Registration Dossier

Administrative data

Endpoint:
dermal absorption
Type of information:
other: Expert statement
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: An extended assessment of the toxicokinetic behaviour of N-Butylpyrrolidone was performed, taking into account the chemical structure, the available physico-chemical-data and the available toxicity data of its structural analogues NMP and NEP.

Data source

Referenceopen allclose all

Reference Type:
other: Expert statement
Title:
Unnamed
Year:
2014
Report date:
2014
Reference Type:
other: QSAR
Title:
Unnamed
Year:
2014
Report date:
2014

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: TGD, Part I, Annex IV, 2003); ECHA guidance R7c., 2012
Deviations:
yes
Principles of method if other than guideline:
Dermal absorption of N-butylpyrrolidone was assessed using its physico-chemical properties and the permeability coefficient calculated by EpiSuite (v.4.1).
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
1-butylpyrrolidin-2-one
EC Number:
222-437-8
EC Name:
1-butylpyrrolidin-2-one
Cas Number:
3470-98-2
Molecular formula:
C8H15NO
IUPAC Name:
1-butylpyrrolidin-2-one

Results and discussion

Percutaneous absorption
Parameter:
percentage
Absorption:
ca. 50 %
Remarks on result:
other: Moderate dermal absorption potential

Any other information on results incl. tables

Based on the physico-chemical properties of NBP, the substance is likely to penetrate the skin to a certain extent as the substance is sufficiently lipophilic to cross the stratum corneum (LogPow of 1.256) and sufficiently soluble in water to partition from the stratum corneum into the epidermis (the substance is fully miscible with water (0 to 100%)). Absorption through the skin is anticipated to be moderate to high if water solubility lies between 100-10,000 mg/L. However, if water solubility is above 10,000 mg/L (ECHA Guidance R.7c, 2012) and logPow value below 0 the substance may be too hydrophilic to cross the lipid rich environment of the stratum corneum. LogPow of NBP is > 0 therefore certain absorption of the chemical through the skin cannot be ruled out. In addition, the molecular weight of 141.2 g/mol indicates a moderate potential to penetrate the skin as well. Additionally, a skin permeability constant Kp of 0.00173 cm/hour was calculated for NBP by EPpiSuite (v4.1; dermwin; please see attached to this endpoint). According to Schumacher et al. (2003; please see attached), dermal absorption should be regarded as relevant if the permeability constant is <10–2and ≥10–4cm/hour. The absorption of NBP via skin is expected to be lower than via the oral route. Moreover, the irritation potential of NBP is weak and delayed (slight erythema persisted in animals till the end of the observation period in the acute dermal study) but it will not enhance penetration through the skin to such rates that would result in a significant bioavailability. According to TGD, Part I (2003) and ECHA Guidance on Toxicokinetics, Part R.7c (2012), 10 % or 100 % absorption can be assigned for substances in case of absence of substance-specific information on absorption rates through the skin and based only on their physico-chemical properties. However, taking into account low bioavailability of NBP demonstrated by the absence of toxicity effects in the acute dermal study, 50% absorption for dermal route is considered more appropriate than the guidance’s worst-case values. The percentage can be used for the purposes of DNEL derivation in case of route-to-route extrapolation.

Applicant's summary and conclusion

Conclusions:
Moderate dermal absorption potential (50 %) is predicted for N-Butylpyrrolidone.
Executive summary:

The evaluation of the physico-chemical properties of the target substance and the results of the available dermal toxicity study allow the allocation of the chemical in question into the group of chemicals with a moderate dermal absorption potential. In detail, due to its molecular weight of 141.2 g/mol, log Pow value of 1.256, high water solubility (miscible with water from 0 to 100 %) as well as permeability constant Kp of 0.00173 cm/hour, the use of a factor of 50 % for the estimation of dermal uptake would be appropriate.