3,5,5-trimethylcyclohex-2-enone

Endpoint summary

Description of key information

The test subststance is an eye irritant and a respiratory irritant but does not irritate the skin.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Remarks:

purity not reported

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: various breeders
- Weight at study initiation: 2-4 kg
- Housing: individually
- Diet: standard diet, ad libitum
- Water: ad libitum

Type of coverage:

other: occlusive and semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.5 mL

Duration of treatment / exposure:

up to 4 hours

Observation period:

The results were assessed 1, 24, 48 and 72 hours and 7 days after removal of the patches

Number of animals:

6 (male and female)

Details on study design:

The dorsal and lateral parts of the trunk were shorn 15-24 hours before treatment. 0.5 mL test substance/patch were applied to 3 cm x 3 cm gauze pads. Four samples were attached to the prepared skin areas of each animal: The patches were fixed and covered by wrapping an air-permeable circular bandage (semi-occlusive method) or air-tight plastic foil (occlusive method) around the animals. The local reactions were determined after 1 and 4 hours exposure both under occlusive and semi-occlusive conditions. After removal of the bandages and patches the treated skin areas were rinsed with water and dried.
Skin changes, i.e. erythema and eschar formation, and edema formation were recorded as indicated by the OECD (1981). In addition, special effects were also recorded. The criteria used to define irritation and corrosion were those given in the EEC directive (EEC, 1983).

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: mean

Score:

0

Max. score:

4

Remarks on result:

other: 1 and 4 hour exposure, occlusive and semiocclusive conditions

Other effects:

No mortality occurred

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

according to guideline

Guideline:

other: Draize Test according to the US Food and Drug Administration, Federal Register No. 191-11

GLP compliance:

no

Species:

rabbit

Strain:

other: albino

Controls:

yes, concurrent no treatment

Amount / concentration applied:

undiluted
Amount applied: 0.1 mL

Duration of treatment / exposure:

not rinsed; rinsed after 2 or 4 seconds, or rinsed after 24 hours

Observation period (in vivo):

7 days and later until complete reversibility

Number of animals or in vitro replicates:

3 (6 are rinsed after 24 hours)

Details on study design:

Not rinsed / rinsed after 2 seconds / 4 seconds (3 animals each)
Ophtalmoscopic examination after 24, 48, and 72 hours, 4 days, 7 days, and later until complete reversibility. Scoring system: Draize et al. (1944). J Pharmacol Exp Ther 82: 377-390

Remarks on result:

other: see 'Irritant/corrosive response data' section for the results

Irritant / corrosive response data:

Scores are averages of results after 24, 48, and 72 hours. All effects are reversible.

Not rinsed
- Cornea: 15/80
- Iris: 0/10
- Conjuntivae: 7/20
- Overall irritation score: 22/110

Rinsed after 2 seconds
- Cornea: 21/80
- Iris: 0/10
- Conjuntivae: 6/20
- Overall irritation score: 27/110

Rinsed after 4 seconds
- Cornea: 12/80
- Iris: 0/10
- Conjuntivae: 5/20
- Overall irritation score: 17/110

Rinsed after 24 hours:
- Cornea: 14/80
- Iris: 0/10
- Conjuntivae: 6/20
- Overall irritation score: 20/110

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Additional information

Skin irritation

One guideline study was performed on rabbits with 0.5 mg (corresponds to 1500 mg isophorone/kg bw) and did not result in significant irritancy (Potokar et al., 1985). Only slight irritations were seen after application of 0.5 ml according to a modified Draize protocol (24 hrs exposure) (Dutertre-Catella, 1976). After application of 200 mg/kg isophorone (24 hrs exposure) only slight erythema and desquamation during the first four days after 4 hours of exposure was observed (Esso Research, 1965). The findings were fully reversible.

 

Eye irritation

Two Draize tests were performed on each 6 male and female rabbits. When applied undiluted to rabbits’ eyes isophorone is moderately to severely irritating to the eyes (Esso Research, 1965; Truhaut et al., 1972). In one study marked irritation was observed which reversed within 14 days but was still present after 7 days (Esso Research, 1965), while in the other study, irritant scores of 14/80 (cornea), 0/10 (iris) and 6/20 (conjunctiva) were reported and had reversed within 7 days (Truhaut et al., 1972).

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is considered to be classified for eye irritation cat. 2, H319 under Regulation (EC) No. 1272/2008, as amended for the 14th time in Regulation (EU) 2020/217.