Registration Dossier

Administrative data

Endpoint:
dermal absorption in vitro / ex vivo
Type of information:
(Q)SAR
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
QSAR has been derived from 182 measured aqueous permeation coefficients on human skin in vitro. The QSAR uses the independent variables log(Kow) and the molecular weight to predict the dependent variable, the aqueous permeation coeffcient. The log(Kow) had a range of -3.7 through 5.5 and the molecular weight a range of 18 to 585. Most industrial chemicals cover both ranges. In addition a QSAR has been derived from97 measured stratum corneum/water partition coeffcient. The QSAR uses the log(Kow) to predict the partition between the stratum corneum and water.
Data waiving:
other justification
Justification for data waiving:
other:
Justification for type of information:
QSAR prediction: migrated from IUCLID 5.6

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
A simple dermal absorption model: derivation and application.
Author:
ten Berge W
Year:
2009
Bibliographic source:
Chemosphere, 75(11):1440-1445, 2009
Reference Type:
publication
Title:
Dermal absorption of chemicals: estimation by IH SkinPerm
Author:
Tibaldi R, ten Berge W, Drolet D
Year:
2014
Bibliographic source:
J Occup Environ Hyg. 11(1):19-31, 2014

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 428 (Skin Absorption: In Vitro Method)
Version / remarks:
Only human skin
Deviations:
not specified
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: Not applicable for QSAR
Radiolabelling:
no

Test animals

Species:
other: Human skin in vitro was used for QSAR derivation.
Strain:
other: Human
Sex:
male/female
Details on test animals and environmental conditions:
Not applicable

Administration / exposure

Type of coverage:
other:
Vehicle:
water
Control animals:
no

Results and discussion

Signs and symptoms of toxicity:
no effects
Dermal irritation:
no effects
Percutaneous absorptionopen allclose all
Dose:
0.1 mg/cm2
Parameter:
percentage
Absorption:
ca. 78 %
Remarks on result:
other: 24 hours
Dose:
0.5 mg/cm2
Parameter:
percentage
Absorption:
ca. 76 %
Remarks on result:
other: 24 hours
Dose:
1 mg/cm2
Parameter:
percentage
Absorption:
ca. 72 %
Remarks on result:
other: 24 hours
Dose:
2 mg/cm2
Parameter:
percentage
Absorption:
ca. 70 %
Remarks on result:
other: 24 hours
Dose:
3 mg/cm2
Parameter:
percentage
Absorption:
ca. 50 %
Remarks on result:
other: 24 hours
Dose:
4 mg/cm2
Parameter:
percentage
Absorption:
ca. 38 %
Remarks on result:
other: 24 hours
Dose:
5 mg/cm
Parameter:
percentage
Absorption:
ca. 30 %
Remarks on result:
other: 24 hours
Conversion factor human vs. animal skin:
Not applicable, because QSAR is derived for human skin.

Applicant's summary and conclusion

Conclusions:
The mean maximum permeation rate of succononitrile through the human skin is 0.032 mg/cm2/hour. This means that in 24 hours no more than 0.77 mg succinonitrile can permeate through 1 cm2 of the skin. The upper 95 percentile of the estimate 0.046 mg/cm2/hour or 1.1 mg/cm2/24 hours. If more than 1 mg succinonitrile per cm2 is applied, the mass > 1 mg/cm2 will not be absorbed, but this evaporates or remains as residue on the skin.
Executive summary:

The QSAR (ten Berge 2009, Tibaldi et al 2014) was used to estimate the permeation rate of succinonitrile through the human skin. The maximum permeation rate was estimated to be 0.032 mg/cm2/hour (95% CL 0.022 -0.046 mg/cm2/hour). In occupational exposure normally 2000 cm2 of the skin might be exposed over a period of 8 hours. The upper confidence limit of 0.046 mg/cm2/hour is used for estimation of the absorption of succinonitrile over a period of 8 hours through 2000 cm2 of the skin ( 8 * 2000 * 0.046). In case of a bodyweight of 60 kg, this results in a dose of 12 mg/kgbw over a period of 8 hours. This dose is too low to cause any signs of acute intoxication.