Estimation of the Percutaneous Absorption of Permethrin in Humans Using the Parallelogram Method

Ross, John H.; Reifenrath, William G.; Driver, Jeffrey

doi:10.1080/15287394.2011.534425

Cited by 24 publications

(24 citation statements)

References 35 publications

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“…Results from HPLC/FSA analysis of extracted feces collected during the 72 hour orally dosed rat study indicated DBDPE was eliminated unchanged in feces after oral administration to female SD rats or male B6C3F1/Tac mice (data not shown). Rat skin is more permeable than human skin for a number of substances, which may explain the differences in dose penetration (Roper et al, 2006, Api et al, 2013, Banks and Birnbaum, 1991, Ross et al, 2011, van Ravenzwaay and Leibold, 2004). These results indicate that dermal exposure to DBDPE contributes a small portion to the total exposure to DBDPE from the environment.…”

Section: Discussionmentioning

confidence: 99%

The biological fate of decabromodiphenyl ethane following oral, dermal or intravenous administration

et al. 2016

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The disposition of decabromodiphenyl ethane (DBDPE) was investigated based on concerns over its structural similarities to decaBDE, high potential for environmental persistence & bioaccumulation, and high production volume.In the present study, female Sprague Dawley rats were administered a single dose of [14C]-DBDPE by oral, topical, or IV routes. Another set of rats were administered 10 daily oral doses of 14C]-DBDPE. Male B6C3F1/Tac mice were administered a single oral dose.DBDPE was poorly absorbed following oral dosing, with 95% of administered [14C]-radioactivity recovered in the feces, 1% recovered in the urine and less than 3% in the tissues at 72 h. DBDPE excretion was similar in male mice and female rats. Accumulation of [14C]-DBDPE was observed in liver and the adrenal gland after 10 daily oral doses.The dermis was a depot for dermally applied DBDPE; conservative estimates predict ~14±8% of DBDPE may be absorbed into human skin in vivo; ~7±4% of the parent chemical is expected to reach systemic circulation following continuous exposure (24 h).Following intravenous administration, 6% of the dose was recovered in urine and 28% in the feces, while ~70% of the dose remained in tissues after 72h, with the highest concentrations found in the liver (42%) and lung (17%).

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Section: Discussionmentioning

confidence: 99%

The biological fate of decabromodiphenyl ethane following oral, dermal or intravenous administration

et al. 2016

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“…To quantify the dermal contact component, we applied the principles of the parallelogram approach to the dermal exposure assessments for both chemicals to estimate a likely level following in vivo human systemic exposures to a relevant dose of dermally-applied FR, as described by Ross et al (59). The hypothesis behind the parallelogram approach has shown data from rat to be within ±3-fold of the values measured in human subjects; however, when studies have been conducted under analogous conditions as part of a matched protocol study, the uncertainty for the predicted value is much lower (85-87).…”

Section: Discussionmentioning

confidence: 99%

“…Because of inconsistent differences in percutaneous absorption between rat and human skin, it is not possible to derive a general adjustment factor for estimation of human percutaneous absorption. However, when these data are available for rat in vivo and for rat and human skin in vitro , the in vivo dermal absorption through human skin can be estimated from the relationship outlined by the parallelogram method (56-59). Briefly, in vivo human exposure is estimated as a function of in vitro human exposure multiplied by a normalization factor based on the same dose applied to rat skin in vivo and in vitro .…”

Section: Methodsmentioning

confidence: 99%

Estimation of human percutaneous bioavailability for two novel brominated flame retardants, 2-ethylhexyl 2,3,4,5-tetrabromobenzoate (EH-TBB) and bis(2-ethylhexyl) tetrabromophthalate (BEH-TEBP)

Knudsen

Hughes

Sanders

et al. 2016

Toxicology and Applied Pharmacology

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2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB) and bis(2-ethylhexyl)tetrabromophthalate (BEH-TEBP) are novel brominated flame retardants used in consumer products. A parallelogram approach was used to predict human dermal absorption and flux for EH-TBB and BEH-TEBP. [14C]-EH-TBB or [14C]-BEH-TEBP was applied to human or rat skin at 100 nmol/cm2 using a flow-through system. Intact rats received analogous dermal doses. Treated skin was washed and tape-stripped to remove “unabsorbed” [14C]-radioactivity after continuous exposure (24h). “Absorbed” was quantified using dermally retained [14C]-radioactivity; “penetrated” was calculated based on [14C]-radioactivity in media (in vitro) or excreta+tissues (in vivo). Human skin absorbed EH-TBB (24±1%) while 0.2±0.1% penetrated skin. Rat skin absorbed more (51±10%) and was more permeable (2±0.5%) to EH-TBB in vitro; maximal EH-TBB flux was 11±7 and 102±24 pmol-eq/cm2/h for human and rat skin, respectively. In vivo, 27±5% was absorbed and 13% reached systemic circulation after 24 h (maximum flux was 464±65 pmol-eq/cm2/h). BEH-TEBP in vitro penetrance was minimal (<0.01%) for rat or human skin. BEH-TEBP absorption was 12±11% for human skin and 41±3% for rat skin. In vivo, total absorption was 27±9%; 1.2% reached systemic circulation. In vitro maximal BEH-TEBP flux was 0.3±0.2 and 1±0.3 pmol-eq/cm2/h for human and rat skin; in vivo maximum flux for rat skin was 16±7 pmol-eq/cm2/h. EH-TBB was metabolized in rat and human skin to tetrabromobenzoic acid. BEH-TEBP-derived [14C]-radioactivity in the perfusion media could not be characterized. Less than 1% of the dose of EH-TBB and BEH-TEHP is estimated to reach the systemic circulation following human dermal exposure under the conditions tested.

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“…The present work provides data to support assessment of risk of dermal exposure of TBBPA to humans. Here, the parallelogram approach (18, 19) has been used to characterize and compare the extent of dermal absorption and penetrance of TBBPA in vivo in rats and in vitro in rat and human skin for prediction of internal dose to humans following dermal exposure to TBBPA.…”

Section: Introductionmentioning

confidence: 99%

Estimation of tetrabromobisphenol A (TBBPA) percutaneous uptake in humans using the parallelogram method

Knudsen

Hughes

McIntosh

et al. 2015

Toxicology and Applied Pharmacology

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Tetrabromobisphenol A (TBBPA) is currently the world’s highest production volume brominated flame retardant. Humans are frequently exposed to TBBPA by the dermal route. In the present study, a parallelogram approach was used to make predictions of internal dose in exposed humans. Human and rat skin samples received 100 nmol of TBBPA/cm2 skin and absorption and penetrance were determined using a flow-through in vitro system. TBBPA-derived [14C]-radioactivity was determined at 6 hour intervals in the media and at 24 hours post-dosing in the skin. The human skin and media contained an average of 3.4% and 0.2% of the total dose at the terminal time point, respectively, while the rat skin and media contained 9.3% and 3.5%, respectively. In the intact rat, 14% of a dermally-administered dose of ~100 nmol/cm2 remained in the skin at the dosing site, with an additional 8% reaching systemic circulation by 24 hours post-dosing. Relative absorption and penetrance was less (10% total) at 24 hours following dermal administration of a ten-fold higher dose (~1,000 nmol/cm2) to rats. However, by 72 hours, 70% of this dose was either absorbed into the dosing-site skin or had reached systemic circulation. It is clear from these results that TBBPA can be absorbed by the skin and dermal contact with TBBPA may represent a small but important route of exposure. Together, these in vitro data in human and rat skin and in vivo data from rats may be used to predict TBBPA absorption in humans following dermal exposure. Based on this parallelogram calculation, up to 6% of dermally applied TBBPA may be bioavailable to humans exposed to TBBPA.

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Estimation of the Percutaneous Absorption of Permethrin in Humans Using the Parallelogram Method

Cited by 24 publications

References 35 publications

The biological fate of decabromodiphenyl ethane following oral, dermal or intravenous administration

The biological fate of decabromodiphenyl ethane following oral, dermal or intravenous administration

Estimation of human percutaneous bioavailability for two novel brominated flame retardants, 2-ethylhexyl 2,3,4,5-tetrabromobenzoate (EH-TBB) and bis(2-ethylhexyl) tetrabromophthalate (BEH-TEBP)

Estimation of tetrabromobisphenol A (TBBPA) percutaneous uptake in humans using the parallelogram method

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