Caryophyllene, Reaction product with Acetic anhydride and acetic acid

Endpoint summary

Description of key information

VETYNAL EXTRA (LD50 > 2000 mg/Kg): Supporting study, Acute Oral Toxicity Study in Rats dated on 2002, performed at RCC Ltd, author G. Arceli

VETYVENAL (LD50 > 2000 mg/Kg): Key study, Acute Oral Toxicity Study in Rats dated 2002,performed at RCC Ltd author Dr. E. Rosner

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

May 17 - June 17 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Specific details on test material used for the study:

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

Species:

rat

Strain:

other: HanBrl: WIST (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

3 males and 3 females (Rat, HanBrl: Wist (SPF)) were used when treated respectively: 8 weeks and 10 weeks old. By unique cage number and corresponding color-coded spots on the tail. Under laboratory conditions, after health examination, only animals without any visible signs of illness were used for the study.

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Details on oral exposure:

The animals received a single dose of the test article on a 2000 mg/kg body weight basis by oral gavage following fasting for 16.5 and 18.5 hours, but with free access to water. Food was provided again approximately 3 hours after dosing.

The application volume was 10 ml/kg body weight.

Rationale: Oral administration was used as this is one possible route of human exposure during manufacture, handling and use of the test article.

Doses:

The dose formulations were made shortly before each dosing occasion. The concentration of the test item dosage was: 2000 mg/kg body weight (single dose). The test item was diluted in vehicule (PEG 300) at a concentration of 0.2 mg/l and administered at a volume dosage of 10 ml/kg.

No. of animals per sex per dose:

3 males and 3 females

Control animals:

no

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No death occurred during the study.

Clinical signs:

No clinical signs were observed during the study period.

Body weight:

The body weight of the animals was within the range commonly recorded for this strain and age.

Other findings:

No macroscopic findings were recorded at necropsy.

Interpretation of results:

GHS criteria not met

Conclusions:

The median lethal dose of VETYVENAL after single oral administration to rats of both sexes, observed over a period of 14 days, could not be estimated as no death occured.

LD50(rat): greather than 2000 mg/kg body weight.

Executive summary:

Two groups, each using three male or three female HanBrl: WIST (SPF) rats were treated with VETYVENAL at 2000 mg/kg by oral gavage. The test article was suspended in vehicle (polyethylene glycol PEG 300) at a concentration of 0.2 mg/l and administered at a volume of 10 ml/kg.

The animals were examined for clinical signs four times during test day 1 and once daily during test days 2-15.

Mortality/viability were recorded together with clinical signs at the same time intervals.

Body weights were recorded on day 1 prior to administration and on days 8 and 15.

All animals were necropsied and examined macroscopically.

No death occurred during the study.

No clinical signs were observed in the females during the course of the study.

The body weight of the animals was within the range commonly recorded for this strain and age.

No macroscopic findings were recorded at necropsy.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

August 29 - September 11 2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

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:

rat

Strain:

other: HanBrl: WIST (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

3 males and 3 females (Rat, HanBrl: Wist (SPF)) were used when treated respectively: 9 weeks and 13 weeks old. Unique cage number and corresponding color-coded spots on the tail. The animals were marked immediately prior to treatment. Under laboratory conditions, after health examination, only animals without any visible signs of illness were used for the study.

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Details on oral exposure:

The animals received a single dose of the test item by oral gavage administration at 2000 mg/kg body weight after being fasted for 17 and 18 hours (access to water was permitted). Food was provided again approximately 3 hours after dos-ing.

The application volume was 10 ml/kg body weight.

Rationale: Oral administration was considered to be an appropriate application method as it is a possible route of human exposure during manufacture, handling and use of the test item.

Doses:

The dose formulations were made shortly before each dosing occasion. The concentration of the test item dosage was: 2000 mg/kg body weight (single dose). The test item was diluted in vehicule (PEG 300) at a concentration of 0.2 mg/l and administered at a volume dosage of 10 ml/kg.

No. of animals per sex per dose:

3 males and 3 females

Control animals:

no

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

< 2 000 mg/kg bw

Based on:

test mat.

Mortality:

All animals survived until the end of the study period.

Clinical signs:

No clinical signs were observed in the females during the course of the study.

Body weight:

The body weight of the animals was within the range commonly recorded for this strain and age.

Gross pathology:

Slightly ruffled fur and hunched posture was observed in all male animals from 2 to 3 hours after administration.

Other findings:

No macroscopic findings were recorded at necropsy.

Interpretation of results:

GHS criteria not met

Conclusions:

The median lethal dose of VETYNAL EXTRA after single oral administration to rats of both sexes, observed over a period of 14 days is:

LD50(rat): greather than 2000 mg/kg body weight.

Executive summary:

Three male and three female HanBrl: WIST (SPF) rats were treated with VETYNAL EXTRA by oral gavage administration at a dosage of 2000 mg/kg body weight. The test item was diluted in vehicle (PEG 300) at a concentration of 0.2 mg/l and administered at a volume dosage of 10 ml/kg.

 

The animals were examined daily during the acclimatization period and mortality, viability and clinical signs were recorded. All animals were examined for clinical signs at approximatively 1, 2, 3 and 5 hours after treatment on day 1 and once daily during test days 2-15. Mortality/viability was recorded twice daily during test days 1-15. Body weights were recorded on day 1 (prior administration) and on days 8 and 15. All animals were necropsied and examined macroscopically.

 

All animals survived until the end of the study period.

 

Slightly ruffled fur and hunched posture was observed in all male animals from 2 to 3 hours after administration. No clinical signs were observed in the females during the course of the study.

 

The body weight of the animals was within the range commonly recorded for this strain and age.

 

No macroscopic findings were recorded at necropsy.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The median lethal dose of VETYVENAL after single oral administration to rats of both sexes, observed over a period of 14 days, could not be estimated as no death occured.

LD50(rat): greather than 2000 mg/kg body weight, according to the CLP Regulation 1272/2008/EC & adaptation 286/2011/EC the cirteria for classification are not met.