Reaction mass of sodium hydrogen N-(1-oxooctadecyl)-L-glutamate and sodium hydrogen N-(1-oxohexadecyl)-L-glutamate

Repeated dose toxicity: oral

Administrative data

Endpoint:

repeated dose toxicity: oral, other

Remarks:

other: Both subchronic and subacute data were used in the prediction. As a worst case, the prediction is submitted as subacute toxicity data.

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

2015

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The following prediction was performed using the OECD QSAR Toolbox using an appropriate category based on the current endpoint (Repeated dose HESS). The prediction was further refined from a large database of metadata based on relevant subcategories.

Justification for type of information:

See Read Across Justification in Section 13..

Cross-reference

Reason / purpose for cross-reference:

other: Target record

Reference

Endpoint:

repeated dose toxicity: oral, other

Remarks:

Both subchronic and subacute data were used in the prediction. As a worst case, the prediction is submitted as subacute toxicity data.

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: QSAR conducted on read across material

Justification for type of information:

See Read Across Justification in Section 13.

Dose descriptor:

NOEL

Effect level:

1 509.766 mg/kg bw/day (nominal)

Based on:

not specified

Sex:

not specified

Basis for effect level:

other: Based on the modelled conditions

Remarks on result:

other: The prediction was based on the average value from the 5 nearest neighbours compared by the prediction descriptors.

Data source

Reference

Reference Type:

other: QSAR

Title:

26.01.2015 11:20 [R]: 1.51E3 mg/kg/day; Estimation for NOEL for CAS 38517-23-6

Author:

Anon.

Year:

2015

Bibliographic source:

OECD QSAR Toolbox v 3.3

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: REACH Guidance on QSARs R.6, May/July 2008

Principles of method if other than guideline:

The repeat dose oral toxicity of the test material was evaluated using a read-across approach. Suitable analogues were found in the OECD QSAR Toolbox using the Repeated Dose Hess category, and the results were refined using relevant subcategories.

GLP compliance:

not specified

Remarks:

As no laboratory work took place, compliance with GLP is not required.

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2,2'-diallyl-4,4'-sulfonyldiphenol

EC Number:

411-570-9

EC Name:

2,2'-diallyl-4,4'-sulfonyldiphenol

Cas Number:

41481-66-7

Molecular formula:

Hill formula: C18 H18 O4 S CAS formula: C18 H18 O4 S

IUPAC Name:

2,2'-Diallyl-4,4'-sulfonyldiphenol

Details on test material:

Main constituent of the multi-constituent test material

Test animals

Species:

rat

Strain:

other: SD

Administration / exposure

Route of administration:

oral: gavage

Results and discussion

Effect levels

Dose descriptor:

NOEL

Effect level:

1 509.766 mg/kg bw/day (nominal)

Based on:

not specified

Sex:

not specified

Basis for effect level:

other: Based on the modelled conditions

Remarks on result:

other: The prediction was based on the average value from the 5 nearest neighbours compared by the prediction descriptors.

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

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

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

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Not categorized by Repeated dose (HESS)

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Not categorized by OECD HPV Chemical Categories

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Amorphous silica silicates OR Aryl substituted peroxy esters OR Benzoates OR Butanedioic acid OR C10+ Aromatics hydrocarbon solvents OR C14+Aliphatics hydrocarbon solvents (less than 2 percent aromatics) OR C9 Aromatics hydrocarbon solvents OR C9-13 Aliphatics hydrocarbon solvents (less than 2 percent aromatics) OR Cadmium (oxide) OR Dialkyl peroxides OR Diarylide yellow pigments OR Ethoxysilanes OR High molecular weight phthalate esters OR Hydrotrope surfactants OR m,p - Cresols OR Nickel and nickel compounds OR Oxo alcohols OR PFOA OR Primary amines OR Propylene glycol ethers OR Secondary amines OR Short chain alkyl methacrylates esters OR Soluble silicates OR Toluene diisocyanates OR Vinylethers OR Zinc metal and salts by OECD HPV Chemical Categories

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Discrete chemical AND Dissociating chemical by Substance Type ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Not categorized by US-EPA New Chemical Categories

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Acid Chlorides OR Acrylates/Methacrylates (Acute toxicity) OR Acrylates/Methacrylates (Chronic toxicity) OR Aldehydes (Acute toxicity) OR Aliphatic Amines OR Alkoxysilanes OR Anhydrides, Carboxylic acid OR Anilines (Acute toxicity) OR Anionic Surfactants OR Benzotriazole-hindered phenols OR Benzotriazoles (Acute toxicity) OR Cationic (quaternary ammonium) surfactants OR Epoxides OR Esters (Acute toxicity) OR Esters (Chronic toxicity) OR Ethylene Glycol Ethers OR Hydrazines and Related Compounds OR Imides (Acute toxicity) OR Neutral Organics OR Nonionic Surfactants OR Persistent, Bioaccumulative and Toxic (PBT) Chemicals OR Phenols (Acute toxicity) OR Phenols (Chronic toxicity) OR Polynitroaromatics (Acute toxicity) OR Substituted Triazines (Acute toxicity) OR Thiols (Acute toxicity) OR Vinyl Sulfones by US-EPA New Chemical Categories

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.3

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >>  Michael-type addition, quinoid structures OR AN2 >>  Michael-type addition, quinoid structures >> Quinones OR AN2 >> Carbamoylation after isocyanate formation OR AN2 >> Carbamoylation after isocyanate formation >> N-Hydroxylamines OR AN2 >> Michael-type addition on alpha, beta-unsaturated carbonyl compounds OR AN2 >> Michael-type addition on alpha, beta-unsaturated carbonyl compounds >> Four- and Five-Membered Lactones OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation >> Geminal Polyhaloalkane Derivatives OR AN2 >> Shiff base formation for aldehydes OR AN2 >> Shiff base formation for aldehydes >> Geminal Polyhaloalkane Derivatives OR AN2 >> Shiff base formation for aldehydes >> Haloalkane Derivatives with Labile Halogen OR AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation OR AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation >> Haloalkenes with Electron-Withdrawing Groups OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Coumarins OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide Side Chain OR Non-covalent interaction >> DNA intercalation >> Quinones OR Radical OR Radical >> Generation of ROS by glutathione depletion (indirect) OR Radical >> Generation of ROS by glutathione depletion (indirect) >> Haloalkanes Containing Heteroatom OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Conjugated Nitro Compounds OR Radical >> Radical mechanism via ROS formation (indirect) >> Coumarins OR Radical >> Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> N-Hydroxylamines OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR Radical >> Radical mechanism via ROS formation (indirect) >> Quinones OR SN1 OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> N-Hydroxylamines OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Conjugated Nitro Compounds OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR SN2 OR SN2 >> Acylation involving a leaving group  OR SN2 >> Acylation involving a leaving group  >> Geminal Polyhaloalkane Derivatives OR SN2 >> Acylation involving a leaving group  >> Haloalkane Derivatives with Labile Halogen OR SN2 >> Acylation involving a leaving group after metabolic activation OR SN2 >> Acylation involving a leaving group after metabolic activation >> Geminal Polyhaloalkane Derivatives OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Haloalkenes with Electron-Withdrawing Groups OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Haloalkane Derivatives with Labile Halogen OR SN2 >> Alkylation, ring opening SN2 reaction OR SN2 >> Alkylation, ring opening SN2 reaction >> Four- and Five-Membered Lactones OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Coumarins OR SN2 >> DNA alkylation OR SN2 >> DNA alkylation >> Alkylphosphates, Alkylthiophosphates and Alkylphosphonates OR SN2 >> DNA alkylation >> Vicinal Dihaloalkanes OR SN2 >> Internal SN2 reaction with aziridinium and/or cyclic sulfonium ion formation (enzymatic) OR SN2 >> Internal SN2 reaction with aziridinium and/or cyclic sulfonium ion formation (enzymatic) >> Vicinal Dihaloalkanes OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Haloalkanes Containing Heteroatom OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation >> Geminal Polyhaloalkane Derivatives by DNA binding by OASIS v.1.3

Domain logical expression index: "i"

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

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Isocyanates and Isothiocyanates OR Acylation >> Isocyanates and Isothiocyanates >> Isothiocyanates OR Michael addition OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems >> Furans 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 SN1 OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic nitro OR SN1 >> Nitrenium Ion formation >> Aromatic phenylureas OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine OR SN2 OR SN2 >> Epoxidation of Aliphatic Alkenes OR SN2 >> Epoxidation of Aliphatic Alkenes >> Halogenated polarised alkenes by DNA binding by OECD

Domain logical expression index: "k"

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

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Direct Acylation Involving a Leaving group OR Acylation >> Direct Acylation Involving a Leaving group >> Acetates OR Michael addition OR Michael addition >> Polarised Alkenes OR Michael addition >> Polarised Alkenes >> Polarised alkene - pyridines OR SNAr OR SNAr >> Nucleophilic aromatic substitution OR SNAr >> Nucleophilic aromatic substitution >> Activated halo-benzenes by Protein binding by OECD

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Group 1 - Alkali Earth Li,Na,K,Rb,Cs,Fr AND Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 16 - Oxygen O by Chemical elements

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Group 11 - Trans.Metals Cu,Ag,Au OR Group 14 - Metalloids Si,Ge OR Group 15 - Phosphorus P OR Group 16 - Sulfur S OR Group 17 - Halogens Br OR Group 17 - Halogens Cl OR Group 17 - Halogens F OR Group 17 - Halogens F,Cl,Br,I,At OR Group 4 - Trans.Metals Ti,Zr,Hf by Chemical elements

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is >= 2.96

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.29

Applicant's summary and conclusion

Conclusions:

Based on the modelled conditions, the subacute NOEL of the test material in the rat was determined to be ca. 1509.8 mg/kg bw/day.

Executive summary:

The repeat dose oral toxicity of the test material was evaluated using a read-across approach. Suitable analogues were found in the OECD QSAR Toolbox using the Repeated Dose Hess category, and the results were refined using relevant subcategories.

Based on the modelled conditions, the subacute NOEL of the test material in the rat was determined to be ca. 1509.8 mg/kg bw/day.

The target chemical falls within the applicability domain of the prediction.