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Description of key information

Prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, repeated dose oral toxicity was predicted for the test compound 2-methoxybenzyl alcohol (612-16-8).The study assumed the use of male and female Wistar rats in chronic study of 2 years. No significant alterations were noted at the dose level of 281.0mg/Kg bw/day. The predicted No Observed Adverse Effect Level (NOAEL) for 2-methoxybenzyl alcohol is considered to be 281.0mg/Kg bw/day. Based on this value it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
repeated dose toxicity: oral
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification
Justification for type of information:
Data is predicted using OECD QSAR toolbox version 3.4 and the supporting QMRF report has been attached
Qualifier:
according to
Guideline:
other: as below
Principles of method if other than guideline:
Prediction is done using QSAR Toolbox version 3.4
GLP compliance:
not specified
Limit test:
no
Specific details on test material used for the study:
- Name of test material (as cited in study report): 2-Methoxybenzyl alcohol
- Molecular formula: C8H10O2
- Molecular weight: 138.165 g/mol
- Substance type: Organic
- Physical state:iquid
-Smiles: O(c1c(cccc1)CO)C
-InChI: 1S/C8H10O2/c1-10-8-5-3-2-4-7(8)6-9/h2-5,9H,6H2,1H3
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
Not specified
Route of administration:
oral: gavage
Details on route of administration:
not specified
Vehicle:
not specified
Details on oral exposure:
not specified
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
2 years
Frequency of treatment:
not specified
Remarks:
not specified
No. of animals per sex per dose:
not specified
Control animals:
not specified
Details on study design:
not specified
Positive control:
not specified
Observations and examinations performed and frequency:
not specified
Sacrifice and pathology:
not specified
Other examinations:
not specified
Statistics:
not specified
Clinical signs:
not specified
Mortality:
not specified
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified
Dose descriptor:
NOAEL
Effect level:
281 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No significant effect were observed at this dose
Remarks on result:
other: No toxic effect were observed
Critical effects observed:
not specified
System:
other: not specified
Organ:
other: not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

The prediction was based on dataset comprised from the following descriptors: NOAEL
Estimation method: Takes average value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

(((("a" or "b" or "c" or "d" or "e" )  and ("f" and ( not "g") )  )  and ("h" and ( not "i") )  )  and ("j" and "k" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Benzyl Alcohols by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Alcohol AND Alkoxy AND Aryl AND Benzyl AND Ether by Organic Functional groups

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Alkoxy AND Benzyl AND Ether AND Overlapping groups by Organic Functional groups (nested)

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Aromatic Carbon [C] AND Hydroxy, aliphatic attach [-OH] AND Olefinic carbon [=CH- or =C<] AND Oxygen, one aromatic attach [-O-] by Organic functional groups (US EPA)

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Alcohol AND Alkylarylether AND Aromatic compound AND Ether AND Hydroxy compound AND Primary alcohol by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OECD

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Michael addition OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Hydroquinones by DNA binding by OECD

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Alcohol AND Alkoxy AND Aryl AND Benzyl AND Ether by Organic Functional groups

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Dihydroxyl group by Organic Functional groups

Domain logical expression index: "j"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.608

Domain logical expression index: "k"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.28

Conclusions:
The predicted No Observed Adverse Effect Level (NOAEL) for 2-methoxybenzyl alcohol (612-16-8) is considered to be 281.0mg/Kg bw/day.
Executive summary:

Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, repeated dose oral toxicity was predicted for the test compound 2-methoxybenzyl alcohol (612-16-8).The study assumed the use of male and female Wistar rats in chronic study of 2 years. No significant alterations were noted at the dose level of 281.0mg/Kg bw/day. The predicted No Observed Adverse Effect Level (NOAEL) for 2-methoxybenzyl alcohol is considered to be 281.0mg/Kg bw/day. Based on this value it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
400 mg/kg bw/day
Study duration:
chronic
Species:
rat
Quality of whole database:
K2 data from OECD QSAR prediction .

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Repeated dose oral toxicity:

Prediction model based estimation and data available for the target chemical was reviewed to determine the toxic nature of 2-methoxybenzyl alcohol (612-16-8) upon repeated exposure by oral, route of exposure. The studies are as mentioned below:

Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, repeated dose oral toxicity was predicted for the test compound 2-methoxybenzyl alcohol (612-16-8).The study assumed the use of male and female Wistar rats in chronic study of 2 years. No significant alterations were noted at the dose level of 281.0mg/Kg bw/day. The predicted No Observed Adverse Effect Level (NOAEL) for 2-methoxybenzyl alcohol is considered to be 281.0mg/Kg bw/day. Based on this value it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation.

Another Repeated dose toxicity study was performed by I.C. Munro et al.( Food and Chemical Toxicology, 2006) to determine the oral toxic nature Benzyl alcohol (100-51-6). The data is taken from Read across substance. The read across substance share a high similarity in structure. So it is acceptable to tale data from analogous structure. Two years chronic toxicity study was conducted on rats to evaluate the toxic nature of the test compound Benzyl alcohol. The test substance was exposed to male and female rats at the concentration of 0, 200 or 400 mg/Kg bw/day by oral gavage. The animals were observed for mortality and clinical signs. No significant mortality or clinical sign observed. The No Observed Effect Level (NOEL) for the test compound Benzyl alcohol is considered to be 400 mg/Kg bw/day. Based on the results of the rat study a NOEL of 400 mg/kg body weight/day was selected for the calculation of the margin of safety of Benzyl alcohol

Based on the data available for the target chemical and its prediction, 2-methoxybenzyl alcohol (612-16-8)does not exhibit toxic nature upon repeated exposure by oral route of exposure and hence is not likely to classify as per the criteria mentioned in CLP regulation.

Justification for classification or non-classification

Based on the data available for the target chemical and its prediction, 2-methoxybenzyl alcohol (612-16-8)does not exhibit toxic nature upon repeated exposure by oral route of exposure and hence is not likely to classify as per the criteria mentioned in CLP regulation.