Essential Oil of Piper nigrum L. (Family: Piperaceae). Obtained by the steam distillation of dried unripe berries.

Endpoint summary

Description of key information

Acute Oral Toxicity:

The LD50 was estimated to be 5998.58 mg/kg bw,when male and female Wistar rats were orally exposed with Black Pepper Oil (8006-82-4) via gavage.Thus, comparing this value with the criteria of CLP regulation,Black Pepper Oil (8006-82-4) can be “Not classified” for Acute Oral Toxicity.

Acute Dermal Toxicity:

The LD50 value was estimated to be 2733.84 mg/kg bw,when male and female New Zealand White rabbits were exposed semiocclusively with Black Pepper Oil (8006-82-4)by dermal application for 24 hours.Thus, comparing this value with the criteria of CLP regulation, Black Pepper Oil (8006-82-4) can be “Not classified” for Acute Dermal Toxicity.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Justification for type of information:

Data is predicted using OECD QSAR toolbox version 3.3 and QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

Prediction was done by using OECD QSAR toolbox v3.3,2017

GLP compliance:

not specified

Test type:

other: Estimated data

Limit test:

no

Specific details on test material used for the study:

- Name of test material (IUPAC name): Black Pepper Oil
- Common name: Pepper oil
- Substance type: Organic

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

No data available

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

No data available

Doses:

5998.58 mg/kg bw

No. of animals per sex per dose:

No data available

Control animals:

not specified

Details on study design:

No data available

Statistics:

No data available

Preliminary study:

No data available

Sex:

male/female

Dose descriptor:

LD50

Effect level:

5 998.58 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50% mortality was observed

Mortality:

No data available

Clinical signs:

No data available

Body weight:

No data available

Gross pathology:

No data available

Other findings:

No data available

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

((((((((("a" or "b" or "c" )  and "d" )  and ("e" and ( not "f") )  )  and "g" )  and ("h" and ( not "i") )  )  and "j" )  and "k" )  and ("l" and ( not "m") )  )  and ("n" and "o" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Alkene OR Allyl OR Cycloalkene by Organic Functional groups ONLY

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Allyl OR Cycloalkene OR Overlapping groups by Organic Functional groups (nested) ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] OR Aliphatic Carbon [-CH2-] OR Aliphatic Carbon [-CH3] OR Olefinic carbon [=CH- or =C<] OR Olefinic carbon [=CH2] OR Tertiary Carbon by Organic functional groups (US EPA) ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.3 ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Non binder, MW>500 OR Non binder, non cyclic structure by Estrogen Receptor Binding

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C by Chemical elements

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Group 16 - Oxygen O by Chemical elements

Domain logical expression index: "j"

Similarity boundary:Target: CC(=C)C1CCC(C)=CC1
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Alkene AND Allyl AND Cycloalkene by Organic Functional groups ONLY

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as No Data by Ultimate biodeg

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as 10 to 100 days by Ultimate biodeg

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is >= 3.18

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.92

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The LD50 was estimated to be 5998.58 mg/kg bw,when male and female wistar rats were orally exposed with Black Pepper Oil (8006-82-4) via gavage.

Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for Black Pepper Oil(8006-82-4).The LD50 was estimated to be 5998.58 mg/kg bw,when male and female wistar rats were orally exposed with Black Pepper Oil(8006-82-4) via gavage.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 998.58 mg/kg bw

Quality of whole database:

Data is Klimicsh 2 and from QSAR Toolbox 3.3. (2017)

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Justification for type of information:

Data is predicted using OECD QSAR toolbox version 3.3 and QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

Prediction was done by using OECD QSAR toolbox v3.3,2017

GLP compliance:

not specified

Test type:

other: no data available

Limit test:

no

Specific details on test material used for the study:

- Name of test material (IUPAC name): Black Pepper Oil
- Common name: Pepper oil
- Substance type: Organic

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

No data available

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

No data available

Duration of exposure:

24 hours

Doses:

2733.84 mg/kg bw

No. of animals per sex per dose:

No data available

Control animals:

not specified

Details on study design:

No data available

Statistics:

No data available

Preliminary study:

No data available

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 733.84 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50% Mortality was observed

Mortality:

No data available

Clinical signs:

No data available

Body weight:

No data available

Gross pathology:

No data available

Other findings:

No data available

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

((((("a" or "b" or "c" )  and "d" )  and ("e" and ( not "f") )  )  and "g" )  and ("h" and "i" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Alkene OR Allyl OR Cycloalkene by Organic Functional groups ONLY

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Allyl OR Cycloalkene OR Overlapping groups by Organic Functional groups (nested) ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] OR Aliphatic Carbon [-CH2-] OR Aliphatic Carbon [-CH3] OR Olefinic carbon [=CH- or =C<] OR Olefinic carbon [=CH2] OR Tertiary Carbon by Organic functional groups (US EPA) ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.3 ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Non binder, MW>500 OR Non binder, non cyclic structure by Estrogen Receptor Binding

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "h"

Parametric boundary:The target chemical should have a value of log Kow which is >= 2.47

Domain logical expression index: "i"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.88

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The LD50 value was estimated to be 2733.84 mg/kg bw,when male and female new zealand white rabbits were exposed semiocclusively with Black Pepper Oil (8006-82-4 )by dermal application for 24 hours.

Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated for black Pepper Oil (8006-82-4 ). TheLD50 was estimated to be 2733.84mg/kg bw,when male and female new Zealand white rabbits were exposed semiocclusively with Pepper Oil (8006-82-4 ) by dermal application for 24 hours.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 733.84 mg/kg bw

Quality of whole database:

Data is Klimicsh 2 and from QSAR Toolbox 3.3. (2017)

Additional information

Acute Oral Toxicity:

In different studies, Black Pepper Oil (8006-82-4) has been investigated for acute oral toxicity to a greater or lesser extent. Often the studies are based on in vivo experiments and estimated data in rodents, i.e. most commonly in rats for Black Pepper Oil (8006-82-4).The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies. The studies are summarised as below:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for Black Pepper Oil(8006-82-4).The LD50 was estimated to be 5998.58 mg/kg bw,when male and female Wistar rats were orally exposed with Black Pepper Oil(8006-82-4) via gavage.

In another experimental study conducted by D. L. J. Opdyke (Food and Cosmetics Toxicology,Volume 16, Supplement 1, 1978, Pages 651-652) for the target substance Black Pepper Oil(8006-82-4). Acute oral toxicity study was done in rats using test material Black Pepper Oil (8006-82-4).No mortality was observed at dose 5000 mg/kg bw. Hence,LD50 value was considered to be >5000 mg/kg bw,when rats were treated with Black Pepper Oil (8006-82-4)orally.

In another experimental study conducted by U.S. National Library of Medicine (Chemidplus Database,U.S. National Library of Medicine,2017) and IFA GESTIS (Gestis Substance Database,2017) for the structurally similar read across substance (+)-Limonene (5989-27-5). Acute oral toxicity study was done in rats using test material (+)-Limonene (5989-27-5).50% mortality was observed at dose 4400 mg/kg bw.Clinical signs like behavioral changes in motor activity (specific assay) and changes in lungs and thorax were observed.Respiratory function tests were depressed.Hence,LD50 value was considered to be 4400 mg/kg bw,when rats were treated with(+)-Limonene (5989-27-5)orally.

In another experimental study conducted by U.S. National Library of Medicine (Chemidplus Database,U.S. National Library of Medicine,2017)and IFA GESTIS (Gestis Substance Database,2017) for the structurally similar read across substance Dipentene (138-86-3). Acute oral toxicity study was done in rats using test material Dipentene(138-86-3) .50% mortality was observed at dose 5300 mg/kg bw. Hence,LD50 value was considered to be 5300 mg/kg bw,when rats were treated with Dipentene(138-86-3)orally.

In another experimental study conducted by D. L. J. Opdyke (Food and Cosmetics Toxicology ,Volume 12, Issues 5–6, Pages 601-805 (October 1974)) and U.S. National Library of Medicine (Chemidplus Database,U.S. National Library of Medicine,2017) for the structurally similar read across substance Citrus aurantium var. amara(68916-04-1). Acute oral toxicity study was done in rats using test material Citrus aurantium var. amara(68916-04-1).No mortality was observed at dose 5000 mg/kg bw. Hence,LD50 value was considered to be >5000 mg/kg bw,when rats were treated with Citrus aurantium var. amara (68916-04-1)orally.

Also these results are further supported by the experimental study conducted by D. L. J. Opdyke (Food and Cosmetics Toxicology,Volume 14, Supplement, 1976, Pages 877-878) ; U.S. National Library of Medicine (HSDB (Hazardous Substances Data Bank); US national Library of Medicine,2017); Richard J. Lewis (Sax's Dangerous Properties of Industrial Materials, 12th Edition, 5 Volume Set,2012) and U.S. National Library of Medicine (Chemidplus Database,U.S. National Library of Medicine,2017) for the structurally similar read across substance 1-methyl-4(1-methylethylidene) cyclohex-1-ene (586-62-9). Acute oral toxicity study was done in 10 rats per sex per dose using test material1-methyl-4(1-methylethylidene) cyclohex-1-ene(586-62-9) at dose 3000 mg/kg bw,3500 mg/kg bw,4000 mg/kg bw and 5000 mg/kg bw.At dose 3000 mg/kg bw no mortality was observed,at dose 3500 mg/kg bw 1 rat died ,at dose 4000 mg/kg bw 5 rats died and at dose 5000 mg/kg bw 6 rats died.Hence,LD50 value was considered to be 4390 mg/kg bw(95% CI 3750 - 5140 mg/kg),when rats were treated with 1-methyl-4(1-methylethylidene) cyclohex-1-ene(586-62-9)orally.

Thus, based on the above studies and predictions on Black Pepper Oil (8006-82-4) and its structurally similar read across substances, it can be concluded that LD50 value was 5998.58 mg/kg bw.Thus, comparing this value with the criteria of CLPregulation,Black Pepper Oil (8006-82-4) can be “Not classified” for Acute Oral Toxicity.

Acute Dermal Toxicity:

In different studies, Black Pepper Oil (8006-82-4) has been investigated for acute dermal toxicity to a greater or lesser extent. Often the studies are based on in vivo experiments and estimated data in rodents, i.e. most commonly in rabbits for Black Pepper Oil (8006-82-4) .The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies. The studies are summarised as below:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated for black Pepper Oil (8006-82-4 ). TheLD50 was estimated to be 2733.84mg/kg bw,when male and female New Zealand White rabbits were exposed semiocclusively with Pepper Oil (8006-82-4 ) by dermal application for 24 hours.

In another experimental study conducted by D. L. J. Opdyke (Food and Cosmetics Toxicology,Volume 16, Supplement 1, 1978, Pages 651-652) for the target substance Black Pepper Oil(8006-82-4). Acute dermal toxicity study was done in rabbits using test material Black Pepper Oil (8006-82-4).No mortality was observed at dose 5000 mg/kg bw. Hence,LD50 value was considered to be >5000 mg/kg bw,when rabbits were treated with Black Pepper Oil (8006-82-4)by dermal application.

In another experimental study conducted by U.S. National Library of Medicine (Chemidplus Database,U.S. National Library of Medicine,2017)and IFA GESTIS (Gestis Substance Database,2017) for the structurally similar read across substance (+)-Limonene (5989-27-5). In acute dermal toxicity study,rabbits were treated with (+)-Limonene (5989-27-5) in the concentration of 5000 mg/kg bw by dermal application.No mortality was observed in treated rabbits at dose 5000 mg/kg bw.Therefore, LD50 value was considered to be >5000 mg/kg bw,when rabbits were treated with (+)-Limonene (5989-27-5)by dermal application.

In another experimental study conducted by IFA GESTIS (Gestis Substance Database,2017) for the structurally similar read across substance Dipentene (138-86-3). In acute dermal toxicity study,rabbits were treated with Dipentene(138-86-3)in the concentration of 5000 mg/kg bw by dermal application.No mortality was observed in treated rabbits at dose 5000 mg/kg bw.Therefore, LD50 value was considered to be >5000 mg/kg bw,when rabbits were treated with Dipentene(138-86-3)by dermal application.

In another experimental study conducted by D. L. J. Opdyke (Food and Cosmetics Toxicology ,Volume 12, Issues 5–6, Pages 601-805 (October 1974)) and U.S. National Library of Medicine (Chemidplus Database,U.S. National Library of Medicine,2017) for the structurally similar read across substance Citrus aurantium var. amara(68916-04-1). In acute dermal toxicity study,rabbits were treated with Citrus aurantium var. amara(68916-04-1) in the concentration of 10000 mg/kg bw by dermal application.No mortality was observed in treated rabbits at dose 10000 mg/kg bw.Therefore, LD50 value was considered to be >10000 mg/kg bw,when rabbits were treated with Citrus aurantium var. amara(68916-04-1)by dermal application.

Also these results are further supported by the experimental study conducted by D. L. J. Opdyke (Food and Cosmetics Toxicology,Volume 14, Supplement, 1976, Pages 877-878) and U.S. National Library of Medicine (HSDB (Hazardous Substances Data Bank) for the structurally similar read across substance 1-methyl-4(1-methylethylidene) cyclohex-1-ene (586-62-9). In acute dermal toxicity study,10 rabbits were treated with 1-methyl-4(1-methylethylidene) cyclohex-1-ene(586-62-9) in the concentration of 5000 mg/kg bw by dermal application for seven days of observation period following exposure.A single 24 hour application of test substance was applied to the clipped abraded abdominal skin of rabbits.Gross necropsies were performed on all animals at study termination. No mortality was observed in treated rabbits at dose 5000 mg/kg bw.No evidence of toxicity from percutaneous absorption of the test substance. Erythema and edema were reported during the first few days of observation, but cleared by the study termination.Therefore, LD50 value was considered to be >5000 mg/kg bw,when rabbits were treated with1-methyl-4(1-methylethylidene) cyclohex-1-ene(586-62-9)by dermal application.

Thus, based on the above studies and predictions on Black Pepper Oil (8006-82-4) and its read across substances, it can be concluded that LD50 value was 2733.84 mg/kg bw.Thus, comparing this value with the criteria of CLP regulation, Black Pepper Oil (8006-82-4) can be “Not classified” for Acute Dermal Toxicity.

Justification for classification or non-classification

Thus, comparing this value with the criteria of CLP regulation, Black Pepper Oil (8006-82-4) can be “Not classified” for Acute Oral and Dermal Toxicity