4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]octane

Endpoint summary

Description of key information

Study conducted according to Annex to EEC directive 92/69/EWG, dated 31 Jul. 1992, for the 17th adaption of the EEC directive 67/548/EWG, 8.4. Acute Toxicity (Skin lrritation); young adult New Zealand White rabbits (4 animals) were dermally exposed to 500 µL of Trioxabicyclooctan (100 % a.i.) for 4 hours to 6.5 cm² skin, result: not classified

Study conducted according to OECD test guideline 405; 100 µL Trioxabicyclooctan (100 % a.i.) were instilled into the conjunctival sac of one eye of 3 young adult New Zealand White rabbits, observation period: 16 days, result: Category 2 (irritating to eyes)

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:

1995-09-08 to 1996-01-09

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

31. July 1992

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Schriever
- Age at study initiation: adults
- Weight at study initiation: males: 2.7 - 2.8 kg; females: 2.6 - 2.8 kg
- Housing: individually in conventional metal cages
- Diet (e.g. ad libitum): pell. Altromin® K ad libitum
- Water (e.g. ad libitum): demineralized water ad libitum
- Acclimation period: > 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-22
- Humidity (%): 64-70
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): 100% a.i.

Duration of treatment / exposure:

4 h

Observation period:

7 days

Number of animals:

4

Details on study design:

TEST SITE
- Area of exposure: 6 cm² each site of the spine
- Type of wrap if used: Both sites (treated and untreated) were covered with a piece of gauze (semi-occlusive) fixed on the skin with Leukoflex®.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): After exposure the gauze was removed and the treated and untreated skin areas were wiped carefully with lukewarm tap water and cotton wool.
- Time after start of exposure: 4 h

OBSERVATION TIME POINTS
(indicate if minutes, hours or days): Clinical observations were performed 30-60 minutes and 24 hours after end of exposure and thereafter daily until day 7 of the test and findings were recorded. Deviating from the method referred to in the study protocol the interval between daily clinical observations between days 4-5 for animal no. 548 and days 2-3 for the other animals was only 16 hours instead of 24 hours. This deviation is not considered to have influenced the result of the study since the animals were without findings on the respective days. Body weights were recorded on day 1 and day 7 of the test. Necropsy was not performed.

SCORING SYSTEM: According to guideline

Irritation parameter:

edema score

Basis:

animal: #1 - #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

erythema score

Basis:

animal: #1 - #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritant / corrosive response data:

The test item provoked on the intact skin of the rabbit after single application only very slight to slight reddening in two males and one female animal only on the appl!ication day. No other findings were observed during the observation period of 7 days.

Interpretation of results:

GHS criteria not met

Conclusions:

According to the system of evaluation recommended by EEC (1 ), the mean values of findings relevant for classification as ".irritant" (reddening· and scab formation, swelling) at the time points 24, 48 and 72 hours after application were 0. Also based to the classification criteria of Regulation (EU) No. 1272/2008 (CLP) the test item does not need to be classified with respect to skin irritation.

Executive summary:

In a primary dermal irritation study according to Annex to EEC directive 92/69/EWG, dated 31 Jul. 1992, for the 17th adaption of the EEC directive 67/548/EWG, 8.4. Acute Toxicity (Skin lrritation), young adult New Zealand White rabbits (4 animals) were dermally exposed to 500 µL of Trioxabicyclooctan (100 % a.i.) for 4 hours to 6.5 cm² skin. Animals then were observed for 7 days.  Irritation was scored by the method recommended by the guideline.

Trioxabicyclooctan provoked on the intact skin of the rabbit after single application only very slight to slight reddening in two males and one female animal only on the application day. No other findings were observed during the observation period of 7 days. According to the system of evaluation recommended by EEC (1 ), the mean values of findings relevant for classification as ".irritant" (reddening· and scab formation, swelling) at the time points 24, 48 and 72 hours after application were 0.

Based on the test results described above, the test item is not considered to be irritating to the skin according to Regulation (EU) No. 1272/2008 (CLP) and the Globally Harmonized System for Classification and Labelling of Chemicals (GHS).

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:

March to June 1996

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:

24 February 1987

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Schriever
- Age at study initiation: adults
- Weight at study initiation: male: 2.6 kg; females: 3.1 kg
- Housing: individually in conventional metal cages
- Diet (e.g. ad libitum): pell. Altromin® K; ad libitum
- Water (e.g. ad libitum): demineralized water; ad libitum
- Acclimation period: 18 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%):52-58
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): 100 % a.i.

Duration of treatment / exposure:

single exposure and observation 0.5, 1 and 2 h after application and once daily afterwards until day 16

Observation period (in vivo):

16 days

Number of animals or in vitro replicates:

3

Details on study design:

SCORING SYSTEM: According to OECD test guideline 405

TOOL USED TO ASSESS SCORE: hand-slit lamp / biomicroscope / fluorescein: not specified

Irritation parameter:

chemosis score

Basis:

animal: #2 #3

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 16 days

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.67

Max. score:

4

Reversibility:

fully reversible within: 16 days

Irritation parameter:

conjunctivae score

Basis:

animal: #2 #3

Time point:

24/48/72 h

Score:

2.67

Max. score:

3

Reversibility:

fully reversible within: 16 days

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.3

Max. score:

3

Reversibility:

fully reversible within: 16 days

Irritation parameter:

iris score

Basis:

animal: #1 - #3

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 16 days

Irritation parameter:

cornea opacity score

Basis:

animal: #2 #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 16 days

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

fully reversible within: 16 days

Test substance/ Calculation for EEC classification
Location (finding)	Time point after end of exposure time	690M	702F	704F
Cornea (opacity	24 h	1.0	1.0	1.0
	48 h	2.0	1.0	1.0
	72 h	2.0	1.0	1.0
Individual mean values		1.67	1.0	1.0
iris	24 h	1.0	1.0	1.0
	48 h	1.0	1.0	1.0
	72 h	1.0	1.0	1.0
Individual mean values		1.0	1.0	1.0
Conjunctivae (reddening)	24 h	2.0	3.0	3.0
	48 h	3.0	3.0	3.0
	72 h	3.0	3.0	3.0
Individual mean values		2.67	3.0	3.0
Conjunctivae (swelling)	24 h	2.0	3.0	3.0
	48 h	1.0	3.0	3.0
	72 h	1.0	2.0	2.0
Individual mean values		1.3	2.67	2.67

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

On the whole, a single application of Trioxabicyclooctan into the conjunctival sac of the rabbit eye provoked severe irritation which lasted for several days after application and which only very slowly normalized over a period of up to 16 days.
Although the rabbit eye reacts more sensitively than the human eye due to anatomical and physiological. differences, similar effects have to be expected on the human eye. Therefore, inadvertent contact of the human eye with this substance should be strictly avoided.

Executive summary:

In a primary eye irritation study according to OECD test guideline 405 (1987), 100 µL Trioxabicyclooctan (100 % a.i.) were instilled into the conjunctival sac of one eye of 3 young adult New Zealand White rabbits. Animals then were observed for 16 days. Irritation was scored by the method recommended by the test guideline.

After application of 100 µL of the test sample into the conjunctival sac, there were slight reactions in the cornea and initially strong changes in the conjunctivae, which are completely reversible within 16 days. According to Regulation (EU) No. 1272/2008 (CLP) the test item is classified as Category 2 (irritating to eyes) based on the results obtained under the conditions described.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation/corrosion:

In a primary dermal irritation study according to Annex to EEC directive 92/69/EWG, dated 31 Jul. 1992, for the 17th adaption of the EEC directive 67/548/EWG, 8.4. Acute Toxicity (Skin lrritation), young adult New Zealand White rabbits (4 animals) were dermally exposed to 500 µL of Trioxabicyclooctan (100 % a.i.) for 4 hours to 6.5 cm² skin. Animals then were observed for 7 days.  Irritation was scored by the method recommended by the guideline.

Trioxabicyclooctan provoked on the intact skin of the rabbit after single application only very slight to slight reddening in two males and one female animal only on the application day. No other findings were observed during the observation period of 7 days. According to the system of evaluation recommended by EEC (1 ), the mean values of findings relevant for classification as ".irritant" (reddening· and scab formation, swelling) at the time points 24, 48 and 72 hours after application were 0.

 

Eye irritation/corrosion:

In a primary eye irritation study according to OECD test guideline 405 (1987), 100 µL Trioxabicyclooctan (100 % a.i.) were instilled into the conjunctival sac of one eye of 3 young adult New Zealand White rabbits. Animals then were observed for 16 days. Irritation was scored by the method recommended by the test guideline.

After application of 100 µL of the test sample into the conjunctival sac, there were slight reactions in the cornea and initially strong changes in the conjunctivae, which are completely reversible within 16 days.

Justification for classification or non-classification

Based on the test results described above, the test item is not considered to be irritating to the skin according to Regulation (EU) No. 1272/2008 (CLP) and the Globally Harmonized System for Classification and Labelling of Chemicals (GHS).

According to Regulation (EU) No. 1272/2008 (CLP) the test item is classified as Category 2 (irritating to eyes) based on the results obtained under the conditions described.