Mentha citrata, ext.

Endpoint summary

Description of key information

Repeated dose toxicity: Oral

The no observed Adverse Effect Level (NOAEL) for the test chemical Mentha citrata, ext for a duration of chronic toxicity study is considered to be 500 mg/Kg bw.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

chronic toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Remarks:

experimental data of read across substances

Justification for type of information:

Data for the target chemical is summarized based on the structurally similar read across chemicals

Reason / purpose for cross-reference:

read-across: supporting information

Reason / purpose for cross-reference:

read-across: supporting information

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

according to guideline

Guideline:

other: Refer below principle

Principles of method if other than guideline:

WoE derived based on the experimental data from structurally and functionally similar read across chemicals

GLP compliance:

not specified

Limit test:

no

Species:

rat

Strain:

Osborne-Mendel

Details on species / strain selection:

No data

Sex:

male/female

Details on test animals or test system and environmental conditions:

1. TEST ANIMALS
- Source: No data available
- Age at study initiation: weanling rats
- Weight at study initiation: No data available
- Fasting period before study: No data available
- Housing: housed individually in wire cages
- Diet (e.g. ad libitum): food ad libitum
- Water (e.g. ad libitum): water ad libitum
- Acclimation period: No data available

ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data available
- Humidity (%):No data available
- Air changes (per hr): No data available
- Photoperiod (hrs dark / hrs light): No data available

IN-LIFE DATES: From: To: No data available

Route of administration:

oral: feed

Details on route of administration:

1. No data

Vehicle:

other: Feed

Details on oral exposure:

1. PREPARATION OF DOSING SOLUTIONS: The test chemical was mixed with feed at dose level of 0, 1000, 2500 or 10000 ppm (0, 100, 250 or 1000 mg/Kg/day).

DIET PREPARATION
- Rate of preparation of diet (frequency): Weekly
- Mixing appropriate amounts with (Type of food): Details not specified
- Storage temperature of food: No data available

VEHICLE
- Justification for use and choice of vehicle (if other than water): Food
- Concentration in vehicle: 0, 1000, 2500 or 10000 ppm (0, 100, 250 or 1000 mg/Kg/day).
- Amount of vehicle (if gavage): No data available
- Lot/batch no. (if required): No data available
- Purity: No data available

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

No data

Duration of treatment / exposure:

18 weeks

Frequency of treatment:

Daily

Remarks:

0, 1000, 2500 or 10000 ppm (0, 100, 250 or 1000 mg/Kg/day).

No. of animals per sex per dose:

1. Total: 80 (40 males and 40 females)
0 mg/Kg bw: 10/sex/dose
100 mg/Kg bw: 10/sex/dose
250 mg/Kg bw: 10/sex/dose
1000 mg/Kg bw: 10/sex/dose

Control animals:

yes, concurrent vehicle

Details on study design:

1. - Dose selection rationale: No data available
- Rationale for animal assignment (if not random): No data available
- Rationale for selecting satellite groups: No data available
- Post-exposure recovery period in satellite groups: No data available
- Section schedule rationale (if not random): No data available

Positive control:

1. No data

Observations and examinations performed and frequency:

1. CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Weekly
- Cage side observations checked in table [No.?] were included. General condition

DETAILED CLINICAL OBSERVATIONS: No data
- Time schedule: No data

BODY WEIGHT: Yes
- Time schedule for examinations: Weekly

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes, weekly
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data
- Time schedule for examinations:

OPHTHALMOSCOPIC EXAMINATION: No data
- Time schedule for examinations: No data
- Dose groups that were examined: No data

HAEMATOLOGY: Yes
- Time schedule for collection of blood: at termination
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: No data
- Parameters checked in table [No.?] were examined. White cell counts, red cell counts, haemoglobins and haematocrits.

CLINICAL CHEMISTRY: No data
- Time schedule for collection of blood: No data
- Animals fasted: No data
- How many animals: No data
- Parameters checked in table [No.?] were examined. No data

URINALYSIS: No data
- Time schedule for collection of urine: No data
- Metabolism cages used for collection of urine: No data
- Animals fasted: No data - Parameters checked in table [No.?] were examined. No data

NEUROBEHAVIOURAL EXAMINATION: No data No data
- Time schedule for examinations:
- Dose groups that were examined:
- Battery of functions tested: sensory activity / grip strength / motor activity / other:

OTHER: No data

Sacrifice and pathology:

1. GROSS PATHOLOGY: Yes, The tissues of all the rats were examined macroscopically at the time of sacrifice. The viscera were removed and the liver, kidneys, spleen, heart, and testes were weighed.

HISTOPATHOLOGY: Yes, The viscera were removed and the liver, kidneys, spleen, heart, and testes were weighed. These organs, the remaining abdominal and thoracic viscera, and one hind leg, for bone, bone marrow, and muscle, were preserved in 10 % buffered formalin-saline solution for histopathological examination.

For routine histopathology, sections were embedded in paraffin wax and stained with haematoxylin and eosin

Other examinations:

1. No data

Statistics:

1. No data

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

no effects observed

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

no effects observed

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

not specified

Description (incidence and severity):

No macroscopic effects were noted in the 100 and 250 mg/Kg group

Other effects:

not specified

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No effects were noted at the mentioned dose level

Critical effects observed:

not specified

Conclusions:

The no observed Adverse Effect Level (NOAEL) for the test chemical Mentha citrata, ext for a duration of chronic toxicity study is considered to be 1000 mg/Kg bw.

Executive summary:

Chronic and subacute toxicity studies were conducted to determine the toxic nature of Mentha citrata, ext upon repeated exposure by oral route. The studies are as mentioned below:

Chronic toxicity oral study for the test compound was studied in male and female Osborne-Mendel rats. The test compound was fed through the diet at a concentration of 0, 1000, 2500 or 10000 ppm (0, 100, 250 or 1000 mg/Kg bw) for 18 weeks. The animals were observed weekly for weight, food intake and general condition. Haematological examinations were made at termination. These examinations included white cell counts, red cell counts, haemoglobins and haematocrits. No effects were noted in the treated animals at the mentioned dose level. Based on the observations made, the no observed Adverse Effect Level (NOAEL) for the test compound in Osborne-Mendel rats is considered to be 1000 mg/Kg bw.

Another Repeated dose oral toxicity study was performed to determine the toxic nature of test chemical. The study was performed using female B6C3F1 mice.The test chemical was mixed with 1% methyl cellulose at dose levels of 0, 94, 188 or 375 mg/Kg/day. The dose for the main study were based on preliminary toxicity study. Test material was administered intragastrically on a daily basis for 5 days at 3 dose levels to B6C3F1 mice. During the study, the animals were observed for signs of toxicity, mortality and changes in body weight and organ weight. A host-resistance assay (Listeria monocytogenes bacterial challenge) was conducted to assess cell-mediate immunity. Humoral immunity was measured by the antibody Plaque-Forming cell (PFC) response to sheep erythrocytes. Cyclophosphamide served as an immunosuppressive positive control agent. No increase in the mortality or significant alteration to the Plaque-Forming cell response was noted. Hence the No Observed Adverse effect level (NOAEL) for female B6C3F1 mice is considered to be 375 mg/Kg/day.

In the same study, repeated dose oral toxicity study was performed to determine the toxic nature of test chemical. The study was performed using female B6C3F1 mice.The test chemical was mixed with corn oil at dose levels of 0, 750, 1500 or 3000 mg/Kg/day. The dose for the main study were based on preliminary toxicity study. Test material was administered intragastrically on a daily basis for 5 days at 3 dose levels to CD1 mice. During the study, the animals were observed for signs of toxicity, mortality and changes in body weight and organ weight. A host-resistance assay (Listeria monocytogenes bacterial challenge) was conducted to assess cell-mediate immunity. Humoral immunity was measured by the antibody Plaque-Forming cell (PFC) response to sheep erythrocytes. Cyclophosphamide served as an immunosuppressive positive control agent.Increased mortality following challenge with L. monocytogenes was noted at 750 mg/kg. The increased mortality observed following challenge with L. monocytogenes was not dose related and therefore considered to be incidental. Significant alteration to the Plaque-Forming cell response was not observed. Hence theNo Observed Adverse effect level (NOAEL) for female CD1 mice is considered to be 750 mg/Kg/day.

Based on the observations made, the no observed Adverse Effect Level (NOAEL) for the test chemical Mentha citrata, ext for a duration of chronic toxicity study is considered to be 1000 mg/Kg bw

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

500 mg/kg bw/day

Study duration:

chronic

Species:

rat

Quality of whole database:

Data is from K2 publication

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Repeated dose toxicity: Oral

Data available for the structurally and functionally similar read across chemicals have been reviewed to determine the toxic nature of Mentha citrata, ext (CAS no 85085 -49 -0). The studies are as mentioned below:

Chronic toxicity oral study for the test compound was studied in male and female Osborne-Mendel rats. The test compound was fed through the diet at a concentration of 0, 1000, 2500 or 10000 ppm (0, 100, 250 or 1000 mg/Kg bw) for 18 weeks. The animals were observed weekly for weight, food intake and general condition. Haematological examinations were made at termination. These examinations included white cell counts, red cell counts, haemoglobins and haematocrits. No effects were noted in the treated animals at the mentioned dose level. Based on the observations made, the no observed Adverse Effect Level (NOAEL) for the test compound in Osborne-Mendel rats is considered to be 500 mg/Kg bw.

Another Repeated dose oral toxicity study was performed to determine the toxic nature of test chemical. The study was performed using female B6C3F1 mice.The test chemical was mixed with 1% methyl cellulose at dose levels of 0, 94, 188 or 375 mg/Kg/day. The dose for the main study were based on preliminary toxicity study. Test material was administered intragastrically on a daily basis for 5 days at 3 dose levels to B6C3F1 mice. During the study, the animals were observed for signs of toxicity, mortality and changes in body weight and organ weight. A host-resistance assay (Listeria monocytogenes bacterial challenge) was conducted to assess cell-mediate immunity. Humoral immunity was measured by the antibody Plaque-Forming cell (PFC) response to sheep erythrocytes. Cyclophosphamide served as an immunosuppressive positive control agent. No increase in the mortality or significant alteration to the Plaque-Forming cell response was noted. Hence the No Observed Adverse effect level (NOAEL) for female B6C3F1 mice is considered to be 375 mg/Kg/day.

In the same study, repeated dose oral toxicity study was performed to determine the toxic nature of test chemical. The study was performed using female B6C3F1 mice.The test chemical was mixed with corn oil at dose levels of 0, 750, 1500 or 3000 mg/Kg/day. The dose for the main study were based on preliminary toxicity study. Test material was administered intragastrically on a daily basis for 5 days at 3 dose levels to CD1 mice. During the study, the animals were observed for signs of toxicity, mortality and changes in body weight and organ weight. A host-resistance assay (Listeria monocytogenes bacterial challenge) was conducted to assess cell-mediate immunity. Humoral immunity was measured by the antibody Plaque-Forming cell (PFC) response to sheep erythrocytes. Cyclophosphamide served as an immunosuppressive positive control agent.Increased mortality following challenge with L. monocytogenes was noted at 750 mg/kg. The increased mortality observed following challenge with L. monocytogenes was not dose related and therefore considered to be incidental. Significant alteration to the Plaque-Forming cell response was not observed. Hence theNo Observed Adverse effect level (NOAEL) for female CD1 mice is considered to be 750 mg/Kg/day.

Based on the observations made, the target chemical Mentha citrata, ext is not likely to be toxic as per the criteria mentioned in CLP regulation.

Justification for classification or non-classification

Based on the observations made, the target chemical Mentha citrata, ext (CAS no 85085 -49 -0) is not likely to be toxic as per the criteria mentioned in CLP regulation.