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Diss Factsheets

Administrative data

Description of key information

Skin irritation: The substance is not a skin irritant.

Eye irritation: The results of a BCOP study conclude that no prediction of eye irritation can be made. The results of an in-vivo eye irritaiton study (non-irritant) have been read-across from an analogue substance (EC 251-201-7).

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
Study period:
16 February 1994 - 31 March 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)
GLP compliance:
yes
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Lot No.of test material: 19004
- Purity: 94.5 %

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: cold and dark place.
Species:
rabbit
Strain:
other: SPF Japanese white rabbits
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Kitayama Labes Co., Ltd
- Age at study initiation: 11 weeks old
- Weight at study initiation: from 2.2 to 2.3 kg
- Housing: each of the animals was housed in a suspended aluminum cage with a wire net at the bottom of it (32W x 48D x 33H cm)
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 25
- Humidity (%): 40 to 70
- Air changes (per hr): 12 times
- Photoperiod (hrs light): 12 hours a day
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 ml
Duration of treatment / exposure:
4 hours
Observation period:
1, 24, 48 and 72 hours after the patches were removed.
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: the dorsal area of the trunk of animals
- Type of wrap if used: a semipermeable soft bandage

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: After 4 hours of exposure, the test substance was wiped off with absorbent cotton saturated with mildly wam water.

OBSERVATION TIME POINTS : 1, 24, 48 and 72 hours after the patches were removed

SCORING SYSTEM:
- Method of calculation: The degrees of formation of erythema and crusts (hereinafter referred to as erythema) and edema were evaluated in accordance with the criteria stipulated in the OECD Guideline
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 1 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 1 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 1 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 1 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 1 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 1 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Other effects:
- Skin reaction: No irritation was observed in any animal up to 72 hours after the patches were removed.
- General state of health: No change was observed in any cases until the observation was completed.
- Body weight: No effect of the test substance was observed in any cases (Table 1).

Table 1: Individual body weights

 Animal No  Before application  72 hours after the removal of patch
 1  2.3 2.4 
 2  2.2 2.2 
 3  2.3 2.4 
Interpretation of results:
GHS criteria not met
Conclusions:
Test item did not cause irritation on the skin of rabbits under the conditions of this test.
Executive summary:

A study was performed to determine the skin irritation potential of the test item. The study was performed according to OECD test guideline 404 and in compliance with GLP.

A single semi-occlusive dose of 0.5 ml of test item was applied to the skin of three SPF Japanese white female rabbits for 4 hours. Animals were observed for 72 hours.

No irritation was observed up to 72 hours after the patches were removed, hence the test item is considered not to be irritating to skin.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
26 February 2019 - 26 February 2019
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)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU method B.47 (Bovine corneal opacity and permeability test method for identifying ocular corrosives and severe irritants)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Species:
cattle
Details on test animals or tissues and environmental conditions:
Source of Bovine Eyes
Eyes from adult cattle (typically 12 to 60 months old) were obtained from a local abattoir as a by-product from freshly slaughtered animals. The eyes were excised by an abattoir employee after slaughter, and were placed in Hanks’ Balanced Salt Solution (HBSS) supplemented with antibiotics (penicillin at 100 IU/mL and streptomycin at 100 μg/mL). They were transported to the test facility over ice packs on the same day of slaughter. The corneas were prepared immediately on arrival.
Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
The EMEM was removed from the anterior chamber of the BCOP holder and 0.75 mL of the test item or control items were applied to the appropriate corneas.
Duration of treatment / exposure:
The holders were gently tilted back and forth to ensure a uniform application of the item over the entire cornea. Each holder was incubated, anterior chamber uppermost, at 32 ± 1 ºC for 10 minutes.
Duration of post- treatment incubation (in vitro):
At the end of the exposure period the test item and control items were removed from the anterior chamber and the cornea was rinsed 3 times with fresh complete EMEM containing phenol red before a final rinse with complete EMEM without phenol red. The anterior chamber was refilled with fresh complete EMEM without phenol red. A post treatment opacity reading was taken and each cornea was visually observed.
The holders were incubated, anterior chamber facing forward, at 32 ± 1 ºC for 120 minutes.
Number of animals or in vitro replicates:
3 replicates
Details on study design:
SELECTION AND PREPARATION OF CORNEAS
All eyes were macroscopically examined before and after dissection. Only corneas free of damage were used.
The cornea from each selected eye was removed leaving a 2 to 3 mm rim of sclera to facilitate handling. The iris and lens were peeled away from the cornea. The isolated corneas were immersed in a dish containing HBSS until they were mounted in Bovine Corneal Opacity and Permeability (BCOP) holders.
The anterior and posterior chambers of each BCOP holder were filled with complete Eagle’s Minimum Essential Medium (EMEM containing 1% v/v fetal bovine serum) without phenol red and plugged. The holders were incubated at 32 ± 1 ºC for 60 minutes. At the end of the incubation period each cornea was examined for defects. Only corneas free of damage were used.The medium from both chambers of each holder was replaced with fresh complete EMEM.
A pre treatment opacity reading was taken for each cornea using a calibrated opacitometer.
Three corneas were randomly allocated to the negative control. Three corneas were also allocated to the test item and three corneas to the positive control item.

NUMBER OF REPLICATES -3

NEGATIVE CONTROL USED
Identification: Sodium chloride 0.9% w/v
Lot: 18/10BB1B
Purity: 0.9%
Supplier: Baxter
Expiry Date: 01 August 2021
Storage Conditions: Room temperature

POSITIVE CONTROL USED
Identification: Ethanol
Batch: STBD7546V
Purity: >99.8%
Supplier: Sigma Aldrich
Expiry Date: 14 March 2023
Storage Conditions: Room temperature

APPLICATION DOSE AND EXPOSURE TIME
The EMEM was removed from the anterior chamber of the BCOP holder and 0.75 mL of the test item or control items were applied to the appropriate corneas. The holders were gently tilted back and forth to ensure a uniform application of the item over the entire cornea. Each holder was incubated, anterior chamber uppermost, at 32 ± 1 ºC for 10 minutes.
At the end of the exposure period the test item and control items were removed from the anterior chamber and the cornea was rinsed 3 times with fresh complete EMEM containing phenol red before a final rinse with complete EMEM without phenol red. The anterior chamber was refilled with fresh complete EMEM without phenol red. A post treatment opacity reading was taken and each cornea was visually observed.
The holders were incubated, anterior chamber facing forward, at 32 ± 1 ºC for 120 minutes.
After incubation the holders were removed from the incubator, the medium from both chambers was replaced with fresh complete EMEM and a final opacity reading was taken. Each cornea was visually observed.


TREATMENT METHOD: closed chamber

POST-INCUBATION PERIOD: yes, 10 minutes

REMOVAL OF TEST SUBSTANCE
At the end of the exposure period the test item and control items were removed from the anterior chamber and the cornea was rinsed 3 times with fresh complete EMEM containing phenol red before a final rinse with complete EMEM without phenol red.

- POST-EXPOSURE INCUBATION: 120 minutes

METHODS FOR MEASURED ENDPOINTS:
- Corneal opacity: The change in opacity for each cornea (including the negative control) was calculated by subtracting the initial opacity reading from the final opacity reading. These values were then corrected by subtracting the average change in opacity observed for the negative control corneas. The mean opacity value of each treatment group was then calculated by averaging the corrected opacity values of each cornea for that treatment group.

- Corneal permeability: passage of sodium fluorescein dye measured with the aid of [UV/VIS spectrophotometry / microtiter plate reader] (OD490)
The corrected OD492 was calculated by subtracting the mean OD492 of the negative control corneas from the OD492 value of each treated cornea. The OD492 value of each treatment group was calculated by averaging the corrected OD492 values of the treated corneas for the treatment group.


SCORING SYSTEM: In Vitro Irritancy Score (IVIS)

DECISION CRITERIA: The test item was classified according to the following prediction model:
IVIS UN GHS
≤ 3 No Category
>3; ≤ 55 No prediction can be made
> 55 Category 1



Irritation parameter:
in vitro irritation score
Run / experiment:
Average
Value:
10.7
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
not determinable
Other effects / acceptance of results:
OTHER EFFECTS:
- Visible damage on test system:
Corneal Epithelium Condition
The corneas treated with the test item were clear post treatment and cloudy post incubation. The corneas treated with the negative control item were clear post treatment and post incubation. The corneas treated with the positive control item were cloudy post treatment and post incubation.

ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: yes
- Acceptance criteria met for positive control: yes
Interpretation of results:
study cannot be used for classification
Conclusions:
No prediction of eye irritation can be made.
Executive summary:

Method

The undiluted test item was applied for 10 minutes followed by an incubation period of 120 minutes. Negative and positive control items were tested concurrently. The two endpoints, decreased light transmission through the cornea (opacity) and increased passage of sodium fluorescein dye through the cornea (permeability) were combined in an empirically derived formula to generate an In Vitro Irritancy Score (IVIS). 

Results

TheIn Vitroirritancy scores are summarized as follows:

Treatment

In VitroIrritancy Score

Test Item

10.7

Negative Control

1.2

Positive Control

40.8

Conclusion

No prediction of eye irritation can be made.

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
start date 4th February 2013, completion date 18th February 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
2012
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
2008
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: JMAFF guidelines (2011); including the most recent partial revisions.
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Specific details on test material used for the study:
Identification: Tetrahydro-6-(3-pentenyl)-2H-pyran-2-one
Description: Clear colourless to pale yellow liquid
Batch: 1000978951
Purity/Composition: 98.0%
Test substance storage: In refrigerator (2-8°C) in the dark under nitrogen
Stability under storage conditions: Stable
Expiry date: 10 May 2014
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Species:Albino rabbit, New Zealand White, (SPF-Quality). Recognized by international guidelines as the recommended test system (e.g. EC, OECD)

Number of animals: 3 Males.

Age and body weight: Animals used within the study were at least 6 weeks old and body weights were at least 1.0 kg.
Identification: Earmark.
Health inspection: At least prior to dosing upon receipt of the animals and prior to dosing. Prior to treatment, it was ensured that the eyes were free from any abnormality.
Animal husbandry

Conditions
Environmental controls for the animal room were set to maintain 18 to 24°C, a relative humidity of 40 to 70%, approximately 15 room air changes/hour, and a 12-hour light/12-hour dark cycle. Any variations to these conditions were maintained in the raw data and had no effect on the outcome of the study.

Accommodation
Animals were individually housed in labeled cages with perforated floors (dimensions 67 x 62 x 55 cm) and shelters (dimensions 40 x 32 x 23 cm). Acclimatization period was at least 5 days before start of treatment under laboratory conditions.

Diet
Pelleted diet for rabbits (Global Diet 2030 from Harlan Teklad®, Mucedola, Milanese, Italy) approximately 100 grams per day. Hay and wooden sticks were available during the study period

Water
Free access to tap water.

Diet, water, bedding and cage enrichment evaluation for contaminants and/or nutrients was performed according to facility standard procedures. There were no findings that could interfere with the study.
Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
0.1 mL of the undiluted test substance.

The test substance was instilled undiluted as delivered by the sponsor. No correction was made for
the purity/composition of the test substance, since the guidelines require a fixed amount to be instilled.
Duration of treatment / exposure:
Each animal was treated by instillation of 0.1 mL of the test substance, in the conjunctival sac of one
of the eyes after gently pulling the lower lid away from the eyeball. The lids were then gently held
together for about one second to prevent loss of the test substance.
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
3 males
Details on study design:
The study was performed in a stepwise manner and was started by treatment of a single rabbit
(sentinel). The two other animals were treated in a similar manner 1 week later, after considering the
degree of eye irritation observed in the first animal.
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
Animal 409
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
mean
Remarks:
Animal 409
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Remarks:
Animal 409
Time point:
24/48/72 h
Score:
1.7
Max. score:
3
Reversibility:
fully reversible within: 7 days
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
Animal 409
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
Animal 425
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
mean
Remarks:
Animal 425
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Remarks:
Animal 425
Time point:
24/48/72 h
Score:
1.7
Max. score:
3
Reversibility:
fully reversible within: 7 days
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
Animal 425
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
Animal 433
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
mean
Remarks:
Animal 433
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Remarks:
Animal 433
Time point:
24/48/72 h
Score:
0.7
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
Animal 433
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
Irritation
Instillation of 0.1 mL of Tetrahydro-6-(3-pentenyl)-2H-pyran-2-one into one eye of each of three rabbits resulted in irritation of the conjunctivae, which consisted of redness, chemosis and discharge. The irritation had completely resolved within 72 hours in one animal and within 7 days in the other two animals.

No iridial irritation or corneal opacity were observed, and treatment of the eyes with 2% fluorescein 24 hours after test substance instillation revealed no corneal epithelial damage.

Corrosion
There was no evidence of ocular corrosion.

For tables summarizing results please refer to attachment "Tables" (attached background material).
Other effects:
Coloration / Remnants
No staining of (peri) ocular tissues by the test substance was observed and no test substance remnants were seen.

Toxicity / Mortality
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.
Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this study, Tetrahydro-6-(3-pentenyl)-2H-pyran-2-one does not have to be classified and has no obligatory labelling requirement for eye irritation according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2011) and the Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures, including all amendments.
Executive summary:

Background

Acute eye irritation/corrosion study with Tetrahydro-6-(3-pentenyl)-2H-pyran-2-one in the rabbit.

The study was carried out based on the guidelines described in:
OECD No.405 (2012) "Acute Eye Irritation / Corrosion"
EC, No 440/2008, B5: "Acute Toxicity: Eye Irritation/Corrosion"
EPA, OPPTS 870.2400 (1998): "Acute Eye Irritation"
JMAFF guidelines (2011); including the most recent partial revisions.

The purpose of this acute eye irritation/corrosion study was to assess the possible irritation or corrosion potential when a single dose of the test substance was placed in the conjunctival sac of the rabbit eye.

Method

Single samples of 0.1 mL of Tetrahydro-6-(3-pentenyl)-2H-pyran-2-one were instilled into one eye of each of three rabbits. Observations were made 1, 24, 48 and 72 hours and 7 days after instillation.

Results

Instillation of the test substance resulted in irritation of the conjunctivae, which consisted of redness, chemosis and discharge. The irritation had completely resolved within 72 hours in one animal and within 7 days in the other two animals.

No iridial irritation or corneal opacity were observed, and treatment of the eyes with 2% fluorescein 24 hours after test substance instillation revealed no corneal epithelial damage.

Conclusions

Under the conditions of this study, Tetrahydro-6-(3-pentenyl)-2H-pyran-2-one does not have to be classified and has no obligatory labelling requirement for eye irritation according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2011) and the Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and
mixtures, including all amendments.

Endpoint:
eye 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:
Please see attached justification "Jasminlactone_Read-across justification" for full details.

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
Jasminlactone (the target substance) and one analogue substance, Tetrahydro-6-(3-pentenyl)-2H-pyran-2-one (the source substances) have been evaluated in a ‘one-to-one’ read across approach (one analogue used to make estimation for a single chemical).
Based on the structural similarities and know properties of the substances (phys-chem and (eco)toxicology), it is proposed that the target and source substance are likely to have a common mechanism if action and share similarities in reactivity.
It is therefore proposed that the structural similarity and properties of the target substance and the structural analogue (sources substance) are sufficiently close for there to be a reasonable expectation of similar effects.
In-vitro eye irritation testing on the target substance was inconclusive to allow classification to be determined. In the interests of animal welfare, it is considered appropriate to read-across in-vivo eye irritation study data on the source substance to conclude on the eye irritation potential and classification of the target substance.


2. SOURCE AND TARGET CHEMICAL(S)
Source substance:
Name: Tetrahydro-6-(3-pentenyl)-2H-pyran-2-one
EC number: 251-201-7
CAS number: 32764-98-0

Target substance:
Name: (Z)-tetrahydro-6-(2-pentenyl)-2H-pyran-2-one
EC number: 247-074-2
CAS number: 25524-95-2


3. ANALOGUE APPROACH JUSTIFICATION
Based on the structural similarity of the source substance and target substance, similarity of physic-chemical properties and similarity in experimental toxicological test data, it is concluded that target substance and the structural analogue (source substance) are sufficiently close for there to be a reasonable expectation of similar effect for the eye irritation endpoint

4. DATA MATRIX
Please see attached justification "Jasminlactone_Read-across justification" for full details.
Reason / purpose for cross-reference:
read-across source
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
Animal 409
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
mean
Remarks:
Animal 409
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Remarks:
Animal 409
Time point:
24/48/72 h
Score:
1.7
Max. score:
3
Reversibility:
fully reversible within: 7 days
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
Animal 409
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
Animal 425
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
mean
Remarks:
Animal 425
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Remarks:
Animal 425
Time point:
24/48/72 h
Score:
1.7
Max. score:
3
Reversibility:
fully reversible within: 7 days
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
Animal 425
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
Animal 433
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
mean
Remarks:
Animal 433
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Remarks:
Animal 433
Time point:
24/48/72 h
Score:
0.7
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
Animal 433
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
Irritation
Instillation of 0.1 mL of Tetrahydro-6-(3-pentenyl)-2H-pyran-2-one into one eye of each of three rabbits resulted in irritation of the conjunctivae, which consisted of redness, chemosis and discharge. The irritation had completely resolved within 72 hours in one animal and within 7 days in the other two animals.

No iridial irritation or corneal opacity were observed, and treatment of the eyes with 2% fluorescein 24 hours after test substance instillation revealed no corneal epithelial damage.

Corrosion
There was no evidence of ocular corrosion.

For tables summarizing results please refer to attachment "Tables" (attached background material).
Other effects:
Coloration / Remnants
No staining of (peri) ocular tissues by the test substance was observed and no test substance remnants were seen.

Toxicity / Mortality
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.
Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this study, Tetrahydro-6-(3-pentenyl)-2H-pyran-2-one does not have to be classified and has no obligatory labelling requirement for eye irritation according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2011) and the Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures, including all amendments.
Executive summary:

Background

Acute eye irritation/corrosion study with Tetrahydro-6-(3-pentenyl)-2H-pyran-2-one in the rabbit.

The study was carried out based on the guidelines described in:
OECD No.405 (2012) "Acute Eye Irritation / Corrosion"
EC, No 440/2008, B5: "Acute Toxicity: Eye Irritation/Corrosion"
EPA, OPPTS 870.2400 (1998): "Acute Eye Irritation"
JMAFF guidelines (2011); including the most recent partial revisions.

The purpose of this acute eye irritation/corrosion study was to assess the possible irritation or corrosion potential when a single dose of the test substance was placed in the conjunctival sac of the rabbit eye.

Method

Single samples of 0.1 mL of Tetrahydro-6-(3-pentenyl)-2H-pyran-2-one were instilled into one eye of each of three rabbits. Observations were made 1, 24, 48 and 72 hours and 7 days after instillation.

Results

Instillation of the test substance resulted in irritation of the conjunctivae, which consisted of redness, chemosis and discharge. The irritation had completely resolved within 72 hours in one animal and within 7 days in the other two animals.

No iridial irritation or corneal opacity were observed, and treatment of the eyes with 2% fluorescein 24 hours after test substance instillation revealed no corneal epithelial damage.

Conclusions

Under the conditions of this study, Tetrahydro-6-(3-pentenyl)-2H-pyran-2-one does not have to be classified and has no obligatory labelling requirement for eye irritation according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2011) and the Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and
mixtures, including all amendments.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation:

Acute dermal irritation/corrosion study  was conducted to determine the skin irritation/corrosion of Jasminlactone. The study was performed according to OECD test guideline 404 (1992), and in compliance with GLP.

 

The effects of 4-hours exposure was investigated in three female SPF Japanese white rabbits. No skin irritation was observed up to 72 hours after the patches were removed, nor any changes in general health or body weights were observed.

 

Under the test conditions Jasminlactone was not found to be irritating to rabbits.

 

Eye irritation:

The Bovine Corneal Opacity and Permeability (BCOP) test was used to identify if Jasminlactone could induce serious eye damage (UN GHS Category 1) or if it does not require classification for eye irritation or serious eye damage (UN GHS No Category) using the corneas of eyes isolated from cattle. The test was conducted according to EC Method B.47 and OEDC test guideline 437, and in compliance with GLP.

 

The undiluted Jasminlactine was applied for 10 minutes followed by an incubation period of 120 minutes at 32 ± 1 ºC. Negative and positive control items were tested concurrently. The decreased light transmission through the cornea (opacity) and increased passage of sodium fluorescein dye through the cornea (permeability) were combined in an empirically derived formula to generate an In Vitro Irritancy Score (IVIS).

Jasminlactone was classified according to the following prediction model: IVIS ≤ 3 No Category; > 3 IVIS ≤ 55 No prediction can be made; IVIS > 55 Category 1. The in vitro irritancy score of Jasminlactone was determined to be 10.7. As it is greater than 3, yet less than 55 no prediction of eye irritation can be made.

Read-across from analogue substance (EC 251-201-7):

Instillation of the test substance resulted in irritation of the conjunctivae, which consisted of redness, chemosis and discharge. The irritation had completely resolved within 72 hours in one animal and within 7 days in the other two animals.

No iridial irritation or corneal opacity were observed, and treatment of the eyes with 2% fluorescein 24 hours after test substance instillation revealed no corneal epithelial damage.

Under the conditions of this study, the test item does not have to be classified.

Justification for classification or non-classification

4-hours dermal exposure of Jasminlactone did not result in erythema, eschar or oedema in any of the test animals, as a result Jasminlactone does not meets the criteria for classification as a skin irritant according to CLP Regulation (Commission Regulation 1272/2008).

Based on the results on an in-vivo eye irritation study on an analogue substance, classification for eye irritation is not required according to CLP regulation.