Oxacycloheptadecan-2-one

Endpoint summary

Description of key information

Oxacycloheptadecan-2-one is not irritating to skin and eyes.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

28 November 1994 - 13 December 1994

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

1992

Deviations:

yes

Remarks:

The study was extended to investigate 5 different concentrations of the test article and a vehicle control on each animal

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Version / remarks:

29 December 1992

Deviations:

yes

Remarks:

The study was extended to investigate 5 different concentrations of the test article and a vehicle control on each animal

GLP compliance:

yes

Specific details on test material used for the study:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at room temperature in the dark
- Stability under test conditions: stable
- Solubility and stability of the test substance in the solvent/vehicle: soluble in ethanol/diethyl phthalate 1:1 (w/w)

Species:

rabbit

Strain:

other: Mol:Russian

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Mollegaard Breeding and Research Centre A/S, Ejby, DK-4623 Lille Skensved
- Weight at study initiation: 2.0-2.3 kg
- Housing: single 62 x 52 cm PPO cages with perforated floor
- Diet (e.g. ad libitum): a pelleted complete rabbit diet "Altromin 2123" from Chr. Petersen, DK-4100 Ringsted, ad libitum.
- Water (e.g. ad libitum): bottles with domestic quality drinking water acidified with hydrochloric acid to pH 2.5 in order to prevent microbial growth, ad libitum
- Acclimation period: at least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 3
- Humidity (%): 55 ± 15
- Air changes (per hr): 10/hour
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 28-11-1994 To: 13-12-1994

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

other: ethanol/diethylphthalate 1:1 (w/w)

Controls:

yes, concurrent vehicle

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): 100% (undiluted test substance), 20%, 10%, 5%, 1% in ethanol/diethylphthalate

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5 mL

NEGATIVE CONTROL
- Amount(s) applied (volume or weight): 0.5 mL ethanol/diethylphthalate 1:1 (w/w)

Duration of treatment / exposure:

4 hours

Observation period:

1, 24, 48, 72 hours, 7 and 14 days

Number of animals:

4 females

Details on study design:

TEST SITE
- Area of exposure: 2.5 x 2.5 cm on a total of 6 test sites: 2 anterior located, 2 centrally located and 2 posterior located. In total 5 different concentrations and a vehicle control were tested on each animal.
- % coverage: 100
- Type of wrap if used: 1 cm wide adhesive tap, fixed with Scanpor tape, 4.5 cm width, loosely wound round the truml

REMOVAL OF TEST SUBSTANCE
- Washing (if done): soap and lukewarm water
- Time after start of exposure: 4 hours

OBSERVATION TIME POINTS
(indicate if minutes, hours or days) 1, 24, 48 and 72 hours, 7 and 14 days after the end of the exposure

SCORING SYSTEM:
- Method of calculation: Draize

Irritation parameter:

erythema score

Remarks:

100% test substance

Basis:

mean

Time point:

24/48/72 h

Score:

1.58

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

probability of weak irritation

Irritation parameter:

edema score

Remarks:

100% test substance

Basis:

mean

Time point:

24/48/72 h

Score:

0.08

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

probability of weak irritation

Irritation parameter:

erythema score

Remarks:

20% test substance

Basis:

mean

Time point:

24/48/72 h

Score:

1.5

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

probability of weak irritation

Irritation parameter:

edema score

Remarks:

20% test substance

Basis:

mean

Time point:

24/48/72 h

Score:

0.08

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

probability of weak irritation

Irritation parameter:

erythema score

Remarks:

10% test substance

Basis:

mean

Time point:

24/48/72 h

Score:

0.92

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

probability of weak irritation

Irritation parameter:

edema score

Remarks:

10% test substance

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no edema observed in any animal at all time points

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Remarks:

5% test substance

Basis:

mean

Time point:

24/48/72 h

Score:

0.415

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

probability of weak irritation

Irritation parameter:

edema score

Remarks:

5% test substance

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no edema observed in any animal at any time point

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Remarks:

1% test substance

Basis:

mean

Time point:

24/48/72 h

Score:

0.92

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

probability of weak irritation

Irritation parameter:

edema score

Remarks:

1% test substance

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no edema observed in any animal at any time point

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Remarks:

vehicle control

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 hours (weak erythema in 1 animal 1 hour post-exposure)

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no edema in any animal at any time point

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

In general slight to well defined erythema was observed 1 to 72 hours after termination of exposure of 100% and 20% concentration of test article. Similarily in general slight erythema was observed 1 to 72 hours alter termination of exposure of 10%, 5% and 1% concentration of test article. Slight oedema was only observed in 1 rabbit 48 hours after termination of exposure of 100% and 20% concentration of test article. Thereafter no oedema was observed.
On day 7 and 14 dose related accumulations of scales were observed in all rabbits. On day 14 the skin of all rabbits was intact.

Interpretation of results:

GHS criteria not met

Conclusions:

In the GLP-compliant guideline study, the test substance oxacyclohexadecan-2-one was not irritating to rabbit skin.

Executive summary:

In a GLP-compliant OECD 404 guideline study, the test substance oxacyclohexadecan-2 -one was tested for skin irritation in 4 rabbits, as a neat substance, 20%, 10%, 5% and 1% solution. Each animal received in total 6 applications (5 tested concentrations and a vehicle control). The exposure was 4 hours under semi-occlusive conditions. In general slight to well defined erythema was observed 1 to 72 hours after termination of exposure of 100% and 20% concentration of test article. Similarily in general slight erythema was observed 1 to 72 hours alter termination of exposure of 10%, 5% and 1% concentration of test article. Slight oedema was only observed in 1 rabbit 48 hours after termination of exposure of 100% and 20% concentration of test article. Thereafter no oedema was observed. Based on the calculated scores (mean for erythema and oedema at 24/48/72 hours of 1.58 and 0.08, respectively) for the neat substance no classification of oxacyclohexadecan-2-one for skin irritation is warranted according to Regulation 1272/2008/EC.

Reference 3

Endpoint:

skin irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The read-across source chemical oxacyclohexadecan-2-one and the target chemical oxacycloheptadecan-2-one are structural homologues of each other, with the only difference between the two being one additional carbon atom in the cyclic aliphatic chain (C15 and C16, respectively). Considering a very long aliphatic chain in both substances, the presence of additional carbon atom (CH2 moiety) in oxacycloheptadecan-2-one is not expected to influence its toxicological properties in comparison to oxacyclohexadecan-2-one. Therefore read-across from oxacyclohexadecan-2-one to oxacycloheptadecan-2-one is considered to be justified.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Both substances are mono-constituent substances of high purity (details on purity are provided in the confidential sections of the robust study summaries) and do not contain toxicologically relevant impurities which could influence their toxicological behavior.

3. ANALOGUE APPROACH JUSTIFICATION
The read-across source chemical oxacyclohexadecan-2-one and the target chemical oxacycloheptadecan-2-one are structural homologues of each other, with the only difference between the two being one additional carbon atom in the cyclic aliphatic chain (C15 and C16, respectively). Considering a very long aliphatic chain in both substances, the presence of additional carbon atom (CH2 moiety) in oxacycloheptadecan-2-one is not expected to influence its toxicological properties in comparison to oxacyclohexadecan-2-one. This is confirmed by the available data on both substances (see data matrix) which confirm nearly identical physico-chemical and (eco)toxicological properties for all endpoints. There are no additional functional groups present in oxacyclohexadecan-2-one which may influence its skin irritating properties. Both substances have comparable physico-chemical properties, i.e. high log Pow (> 4) and poor water solubility (< 1 mg/L), thus their ability to penetrate the skin is expected to be comparable. Therefore read-across from oxacyclohexadecan-2-one to oxacycloheptadecan-2-one is considered to be justified.

4. DATA MATRIX (data on oxacyclohexadecan-2-one taken from its dissiminated REACH dossier available on the ECHA website):

Substance Oxacycloheptadecan-2-one Oxacyclohexadecan-2-one
Molecular formula C16H30O2 C15H28O2
Molecular weight 254.4 240.38 g/mol
Melting point 35 °C 34.6 °C
Boiling point 265-275 °C 325 °C
Water solubility 0.103 mg/L 0.34 mg/L
Log Pow 7.3 5.79
Vapour pressure <= 0.053 Pa at 25 °C 0.085 Pa at 25 °C
Acute oral toxicity LD50 > 5000 mg/kg bw LD50 > 5000 mg/kg bw
Acute dermal toxicity LD50 > 5000 mg/kg bw LD50 > 5000 mg/kg bw
Skin irritation Read-across Not irritating
Eye irritation Not irritating Not irritating
Skin sensitization Read-across Not sensitizing
Repeated dose toxicity NOAEL > 1000 mg/kg bw/day NOAEL > 1000 mg/kg bw/day
Reproductive toxicity NOAEL > 1000 mg/kg bw/day NOAEL > 1000 mg/kg bw/day
Developmental toxicity NOAEL > 1000 mg/kg bw/day NOAEL > 1000 mg/kg bw/day
Toxicity to fish 96-h LC50 > solubility limit EC50 > solubility limit
Toxicity to daphnia Read-across 48-h EC50 > 0.17 mg/L
Toxicity to algae 72-h ErC50 > 0.004 mg/L 72h ErC50 > 0.47 mg, 72h ErC10 = 0.42 mg/L

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

erythema score

Remarks:

100% test substance

Basis:

mean

Time point:

24/48/72 h

Score:

1.58

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

probability of weak irritation

Irritation parameter:

edema score

Remarks:

100% test substance

Basis:

mean

Time point:

24/48/72 h

Score:

0.08

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

probability of weak irritation

Irritation parameter:

erythema score

Remarks:

20% test substance

Basis:

mean

Time point:

24/48/72 h

Score:

1.5

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

probability of weak irritation

Irritation parameter:

edema score

Remarks:

20% test substance

Basis:

mean

Time point:

24/48/72 h

Score:

0.08

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

probability of weak irritation

Irritation parameter:

erythema score

Remarks:

10% test substance

Basis:

mean

Time point:

24/48/72 h

Score:

0.92

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

probability of weak irritation

Irritation parameter:

edema score

Remarks:

10% test substance

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no edema observed in any animal at all time points

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Remarks:

5% test substance

Basis:

mean

Time point:

24/48/72 h

Score:

0.415

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

probability of weak irritation

Irritation parameter:

edema score

Remarks:

5% test substance

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no edema observed in any animal at any time point

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Remarks:

1% test substance

Basis:

mean

Time point:

24/48/72 h

Score:

0.92

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

probability of weak irritation

Irritation parameter:

edema score

Remarks:

1% test substance

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no edema observed in any animal at any time point

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Remarks:

vehicle control

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 hours (weak erythema in 1 animal 1 hour post-exposure)

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no edema in any animal at any time point

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

In general slight to well defined erythema was observed 1 to 72 hours after termination of exposure of 100% and 20% concentration of test article. Similarily in general slight erythema was observed 1 to 72 hours alter termination of exposure of 10%, 5% and 1% concentration of test article. Slight oedema was only observed in 1 rabbit 48 hours after termination of exposure of 100% and 20% concentration of test article. Thereafter no oedema was observed.
On day 7 and 14 dose related accumulations of scales were observed in all rabbits. On day 14 the skin of all rabbits was intact.

Interpretation of results:

GHS criteria not met

Conclusions:

In the GLP-compliant guideline study, the read-across analogue test substance oxacyclohexadecan-2-one was not irritating to rabbit skin. These results can be read across to oxacycloheptadecan-2-one.

Executive summary:

In a GLP-compliant OECD 404 guideline study, the read-across analogue test substance oxacyclohexadecan-2 -one was tested for skin irritation in 4 rabbits, as a neat substance, 20%, 10%, 5% and 1% solution. Each animal received in total 6 applications (5 tested concentrations and a vehicle control). The exposure was 4 hours under semi-occlusive conditions. In general slight to well defined erythema was observed 1 to 72 hours after termination of exposure of 100% and 20% concentration of test article. Similarily in general slight erythema was observed 1 to 72 hours alter termination of exposure of 10%, 5% and 1% concentration of test article. Slight oedema was only observed in 1 rabbit 48 hours after termination of exposure of 100% and 20% concentration of test article. Thereafter no oedema was observed. Based on the calculated scores (mean for erythema and oedema at 24/48/72 hours of 1.58 and 0.08, respectively) for the neat substance no classification of oxacyclohexadecan-2-one for skin irritation is warranted according to Regulation 1272/2008/EC. These results can be read across to oxacycloheptadecan-2-one.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In a GLP-compliant OECD 404 guideline study performed with a structural analogue of oxacycloheptadecan-2 -one, oxacyclohexadecan-2 -one, the test substance was tested for skin irritation in 4 rabbits as a neat substance, 20%, 10%, 5% and 1% solution. Each animal received in total 6 applications (5 tested concentrations and a vehicle control). The exposure was 4 hours under semi-occlusive conditions. In general slight to well defined erythema was observed 1 to 72 hours after termination of exposure of 100% and 20% concentration of test article. Similarily in general slight erythema was observed 1 to 72 hours alter termination of exposure of 10%, 5% and 1% concentration of test article. Slight oedema was only observed in 1 rabbit 48 hours after termination of exposure of 100% and 20% concentration of test article. Thereafter no oedema was observed. Based on the calculated scores (mean for erythema and oedema at 24/48/72 hours of 1.58 and 0.08, respectively) for the neat substance oxacyclohexadecan-2-one is considered to be not irritating to rabbit skin. This conclusion can be read across to oxacycloheptadecan-2 -one.

In a Bovine Corneal Opacity and Permeability test (BCOP) performed with oxacycloheptadecan-2-one according to OECD guideline 437 and GLP principles, undiluted test substance did not induce ocular irritation through opacity or permeability, resulting in a mean in vitro irritancy score of -0.7 after 10 minutes of treatment.

The mean in vitro irritancy score of the positive control (ethanol) was 61.8, and the mean in vitro irritancy score of the negative control (physiological saline) was -0.8. It was therefore concluded that the test conditions were adequate and that the test system functioned properly. Since oxacycloheptadecan-2-one induced an IVIS ≤ 3, the substance was concluded to be not irritating to eyes.

Justification for classification or non-classification

Based on mean erythema and oedema scores at 24, 48 and 72 hours of 1.58 and 0.08 in the in vivo skin irritation study with a structural analogue oxacyclohexadecan-2 -one and the IVIS score of -0.7 in a BCOP test with oxacycloheptadecan-2 -one, classification for skin and eye irritation is not warranted according to Regulation (EC) 1272/2008.