Hexan-4-olide

Endpoint summary

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin corrosion: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 431 (In Vitro Skin Corrosion: Reconstructed Human Epidermis (RHE) Test Method)

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

Test Item
Designation in Test Facility: 17092503G
Date of Receipt: 25. Sep. 2017
Condition at Receipt: Room temperature, in proper conditions
Specification
The following information concerning identity and composition of the test item was provid-ed by the sponsor.
Name gamma-Dodecalactone
Batch no. 050170905
Appearance clear, colorless liquid
Composition gamma-Dodecalactone
Purity 99.02%
Homogeneity homogeneous
Expiry date 28. Dec. 2018
Storage Room Temperature: (20 ± 5°C)

The following additional information, provided by the sponsor too, was relevant to the conduct of the study, according to OECD 431:
CAS No. 2305-05-7
EINECS-No. 218-971-6
Stability H2O: unknown; EtOH: unknown; acetone: unknown; CH3CN: unknown; DMSO: unknown
Solubility H2O: unknown; EtOH: 0.1 - 1 g/L; acetone: unknown; CH3CN: unknown; DMSO: unknown
Structural Formula not stated
SMILES Code not stated

Test system:

human skin model

Source species:

human

Cell type:

non-transformed keratinocytes

Details on animal used as source of test system:

Specification
The test system is a commercially available EpiDermTM-Kit, procured by MatTek.
The EpiDermTM tissue consists of human-derived epidermal keratinocytes which have been cultured to form a multi-layered, highly differentiated model of the human epidermis. It consists of organized basal, spinous and granular layers, and a multi-layered stratum corneum containing intercellular lamellar lipid layers arranged in patterns analogous to those found in vivo. The EpiDermTM tissues are cultured on specially prepared cell cultures inserts.
Origin
EpiDermTM tissues were procured from MatTek In Vitro Life Science Laboratories, Bratislava.
Designation of the kit: EPI-200-SCT
Day of delivery: 28. Nov. 2018
Batch: 28671

Vehicle:

unchanged (no vehicle)

Control samples:

yes, concurrent negative control

yes, concurrent positive control

Amount/concentration applied:

50ul

Duration of treatment / exposure:

3min and 1h

Number of replicates:

3

Irritation / corrosion parameter:

% tissue viability

Run / experiment:

3 Minutes Experiment

Value:

ca. 113.3

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: non-corrosive to skin

Irritation / corrosion parameter:

% tissue viability

Run / experiment:

1 h Experiment

Value:

ca. 113.9

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: non-corrosive to skin

Interpretation of results:

GHS criteria not met

Conclusions:

The mean value of relative tissue viability of the test item was increased to 113.3% after 3 minutes treatment. This value is above the threshold for corrosivity (50%). After 1 hour treatment, the mean value of relative tissue viability of the test item was increased to 113.9%, lying above the threshold for corrosivity (15%). Therefore, the test item is consid-ered as non-corrosive to skin.

Reference 2

Endpoint:

skin irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)

GLP compliance:

yes

Test system:

human skin model

Source species:

human

Cell type:

non-transformed keratinocytes

Cell source:

other: EpiDermTM tissues were procured from MatTek In Vitro Life Science Laboratories, Brati-slava.

Source strain:

not specified

Vehicle:

unchanged (no vehicle)

Details on test system:

The test system is a commercially available EpiDermTM-Kit, procured by MatTek.
The EpiDermTM tissue consists of human-derived epidermal keratinocytes which have been cultured to form a multi-layered, highly differentiated model of the human epidermis. It consists of organized basal, spinous and granular layers, and a multi-layered stratum corneum containing intercellular lamellar lipid layers representing main
lipid classes analogous to those found in vivo. The EpiDermTM tissues are cultured on specially prepared cell culture inserts.

Control samples:

yes, concurrent negative control

yes, concurrent positive control

Amount/concentration applied:

30 µL of the test item were pipetted onto a nylon mesh on a microscope slide.

Duration of treatment / exposure:

1 hour

Duration of post-treatment incubation (if applicable):

23 hours 35 minutes

Number of replicates:

3

Irritation / corrosion parameter:

% tissue viability

Run / experiment:

Reconstructed human Epidermis (RhE) Test Method following EU-Method B.46 resp. OECD 439

Value:

ca. 4.2

Vehicle controls validity:

not examined

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

positive indication of irritation

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

The mean value of relative tissue viability of the test item was reduced to 4.2 % after the treatment. This value is below the threshold for skin irritation (50%). Therefore, the test item is considered as irritant to skin.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying i) Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring Classification for Eye Irritation or Serious Eye Damage)

GLP compliance:

yes

Species:

other: Bos primigenius Taurus (fresh bovine corneas)

Strain:

not specified

Details on test animals or tissues and environmental conditions:

Fresh bovine eyes were obtained from the slaughterhouse Müller Fleisch GmbH, Enzstr. 2-4, 75217 Birkenfeld, Germany, on the day of the test. The cattle were between 12 and 60 months old. The eyes were transported to the test facility in Hanks’ Balanced Salt Solution with 1% Penicillin-Streptomycin solution (Penicillin 100 U/mL, Streptomycin 100 µg/mL) in a suitable cooled container within 1 hour.

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent positive control

yes, concurrent negative control

Amount / concentration applied:

The respective substance (negative control solution, test item or positive control) was ap-plied by pipetting 750 µL of the appropriate liquid through the refill hole in the holder on the cornea.

Duration of treatment / exposure:

Exposure time of the test item on the corneas was 10 minutes at 32 ± 1 °C.

Duration of post- treatment incubation (in vitro):

After thorough rinsing with cMEM with phenol red and final rinsing with cMEM without phenol red, the anterior chamber was filled with cMEM without phenol red, and the corneas were stored for additional 2 hours at 32 ± 1 °C (post-incubation).

Number of animals or in vitro replicates:

3

Irritation parameter:

in vitro irritation score

Run / experiment:

Bovine Corneal Opacity and Permeability (BCOP) Test Method following OECD Guideline 437 and EU Method B.47

Value:

ca. 0.22

Vehicle controls validity:

not examined

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

no indication of irritation

Interpretation of results:

GHS criteria not met

Conclusions:

The test item gamma-Dodecalactone showed no effects on the cornea of the bovine eye. The calculated IVIS is 0.22.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available