3,5-dihydroxy-2,6,6-tris(3-methylbuten-2-yl)-4-(3-methyl-1-oxobutyl)cyclohexa-2,4-dien-1-one

Endpoint summary

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

Oil-rich hop extract batch no. BI/YYF/1701

Test system:

human skin model

Source species:

human

Cell type:

non-transformed keratinocytes

Irritation / corrosion parameter:

% tissue viability

Value:

ca. 5.65

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 study performed on hop extract is relevant for beta acids, since hop extract may contain up to ca. 64% beta acids, and the extract tested here contained 38% beta acids. Hop extract (Oil rich) is classfied as irritant to human 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)

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

Batch no. EXP 5

Test system:

human skin model

Source species:

human

Cell type:

non-transformed keratinocytes

Irritation / corrosion parameter:

% tissue viability

Value:

ca. 27.1

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:

Hop beta acids, potassium resin, is classfied as irritant to human skin.

Reference 3

Endpoint:

skin corrosion: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

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:

Batch no. EXP 5

Test system:

human skin model

Source species:

human

Cell type:

non-transformed keratinocytes

Vehicle:

unchanged (no vehicle)

Irritation / corrosion parameter:

% tissue viability

Run / experiment:

Tissue viability measured after 1 hour

Value:

ca. 85.4

Positive controls validity:

valid

Interpretation of results:

GHS criteria not met

Conclusions:

Notes from study report: "The test item did not reduce the viability below 50% after 3 min nor below 15% after 1h and should be considered as non-corrosive."

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

1 (reliable without restriction)

Justification for type of information:

The study performed on hop extract is relevant for beta acids, since hop extract may contain up to ca. 64% beta acids, and the extract tested here contained 38% beta acids. An eye irritation study according to OECD test guideline 492 has been commissioned and an update will be made once results are available. The skin irritation studies performed on this substance indicate that a preliminary classification of eye irritation category 2 is appropriate, pending the results of the study planned.

Qualifier:

according to guideline

Guideline:

other: OECD 439

Version / remarks:

Weight of evidence to support study planned

GLP compliance:

yes (incl. QA statement)

Irritation parameter:

other: % tissue viability

Remarks:

Weight of evidence supporting study

Value:

ca. 5.65

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

positive indication of irritation

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

An eye irritation study according to OECD test guideline 492 has been commissioned and an update will be made once results are available. The skin irritation studies performed on this substance, together with a long history of use as a food ingredient, indicate that a preliminary classification of eye irritation category 2 is appropriate, pending the results of the study planned.

Reference 2

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

1 (reliable without restriction)

Justification for type of information:

An eye irritation study according to OECD test guideline 492 has been commissioned and an update will be made once results are available. The skin irritation studies performed on this substance indicate that a preliminary classification of eye irritation category 2 is appropriate, pending the results of the study planned.

Qualifier:

according to guideline

Guideline:

other: OECD 439

Version / remarks:

Weight of evidence to support study planned

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

Batch no. EXP 5

Irritation parameter:

other: % tissue viability

Remarks:

Weight of evidence supporting study

Value:

ca. 27.1

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

positive indication of irritation

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

An eye irritation study according to OECD test guideline 492 has been commissioned and an update will be made once results are available. The skin irritation studies performed on this substance indicate that a preliminary classification of eye irritation category 2 is appropriate, pending the results of the study planned.

Reference 3

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

disregarded due to major methodological deficiencies

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Justification for type of information:

Note this was performed in the US and would not have been permitted on three rabbits in Europe. Also, even if with only one animal, the test shouold have been terminated as soon as it becam apparant that corneal opacity was not improving.
The results have been disregarded as there was no record made of the pH of this product. New in-vitro tests have been initiated in 2018.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

Batch no. RD11-627. Purity: 44.0% beta acids

Species:

rabbit

Strain:

New Zealand White

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.1 mL dose in the conjunctival sac of right eye. The contralateral eye remained untreated and served as the control.

Duration of treatment / exposure:

Up to 21 days

Number of animals or in vitro replicates:

3

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24 h

Score:

1

Max. score:

1

Reversibility:

not fully reversible within: 21 d

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

48 h

Score:

1.33

Max. score:

2

Reversibility:

not fully reversible within: 21 d

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

72 h

Score:

1.66

Max. score:

2

Reversibility:

not fully reversible within: 21 d

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

21 d

Score:

4

Max. score:

4

Reversibility:

not reversible

Irritant / corrosive response data:

The classification was based on the corneal opacity.
Iris score was 1 throughout, but was difficult to assess once the cornea became damaged
There was slight improvement of conjunctival scores during the 21 day observation period.
The test laboratory made observations that suggested that the animals were not distressed, although UK law would not have permitted this study. The registrant was not responsible for the conduct of this test.

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

Notes from the study report: "According to the Kay and Calandra Evaluation Criteria, KBR is considered to be a very severe irritant to the ocular tissue of the rabbit."

IMPORTANT QUALIFIER: These results were made available by J I Haas for the purpose of supporting the REACH regitsration. The tests themselves were commissioned for a separate USA regulatory submission. It was considered that much of the severe irritation may have been due to excess KOH present in the KBR resin. Accordingly, new resins were carefullly prepared for REACH, avoiding any excess KOH, and were tested for skin irritation (see endpoint skin irritation / corrosion.002 and .003). They will also be tested in an in vitro eye irritation test (study planned), with results added as an update to this dossier. The skin irritation / corrosion results indicate that the substance should be provisionally classfied as eye irritant category 2, to be updated once the new in vitro tests are completed.

Reference 4

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

OECD Guideline 492 (Reconstructed Human Cornea-like Epithelium (RhCE) Test Method for Identifying Chemicals Not Requiring Classification and Labelling for Eye Irritation or Serious Eye Damage)

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

Batch no. EXP 5

Irritation parameter:

other: Percentage of viability

Value:

ca. -11.78

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Other effects / acceptance of results:

Notes from the study report:

Prior to the study, the required preliminary test confirmed that the test item interfered with MTT or solvent and so parallel tests using freeze-killed tissues were also performed to allow for data correction.

Due to the high MTT-reducing activity of the test item, no conclusive classification of the eye irritancy potential of Potassium Beta Resin could be determined and therefore the outcome is Inconclusive.

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

The substance interfered with the detection system and so no prediction was possible. Given that the substance is a moderate skin irritant, Category 2 classification as a precaution is reasonable.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)