Hydrocotyle asiatica, ext.

Endpoint summary

Description of key information

Centella asiatica dry ext. is of low acute oral and dermal toxicity. The experimental LD50 are > 2000 mg/kg bw for both routes of exposure.

Inhalation toxicity is not expected, since no exposure is foreseen for Centella asiatica dry ext.

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

Study period:

2013

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

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

female

Route of administration:

oral: gavage

Vehicle:

water

Doses:

2000 mg/kg

No. of animals per sex per dose:

3 female for step.
Two step.
Total 6 female

Control animals:

no

Key result

Sex:

female

Dose descriptor:

LD50 cut-off

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Mortality:

no

Clinical signs:

no

Gross pathology:

no

Interpretation of results:

GHS criteria not met

Conclusions:

CENTELLA 36CT60090 is not classified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

exposure considerations

Justification for data waiving:

the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size

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

Study period:

2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

2017

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Species/strain: WISTAR rats Crl: WI(Han)
Source: Charles River, 97633 Sulzfeld, Germany
Sex: female (non-pregnant and nulliparous)
Number of animals: 3 animals
Body weight at the
beginning of the study: 215 – 226 g
Age at the
beginning of the study: 12 - 14 weeks
The animals were derived from a controlled full-barrier maintained breeding system (SPF). According to the German Act on Animal Welfare the animals were bred for experimental purposes.
This study was performed in an AAALAC-accredited laboratory. According to German animal protection law, the study type has been reviewed and accepted by local authorities. Furthermore, the study has been subjected to Ethical Review Process and was authorised by the Bavarian animal welfare administration.

Type of coverage:

semiocclusive

Vehicle:

water

Remarks:

sterile water

Duration of exposure:

24h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

1female + 2 female

Control animals:

yes

Details on study design:

Procedure Dose Range Finding Test
One animal was dosed at a dosage of 2000mg/kg body weight. As the animal survived without showing any signs of systemic toxicity, this dose was used as a starting dose for the main study.

Procedure Main Test
The dose was administered to two animals sequentially. As both animals survived at 2000 mg/kg body weight without showing any signs of systemic toxicity, no further dose was tested.

Exposure Period
The test item was held in contact with the skin throughout a 24-hour period. At the end of the exposure period the residual test item was removed using aqua ad injectionem (sterile water).

Observation Period
All animals were observed for 14 days after dosing.

Primary Skin Irritation
Signs of erythema and oedema were assessed using the scoring system laid down in OECD Guideline 404, 24, 48 and 72 hours after patch removal

Key result

Sex:

female

Dose descriptor:

other: ATE

Remarks:

2000mg/kg bw

Effect level:

>= 2 000 - <= 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

no indication of skin irritation up to the relevant limit dose level

Mortality:

0

Clinical signs:

0

Body weight:

unchanged

Gross pathology:

0

 Table: Absolute Body Weights [g] and Body Weight Change [%] - DRF and Main Study

Dose: 2000 mg/kg body weight
Animal No. / Sex	Absolute Body Weights [g]			Body Weight Change [%]
	Day 1	Day 8	Day 15	Day 1-15
1 / female	215	218	215	0
2 / female	222	220	233	5
3 / female	226	227	233	3

bw = body weight

Pathology

No specific gross pathological changes were recorded for any animal (for individual data seeTable9).

Table:  Macroscopic Findings - Individual Data – DRF and Main Study

Dose: 2000 mg/kg bw
Animal No. / Sex	Organ	Macroscopic Findings
1 / female	-	nsf
2 / female	-	nsf
3 / female	-	nsf

nsf = no specific findings

 Acute Toxicity Estimate (ATE)

Table: Acute Toxicity Estimate (ATE) according to GHS, 2017[9]

Dose (mg/kg bw)	Number of Animals Investigated (Main Study)	Number of Intercurrent Deaths	Category	ATE (mg/kg bw)
2000 mg/kg bw	3 females	0	5	2000 < ATE≤5000

bw = body weight

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of the present study, single dermal application of the test item Centella asiatica dry ext. to rats at a dose of 2000 mg/kg body weight was associated with no mortality and neither signs of toxicity nor signs of irritation.
According to OECD guideline 402 the test item Centella asiatica dry ext. has no obligatory labelling requirement for percutaneous toxicity and is unclassified.
The Acute Toxicity Estimate according to GHS (Globally Harmonized Classification System), 2017 was determined to be 2000 < ATE ≤ 5000 mg Centella asiatica dry ext. / kg body weight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Justification for classification or non-classification

According to the experimental results, no classification is deemed necessary regarding acute toxicity endpoints.