Apple, Malus sylvestris, ext.

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

September-October 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: OECD guidance document 129

Version / remarks:

July 20th, 2010

Deviations:

yes

Remarks:

This deviation has no impact on the test item result.

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: ECVAM protocol 139

Version / remarks:

DB-ALM 139 protocol and EURL ECVAM Recommendation, April 2013

Deviations:

no

GLP compliance:

yes

Test type:

other: 3T3 NRU method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Apple, Malus sylvestris, ext.

EC Number:

286-475-7

EC Name:

Apple, Malus sylvestris, ext.

Cas Number:

85251-63-4

IUPAC Name:

Apple, Malus sylvestris, ext.

Test material form:

solid: particulate/powder

Test animals

Species:

other: N/A

Strain:

other: N/A

Details on test animals or test system and environmental conditions:

N/A

Administration / exposure

Route of administration:

other: N/A

Vehicle:

other: N/A

Results and discussion

Preliminary study:

Range finding test: The IC50 has been estimated to 40.23 mg/ml.

Effect levels

Key result

Dose descriptor:

LD50

Effect level:

ca. 5 297 mg/kg bw

Based on:

test mat.

Mortality:

N/A

Clinical signs:

N/A

Body weight:

N/A

Gross pathology:

N/A

Other findings:

The IC50 for test 1 is equal to 42.31 mg/ml, leading to a LD50 equal to 5559 mg/kg.
The IC50 for test 2 is equal to 32.42 mg/ml, leading to a LD50 equal to 5035 mg/kg

Any other information on results incl. tables

Interpretation:

The test has been evaluated in Acute Tox, an integrated in the EU FP6 project on the optimization and prevalidation of anin vitrotest for predicting human acute oral toxicity.

 The NICEATM/ICCVAM Peer review panel report (2006) has confirmed that the test do not allow to predict each of the GHS acute oral toxicity categories. However the test may be used to determine the starting doses for acute oral in vivo toxicity. ICCVAM Test method evaluation report (2006) therefore proposed a regression model, based on rat acute oral toxicity data, in order to predict LD₅₀value from the IC₅₀value obtained with the 3T3 NRU method.

The regression models are as follow:

 

Millimole regression model:    log LD₅₀(mmol/kg) = 0.439 log IC₅₀(mM) + 0.621

 Weight regression model:        log LD₅₀(mg/kg) = 0.372 log IC₅₀(µg/ml) + 2.024

 

EURL ECVAM Recommendation from April 2013 has confirmed that the 3T3 NRU Cytotoxicity Assay can be used in an integrated strategy to support identification of non-classified substances when using a threshold of > 2000 mg/kg. This threshold was used for non-classification by EU CLP.

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the retained experimental conditions, the mean LD50 of the test item is equal to 5297 mg/kg, which is higher than 2000 mg/kg. The test item may be not classified for acute toxicity according to the CLP classification

Executive summary:

Under the retained experimental conditions, the mean LD50 of the test item is equal to 5297 mg/kg, which is higher than 2000 mg/kg. The test item may be not classified for acute toxicity according to the CLP classification