Caryophyllene, Reaction product with Acetic anhydride and acetic acid

Endpoint summary

Description of key information

VETYNAL EXTRA (not irritating): Key study, Primary Skin irritation Study in Rabbits (4-Hour Semi-Occlusive Application), author G. Arcelin dated on 2002 performed at RCC Ltd laboratory

Ro 83-0825 (Vetyvenal)(not irritating): Supporting study, Primary skin irritation study in rabbits, author W. H. Braun dated on 1999 performed at RCC Ltd laboratory

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

June 8 - 17 1999

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)

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

Name (as stated in the report): VETYVENAL
Batch: 285526
Expiration date: March 25, 2003

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

There were 3 animals per test (one male and two females). All were 13 weeks old at treatment. The identification was done by unique cage number and corresponding ear number. The acclimatization was done under laboratory conditions after health examination. Only animals without any visual signs of illness were used for the study.

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

0.5 ml (per animal) of undiluted Ro 83-0825 (Vetyvenal) was applied.

Duration of treatment / exposure:

4 hours

Observation period:

1, 24, 48 and 72 hours

Number of animals:

3

Details on study design:

Approximately three days before treatment, the dorsal fur was clipped with an electric clipper, exposing an area of approximately 100 cm2 (10 cm x 10 cm). The skin of the animals was examined approximately 24 hours before treatment, and, if necessary, regrown fur was again clipped.

Animals with overt signs of skin injury or marked irritation which may have interfered with the interpretation of the results were not used in the test.

One the day of treatment, the test article as applied to approximately 6 cm2 of the intact skin of the clipped area. It was covered with a 2.5 cm x 2.5 cm patch of surgical gauze and the gauze was covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and anchored with tape.

The duration of treatment was 4 hours. Then the dressing was removed and the skin was flushed with lukewarm tap water to clean the application site so that any reactions (erythema) were clearly visible at that time.

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Reversibility:

not specified

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Reversibility:

not specified

Irritant / corrosive response data:

Application of the test article to healthy intact rabbit skin resulted in a primary irritation score of 0.00.
Local signs (mean values from 24 to 72 hours) consisted of grade 0.00 erythema and grade 0.00 oedema. No signs of irritation were observed.

No irrevesible alterations of the treated skin were obsreved nor were corrosive effect evident on the skin.

Other effects:

No clinical signs of systemic toxiciy wre observed in the animals during the test and observation period, and no mortality occured.

Interpretation of results:

GHS criteria not met

Conclusions:

Based upon the referred classification criteria, Ro 83-0825 (Vetyvenal) is considered to be “not irritating” to rabbit skin.

Executive summary:

To assess the primary skin irritation potential of Ro 83-0825 (Vetyvenal), a primary skin irritation study was performed in three (one male and two females) young adult New Zealand White rabbits.

 

The fur of the left flank was clipped and 0.5 ml of Ro 83-0825 (Vetyvenal) was applied epicutaneously to an area of 0.6 cm2 and then covered with a semi-occlusive dressing approximately four hours. After removal of the dressing and test aticle, the skin reactions (erythema/eschar, as well as oedema) were evaluated 1, 24, 48 and 72 hours after application. The primary irritation score was calculated to reflect and classify the irritant potential of the test article.

 

The dermal exposure to Ro 83-0825 (Vetyvenal) caused no signs of irritation.

 

The primary irritation score for Ro 83-0825 (Vetyvenal) was 0.00 (the maximum attainable score is 8.0).

 

Following evaluation of the experimental data according to the EEC classification criteria, Ro 83-0825 (Vetyvenal) is classified as “not irritating” to rabbit skin.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

September 10 - September 24 2002

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)

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

Name (as stated in the report): VETYNAL Extra
Batch: 9000474504
Expiration date: June 15, 2004

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

There were 3 animals per test (one male and two females). The male was 11-12 weeks old and the females were 10-12 weeks old at treatment. The identification was done by unique cage number and corresponding ear number. The acclimatization was done under laboratory conditions after health examination. Only animals without any visual signs of illness were used for the study.

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

0.5 ml (per animal) of undiluted VETYNAL EXTRA was applied.

Duration of treatment / exposure:

4 hours

Observation period:

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

Number of animals:

3

Details on study design:

Four days before treatment, one flank was clipped with an electric clipper, exposing an area of approximately 100 cm2 (10 cm x 10 cm). The skin of the animals was examined one day before treatment, and regrown fur of all animals was again clipped.

Animals with overt signs of skin injury or marked irritation which may have interfered with the interpretation of the results were not used in the test.

One the day of treatment, 0.5 ml of VETYNAL EXTRA was placed on a surgical gauze patch (ca. 4 cm x 4 cm). This gauze patch was applied to the intact skin of the clipped area. The patch was covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and anchored with tape.

The duration of treatment was 4 hours. Then the dressing was removed and the skin was flushed with lukewarm tap water to clean the application site so that any reactions (erythema) were clearly visible at that time.

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.33

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.33

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.33

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible

Irritant / corrosive response data:

The test item did not induce significant or irreversible damage to the skin.

Other effects:

The test item caused no staining of the treated skin. No corrosive effects were notes on the treated skin of any animal at any of the measuring intervals.

Interpretation of results:

GHS criteria not met

Conclusions:

Based upon the referred classification criteria (Comission Directive 2001/59/EC of August 06, 2001), VETYNAL EXTRA is considered to be “not irritating” to rabbit skin.

Executive summary:

The primary skin irritation potential of VETYNAL EXTRA was investigated by topical semi-occlusive application of 0.5 ml to the intact left flank of each of three young adult New Zealand White rabbits. The duration of treatment was four hours. The scoring of skin reactions was performed 1, 24, 48 and 72 hours, as well as 7 days after removal of the dressing.

The mean score was calculated across 3 scoring times (24, 48 and 72 hours after patch removal) for each animal for erythema/eschar grades and for oedema grades, separately. The mean erythema/eschar scores for the three animals were 1.00, 1.33 and 1.33 respectively and the mean oedema scores were 0.33, 0.33 and 0.00, respectively.

 

The application of VETYNAL EXTRA to the skin resulted in mild signs of irritation such as erythema, oedema and scaling These effects were reversible and were no longer evident 7 days after treatment, the end of the observation period for all animals. The test item caused no staining of the treated skin. No corrosive effects were notes on the treated skin of any animal at any of the measuring intervals.

Thus, the test item did not induce significant or irreversible damage to the skin.

 

Based upon the referred classification criteria (Comission Directive 2001/59/EC of August 06, 2001), VETYNAL EXTRA is considered to be “not irritating” to rabbit skin.

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:

June 15 - 24 1999

Reliability:

1 (reliable without restriction)

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

Name (as stated in the report): VETYVENAL
Batch: 285526
Expiration date: March 25, 2003

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

There were 3 animals per test (one male and two females). They were all aged at treatment of 13 weeks. The identification was done by unique cage number and corresponding ear number. The acclimatization was done under laboratory conditions after health examination. Only animals without any visual signs of illness were used for the study.

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.1 ml (per animal) of undiluted Ro 83-0825 (Vetyvenal) was applied.

Duration of treatment / exposure:

1, 24, 48 and 72 hours

Observation period (in vivo):

1, 24, 48 and 72 hours

Number of animals or in vitro replicates:

3 animals

Details on study design:

The eyes of the animals were examined one day prior to test article administration.

Animals with overt signs of ocular injury or irritation which may have interfered with the interpretation of the results were not used in the test.

On the day of treatment, the test article (undiluted) was placed in the conjunctival sac of the left eye of each animal 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 article. The right eye remained untreated and served as the reference control.

In cases of equivocal results when comparing the treated and untreated eyes, the illustrated guide from the Consumer Product Safety Commission, Washington, D. C. 20207 was used for additional control purposes (Washington, 1977).

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 1/24/48/72 hours

Score:

0

Reversibility:

fully reversible

Irritant / corrosive response data:

Application of the test article to healthy conjuncitvae resulted in a primary irritation score of 0.00.

In all animals, slight reddening of the conjunctivae as well as moderate watery discharge was observed, one hour after treatment. All signs of irritation were reversible after 24 hours.

No corrosion of the cornea was observed at any of the reading times

Other effects:

No staining by the test article was observed.

Interpretation of results:

GHS criteria not met

Conclusions:

Based upon the referred classification criteria, Ro 83-0825 (Vetyvenal) is considered to be “not irritating” to rabbit eye.

Executive summary:

To assess the primary eye irritation potential of Ro 83-0825 (Vetyvenal), a primary eye irritation study was performed in three (one male and two females) young adult New Zealand White rabbits.

The left eye of each animal was exposed to the test article by instilling 0.1 ml of Ro 83-0825 (Vetyvenal) into the conjunctival sac. The treated eyes were not rinsed after instillation. Corneal, iridic and conjunctival irritation was evaluated at 1, 24, 48, and 72 hours after instillation. The primary irritation score was calculated to reflect and classify the irritant potential of the test article.

 

The single instillation of into the conjunctival sac caused slight reddening of the conjunctivae as well as moderate discharge in all animals, one hour after treatment. All signs of irritation were reversible after 24 hours.

 

No staining of the cornea, sclera or conjunctivae nor was corrosion by the test article observed.

 

The Primary Irritation Score for Ro 83-0825 (Vetyvenal) was 0.00 (the maximum attainable score is 13.0).

 

Following evaluation of the experimental data (summarized in the table’s report on page 19) according to the EEC classification criteria, Ro 83-0825 (Vetyvenal) is classified as “not irritating” to rabbit eye.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Skin irritation

To assess the primary skin irritation potential of Ro 83-0825 (Vetyvenal), a primary skin irritation study was performed in three (one male and two females) young adult New Zealand White rabbits.

The dermal exposure to Ro 83-0825 (Vetyvenal) caused no signs of irritation.

The primary irritation score for Ro 83-0825 (Vetyvenal) was 0.00 (the maximum attainable score is 8.0).

Following evaluation of the experimental data according to the CLP Regulation 1272/2008/EC criteria, Ro 83-0825 (Vetyvenal) is classified as “not irritating” to rabbit skin.

Eye irritation

No staining of the cornea, sclera or conjunctivae nor was corrosion by the test article observed.

The Primary Irritation Score for Ro 83-0825 (Vetyvenal) was 0.00 (the maximum attainable score is 13.0).

Following evaluation of the experimental data (summarized in the table’s report on page 19) according to the EEC classification criteria, Ro 83-0825 (Vetyvenal) is classified as “not irritating” to rabbit eye.