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Reference
Endpoint:
dermal absorption, other
Remarks:
QSAR
Type of information:
(Q)SAR
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification
Qualifier:
according to guideline
Guideline:
other: REACH Guidance on QSARs R.6
Qualifier:
according to guideline
Guideline:
other: REACH Guidance on IR&CSA, Chapter R.14, Occupational exposure assessment Update to change the scope of the guidance from exposure estimation to exposure assessment
Principles of method if other than guideline:
IH SkinPerm (v2.04) is a mathematical tool for estimating dermal absorption. The rate of mass build-up (or loss) on the skin comes from the deposition rate onto the skin minus the absorption rate into the Stratum Corneum (SC) and the amount evaporating from the skin to the air.
Species:
other: human
Type of coverage:
open
Vehicle:
unchanged (no vehicle)
Details on study design:
DATA INPUT
Molecular weight: 452 g/mol
Temperature: 20°C
Vapour Pressure: 0.00000017 Pa
Water solubility: 1,89 mg/L
Log Kow: 5,62
Density: 1120 mg/cm3
Melting point: -29°C

SCENARIO PARAMETERS
- Instantaneous deposition
Deposition dose*: 1000 mg
Affected skin area**: 1000 cm²
Maximum skin adherence***: 2 mg/cm²
Thickness of stagnant air****: 1 cm
Weight fraction: 1
Timing parameters
. Start deposition: 0 hr
. End time observation: 8 hr
Report parameters
. Calculation (intervals/hr): 10000
. Report (intervals/hr): 100

- Deposition over time
Affected skin area**: 1000 cm²
Maximum skin adherence***: 1 mg/cm²
Dermal deposition rate: 2 mg/cm²/hr
Thickness of stagnant air****: 1 cm
Weight fraction: 1
Timing parameters
. Start deposition: 0 hr
. Duration of deposition: 8hr
. End time observation*: 8 hr
Report parameters
. Calculation (intervals/hr): 10000
. Report (intervals/hr): 100

*Default value defined according to the internal validation study
**Estimated skin surface of two hands of an adult.
***The skin adherence field is greyed out and a default of -1 is indicated if the substance is a liquid at 25°C. Smart logic is built into IH SkinPerm; the program recognizes whether a substance is a solid or liquid at standard temperature (25°C) based on the physicochemical properties. For substances
that are solids at 25°C a maximum adherence value up to 2 mg/cm² is allowed based on studies of soil-on-skin adherence. If the deposition rate results in an increase above the input figure (0.2-2 mg/cm²), it is assumed that the surplus disappears just by removal from the skin.
*** 3 cm if clothing involved, 1 cm if bare skin involved

Time point:
8 h
Dose:
1000 mg
Parameter:
percentage
Absorption:
0.08 %
Remarks on result:
other: Instantaneous deposition
Time point:
8 h
Dose:
1 mg/cm²/h
Parameter:
percentage
Absorption:
0.005 %
Remarks on result:
other: Deposition over time for 8 hr
Conclusions:
The dermal absorption of Ethoxylated Bisphenol A dimethacrylate is estimated to be low (< 10%).
Executive summary:

The dermal absorption of Ethoxylated Bisphenol A dimethacrylate leads to the following results, obtained using the SkinPerm v2.04 model according to the input date :

 

Instantaneous deposition

 

Deposition over time

End time observation 8 hr

Total deposition (mg)

1000

2000

Fraction absorbed (%)

0.0823

0.00514

Amount absorbed (mg)

0,823

0.823

Lag time stratum corneum (min)

138

Max. derm. abs. (mg/cm²/h)

0.0000514

Description of key information

No experimental toxicokinetic study is available on Ethoxylated bisphenol A dimethacrylate. However, as per REACH guidance document R7.C, information on absorption, distribution, metabolism and excretion may be deduced from the physicochemical properties and QSAR predictions.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential
Absorption rate - oral (%):
100
Absorption rate - dermal (%):
10
Absorption rate - inhalation (%):
100

Additional information

No experimental toxicokinetic study is available on Ethoxylated bisphenol A dimethacrylate. However, as per REACH guidance document R7.C, information on absorption, distribution, metabolism and excretion may be deduced from the physicochemical properties, including:


-Molecular weight: mean 452 ; range [384;972]


-Water solubility: 1.89 mg/L 


-Partition coefficient Log Kow: 5.62


-Vapour pressure: 0.117 10^-6 Pa (20°C)


 


ABSORPTION


The value of log Kow (> 5) and the low water solubility are in the range suggestive of low absorption from the gastro-intestinal tract subsequent to oral ingestion. Indeed the absorption of highly lipophilic substances may be limited by the inability of such substances to dissolve into GI fluids. No adverse effect was observed in the oral acute toxicity study in rats treated with 2000 mg/kg/d. However, 100% of oral absorption is taken into account for risk assessment.


 


With low water solubility, a high value of log Kow and a molecular mass near to 500 g/mol, dermal absorption is anticipated to be low. Moreover, the acrylates are known to bind to skin components, and this binding decreases their dermal absorption. Based on the IH skin Perm (QSAR), the dermal absorption of Ethoxylated Bisphenol A dimethacrylate is estimated to be low (< 10%). Ethoxylated bisphenol A dimethacrylate is not skin irritating or skin sensitizer.


For risk assessment, 10% of dermal absorption is taken into account.


 


Based on the very low value of the vapour pressure, Ethoxylated bisphenol A dimethacrylate is not a volatile substance. However 100% of absorption after inhalation exposure is taken into account for risk assessment. 


 


 


DISTRIBUTION and METABOLISM


The molecule is lipophilic (log Kow >5), it is likely to distribute into cells and the intracellular concentration may be higher than extracellular concentration particularly in fatty tissues.


No specific data is available on the metabolism of Ethoxylated bisphenol A dimethacrylate.


 


ELIMINATION


Due to the low water solubility and a moderate molecular mass (near to 500 g/mol), the excretion of Ethoxylated bisphenol A dimethacrylate in the urines is not expected. An excretion via bile and faeces is possible.


 


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