toxin to CD-1 and B6C3F1 mice; however, BBP caused dose-dependent microscopic degenerative changes in the testes of male F344 rats. BBP was nonmutagenic in the Ames Test, L5178Y TK mouse lymphoma mutagenesis assay, dominant lethal mutagenicity assay, and BALB/3T3 cell transformation assay. An increase in the incidence of mononuclear cell leukemia in female F344/N rats was not considered to be related to the exposure to high doses of BBP. BBP was not carcinogenic in studies using B6C3F1 and A/St mice.
Slight transient dermal and ocular irritation was produced by undiluted BBP in rabbits. In human dermal studies, BBP was not a significant irritant nor sensitizer.
On the basis of data presented in this report, it is concluded that butyl benzyl phthalate is a safe cosmetic ingredient in the present practices of use and concentration.
2. NATIONAL LIBRARY OF MEDICINE (NLM). (1989). NLM Chemline database.
3.
3. Kluwe, W.M. (1982). Overview of phthalate ester pharmacokinetics in mammalian species. Environ. Health Perspect.45, 3–10.
4.
4. Thomas, J.A., and Thomas, M.J. (1984). Biological effects of di-(2-ethylhexyl) phthalate and other phthalic acid esters. Crit. Rev. Toxicol.13(4), 283–318.
5.
5. Hawley, C.G. (Editor). (1971). The Condensed Chemical Dictionary. New York: Van Nostrand Reinhold Company, p. 139.
6.
6. Sax, N.I. (Editor). (1979). Dangerous Properties of Industrial Materials, 5th ed.New York: Van Nostrand Reinhold Company, p. 443.
7.
7. Giam, C.S., and Wong, M.K. (1987). Plasticizers in food. J. Food Prot.50(9):769–82.
8.
8. Little, Arthur D., Inc. (1981). Exposure and risk assessment for phthalate esters (Di(2-ethylhexyl) phthalate, Di-n-butyl phthalate, Dimethyl phthalate, Diethyl phthalate, Di-n-octyl phthalate, Butyl benzyl phthalate). Prepared for the Environmental Protection Ageny. NTIS pub. no.: PB85–211936.
9.
9. Leyder, F., and Boulancer, P. (1983). Ultraviolet absorption, aqueous solubility, and octanol-water partition for several phthalates. Bull. Environ. Contam. Toxicol.30, 152–7.
10.
10. Rittfeldt, L., Ahlberg, M.S., Zingmark, P-A., and Santesson, J. (1983). Occupational exposure to benzyl chloride and benzal chloride due to contaminated butylbenzyl phthalate. Scand. J. Work Environ. Health9(4), 367–8.
11.
11. NATIONAL TOXICOLOGY PROGRAM. (1982). Carcinogenesis bioassay of butyl benzyl phthalate (CAS No. 85–68–7) in F344/N rats and B6C3F1 mice (feed study). (NTP No. 80–25; NIH Publication No. 82–1769; PB83–118398). Washington, DC, U.S. Department of Health and Human Services.
12.
12. Howard, P.H., Baneriee, S., and Robillard, K.H. (1985). Measurement of water solubilities, octanol/water partition coefficients and vapor pressures of commercial phthalate esters. Environ. Toxicol. Chem.4(5), 653–62.
13.
13. INTERNATIONAL AGENCY FOR RESEARCH ON CANCER (IARC). (1976). Benzyl chloride. IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. Lyon, France: IARC. 2,218.
14.
14. Kopfler, F.C., Melton, R.G., Mullaney, J.L., and Tardiff, R.G. (1975). Human exposure to water pollutants. Prepr. Pap. Natl. Meet., Div. Environ. Chem., Am. Chem. Soc.15(1), 185–7.
15.
15. Pankow, J.F., Ligocki, M.P., Rosen, M.E., Isabelle, L.M., and Hart, K.M. (1988). Adsorption/thermal desorption with small cartridges for the determination of trace aqueous semivolatile organic compounds. Anal. Chem.60(1), 40–7.
16.
16. Stein, V.B., Amin, T.A., and Narang, R.S. (1987). Simplified method for determining polychlorinated biphenyls, phthalates, and hexachlorocyclo-hexanes in air. J. Assoc. Off. Anal. Chem.70(4): 721–3.
17.
17. Shafer, K.H., Cooke, M., Deroos, F., Jakobsen, R.J., Rosario, O., and Mulik, J.D. (1981). Wall-coated open tubular capillary column gas chromatography—Fourier transform IR and gas chromatography—mass spectrometry identifying toxic organic pollutants. Appl. Spectrosc.35(5), 469–72.
18.
18. Ramsey, J.D., Lee, T.D., Osselton, M.D., and Moffat, A.C. (1980). J. Chromatog.184(2), 185–206. (Gas-liquid chromatographic retention indices of 296 non-drug substances on SE-30 or OV-1 likely to be encountered in toxicological analyses.)
19.
19. Nikitakis, J. (ed). (1988). CTFA Cosmetic Ingredient Handbook. CTFA: Washington, DC pp 133–4.
20.
20. FOOD AND DRUG ADMINISTRATION (FDA). (1989). FDA product formulation computer printout.
21.
21. FDA. (1984). FDA product formulation computer printout.
22.
22. CODE OF FEDERAL REGULATIONS (CFR). (1982). Title 21, Part 720.4.
23.
23. COSMETIC, TOILETRY, and FRAGRANCE ASSOCIATION (CTFA). (1984). CTFA List of Japanese Cosmetic Ingredients. Washington, DC: CTFA, p. 11.
24.
24. Gledhill, W.E., Kaley, R.C., Adams, W.J., Hicks, O., Michael, P.R., and Saeger, V.W. (1980). An environmental safety assessment of butyl benzyl phthalate. Environ. Sci. Technol.14(3), 301–5.
25.
25. Eigenberg, D.A., Bozigian, H.P., Carter, D.E., and Sipes, I.G. (1986). Distribution, excretion, and metabolism of butylbenzyl phthalate in the rat. J. Toxicol. Environ. Health17(4), 445–56.
26.
26. Castle, L., Mercer, A.J., Startin, J.R., and Gilbert, J. (1988). Migration from plasticized films into foods 3. Migration of phthalate, sebacate, citrate, and phosphate esters from films used for retail food packaging. Food Additives Contam.5(1), 9–20.
27.
27. Lawrence, W.H. (1979). Phthalate Esters: The Question of Safety. Toxicology Annual. Vol. 3. New York: Marcel Dekker, Inc., pp. 89–139.
28.
28. FOOD CHEMICAL NEWS GUIDE. (1988). Guide to the current status of food additives and color additives. Washington, DC: The Food Chemical News Guide. p. 70.2.
29.
29. CODE OF FEDERAL REGULATIONS (CFR). (1984). Title 21, Part 175.105. Indirect Food Additives: Adhesives and Components of Coatings. Adhesives. Government Printing Office, Washington, D.C.
30.
30. CFR (1984). Title 21, Part 175.300. Indirect Food Additives: Adhesives and Components of Coatings. Resinous and polymeric coatings. Government Printing Office, Washington, D.C.
31.
31. CFR (1984). Title 21, Part 175.320. Indirect Food Additives: Adhesives and Components of Coatings. Resinous and polymeric coatings for polyolefin films. Government Printing Office, Washington, D.C.
32.
32. CFR (1984). Title 21, Part 176.170. Indirect Food Additives: Paper and Paperboard Components. Components of paper and paperboard in contact with aqueous and fatty foods. Government Printing Office, Washington, D.C.
33.
33. CFR (1984). Title 21, Part176.180. Indirect Food Additives: Paper and Paperboard Components. Components of paper and paperboard in contact with dry foods. Government Printing Office, Washington, D.C.
34.
34. CFR (1984). Title 21, Part 177.2420. Indirect Food Additives: Polymers. Polyester resins, cross-linked. Government Printing Office, Washington, D.C.
35.
35. CFR (1984). Title 21, Part 178.3740. Indirect Food Additives: Adjuvants, Production Aids, and Sanitizers. Plasticizers in polymeric substances. Government Printing Office, Washington, D.C.
36.
36. Barber, E.D., Astill, B.D., Moran, E.J., Schneider, B.F., Gray, T.J.B., Lake, B.G., and Evans, J.G. (1987). Peroxisome induction studies on seven phthalate esters. Toxicol. Ind. Health3(2), 7–24.
37.
37. Kasuya, M. (1980). Toxicity of butylbenzyl phthalate (BBP) and other phthalate esters to nervous tissue in culture. Toxicol. Letters6(6), 373–78.
38.
38. Pfuderer, P. and Francis, Pa. (1975). Phthalate Esters: Heartrate Depressors in the Goldfish: Bull. Environ. Contam. Toxicol.13(3): 275–9.
39.
39. Ekwall, B., Nordenstein, C., and Albanus, L. (1982). Toxicity of 29 plasticizers to He La cells in the MIT-24 system. Toxicology24(3–4), 199–210.
40.
40. Calley, D., Autian, J., and Guess, W.L. (1966). Toxicology of a series of phthalate esters. J. Pharm. Sci.55(2), 158–62.
41.
41. LITTON BIONETICS, INC. (1985). Evaluation of Butyl Benzyl Phthalate in the mouse lymphoma toxicity assay. Final Report. Submitted to Chemical Manufacturer's Association. Report obtained from the Environmental Protection Agency (EPA) through a Freedom of Information (FOI) request.
42.
42. LITTON BIONETICS, INC. (1985). Evaluation of Butyl Benzyl Phthalate in the in vitro transformation of BALB/3T3 cells assay. Final Report. Submitted to Chemical Manufacturer's Association. Report obtained from EPA through FOI request.
43.
43. Agarwal, D.K., Maronpot, R.R., Lamb, J.C. Iv., and Kluwe, W.M. (1985). Adverse effects of butyl benzyl phthalate on the reproductive and hematopoietic systems of male rats. Toxicology35(3), 189–206.
44.
44. Hammond, B.G., Levinskas, C.J., Robinson, E.C., and Johannsen, F.R. (1987). A review of the subchronic toxicity of butyl benzyl phthalate. Toxicol. Ind. Health3(2), 79–98. (Summary of various Monsanto studies).
45.
45. Hodge, H.C., and Sterner, J.H. (1949). Tabulation of toxicity classes. Am. Ind. Hyg. A. Quart.10, 93–6.
46.
46. Mallette, F. and Von Haam, E. (1952). Studies on the toxicity and skin effects of compounds used in the rubber and plastic industries: II Plasticizers. Archives of Industrial Hygiene and Occupational Medicine6(3):231–6.
47.
47. MONSANTO CHEMICAL COMPANY. (1983). Six week study of santicizer 160 plasticizer administered in the feed to Sprague-Dawley rats: Neuropathological Study Final Report. Monsanto Study No. AE-81–290. Report obtained from EPA through FDI request.
48.
48. MONSANTO CHEMICAL COMPANY. (1961). 90-day subacute oral toxicity of butyl benzyl phthalate—albino rats. Unpublished data obtained through Freedom of Information (FOI) request.
49.
49. MONSANTO CHEMICAL COMPANY. (1961). Subacute oral toxicity of butyl benzyl phthalate—dogs. Unpublished data obtained through FOI request.
50.
50. Bishop, J.B., Teaf, C.M., and Bhooshan, B. (1987). Assessment of fetal death rate among in utero progeny of B6C3F1 and CD-1 mice after subcutaneous injections of males with butylbenzylphthalate BBP. (Abstr). Environ. Mutagen9(Suppl. 8), 15.
51.
51. Field, E.A., Sleet, R.B., Price, J. Marr, M.C., Myers, C.B., Morrissey, R.E., and Schwetz, B.A. (1989). Developmental Toxicity Evaluation of Butyl Benzyl Phthalate (CAS No. 85–68–7) Administered in Feed to CD-Rats on Gestation days 6–15. Final Study Report NTP/NIEHS Contract No. N01-ES-95255.
52.
52. NATIONAL TOXICOLOGY PROGRAM. (1990). Development Toxicity of Butyl Benzyl Phthalate (CAS No. 85–68–7) in CD-I-Swiss mice. NTP #90–114. U.S. Department of Health and Human Services, Washington, DC.
53.
53. Zeiger, E., Haworth, S., Mortelmans, K., and Speck, W. (1985). Mutagenicity testing of di-(2-ethylhexyl) phthalate and related chemicals in Salmonella. Environ. Mutagen.7(2), 213–32.
54.
54. Kozombo, W.J., Kroll, R., and Rubin, R.J. (1982). Assessment of the mutagenicity of phthalate esters. Environ. Health Perspect.45:103–9.
55.
55. Kurata, H. (1975). Studies on the mutagenic effects of phthalates. Report to Ministry of Health and welfare (Japan), Scientific Research on Food Hygiene Program. (See Ref #56).
56.
56. Omori, Y. (1976). Recent progress in safety evaluation studies on plasticizers and plastics and their controlled use in Japan. Environ. Health Perspect.17, 203–9.
57.
57. IARC. (1982). Butyl benzyl phthalate. IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Lyon, France: IARC. 29, 193–201.
58.
58. Myhr, B.C., Bowers, L.R., and Caspary, W.J. (1986). Results from the testing of coded chemicals in the L5178Y TK+/-mouse lymphoma mutagenesis assay. (From Abstract). Environ. Mutagen.8(Suppl. 6), 58.
59.
59. Theiss, J.C., Stoner, G.D., Shimkin, M.B., and Weisburger, E.K. (1977). Test for carcinogenicity of organic contaminants of United States drinking waters by pulmonary tumor response in Strain A mice. Cancer Res.37:2717–2720. In: IARC, 1982 (See Ref #57).
60.
60. Ashby, J., and Tennant, R.W. (1988). Chemical structure, Salmonella mutagenicity and extent of carcinogenicity as indicators of genotoxic carcinogenesis among 222 chemicals tested in rodents by the U.S. NCI/NTP. Mutat. Res.204(1), 17–115.
