Isopropyl benzoate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

other: review article

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The Cosmetic Ingredient Review Expert Panel, comprised of U.S. toxicologists and chemists, under the auspices of the U.S. Food and Drug Administration (FDA), provides safety and risk assessment overviews of cosmetic ingredients. The conclusions of this independent body are considered thorough and valid for use in cosmetic applications.

Data source

Reference

Reference Type:

review article or handbook

Title:

Safety assessment of alkyl benzoates as used in cosmetics

Author:

Becker LC, Bergfeld WF, Belsito DV, et al.

Year:

2012

Bibliographic source:

Int. J. Toxicol. 31:342S-72S

Materials and methods

Objective of study:

toxicokinetics

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

This is a review article authored by the Expert Panel of the CIR, summarizing numerous studies. This summary does not follow a test guideline.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Isopropyl benzoate

EC Number:

213-361-6

EC Name:

Isopropyl benzoate

Cas Number:

939-48-0

Molecular formula:

C10H12O2

IUPAC Name:

propan-2-yl benzoate

Constituent 2

Reference substance name:

13-361-6

IUPAC Name:

13-361-6

Constituent 3

Reference substance name:

propan-2-yl benzoate

IUPAC Name:

propan-2-yl benzoate

Test material form:

not specified

Test animals

Species:

other: various species, compliation of data

Administration / exposure

Route of administration:

oral: unspecified

Results and discussion

Any other information on results incl. tables

Orally administered benzoate esters are metabolized to benzoic acid and the corresponding alcohols, and the acid is further metabolized to benzyl glucuronide and benzoyl CoA, an intermediate in the formation of hippuric acid, which is the principal metabolite excreted in the urine.

In general, esters can be hydrolyzed to the parent alcohol and acid by enzymes. Secondary and tertiary esters are hydrolyzed more slowly than primary esters. These enzymes are in essentially all tissues, including the respiratory tract, skin, and gastrointestinal tract, and blood. 

Data on benzyl alcohol show that it is converted into benzoic acid by simple oxidation. Orally consumed benzoic acid is absorbed from the gastrointestinal tract and conjugated with glycine in the liver. The resulting hippuric acid is excreted in the urine (75%-100% within 6 hours). Dermally applied benzoic acid is also excreted in the urine within 24 hours.

In general, alcohols can be metabolized by alcohol dehydrogenases to aldehydes (primary alcohols) or ketones (secondary alcohols). Aldehydes are further metabolized by aldehyde dehydrogenases to the correspondingacids.

Benzoic esters are not absorbed through the skin as rapidly as alkyl esters. If alkyl benzoates are absorbed and metabolized, the alcohols resulting from ester hydrolysis can be oxidized via alcohol dehydrogenases to produce the corresponding aldehyde or ketone. As noted above, these aldehydes can be further oxidized via aldehyde dehydrogenases, aldehyde oxidases, or xanthine oxidases to the corresponding acids.

 

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): no bioaccumulation potential based on study results
Orally administered benzoate esters are metabolised to benzoic acid and the corresponding alcohol. These are readily broken down and excreted.