Free and total urinary 2-butoxyacetic acid following dermal and inhalation exposure to 2-butoxyethanol in human volunteers

Objectives: To assess excretion kinetics of free and total (free + conjugated) 2-butoxyacetic acid (BAA) following dermal and inhalation exposure to butoxyethanol (BE). Methods: Six male volunteers were dermally exposed for 4 h to a 50% aqueous solution of BE on an area of 40 cm(2) of the volar forearm. Six other male volunteers were exposed by inhalation (mouth only) to 93 ring m(-3) BE for 30 min. As biological indices of exposure, BE in blood and total and free BAA in urine were measured. Results: Following inhalation exposure, the 24-h cumulative excretion of free and total BAA in urine amounted to 5.5 +/- 2.7 and 12.8 +/- 4.0 mg, respectively. After dermal exposure, 147.1 +/- 61.0 and 346 +/- 52 mg, respectively, of free and total BAA were excreted in urine up to 48 h after the onset of exposure. The proportion of conjugated BAA in single urine samples increased after dermal exposure in time from 45 +/- 30% in the first collection period to 92 +/- 2% after 48 h. The elimination half-life of total BAA following dermal exposure was longer than that of free BAA (5.1 +/- 0.6 and 3.8 +/- 0.4 h, respectively). The interindividual variation in the cumulative excreted amount after inhalatory exposure was higher (49%) for free BAA than for total BAA (31%). The average dermal flux amounted to 3.5 mg cm(-2) h(-1) independently of whether free or total BAA was used for the calculation, and, again, the interindividual variation in the estimated fluxes was higher for free BAA than for total BAA (41% and 15%, respectively). Conclusion: The interindividual variation in the extent of conjugation is large, and the degree of conjugation increases with time. Due to lower interindividual variability, total BAA is superior to free BAA as a biornarker of exposur

Repeated topical treatment, in contrast to single oral doses, with Vitamin A-containing preparations does not affect plasma concentrations of retinol, retinyl esters or retinoic acids in female subjects of child-bearing age

Background: Vitamin A is widely used in cosmetic preparations. Given that oral Vitamin A and its metabolites present a potential reproductive risk, the present study investigated the effect of topical Vitamin A on human endogenous plasma levels of Vitamin A and its metabolites. Methods: Two groups of 14 female volunteers of child-bearing age were kept on a Vitamin A-poor diet and treated topically for 21 days with creams containing 0.30% retinol or 0.55% retinyl palmitate on approximately 3000 cm2 of their body surface area, amounting to a total of approximately 30,000 IU Vitamin A/subject/day. After a 12-day wash-out period, the study groups received single oral doses of 10,000 IU or 30,000 IU retinyl palmitate (RP), corresponding to the maximal EU allowance during pregnancy or three-times higher, respectively. Blood samples were collected over 24 h on study days -3 (pre-study), 1, 21 (first and last days of topical treatment) and 34 (oral administration) at 0, 1, 2, 4, 6, 8, 12, 14-16 h and 24 h after treatment for determination of plasma concentrations of retinol (REL), retinyl palmitate (RP), oleate (RO) and stearate (RS), 9-cis-, 13-cis-, all-trans- (AT), 13-cis-4-oxo- or AT-4-oxo-retinoic acids (RAs). Results: With the exception of transient mild (RP-group) to moderate (REL-group) local irritation on the treatment sites, no adverse local or systemic effects were noted. On days 1 or 21 of topical treatment, no changes were measured in individual or group mean plasma Cmax, AUC0-24 h or other pharmacokinetic parameters of REL, retinyl esters or RAs relative to pre-study data. In contrast, single oral doses of RP at 10,000 IU or 30,000 IU produced dose-related and sustained increases in Cmax and AUC0-24 h values of plasma RP, RO, RS, 13-cis- and 13-cis-4-oxo-RAs, as well as a transient increase in AT-RA. In conclusion, our results provide evidence that human topical exposure to retinol- or retinyl ester-containing cosmetic creams at 30,000 IU/day and maximal use concentrations do not affect plasma levels of retinol, retinyl esters or RAs, whereas single oral doses at 10,000 IU or 30,000 IU produce significant increases in plasma retinyl esters and RAs. © 2005 Elsevier Ireland Ltd. All rights reserved