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Toxicological information

Exposure related observations in humans: other data

Administrative data

Endpoint:
exposure-related observations in humans: other data
Type of information:
experimental study
Adequacy of study:
key study
Study period:
5 June 2020 to 9 October 2020
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2020
Report date:
2020

Materials and methods

Type of study / information:
Double blind, randomised investigation of the hydrating efficacy and the skin barrier integrity efficacy of hydrocarbon substances in human volunteers.
Endpoint addressed:
skin irritation / corrosion
other: skin hydration and skin barrier efficacy
Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
A double-blind, randomised trial in volunteers.
Skin hydration was assessed by measurement of skin capacitance compared with a placebo, a negative control and a positive (hydrating) control. Measurement of skin capacitance is a standard method for the assessment of skin hydration (Qassem, 2019).
Skin barrier integrity efficacy was assessed by measurement of the skin transepidermal water loss (TEWL) compared with a placebo and a negative control. Measurement of TEWL is a standard method for the assessment of skin barrier function, increase in TEWL indicates skin irritation (Kovács et al., 2020). A decrease in TEWL indicates enhancement of the barrier function of the skin (Kottner et al., 2015).
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Hydrocarbons, C18-C24, iso-alkanes <2% aromatics
EC Number:
940-734-7
Molecular formula:
C18H38, C19H40, C20H42, C21H44, C22H46, C23H48, C24H50
IUPAC Name:
Hydrocarbons, C18-C24, iso-alkanes <2% aromatics
Test material form:
liquid

Method

Ethical approval:
confirmed, but no further information available
Remarks:
The Clinical Investigation Plan was approved by the Ethics Committee for Health of Inovapotek. Subsequent revisions to the procedure included making alterations recommended by the Ethics Committee.
Details on study design:
Healthy adult volunteers not suffering from skin disease were split into four groups. Test areas, eight per subject, four per forearm, were outlined using plastic marker. Each group had a different set of test substances. Ten test substances were tested at two different concentrations, 5% and 100%.
Each subject received a single application of five test substances, with a placebo, a negative control (water), and a positive control (for skin capacitance measurement)
Volume applied: 2 µl/cm²
Placebo: Span 80 (0.65%) and Tween 80 (0.20%) in water
Negative control: water
Positive control for the skin capacitance measurements: aqueous solution of glycerine at 85%,
Justification for choice of positive control: not given in report, however, glycerine is a known moisturiser and not classified for skin defatting from repeated skin contact (Lodén, 2002; Milani, 2017).
Measurement of skin capacitance
- Frequency of measurement of skin capacitance: before application, then at 2, 4, 8 and 24 hours
- Replication: measurements made in triplicate
- Equipment for measurement of skin capacitance: Corneometer®
Measurement of skin transepidermal water loss (TEWL)
- Frequency of measurement of TEWL: before application, then at 2, 4, 8 and 24 hours
- Replication: measurements made in triplicate
- Equipment for measurement of TEWL: Tewameter®
Statistical analysis: Wilcoxon test; Student’s T-test. Extreme outliers were identified by statistical analysis, and removed from the analysis of differences and mean values.
Details on exposure:
single application
Volume applied: 2 µl/cm²
Measurements: 0, 2, 4, 8 and 24 hours

Results and discussion

Results:
Application of Hydrocarbons, C18-C24, isoalkanes, <2% aromatics (Shell GTL Solvent GS310) resulted in a statistically significant increase in the skin hydration relative to the placebo up to 8 hours after application at concentrations of 5% and 100%. 24 hours after application the hydration level had decreased to be close to the baseline level.
Application of Hydrocarbons, C18-C24, isoalkanes, <2% aromatics (Shell GTL Solvent GS310) decreased the TEWL relative to the placebo up to 24 hours after application at a concentration of 100%, indicating an improvement of the skin barrier condition. The TEWL was unchanged after application at a concentration of 5%.

Any other information on results incl. tables

See Tables of results attached to this summary.

Applicant's summary and conclusion

Conclusions:
In a study involving human volunteers, a single cutaneous application of Hydrocarbons, C18-C24, isoalkanes, <2% aromatics (Shell GTL Solvent GS310) resulted in a statistically significant increase in skin hydration relative to the placebo up to 8 hours after application at concentrations of 5% and 100%, and a decrease in the TEWL relative to the placebo up to 24 hours after application at a concentration of 100%. The TEWL was unchanged after application at a concentration of 5%.
These results indicate that, after a single application Hydrocarbons, C18-C24, isoalkanes, <2% is effective as a skin moisturiser and improves the skin barrier by decreasing the transepidermal water loss. Based on these results, it is concluded that the test substance does not require classification for skin defatting from repeated skin contact.
Executive summary:

Repeated dermal contact with petroleum-derived hydrocarbons causes skin dryness and cracking, and Hydrocarbons, C18-C24, isoalkanes, <2% aromatics was formerly classified for skin defatting from repeated skin contact: EUH066, based on prediction. To establish whether this classification was justified, a study has been conducted with volunteers to investigate the hydrating efficacy and the skin barrier integrity efficacy of a number of substances in a double-blind, randomised study. The test substances included Hydrocarbons, C18-C24, isoalkanes, <2% aromatics.

Skin hydration was assessed by measurement of skin capacitance compared with a placebo (Span 80 (0.65%) and Tween 80 (0.20%) in water), a negative control (water), and a positive control. The positive control was an aqueous solution of glycerine at 85%, glycerine is a known moisturiser and not classified for skin defatting from repeated skin contact.

Skin barrier integrity efficacy was assessed by measurement of the skin transepidermal water loss (TEWL) compared with a placebo (Span 80 (0.65%) and Tween 80 (0.20%) in water) and a negative control (water).

Healthy adult volunteers were split into four groups. Each subject received a single application of 2 µl/cm² of five test substances, a placebo, a negative control and, for the skin capacitance measurement, a positive control. Test and control substances were applied to eight separate sites, four on each forearm, of each volunteer in the group. Each group had a different set of test substances.

Ten test substances were tested at two different concentrations, 5% and 100%. The test substances, referred to in the report by product name only, were:

- Hydrocarbons, C9-C11, n-alkanes isoalkanes, <2% aromatics (Shell GTL Solvent GS190)

- Hydrocarbons, C11-C16, n-alkanes isoalkanes, <2% aromatics (Shell GTL Solvent GS1927)

- Hydrocarbons, C10-C13, n-alkanes isoalkanes, <2% aromatics (Shell GTL Solvent GS215)

- Hydrocarbons, C14-C16, n-alkanes isoalkanes, <2% aromatics (Shell GTL Solvent GS250)

- Hydrocarbons, C15-C19, n-alkanes isoalkanes, <2% aromatics (Shell GTL Solvent GS270)

- Hydrocarbons, C18-C24, isoalkanes, <2% aromatics (Shell GTL Solvent GS310)

- Shell GTL Normal Paraffin 10-13

- Shell Risella X 415

- Saraline 185V

- Distillates (petroleum), hydrotreated light (C13-C15 alkanes and naphthenics) (EC No. 265-149-8; ShellSol D100)

The skin hydration measurements were performed at each test site, in triplicate, before application of the test and control substances, and at 2 hours, 4 hours, 8 hours and 24 hours after application.

The skin transepidermal water loss (TEWL) measurements were performed at the same test sites and time intervals as the skin hydration measurements.

Application of Hydrocarbons, C18-C24, isoalkanes, <2% aromatics (Shell GTL Solvent GS310) resulted in a statistically significant increase in the skin hydration relative to the placebo up to 8 hours after application at concentrations of 5% and 100%. 24 hours after application the hydration level had decreased to be close to the baseline level.

Application of Hydrocarbons, C18-C24, isoalkanes, <2% aromatics (Shell GTL Solvent GS310) decreased the TEWL relative to the placebo up to 24 hours after application at a concentration of 100%, indicating an improvement of the skin barrier condition. The TEWL was unchanged after application at a concentration of 5%.

These results indicate that, after a single application, Hydrocarbons, C18-C24, isoalkanes, <2% is effective as a skin moisturiser and improves the skin barrier by decreasing the transepidermal water loss. Based on these results, it is concluded that the test substance does not require classification for skin defatting from repeated skin contact.