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Description of key information

 


The substance (CAS 1427388 -03 -1) can be structurally divided into a 'body' and three 'arms'.


The three 'arms' are identified as 2-(2 -Vinyloxyethoxy)ethyl acrylate (VEEA - CAS: 86273 -46 -3) and is registered between 10 -100 tonnes/year. The body is identified as Omnipol TX but has no reliable, useful experimental data. Read-across to VEEA is proposed, in combination with QSAR estimation for the full substance.


VEEA is classified as Acute Toxic Cat. 4 - oral route. Based on QSAR the full substance (CAS 1427388 -03 -1) would not be classified. However following the precautionary principle, the full substance will be classified as Acute Toxic Cat. 4 - oral route.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Study period:
Between: 10th September 2003 and 07th November 2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
[Please provide information for all of the points below. Indicate if further information is included as attachment to the same record, or elsewhere in the dataset (insert links in 'Cross-reference' table)]

See attached justification
Reason / purpose for cross-reference:
read-across source
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
Date of inspection: November 2002 Date of Signature: March 2003
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
other: HanBrl: Wist (SPF)
Sex:
female
Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:RCC Ltd, Laboratory Animal Services, CH-4414 Fullinsdorf, Switzerland

- Age at study initiation: 12 weeks

- Fasting period before study: Approximately between 17 and 18 hours.

- Housing: In groups of three in Makrolon type-4 cages with wire mesh tops and standard softwood bedding ('Lignocel' Schill AG, CH-4132 Muttenz,Switzerland).

- Diet (e.g. ad libitum):Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, batch No. 4/03 and 54/03 (Provimi Kliba AG. CH-4303, Kaiseraugst, Switzerland, ad libitum

- Water (e.g. ad libitum): Community tap water from Fullinsdorf in Switzerland ad libitum.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): Set to achieve limits of 19 deg C to 25 deg C.

- Humidity (%): Set to achieve limits of 30 to 70%.

- Air changes (per hr): The rate of air exchanges was 10 to 15 changes per hour.

- Photoperiod (hrs dark / hrs light): automatically controlled light cycle of 12 hours light and 12 hours dark.

IN-LIFE DATES: From: Day 0 To: end of study
Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Details on oral exposure:

VEHICLE
- Concentration in vehicle: The test item was diluted in vehicle (PEG 300) at concentrations of 0.2 g/mL and 0.03 g/ml, respectively and administered at a volume dosage of 10 mL/kg.

- Amount of vehicle (if gavage): 10ml/kg

- Justification for choice of vehicle: The vehicle was chosen after a non-GLP solubility trial which was performed before the study initiation date. This trial formulation is excluded from the GLP statement of compliance. PEG 300 was found to be a suitable vehicle.

- Lot/batch no. (if required): 448174/1 21203148

MAXIMUM DOSE VOLUME APPLIED:
2000 mg/kg

The test material was administered orally undiluted at a dose level of 2000 mg/kg, and as a solution in arachis oil BP at a dose level of 300 mg/kg.

Dosing was performed sequentially.

DOSAGE PREPARATION (if unusual):
In the absence of data regarding the toxicity of the test material, 300 mg/kg was chosen as the starting dose.

The volume administered to each animal was calculated according to the fasted bodyweight at the time of dosing. Treatment of animals was sequential. Sufficient time was allowed between each group and each dose level to confirm the survival of the previously dosed animals.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Dose levels are in terms of the test item as supplied by the sponsor. In the absence of data regarding the toxicity of the test material, 300 mg/kg was chosen as the starting dose.
Doses:

300 (with vehicle) and 2000 (undiluted) mg/kg.
No. of animals per sex per dose:

3 females at 2000 mg/kg bw
6 females at 300 mg/kg bw
Control animals:
no
Details on study design:

- Duration of observation period following administration: 18 days


- Frequency of observations and weighing: Observations were monitored during acclimitisation and at approximately 1, 2, 3 and 5 hours after dosing and daily from day 2 to 18.


- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight, necropsy.
Statistics:
None recorded.
Preliminary study:
Not applicable.
Sex:
female
Dose descriptor:
LD50
Effect level:
< 2 000 mg/kg bw
Mortality:
All 2000 mg/kg treated animals were found dead 5 hours after treatment.
Clinical signs:
other: Slightly ruffled fur with hunched posture was noted in all 2000 mg/kg treated animals 3 hours after administration, No clinical signs were observed in the 300 mg/kg treated animals during the course of the study.
Gross pathology:
All animals which died spontaneously during the observation period were necropsied as soon as they were found dead. All surviving animals were killed at the end of the observation period by an intraperitoneal injection of Vetanarcol at a dose of at least 2.0 mUkg body weight (equivalent to at least 324 mg sodium pentobarbitone/kg body weight) and discarded after macroscopic examinations were performed. No organs or tissues were retained. No macroscopic findings were recorded at necropsy.
Other findings:
- Organ weights: not retained

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The median lethal dose of 2-(2'-Vinyloxy ethoxy) ethyl acrylate after single oral administration to female rats, observed over a period of 14 days is:
300 mg/kg body weight < LD50 (female rat) < 2000 mg/kg body weight.
This corresponds with Acute Tox 4.
Executive summary:

Three groups, each of three female HanBrl: WIST (SPF) rats were treated with 2-(2'Vinyloxy ethoxy) ethyl acrylate by oral gavage administration at a dosage of 2000 mg/kg or 300 mg/kg body weight. The test item was diluted in vehicle (PEG 300) at concentrations of 0.2 g/mL and 0.03 g/ml, respectively and administered at a volume dosage of 10 mL/kg. The animals were examined daily during the acclimatization period and mortality, viability and clinical signs were recorded. All animals were examined for clinical signs at approximately 1, 2, 3 and 5 hours after treatment on day 1 and once daily during test days 2-15. Mortality/viability was recorded twice daily during test days 1-15. Body weights were recorded on day 1 (prior to administration) and on days 8 and 15. All animals were necropsied and examined macroscopically. The following females were treated and percentage of mortality was observed: 2000 mg/kg: 100% and 300 mg/kg: 0%.

All 2000 mg/kg treated animals were found dead 5 hours after treatment. Slightly ruffled fur with hunched posture was noted in all 2000 mg/kg treated animals 3 hours after administration. No clinical signs were observed in the 300 mg/kg treated animals during the course of the study. The body weight of the animals was within the range commonly recorded for this strain and age. No macroscopic findings were recorded at necropsy.

Endpoint:
acute toxicity: oral
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Justification for type of information:
1. SOFTWARE
T.E.S.T. v4.2.1

2. MODEL (incl. version number)
T.E.S.T. v4.2.1

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
CC(OCCOCCOC(=O)C=C)OCC(COC(C)OCCOCCOC(=O)C=C)(COC(C)OCCOCCOC(=O)C=C)NC(=O)COC1C=CC2=C(C=1)C(=O)C1C=CC=CC=1S2

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
[[Explain how the model fulfils the OECD principles for (Q)SAR model validation. Consider attaching the QMRF and/or QPRF or providing a link]
See attached documentation

5. APPLICABILITY DOMAIN
[Explain how the substance falls within the applicability domain of the model]
See attached documentation

6. ADEQUACY OF THE RESULT
[Explain how the prediction fits the purpose of classification and labelling and/or risk assessment]
Useful as part of a weight of evidence approach.
Qualifier:
according to guideline
Guideline:
other: Guidance on information requirements and chemical safety assessment Chapter R.6: QSARs and grouping of chemicals
Version / remarks:
2008
Species:
rat
Dose descriptor:
LD50
Effect level:
4 637 mg/kg bw
Remarks on result:
other: Based on the nearest neighbour algorithm


















EndpointExperimental valuePredicted valueb
Oral rat LD50 -Log10(mol/kg)N/AN/A
Oral rat LD50 mg/kgN/AN/A

bThe consensus prediction for this chemical is considered unreliable since only one prediction can only be made


 





















MethodPredicted value
-Log10(mol/kg)
Hierarchical clusteringN/A
FDAN/A
Nearest neighbor2.31

 


 Nearest neighbor:



























Endpoint



Predicted value – Consensus method



Predicted value -Hierarchical clustering method



Predicted value – FDA method



Predicted value – Nearest Neighbor Method



Oral rat LD50


-Log10 (mol/kg)



2.31



NA



NA



2.31



Oral rat LD50mg/kg



4636.71



NA



NA



4636.71



 


 Hierarchical method:The toxicity for a given query compound is estimated using the weighted average of the predictions from several different models. The different models are obtained by using Ward’s method to divide the training set into a series of structurally similar clusters. A genetic algorithm based technique is used to generate models for each cluster. The models are generated prior to runtime.


FDA method: The prediction for each test chemical is made using a new model that is fit to the chemicals that are most similar to the test compound. Each model is generated at runtime.


Nearest neighbor method: The predicted toxicity is estimated by taking an average of the 3 chemicals in the training set that are most similar to the test chemical.


Consensus method: The predicted toxicity is estimated by taking an average of the predicted toxicities from the above QSAR methods (provided the predictions are within the respective applicability domains)

Conclusions:
The T.E.S.T. QSAR estimated the oral rat LD50 to be around 4637 mg/kg based on the nearest neighbour algorithm. The consensus method could not be applied because only one out of three algorithm resulted in a prediction.
Executive summary:

 


QPRF:T.E.S.T. v 4.2.1


 




















































































1.



Substance



See “Test material identity”



2.



General information



 



2.1



Date of QPRF



21/08/2021



2.2



QPRF author and contact details



Karel Viaene


karel.viaene@arche-consulting.be



3.



Prediction



3.1



Endpoint
(OECD Principle 1)



Endpoint



Oral rat LD50 (amount of chemical in mg/kg body weight that causes 50% of rats to die after oral ingestion)



3.2



Algorithm
(OECD Principle 2)



Model or submodel name



T.E.S.T.



Model version



v. 4.2.1



Predicted value (model result)



See “Results and discussion”


 


 


 



Input for prediction



- Chemical structure via SMILES code



Descriptor values



Different methods are used to derive the toxicity value (see result)



3.3



Applicability domain
(OECD principle 3)



Domains:



- Compounds can only contain the following element symbols: C, H, O, N, F, Cl, Br, I, S, P, Si, or As


- Compounds must represent a single pure component



- Substance contains only allowed elements


 


 


-Substance represents a single pure component



3.4



The uncertainty of the prediction
(OECD principle 4)



Statistical accuracy for training dataset:


n = 7420






















Method



R2


 



Hierarchical



0.578



Nearest neighbor



0.557



Consensus



0.633



 


The consensus method achieved the best results in terms of both prediction accuracy and prediction coverage. The hierarchical method achieved slightly better prediction accuracy than the nearest neighbor and FDA methods but the prediction coverage was lower (83%).



3.5



The chemical mechanisms according to the model underpinning the predicted result
(OECD principle 5)



 


Hierarchical method:The toxicity for a given query compound is estimated using the weighted average of the predictions from several different models. The different models are obtained by using Ward’s method to divide the training set into a series of structurally similar clusters. A genetic algorithm based technique is used to generate models for each cluster. The models are generated prior to runtime.


FDA method: The prediction for each test chemical is made using a new model that is fit to the chemicals that are most similar to the test compound. Each model is generated at runtime.


Nearest neighbor method: The predicted toxicity is estimated by taking an average of the 3 chemicals in the training set that are most similar to the test chemical.


Consensus method: The predicted toxicity is estimated by taking an average of the predicted toxicities from the above QSAR methods (provided the predictions are within the respective applicability domains)


 


     

 


References


- User’s Guide for T.E.S.T. (version 4.2) (Toxicity Estimation Software Tool) – A program to estimate toxicity from molecular structure. US EPA


 

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
>= 300 - <= 2 000 mg/kg bw

Additional information

Justification for classification or non-classification