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Dermal absorption

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dermal absorption
Type of information:
experimental study
Adequacy of study:
key study
2 (reliable with restrictions)

Data source

Reference Type:
Dibutyl phthalate
Bibliographic source:
Priority Existing Chemical Assessment Report No. 36, ISBN 978-0-9874434-4-1

Materials and methods

Results and discussion

Applicant's summary and conclusion

DBP absorption via the dermal route in humans is low .
Dermal absorption in rat is 40 times higher in comparison to humans, therefore studies in rats about dermal DBP absorption are not representative for human skin.
Executive summary:

Absorption via the dermal route and subsequent elimination was assessed after application of 43.7 mg/kg 14C-DBP in ethanol (with occlusion) to the clipped skin of male F344 rats, followed by measurements of the excreted 14C radiolabel. Over seven days, DBP was excreted in urine and faeces at a nearly constant rate of approximately 10–12 % of the applied dose each day. Around one third of the applied dose remained at the site of application (Elsisi et al. 1989). In a comparative in vitro study, Scott et al. (1987) demonstrated that the rate of dermal absorption for DBP is about 40 times greater in rat than in human epidermal skin preparations (93.35 μg/cm2/h and 2.40 μg/cm2/h, respectively). More recently, Janjua et al. (2007 ND, 2008 ND) examined systemic uptake and elimination of DBP after dermal application in human volunteers. About 40 g of a standard cosmetic lotion formulation without (during control week) or with 2 % DBP (during treatment week) was applied to the whole body of 26 adult males for five consecutive days. The volunteers did not use any phthalate containing cosmetics for three weeks before the treatment week. Serum and urine concentrations of the primary metabolite, monobutyl phthalate (MBP), were measured. Urine was collected as individual samples at different time points during the first day of the treatment week and as 24-hour pools on all consecutive days. Results demonstrated increases in MBP in serum and urine within a few hours of application. An average of 1.82 % (range 0.11–5.94 %) of the applied DBP dose was recovered in urine as MBP during the treatment week. Taking into consideration the studies in rodents that demonstrate absence of significant bioaccumulation of DBP in any organs or tissues, the studies by Janjua et al. suggest that DBP absorption via the dermal route in humans under conditions of usual cosmetic application is low. A study with hairless guinea pigs (Doan et al. 2010 ND) that compared in vivo and in vitro skin absorption of DBP from an oil-in-water emulsion, found that in vivo, 62.0 % ±2.0 % (mean of three animals ±SEM) of the applied dose (AD) was systematically absorbed. Most of this (60.4 ±1.8 %AD) was excreted in the urine and less than 2 % was found in other tissues (ovaries, kidneys, liver). The amount of applied dose retained in the skin after 24 hours was 2.2 ±0.3 % AD; 7.4 ±2.3 % AD was trapped as volatile material in the first hour after dosing. The amount of DBP absorbed in vivo after 24 hours closely agreed with the amount of DBP found in the receptor fluid in vitro after 72 hours, suggesting that in vitro DBP is a lipophilic chemical that can initially form a reservoir in skin, and can slowly diffuse out of the skin into the receptor fluid. The relative permeability of human and guinea pig skin for DBP from this particular oil-in-water emulsion has not been compared.