Cassava, ext.

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Remarks:

In vitro acute toxicity test

Type of information:

experimental study

Adequacy of study:

key study

Study period:

August 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:

According to the OECD guidance document, hill function analylis was performed by GraphPad PRISM 5.01. The software is not validated which is a deviation from GLP. A polynomial r egression by excel confirmed the positive controle dose-response R^2.

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: ECVAM protocol 139

Version / remarks:

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

GLP compliance:

yes

Test type:

other: 3T3 NRU method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Cassava, ext.

EC Number:

296-251-0

EC Name:

Cassava, ext.

Cas Number:

92456-72-9

IUPAC Name:

Cassava, 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:

The IC50 has been estimated to 6.12 mg/ml

Effect levels

Effect levels 1

Key result

Dose descriptor:

LD50

Effect level:

ca. 3 032 mg/kg bw

Based on:

test mat.

Effect levels 2

Key result

Dose descriptor:

LD50

Effect level:

ca. 3 045 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 8.29 mg/ml, leading to LD50 equal to 3032 mg/kg
The IC50 for test 2 is equal to 8.39 mg/ml, leading to LD50 equal to 3045 mg/kg

Any other information on results incl. tables

Interpretation of results:

The test has been evaluated in Acute Tox, an integrated in the EU PF6 project on optimization and prevalidation of an in vitro test for predicting human acute orale toxicity.

The NICEATM/ICCVAM Peer review panel report (2006) has confirmed that the test do not allow to predict each of the GHS acute orale 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 toxicity data, in order to predict LD50 value from the IC50 value obtained withe the 3T3 NRU method.

The regression models are as follow:

Milimole regression model: log LD50 (mmol/kg) = 0.439 log IC (mM) + 0.621

Weight regression model: log LD50 (mg/kg) = 0.372 log IC (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 > 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 3038.50 mg/kg, which is higher than 2000 mg/kg. The test item may be not classified for acute toxicity according to CLP classification.

Executive summary:

Under the retained experimental conditions, the mean LD50 of the test item is equal to 3038.50 mg/kg, which is higher than 2000 mg/kg. The test item may be not classified for acute toxicity according to CLP classification.