Cashew (Anacardium occidentale) Nutshell Extract, Decarboxylated, Distilled, oligomerisation products with 1-chloro-2,3-epoxypropane

Endpoint summary

Description of key information

- Acute oral toxicity [OECD 423, acute toxic class method; GLP]: LD₅₀ in female rats >2000 mg/kg bw.

- Acute inhalation toxicity: Taking into account the very low vapour pressure of the registration substance, exposure via the inhalation route is unlikely; it is therefore considered justified to omit this endpoint information.

- Acute dermal toxicity [OECD 402, standard acute method; GLP]: LD₅₀ in male/female rats >2000 mg/kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

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)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories France, Boîte postale 0109, 69592 L’ARBRESLE , France
- Age at study initiation: 8 and 12 weeks
- Weight at study initiation: 150 and 250 g
- Fasting period before study: yes (approx. 12h)
- Housing: transparent polycarbonate (macrolone type III) cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 3°C
- Humidity (%): 50 % ± 20 %
- Air changes (per hr): approximately 10
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 1000 mg per mL

MAXIMUM DOSE VOLUME APPLIED: 2 mL per kg of body weight per animal

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: no toxicity expected

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily/ 3 times per week
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

none

Clinical signs:

other: Behaviour, impact on RS or CNS

Body weight:

other body weight observations

Remarks:

The body weight gain per day was calculated for each animal, as well as the average of the body weight gain per day for each study group. Averages of body weight gain per day are: for group 1 (2000 mg/kg CARDOLITE NC-513): 3.2 g/day for group 2 (2000 mg/kg CARDOLITE NC-513): 0.6 g/day The comparison to published results in literature as well as to the results obtained in other studies performed by the laboratory revealed that growth of all animals of the study group 1 is in the same range than growth of normally untreated SD (Sprague Dawley) rats, in contrary of the growth of the animals for the group 2. Weight gain for the group 1 is about five times higher than in group 2. Furthermore, a weight loss peak was recorded for each group approximately at the same time: from day 8 to day 11 for both groups. Nevertheless, this weight loss is more remarkable in group 2 than in group 1

Gross pathology:

No abnormalities were recorded during the macroscopic examination.

Other findings:

Oral gavage at dose level of 2000 mg per kg body weight of the test item, CARDOLITE NC-513, may influence the food consumption and may have an impact on the appetite.

Interpretation of results:

other:

Remarks:

EU GHS criteria not met

Conclusions:

In a GLP-study according to OECD Test Guideline 423, the acute oral LD50 of the registered substance was determined to be > 2000 mg/kg bw.

Executive summary:

The results obtained in a GLP-study according to OECD Test Guideline 423 indicate that a single administration of CARDOLITE NC-513 at 2000 mg/kg on female rats did not result in behavior changes. No clinical signs were detected during the study.

However CARDOLITE NC-513 had an influence on food consumption and on weight gain especially in group 2.

Due to the low number of animals no statistical analysis was performed.

In consequence no statistical difference could be highlighted.

Some differences were observed between both groups despite the fact that both groups were injected with the same dose of CARDOLITE NC-513 (2000 mg/kg) using the same conditions of injection,

In conclusion oral gavage at dose level of 2000 mg per kg body weightof the test item, CARDOLITE NC-513, may influence the food consumption and may have an impact on the appetite, but has no lethal effect on animals.

The LD₅₀ cut off of the test item CARDOLITE NC-513 is higher than 2000 mg/kg body weight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Quality of whole database:

Reliable GLP study

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:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

some minor deviations (no impact)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories France, Boîte postale 0109, 69592 L’ARBRESLE , France
- Age at study initiation: no information
- Weight at study initiation: 200 - 300 g
- Fasting period before study: no
- Housing: transparent polycarbonate (macrolone type III) cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 3°C
- Humidity (%): 50 % ± 20 %
- Air changes (per hr): approximately 10
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Duration of exposure:

24h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

no

Clinical signs:

other: One day after the application coordination was impacted during a period of one day. Skin from almost all animals was affected: desquamation, small wounds, and skin irritation

Body weight:

other body weight observations

Remarks:

reduced female body weight gain due to reduced food consumption

Interpretation of results:

other: EU GHS criteria not met

Conclusions:

In a GLP-study according to OECD Test Guideline 402 conducted as a limit test, the acute dermal LD50 of the registered substance was determined to be > 2000 mg/kg bw.

Executive summary:

The results of a limit test according to OECD Test Guideline 402 indicate that a single dermal application of CARDOLITE NC-513 at 2000 mg/kg on female and male rats did not result in major behavior changes. One day after the application coordination was impacted during a period of one day but no other clinical signs were detected during the study. Some reversible effects on skin such as desquamation, small wounds, and skin irritation were observed. Kidney abnormalities (such as hemorrhagic stain) for male and female were recorded during the macroscopic examination after necropsy. CARDOLITE NC-513 had an influence on food consumption and on weight gain for

female In conclusion dermal application at dose level of 2000 mg per kg body weight of the test item, CARDOLITE NC-513, may influence the food consumption and may have an impact on the appetite for female.

In conclusion the LD₅₀ of the test item CARDOLITE NC-513 is higher than 2000 mg/kg body weight by dermal route in the rat.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Quality of whole database:

Reliable GLP study

Additional information

No mortality was observed in an acute oral and an acute dermal toxicity study up to the limit test concentration of 2000 mg/kg bw.

Justification for classification or non-classification

On the basis of the available acute toxicity data via the oral and dermal route, the registration substance does not require classification for lethal effects following a single exposure according to Regulation 1272/2008/EC.