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1,1-diphenylethane is a clear low viscosity liquid used in high voltage power capacitors and a major (58.4%) constituent of Benzene Ethylenated By Products (CAS number 68608-82-2 and EC number 271-802-8). On the basis of its use, the major routes of human exposure are expected to be through dermal contact and/or inhalation. The oral LD50of the Nisseki SAS-40 (containing 1,1-diphenylethane, 1,2-diphenylethane, dibenzyl, benzyltoluene, diphenylmethane and ditolylmethane) in the rat is estimated to be 2531 mg/kg [3]. At the high dose of 5000 mg/kg, 70-90% animals died within 24 hours of dosing; whereas, it took up to 4 days at the lower doses [3]. Necropsy showed test material effects on lungs, liver, spleen and kidneys along with hemorrhage of small and large intestine and glandular and non-glandular gastric epithelia. These results suggest moderate absorption after oral ingestion and subsequent organ effects leading to death at high doses. The rate of oral absorption in humans was estimated using ADC ADME4.95(Advance Chemistry Development, Inc,,) through QSAR. The permeability of 1,1-diphenylethane through jejunum was predicted to be 5.9 x 10-4cm/s (equivalent to 2.124 cm/h) and the rate of absorption (ka) of 0.101 min-1.


1,2-diphenylethane is a solid at room temperature with a melting point of 50-53oC. The oral LD50of 1,2-diphenylethane in rats has been reported to be > 5 g/kg; dermal LD50to rabbits was also >5 g/kg [4]. The lowest lethal dose of 1,2-diphenylethane was reported 1000 mg/kg to mice after intraperitoneum injection [5]. 1,2-diphenylethane is not a skin irritant or sensitizer [6]. 1,2-diphenylethane has been reported to absorbed from the GI tract and cause increase liver weight [7]. The permeability of 1,2-diphenylethane through jejunum was predicted to be 5.77 x 10-4cm/s and the rate of absorption (ka) of 0.101 min-1.


Dermal toxicity of the mixture containing 1,1-diphenylethane is low (LD50>2000 mg/kg). Of 10 rats given a single 24-hour occluded application to the shaved skin, none died and there were no signs of systemic toxicity or dermal irritation [8]. Given the mortality after oral route, it is reasonable to conclude that the test material is not well absorbed by the dermal route of exposure. Due to the absence of real dermal penetration data, the dermal penetration was estimated using DERMWIN™ (version 1.43, US EPA,,) using Guy and Potts QSAR model. The estimated dermal permeability was 0.13 cm/h.


Given the dermal LD50of 1,2-diphenylethane to be >5 g/kg, its dermal absorption is limited. The DERMWIN predicted dermal permeability of 1,2-diphenylethane was 0.37 cm/h.



Due to its relative lipophilicity (log Pow= 4.37), 1,1-diphenylethane may be expected to partition into fatty tissues. The predicted volume of distribution (Vd) is 2.9 L/kg. QSAR estimated binding to plasma proteins will be approximately 97%.


Due to its relative lipophilicity (log Pow= 4.19), 1,2-diphenylethane may be expected to partition into fatty tissues. The predicted volume of distribution (Vd) is 2.8 L/kg. QSAR estimated binding to plasma proteins will be approximately 98%.



In rat liver microsomes, 1, 2-Diphenylethane was reported to metabolize to 1-(p-hydroxyphenyl)-2-phenylethane (aromatic hydroxylation) and1,2-diphenyl-l-hydroxyethane(aliphatic hydroxylation). The 1,2-diphenyl-l-hydroxyethane was further oxidized to the corresponding ketone in this microsomal system [9].


Based on the metabolic fate of 1,2-diphenylethane, the 1,1-diphenylethane isomer would also be expected to be metabolized to both aromatic and aliphatic hydroxylated products. The aliphatic metabolites could be both 1,1-diphenyl-1-hydroxyethane and 1,1-diphenyl-2-hydroxyethane. The major aromatic hydroxylated metabolite would be predicted to be 4-(1-phenylethyl)phenol.


No metabolism data has been reported for mono alkenyl benzene components of this material. For isomers with the C=C bond directly attached to the aromatic ring, the mono alkenyl benzene would be expected to be metabolized via epoxidation of the alkenyl group, as described for styrene metabolism [10-12]. The formed epoxide would also be expected to conjugate with glutathione [13]. The aromatic ring would also expected to hydroxylated by cytochrome P450 to form 4-alkenylphenol or 2-alkenylphenol products [14]. 


For isomers with C=C bond not directly attached to the aromatic ring, the mono alkenyl benzene would expected to mainly be metabolized to side chain hydroxylated metabolites as described for ethylbenzene [15-17]. Hydroxylation of the aromatic ring would be a minor pathway [18, 19].



All of the oxidative metabolites would be expected to be highly conjugated with sulfate, glucuronide, or glutathione. These Phase-2 metabolites would be much more water-soluble than the parent compounds, therefore would be expected to be rapidly excreted, primarily in urine.


  1. National Industrial Chemicals Notification and Assessment Scheme of. Full Public Report on 1,1’-diphenylethane,,. Report No. NA/84, 1999.
  2. The Merck Index, An encyclopedia of Chemicals, Drugs, and Biologicals, 11thedition (Budavari, S., O’Neil, M.J., Smith, A., Heckelman, P.E., editors), Merck and Co., Inc.,,.
  3. Nisseki SAS-40: Acute Oral Toxicity Test in the Rat. Data on file, Nippon Petrochemicals Company Ltd.,,, Report No: 4538-230/7, 1990.
  4. Baily, D.E. (1976). Report to RIFM, 21 May.
  5. National Institute for Occupational safety and Health (1976). Registry of Toxic Effects of Chemical Substances, 1976 Edition (Christensen, H.E. and Fairchild, E.J., Eds.) Entry number DT 43750, p. 227. NIOSH, Washington.
  6. Epstein, E.L. (1976). Report to RIFM, 27 May.
  7. Gershbein, L.L. (1975). Liver regeneration as influenced by the structure of aromatic and heterocyclic compounds. Res. Commun. Chem. Path. Pharmac. 11, 445.
  8. Nisseki SAS-40: Acute Dermal Toxicity (Limit Test) in the Rat. Data on file, Nippon Petrochemicals Company Ltd.,,, Report No: 4539-230/8, 1990.
  9. Sipal, Z., and Zelingerova, J. (1978) Hydroxylation of diphenylmetane and diphenylethane. Ceskoslovenska farmacie 440, 180-183.
  10. Leibman, K.C. (1975) Metabolism and toxicity of styrene. Environmental health perspectives 11, 115-119.
  11. Watabe, T., Isobe, M., Sawahata, T., Yoshikawa, K., Yamada, S., and Takabatake, E. (1978) Metabolism and mutagenicity of styrene. Scandinavian journal of work, environment & health 4 Suppl 2, 142-155.
  12. Watabe, T., Ozawa, N., and Yoshikawa, K. (1981) Stereochemistry in the oxidative metabolism of styrene by hepatic microsomes. Biochemical pharmacology 30, 1695-1698.
  13. Watabe, T.,, A., Ozawa, N., and Isobe, M. (1981) Glutathione S-conjugates of phenyloxirane. Biochemical pharmacology 30, 390-392.
  14. Watabe, T.,, A., Aizawa, T., Sawahata, T., Ozawa, N., Isobe, M., and Takabatake, E. (1982) Studies on metabolism and toxicity of styrene. IV. 1-Vinylbenzene 3, 4-oxide, a potent mutagen formed as a possible intermediate in the metabolism in vivo of styrene to 4-vinylphenol. Mutation research 93, 45-55.
  15. Engstrom, K., Riihimaki, V., and Laine, A. (1984) Urinary disposition of ethylbenzene and m-xylene in man following separate and combined exposure. International archives of occupational and environmental health 54, 355-363.
  16. Engstrom, K.M. (1984) Metabolism of inhaled ethylbenzene in rats. Scandinavian journal of work, environment & health 10, 83-87.
  17. Engstrom, K.M. (1984) Urinalysis of minor metabolites of ethylbenzene and m-xylene. Scandinavian journal of work, environment & health 10, 75-81.
  18. ,, Rick, D.L., McClymont, E.L., Zhang, F., Bartels, M.J., and Bus, J.S. (2009) Mechanism of ethylbenzene-induced mouse-specific lung tumor: metabolism of ethylbenzene by rat, mouse, and human liver and lung microsomes. Toxicol Sci 107, 352-366.
  19. Kiese, M., and Lenk, W. (1974) Hydroxyacetophenones: urinary metabolites of ethylbenzene and acetophenone in the rabbit. Xenobiotica; the fate of foreign compounds in biological systems 4, 337-343.

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