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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
calculation (if not (Q)SAR)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Published data in readily available literature. Clayton GD & Clayton FE (eds.) are commonly accepted as trustworthy and useful reference

Data source

Reference
Reference Type:
review article or handbook
Title:
Patty's Industrial Hygiene and Toxicology
Author:
Clayton GD & Clayton FE (eds.)
Year:
1982
Bibliographic source:
Eds. Clayton & Clayton, Wiley New York, 3rd ed., Vol 2C, 4636-4703

Materials and methods

Objective of study:
metabolism
toxicokinetics
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Methods:in vivo. Reviewed summary for toxicokinetics and metabolism
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Radiolabelling:
not specified

Test animals

Details on species / strain selection:
Reviewed summary for toxicokinetics and metabolism

Results and discussion

Any other information on results incl. tables

TK data in animals (Cited from Patty's Industrial Hygiene and Toxicology, 1982):

Pharmacokinetics. The plasma half-life of benyl alcohol administered as a 2.5 percent solution in saline was found to be approximately 1.5 hr in dogs injected intravenously at doses of 52 and 105 mg/kg (456).

Metabolism/Excretion. Benzyl alcohol is oxidized by ADH. Winer (331) reports the activity of ADH on benzyl alcohol to be slighthly less than on ethanol. Von Wartburg (230) reports benzyl alcohol to be approximately one-half as active as ethanol in reaction with ADH and to have affinity to ADH roughly equal to that of isopropyl and butyl alcohols. The animal organism readily oxidizes benzyl alcohol to benzoic acid, which, after conjugating with glycine is rapidly eliminated as hippuric acid in the urine. Rabbits given 1 g of benzyl alcohol subcutaneously eliminated 300 to 400 mg of hippuric acid within the following 24 hr (463). Within 6 hr after the oral administration of 0.40 g benzyl alcohol/kg of body weight, rabbits eliminated 65.7 percent of the dose as hippuric acid in the urine (464). Chief metabolic products are benzoic and hippuric acids. Metabolites identified in the urine of rabbits given an oral dose of 0.25 g/kg benzyl alcohol are given in the following tabulation: (465)

 

 

 Metabolite

Percent of Dose

 Range (No. of Experiments)

  1. Mercapturic acid

 0 -4 (326)

  2. Glycine conjugate

74 

 71 -76 (111)

  3. Copper reducing material (as glucuronic acid)

 4 -15 (111)

  4. Glucosiduronic acid

14 

 6 - 23 (111) 

  5. Ethereal sulfate

 0 (452)

  6. Ether-soluble acid

84 

 80 -90 (111)

 

TK data in humans

Metabolism/Excretion. Humans readily oxidize benzyl alcohol to benzoic acid, which, after conjugation with glycine, is rapidly eliminated as hippuric acid in the urine. Within 6 hr after taking 1.5 g of benzyl alcohol orally, human subjects eliminated 75 to 85 percent of the dose in the urine as hippuric acid (467).

456: E.T Kimura, T.D. Darby, R.A. Krause, and H.D. Brondyk, Toxicol. Appl. Pharmacol., 18(1), 60 (1971).

331: A.D. Winer, Acta Chem. Scand. 12, 1695 (1958), Cited by R. Derache, Int. Encycl. Pharmacol. Ther., 20, 507 (1970).

230: J. Von Wartburg, "The Metabolism of Alcohol in Normals and Alcoholics: Enzymes", Chapter 2 in B. Kissin, Eds., The Biology of Alcoholism, Vol. 1, Plenum, New York, 1971, pp. 63-91.

463: J.A. Stekol, J. Biol. Chem., 128, 199 (1939).

464: S.L Diack and H.B. Lewis,)J. Biol. Chem., 77, 89 (1928).

465: H.G. Bray, S.P. James, and W.V. Thorpe, Biochem. J., 70, 570 (1958).

467: I. Snapper, A. Grunbaum, and S. Sturkop, Biochem. Z., 155, 163 (1925)

Applicant's summary and conclusion

Conclusions:
From the available data it is concluded that it is unlikely that Benzyl alcohol causes genetic effects or has an effect on male or female fertility and has no bioaccumulation potential.