Percutaneous absorption of neat and aqueous solutions of 2-butoxyethanol in volunteers

Abstract

Objectives

To study the influence of the presence of water on the dermal absorption of 2-butoxyethanol (BE) in volunteers.

Methods

Six male volunteers were dermally exposed to 50%, 90% or neat w/w BE for 4 h on the volar forearm over an area of 40 cm². An inhalation exposure with a known input rate and duration served as a reference dosage. The dermal absorption parameters were calculated from 24-h excretion of total (free + conjugated) butoxyacetic acid (BAA) in urine and BE in blood, measured after both inhalation and dermal exposure.

Results

The dermal absorption of BE from aqueous solutions was markedly higher than that of neat BE. The time-weighted average dermal fluxes were calculated from the urine and blood data and expressed in milligrammes per square centimetre per hour. The dermal fluxes obtained from cumulative 24-h excretion of BAA amounted to 1.34±0.49, 0.92±0.60 and 0.26±0.17 mg cm⁻² h⁻¹ for 50%, 90% and neat BE, respectively. The dermal fluxes calculated from the BE blood data amounted to 0.92±0.34 and 0.74±0.25 mg cm⁻² h⁻¹ for 50% and 90% BE, respectively. The permeation rates into the blood reached a plateau between 60 and 120 min after the start of exposure, indicating achievement of steady-state permeation. The apparent permeability coefficient K _p , was 1.75±0.53×10⁻³ and 0.88±0.42×10⁻³ cm h⁻¹ for 50% and 90% BE, respectively.

Conclusion

The percutaneous absorption of BE from aqueous solution increased markedly when compared with neat BE. Even water content as low as 10% led to an approximate fourfold increase in the permeation rates. These findings are important for the health risk assessment of occupational exposure to BE, since BE is commonly used in mixtures that contain water. Exposure to aqueous solutions of 50% and 90% of BE may result in substantial skin absorption: if a 60-min skin contact of 1,000 cm² is assumed, dermal uptake would be four-times higher than the pulmonary uptake of an 8-h occupational exposure at a TLV of 100 mg m⁻³. This clearly justifies the skin notation for BE. For the purpose of biological monitoring, both BE in blood and BAA in urine were shown to be reliable indicators of exposure.