Octahydro-2H-1-benzopyran-2-one

Endpoint summary

Description of key information

Skin corrosion: (OECDTG 404): Not corrosive

Skin irritation (OECD TG 404): Not irritating
Eye irritation and severe damage (OECD TG 405): Severe irritating

Respiratory irritation (in absence of human data): Not irritating

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:

03 December, 1979 - 06 February, 1980

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Reliability has been presented as 2 because similar to OECD Guideline protocol has been followed but not GLP.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

(1981)

Deviations:

yes

Remarks:

no details on purity, no details on animal housing and environmental conditions

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 9 - 12 weeks
- Animals in the telogen phase of hair growth were selected.

ENVIRONMENTAL CONDITIONS
No data

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

other: Adjacent areas of the untreated skin of each animal served as controls.

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 mL

Duration of treatment / exposure:

4 hours

Observation period:

24, 48 and 72 hours

Number of animals:

8

Details on study design:

TEST SITE:
The whole dorsal surface was clipped 3-4 days before application of the test substance.

TREATMENT
Occlusive patches were prepared by attaching a piece of thin flexible polythene (3 cm x 3 cm) to a piece of zinc oxide plaster 9 cm x 2.5 cm. A 2.5 cm square of cotton gaue was laid on the polythene such that the edges of the patch were attached to the zinc oxide plaster. The undiluted test substance was applied to a dry patch. The patches were firmly attached to ensure good contact between the skin and test substance. The animals were immobilised in a canvas body sleeve for 4 hours after application of the patch.

REMOVAL OF TEST SUBSTANCE
Four hours after the application, the patches were removed and the skin are wiped clean of excess material.

OBSERVATIONS
- Mortality/Viability and Clinical signs: Daily
- Body Weight: At the start of acclimatization, day 1 (application day) and at termination (day 15)
- Irritation: The skin sites were assessed for irritation immediately after treatment, and at 24, 48 and 72 hours. The irritation scores and a description of all other (local) effects were recorded.

SCORING SYSTEM:
The irritation was assessed according to the numerical scoring system according to OECD 404 (1981).

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

12

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

12

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

erythema score

Basis:

animal:

Remarks:

#3 and #8

Time point:

24/48/72 h

Score:

1

Max. score:

12

Reversibility:

not fully reversible within: 72 hours

Irritation parameter:

erythema score

Basis:

animal:

Remarks:

#4 and #6

Time point:

24/48/72 h

Score:

0.67

Max. score:

12

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

1.67

Max. score:

12

Reversibility:

not fully reversible within: 72 hours

Irritation parameter:

erythema score

Basis:

animal:

Remarks:

#7

Time point:

24/48/72 h

Score:

1

Max. score:

12

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.67

Max. score:

12

Reversibility:

not fully reversible within: 72 hours

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

12

Irritation parameter:

edema score

Basis:

animal: #3 and #6

Time point:

24/48/72 h

Score:

0.33

Max. score:

12

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

edema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0.67

Max. score:

12

Reversibility:

fully reversible within: 24 hours

Irritation parameter:

edema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

1.33

Max. score:

12

Reversibility:

not fully reversible within: 72 hours

Irritation parameter:

edema score

Basis:

animal: #7

Time point:

24/48/72 h

Score:

0.67

Max. score:

12

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

edema score

Basis:

animal: #8

Time point:

24/48/72 h

Score:

1

Max. score:

12

Reversibility:

not fully reversible within: 72 hours

Irritant / corrosive response data:

Reaction grades erythema 72 hours after treatment: three animals marginal/very slight and five animals no effects observed. Reaction grades oedema 72 hours after treatment: three animals marginal/very slight and five animals no effects observed. Six animals showed also marginal/very slight cracking and two animals showed marginal/ very slight scaling, 2 animals showed no cracking/scaling. No results on the reversibility as the observation period was not extended to 7 days.

Other effects:

- No mortality occurred

Skin irritation response data (for the undiluted test substance)

Observation time	24 hours		48 hours		72 hours
Animal no.:	erythema	oedema	erythema	oedema	erythema	oedema
1	-	1	-	-	-	1
2	1	-	-	-	-	-
3	1	1	1	-	1	-
4	2	2	-	-	-	-
5	3	2	1	1	1	1
6	2	1	-	-	-	-
7	2	1	1	1	-	-
8	1	1	1	1	1	1

1 = marginal/very slight

2 = slight

3 = fairly distinct

4 = quite distinct

6 = becoming well developed

8 = well developed

10= becoming severe

12= severe

Interpretation of results:

other: Not a skin irritant.

Remarks:

According to Regulation (EC) No. 1272/2008 and its amendments

Conclusions:

In a skin irritation study with rabbits, performed equivalent to OECD 404 guideline, limited irritation was observed. As the substance showed marginal /very slight irritating to skin 72 hours after treatment and the symptoms were less than 24 and 48 after treatment, the substance does not have to be classified for skin irritation.

Executive summary:

The substance was tested in 8 rabbits in a skin irritation test equivalent to OECD TG 404 test guideline.Reaction grades of erythema 72 hours after treatment showed three animals with marginal/very slight whereas five animals showed no effects. Reaction grades of oedema 72 hours after treatment showed three animals with marginal/very slight and five animals showed no effects. No results on the reversibility as the observation period was not extended to 7 days. As the substance showed marginal /very slight irritating to skin 72 hours after treatment and the symptoms were less than 24 and 48 after treatment, the substance does not have to be classified for skin irritation.

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

Study period:

28 April, 1980 - 29 May, 1980

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Reliability has been presented as 2 because similar to OECD Guideline protocol has been followed but not GLP.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

(1981)

Deviations:

yes

Remarks:

no details on purity, no details on animal housing and environmental conditions

Principles of method if other than guideline:

Modified Federal Hazardous Substances Labelling Act Method.

GLP compliance:

no

Species:

rabbit

Strain:

other: Morton

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Morton
- Age at study initiation: 8 weeks
- Weight at study initiation: 1.9 kg

ENVIRONMENTAL CONDITIONS
No data.

Vehicle:

unchanged (no vehicle)

Controls:

other: One eye of each animal remained untreated and served as the reference control.

Amount / concentration applied:

Amount applied: 0.1 mL

Duration of treatment / exposure:

Single instillation on Day 1

Observation period (in vivo):

21 days

Number of animals or in vitro replicates:

1 female

Details on study design:

STUDY DESIGN
The test material was applied undiluted in 1 animal.

TREATMENT
The substance was applied to one eye of a rabbit by gently pulling the lower lid away from the eye ball and placing 0.1 mL in the sac so formed. Test and control eye were pre-treated with corneal anaesthetic.

REMOVAL OF TEST SUBSTANCE
-Washing: No

OBSERVATIONS
- Irritation:
The eyes were examined 24 hours after treatment and thereafter at daily intervals and graded for corneal, conjunctival and iridial damage. Eyes were examined before application of materials and at daily intervals afterwards with a slit lamp and corneal swelling is measured.
The irritation scores and a description of all other (local) effects were recorded. The irritation was assessed according to OECD 405 (1981).

Irritation parameter:

cornea opacity score

Basis:

animal #1

Remarks:

(mean)

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Irritation parameter:

iris score

Basis:

animal #1

Remarks:

(mean)

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #1

Remarks:

(mean)

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 8 days

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

(mean)

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 4 days

Irritant / corrosive response data:

The substance caused a moderate corneal opacity affecting all the cornea, with associated corneal swelling. The animal also had slight conjunctivitis and discharge, with purvulent exudate in the conjuctival folds. The corneal opacity effects (max. score 1) were not fully reversible within 21 days. The conjunctival redness effects (max. score 1) was fully reversible within 8 days. Chemosis (max. score 1) was observed but fully reversible within 4 days.
The animal developed pannus at day 8 which was visible at the end of the test at 21 days, associated with a persistent opacity.

Ocular Irritant response data (for the undiluted test substance)

	Time after administration
	15 minutes	24 hours	48 hours	72 hours
Cornea score (opacity)	-	1	1	1
Iris score	-	0	0	0
Conjunctivae score (redness)	1	1	1	1
Chemosis score	1	1	1	1

Interpretation of results:

other: Serious eye damage, Category 1

Remarks:

According to Regulation (EC) No. 1272/2008 and its amendments.

Conclusions:

In an eye irritation study with one female rabbit, performed equivalent to OECD 405 guideline, irritation was observed. Based on the results of this study, the substance is considered an eye irritant.

Executive summary:

The substance was tested in an eye irritation test in one female rabbit equivalent to OECD 405 guideline. The substance caused a moderate corneal opacity affecting all the cornea, with associated corneal swelling. The animal also had slight conjunctivitis and discharge, with purvulent exudate in the conjuctival folds. The corneal opacity effects (max. score 1) were not fully reversible within 21 days. The conjunctival redness effects (max. score 1) was fully reversible within 8 days. Chemosis (max. score 1) was observed but fully reversible within 4 days. The animal developed pannus at day 8 which was visible at the end of the test at 21 days, associated with a persistent opacity. The results showed that the substance is considered to be severe irritating to eyes.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

Skin irritation OECD TG 404:

The substance was tested in 8 rabbits in a skin irritation test equivalent to OECD TG 404 test guideline. Reaction grades of erythema 72 hours after treatment showed three animals with marginal/very slight whereas five animals showed no effects. Reaction grades of oedema 72 hours after treatment showed three animals with marginal/very slight and five animals showed no effects. No results on the reversibility as the observation period was not extended to 7 days. As the substance showed marginal /very slight irritating to skin 72 hours after treatment and the symptoms were less than 24 and 48 after treatment, the substance does not have to be classified for skin irritation.

Eye irritation OECD TG 405:

The substance was tested in an eye irritation test in one female rabbit equivalent to OECD 405 guideline. The substance caused a moderate corneal opacity affecting all the cornea, with associated corneal swelling. The animal also had slight conjunctivitis and discharge, with purvulent exudate in the conjuctival folds. The corneal opacity effects (max. score 1) were not fully reversible within 21 days. The conjunctival redness effects (max. score 1) was fully reversible within 8 days. Chemosis (max. score 1) was observed but fully reversible within 4 days. The animal developed pannus at day 8 which was visible at the end of the test at 21 days, associated with a persistent opacity. The results showed that the substance is considered to be severe irritating to eyes.

Respiratory irritation

There are no occupational or consumer data indicating respiratory tract irritation. There are also no relevant experimental guidelines or results available that indicate respiratory irritation, therefore respiratory irritation is not anticipated. The ECHA guidance presents (R7a: 7.1.12.1) that respiratory irritation maybe be indicated when the substance is a severe irritant. The substance is not a skin irritant but is a severe eye irritant. In absence of other supporting respiration irritation information the substance is regarded a non-respiratory irritant.

Justification for classification or non-classification

Based on the results in the skin irritation test, the substance does not need to be classified for this endpoint according to EU CLP ((EC) No. 1272/2008 and its amendments). Based on the results in the eye irritation test the substance needs to be classified as an eye irritant. According to EU CLP (1272/2008 and its amendments) Category 1, H318: Causes serious eye damage is assigned. In absence of human data the substance does not need to be classified for respiratory irritation in accordance with EU CLP )1272/2008 and its amendments).