Reaction mass of Cardanol diene and Cardanol monoene and Cardanol triene 

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

The Reaction mass of Cardanol diene and Cardanol monoene and Cardanol triene was found to be non genotoxic for S. typhimurium TA 102 & Chinese hamster Lung (CHL).

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Justification for type of information:

QSAR prediction

Principles of method if other than guideline:

Data is predicted by QSAR toolbox version 3.2

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Species / strain / cell type:

S. typhimurium TA 102

Additional strain / cell type characteristics:

not specified

Metabolic activation:

without

Species / strain:

S. typhimurium TA 102

Metabolic activation:

without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

Positive controls validity:

not specified

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

The prediction was based on dataset comprised from the following descriptors: "Gene mutation"
Estimation method: Takes highest mode value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

((((((("a" or "b" or "c" or "d" or "e" or "f" )  and ("g" and ( not "h") )  )  and ("i" and ( not "j") )  )  and "k" )  and ("l" and ( not "m") )  )  and "n" )  and ("o" and "p" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Phenols (Chronic toxicity) by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Alkene AND Allyl AND Aryl AND Benzyl AND Phenol by Organic functional groups

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Allyl AND Benzyl AND Overlapping groups AND Phenol by Organic functional groups (nested)

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Alcohol, olefinic attach [-OH] AND Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Aromatic Carbon [C] AND Hydroxy, aromatic attach [-OH] AND Olefinic carbon [=CH- or =C<] AND Olefinic carbon [=CH2] 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 Aromatic compound AND Hydroxy compound AND Phenol by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "f"

Similarity boundary:Target: c1(O)cc(CCCCCCCC=CCC=CCCC)ccc1_c1(O)cc(CCCCCCCCCCCCCCC)ccc1_c1(O)cc(CCCCCCCC=CCC=CCC=C)ccc1_c1(O)cc(CCCCCCCC=CCCCCCC)ccc1
Threshold=50%,
Dice(Atom centered fragments)

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.1

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Michael addition OR Michael addition >> alpha, beta-unsaturated carabonyl compounds OR Michael addition >> alpha, beta-unsaturated carabonyl compounds >> Four- and Five-Membered Lactones OR Michael addition >> Quinone type compounds OR Michael addition >> Quinone type compounds >> Quinones OR Radical OR Radical >> Generation of reactive oxygen species OR Radical >> Generation of reactive oxygen species >> Coumarins OR Radical >> Radical mechanism by ROS formation OR Radical >> Radical mechanism by ROS formation >> Nitro Compounds OR Radical >> Radical mechanism by ROS formation >> Quinones OR Radical >> ROS formation after GSH depletion OR Radical >> ROS formation after GSH depletion >> Aromatic and Heterocyclic Primary Amines OR SN1 OR SN1 >> Nitrenium ion formation OR SN1 >> Nitrenium ion formation >> Aromatic and Heterocyclic Primary Amines OR SN1 >> Nitrenium ion formation >> N-hydroxylamines OR SN1 >> Nitrenium ion formation >> Nitro Compounds OR SN2 OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Haloalkanes Containing Heteroatom OR SN2 >> P450-mediated epoxidation OR SN2 >> P450-mediated epoxidation >> Coumarins OR SN2 >> Ring opening SN2 reaction OR SN2 >> Ring opening SN2 reaction >> Four- and Five-Membered Lactones by DNA binding by OASIS v.1.1

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules (GSH) by Protein binding potency

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Extremely reactive (GSH) OR Extremely reactive (GSH) >> Naphthoquinones (MA) OR Highly reactive (GSH) OR Highly reactive (GSH) >> Vinylene-sub. chalcones (MA) OR Moderately reactive (GSH) OR Moderately reactive (GSH) >> Substituted 1-Alken-3-ones (MA) by Protein binding potency

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as No superfragment by Superfragments

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules by Keratinocyte gene expression

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Low gene expression OR Low gene expression >> Vaniline derivatives OR Very high gene expression OR Very high gene expression >> Activated halo-benzenes by Keratinocyte gene expression

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Not bioavailable by Lipinski Rule Oasis

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is >= 5.91

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is <= 9

Conclusions:

Interpretation of results (migrated information):negativeBased on the QSAR prediction done for Reaction mass of Cardanol diene and Cardanol monoene and Cardanol triene for genetic toxicity on S. typhimurium TA 102 it was estimated to give negative result in gene mutation. Based on these results it can be concluded that Cardanol is not genetoxic substance.

Executive summary:

Based on the QSAR prediction done for Reaction mass of Cardanol diene and Cardanol monoene and Cardanol triene  for genetic toxicity on S. typhimurium TA 102 it was estimated to give negative result in gene mutation. Based on these results it can be concluded that Cardanol is not genetoxic substance.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vitro:

Gene toxicity (In-vitro):

No. of studies of Cardanol reviewed for genetic toxicity from reliable sources having Klimisch rating 2 & 4.

 

The summary of the results are presented below

   

Sr.No	Endpoint	Interpretation of Results	Species/Strain	Sources
1	In vitro Genetic toxicity	Negative with or without metabolic activation	S. typhimurium TA 102	Predicted data from QSAR
2	In vitro Genetic toxicity	Negative with or without metabolic activation	S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102	Study report of RA Cas
3	Chromosome Aberration	Negative with or without metabolic activation	Chinese hamster Lung (CHL)	Predicted datafromQSAR
4	In vitro Genetic toxicity	Negative with or without metabolic activation	S. typhimurium TA 1535, TA 98, TA 100	Publication of RA Cas
5	In vitro Genetic toxicity	Negative with or without metabolic activation	S. typhimurium TA98 and TA 100	Publication of RA Cas

By applying weight of evidence approach to the target & read across chemical , it can be concluded that the substance is non-genotoxic.

 

Gene toxicity (In-vivo):

No. of studies of Cashew nut shell liquid(CNSL) reviewed for genetic toxicity from reliable sources having Klimisch rating 2 .

 

The summary of the results are presented below

   

Sr.No	Endpoint	Interpretation of Results	Species/Strain	Sources
1	In vivo Genetic toxicity	Negative	A. cepa root meristems	Publication data
3	Chromosome Aberration	Negative	A. cepa root meristems	Publication data

 

By applying weight of evidence approach to the read across chemical Cashew nut shell liquid, it can be concluded that the substance is non-genotoxic.

Justification for selection of genetic toxicity endpoint
Based on the prediction result done for Cardanol for genetic toxicity on S. typhimurium TA 102 it was estimated to give negative result in gene mutation.also it was observed that Cardanol shows negative results in Chinese hamster cultured cells. thus it can be concluded that Cardanol is not genetoxic substance.

Justification for classification or non-classification

Considering the weight of evidence appraoch from the various data available, it can be conclided that Reaction mass of Cardanol diene and Cardanol monoene and Cardanol triene  (CAS No 37330 -39 -5) shall not exhibit genotoxic effects and hence is not classified as a genotixic chemical.