Registration Dossier

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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
sub-chronic toxicity: oral
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Qualifier:
according to guideline
Guideline:
other:
Principles of method if other than guideline:
Prediction is done using QSAR Toolbox version 3.1
GLP compliance:
not specified
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Route of administration:
oral: gavage
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
90 days
Dose descriptor:
NOAEL
Effect level:
419 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
not specified
Basis for effect level:
other: Change in body weight
Critical effects observed:
not specified

The prediction was based on dataset comprised from the following descriptors: LOEL, LOEL, NOEL, NOEL calculated, study LOEL, studyNOEL"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" or "i" or "j" or "k" or "l") and("m" and(not "n")) ) and((("o" or "p" or "q" or "r" or "s") and("t" and(not "u")) ) or(("v" or "w" or "x" or "y" or "z") and("aa" and(not "ab")) ) ) ) and("ac" and "ad") )

Domain logical expression index: "a"

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

Domain logical expression index: "b"

Referential boundary:The target chemical should be classified as Aromatic amine AND Aryl AND Phenol by Organic functional groups

Domain logical expression index: "c"

Referential boundary:The target chemical should be classified as Aromatic amine 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 Aliphatic Nitrogen, one aromatic attach [-N] AND Amino, aliphatic attach [-N<] AND Aromatic Carbon [C] AND Hydroxy, aromatic 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 Amine AND Aromatic compound AND Hydroxy compound AND Phenol AND Tertiary amine AND Tertiary mixed amine by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "f"

Referential boundary:The target chemical should be classified as Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "g"

Referential boundary:The target chemical should be classified as Moderate binder, NH2 group OR Moderate binder, OH grooup OR Non binder, impaired OH or NH2 group OR Non binder, MW>500 OR Non binder, without OH or NH2 group OR Strong binder, NH2 group OR Strong binder, OH group OR Weak binder, NH2 group OR Very strong binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "h"

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

Domain logical expression index: "i"

Referential boundary:The target chemical should be classified as Aromatic amine AND Aryl AND Phenol by Organic functional groups

Domain logical expression index: "j"

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

Domain logical expression index: "k"

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 Aliphatic Nitrogen, one aromatic attach [-N] AND Amino, aliphatic attach [-N<] AND Aromatic Carbon [C] AND Hydroxy, aromatic attach [-OH] AND Olefinic carbon [=CH- or =C<] AND Oxygen, one aromatic attach [-O-] by Organic functional groups (US EPA)

Domain logical expression index: "l"

Referential boundary:The target chemical should be classified as Amine AND Aromatic compound AND Hydroxy compound AND Phenol AND Tertiary amine AND Tertiary mixed amine by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "m"

Referential boundary:The target chemical should be classified as No alert found by Protein binding by OASIS v1.1

Domain logical expression index: "n"

Referential boundary:The target chemical should be classified as Acylation OR Acylation >> Acyl transfer via nucleophilic addition reaction OR Acylation >> Acyl transfer via nucleophilic addition reaction >> Isocyanates and isothiocyanates OR Acylation >> Direct acylation involving a leaving group OR Acylation >> Direct acylation involving a leaving group >> Carbamates OR Acylation >> Direct acylation involving a leaving group >> N-acylamides OR Acylation >> Direct acylation involving a leaving group >> Sulphonyl halides OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR Acylation >> Ester aminolysis >> Dithiocarbamates OR Acylation >> Ester aminolysis >> Dithioesters OR Acylation >> Ester aminolysis or thiolysis OR Acylation >> Ester aminolysis or thiolysis >> Activated alkyl or aryl esters OR Acylation >> Ester aminolysis or thiolysis >> Diarylesters OR Acylation >> Ring opening acylation OR Acylation >> Ring opening acylation >> Active cyclic agents OR Michael addition OR Michael addition >> Michael addition on conjugated systems with electron withdrawing group OR Michael addition >> Michael addition on conjugated systems with electron withdrawing group >> alpha,beta-carbonyl compounds with polarized double bonds OR Michael addition >> Michael addition on conjugated systems with electron withdrawing group >> Cyanoalkenes OR Michael addition >> Michael addition on conjugated systems with electron withdrawing group >> Nitroalkenes OR Michael addition >> Michael addition on conjugated systems with electron withdrawing group >> Vinyl sulfonyl compounds OR Michael addition >> Michael type addition on vinyl pirydines and activated ethenylarenes OR Michael addition >> Michael type addition on vinyl pirydines and activated ethenylarenes >> Activated electrophilic ethenylarenes OR Michael addition >> Michael type addition on vinyl pirydines and activated ethenylarenes >> Vinyl pyridines OR Michael addition >> Quinone type compounds OR Michael addition >> Quinone type compounds >> Naphtoquinone and naphtoquinone imines OR Michael addition >> Quinone type compounds >> Quinone (di)imines OR Michael addition >> Quinone type compounds >> Quinone methides OR Michael addition >> Quinone type compounds >> Quinones OR Nucleophilic addition OR Nucleophilic addition >> Addition to Carbon-hetero double/triple bond OR Nucleophilic addition >> Addition to Carbon-hetero double/triple bond >> Ketones OR Nucleophilic addition >> Addition to Carbon-hetero double/triple bond >> Thiocyanates OR Nucleophilic addition >> Nucleophilic addition at polarized N-functional double bond OR Nucleophilic addition >> Nucleophilic addition at polarized N-functional double bond >> C-Nitroso compounds OR Schiff base formation OR Schiff base formation >> Nucleophilic cycloaddition to diketones OR Schiff base formation >> Nucleophilic cycloaddition to diketones >> Diketones OR Schiff base formation >> Pyrazolones and pyrazolidinones derivatives OR Schiff base formation >> Pyrazolones and pyrazolidinones derivatives >> Pyrazolones and pyrazolidinones OR Schiff base formation >> Schiff base formation with carbonyl compounds OR Schiff base formation >> Schiff base formation with carbonyl compounds >> Aldehydes OR SN1 OR SN1 >> Nucleophilic substitution (SN1) on alkyl (aryl) mercury cations OR SN1 >> Nucleophilic substitution (SN1) on alkyl (aryl) mercury cations >> Mercury compounds OR SN2 OR SN2 >> Interchange reaction with sulphur containing compounds OR SN2 >> Interchange reaction with sulphur containing compounds >> Thiols and disulfide compounds OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> alpha-activated haloalkanes OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> alpha-haloalkanes OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Phosphonates OR SN2 >> Nucleophilic substitution on benzylic carbon atom OR SN2 >> Nucleophilic substitution on benzylic carbon atom >> alpha-activated benzyls OR SN2 >> Nucleophilic substitution on heterocyclic sulfenamides OR SN2 >> Nucleophilic substitution on heterocyclic sulfenamides >> Heterocyclic sulfenamides OR SN2 >> Ring opening SN2 reaction OR SN2 >> Ring opening SN2 reaction >> Epoxides, Aziridines and Sulfuranes OR SNAr OR SNAr >> Nucleophilic aromatic substitution on activated halogens OR SNAr >> Nucleophilic aromatic substitution on activated halogens >> Activated haloarenes by Protein binding by OASIS v1.1

Domain logical expression index: "o"

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

Domain logical expression index: "p"

Referential boundary:The target chemical should be classified as Aromatic amine AND Aryl AND Phenol by Organic functional groups

Domain logical expression index: "q"

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

Domain logical expression index: "r"

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 Aliphatic Nitrogen, one aromatic attach [-N] AND Amino, aliphatic attach [-N<] AND Aromatic Carbon [C] AND Hydroxy, aromatic attach [-OH] AND Olefinic carbon [=CH- or =C<] AND Oxygen, one aromatic attach [-O-] by Organic functional groups (US EPA)

Domain logical expression index: "s"

Referential boundary:The target chemical should be classified as Amine AND Aromatic compound AND Hydroxy compound AND Phenol AND Tertiary amine AND Tertiary mixed amine by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "t"

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

Domain logical expression index: "u"

Referential boundary:The target chemical should be classified as Acylation OR Acylation >> Direct acyation involving a leaving group OR Acylation >> Direct acyation involving a leaving group >> Geminal Polyhaloalkanes OR Elimination (E2) OR Elimination (E2) >> E2 elimination reaction with epoxide formation OR Elimination (E2) >> E2 elimination reaction with epoxide formation >> Haloalcohols OR 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 >> Quinoneimine Derivatives 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 >> Generation of reactive oxygen species >> Thiols OR Radical >> Radical mechanism by ROS formation OR Radical >> Radical mechanism by ROS formation >> Geminal Polyhaloalkanes OR Radical >> Radical mechanism by ROS formation >> Nitro Compounds OR Radical >> Radical mechanism by ROS formation >> Nitroso compounds OR Radical >> Radical mechanism by ROS formation >> Quinones OR Radical >> Radical mechanism by ROS formation >> Specific Imine and Thione Derivatives OR Radical >> ROS formation after GSH depletion OR Radical >> ROS formation after GSH depletion >> Aromatic and Heterocyclic Primary Amines OR Radical >> ROS formation after GSH depletion >> Haloalcohols OR Radical >> ROS formation after GSH depletion >> Quinoneimine Derivatives OR Schiff base fomers OR Schiff base fomers >> Direct acting Schiff base formers OR Schiff base fomers >> Direct acting Schiff base formers >> Geminal Polyhaloalkanes OR Schiff base fomers >> Direct acting Schiff base formers >> Specific Acetate Esters OR Schiff base fomers >> Multi-step Shiff base formation OR Schiff base fomers >> Multi-step Shiff base formation >> Haloalkanes Containing Electron-Withdrawing Groups OR SN1 OR SN1 >> Carbenium ion formation OR SN1 >> Carbenium ion formation >> Nitroso compounds OR SN1 >> Carbenium ion formation >> Polycyclic Aromatic Hydrocarbons OR SN1 >> Carbenium ion formation >> Specific Acetate Esters OR SN1 >> Glutathione-induced nitrenium ion formation OR SN1 >> Glutathione-induced nitrenium ion formation >> Nitroso compounds OR SN1 >> Nitrenium and/or Carbenium ion formation OR SN1 >> Nitrenium and/or Carbenium ion formation >> Urea Derivatives 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 SN1 >> Non-enzymatic nitroso radical and/or nirtosonium cation formation OR SN1 >> Non-enzymatic nitroso radical and/or nirtosonium cation formation >> Nitroso compounds OR SN1 >> Non-enzymatic nitroso radical and/or nirtosonium cation formation >> Urea Derivatives OR SN2 OR SN2 >> Acylating agents OR SN2 >> Acylating agents >> Specific Acetate Esters OR SN2 >> Carbenium Ion Formation OR SN2 >> Carbenium Ion Formation >> Diazoalkanes OR SN2 >> Diazonium ion formation OR SN2 >> Diazonium ion formation >> Specific Imine and Thione Derivatives OR SN2 >> Direct Acting Epoxides and Related OR SN2 >> Direct Acting Epoxides and Related >> Epoxides, Aziridines OR SN2 >> Epoxidation of Aliphatic Alkenes OR SN2 >> Epoxidation of Aliphatic Alkenes >> Polarized Haloalkene Derivatives OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Geminal Polyhaloalkanes OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Haloalkanes Containing Electron-Withdrawing Groups OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Haloalkanes Containing Heteroatom OR SN2 >> P450-mediated epoxidation OR SN2 >> P450-mediated epoxidation >> Coumarins OR SN2 >> P450-mediated epoxidation >> Polarized Haloalkene Derivatives OR SN2 >> P450-mediated epoxidation >> Polycyclic Aromatic Hydrocarbons OR SN2 >> Ring opening SN2 reaction OR SN2 >> Ring opening SN2 reaction >> Four- and Five-Membered Lactones OR SN2 >> SN2 at sp3 and activated sp2 carbon atom OR SN2 >> SN2 at sp3 and activated sp2 carbon atom >> Polarized Haloalkene Derivatives OR SN2 >> SN2 at sp3-carbon atom OR SN2 >> SN2 at sp3-carbon atom >> Alkylphosphates, Alkylthiophosphates and Alkylphosphonates OR SN2 >> SN2 at sp3-carbon atom >> Specific Acetate Esters OR SN2 >> SN2 at sp3-carbon atom >> Sulfonates and Sulfates OR SN2 >> SN2 at sulfur atom OR SN2 >> SN2 at sulfur atom >> Sulfonyl Halides by DNA binding by OASIS v.1.1

Domain logical expression index: "v"

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

Domain logical expression index: "w"

Referential boundary:The target chemical should be classified as Aromatic amine AND Aryl AND Phenol by Organic functional groups

Domain logical expression index: "x"

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

Domain logical expression index: "y"

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 Aliphatic Nitrogen, one aromatic attach [-N] AND Amino, aliphatic attach [-N<] AND Aromatic Carbon [C] AND Hydroxy, aromatic attach [-OH] AND Olefinic carbon [=CH- or =C<] AND Oxygen, one aromatic attach [-O-] by Organic functional groups (US EPA)

Domain logical expression index: "z"

Referential boundary:The target chemical should be classified as Amine AND Aromatic compound AND Hydroxy compound AND Phenol AND Tertiary amine AND Tertiary mixed amine by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "aa"

Referential boundary:The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine by DNA binding by OECD

Domain logical expression index: "ab"

Referential boundary:The target chemical should be classified as Acylation OR Acylation >> Isocyanates and Isothiocyanates OR Acylation >> Isocyanates and Isothiocyanates >> Isothiocyanates OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Formamides 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 of Heterocyclic Ring Systems >> Thiophenes-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 >> 5-alkoxyindoles OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Alkyl phenols 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 OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Methylenedioxyphenyl OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Polycyclic (PAHs) and heterocyclic (HACs) aromatic hydrocarbons-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated amides OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated ketones OR Michael addition >> Quinones and Quinone-type Chemicals OR Michael addition >> Quinones and Quinone-type Chemicals >> Quinones OR No alert found OR Schiff base formers OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  >> Ethanolamines (including morpholine) OR Schiff base formers >> Chemicals Activated by P450 to Mono-aldehydes OR Schiff base formers >> Chemicals Activated by P450 to Mono-aldehydes >> Thiazoles OR Schiff base formers >> Direct Acting Schiff Base Formers OR Schiff base formers >> Direct Acting Schiff Base Formers >> Alpha-beta-dicarbonyl OR SN1 >> Carbenium Ion Formation OR SN1 >> Carbenium Ion Formation >> Allyl benzenes OR SN1 >> Carbenium Ion Formation >> Diazoalkanes OR SN1 >> Carbenium Ion Formation >> Polycyclic (PAHs) and heterocyclic (HACs) aromatic hydrocarbons-SN1 OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation >> Aromatic azo OR SN1 >> Nitrenium Ion formation >> Aromatic N-hydroxylamines OR SN1 >> Nitrenium Ion formation >> Aromatic nitro OR SN1 >> Nitrenium Ion formation >> Aromatic nitroso OR SN1 >> Nitrenium Ion formation >> Aromatic phenylureas OR SN1 >> Nitrenium Ion formation >> Primary (unsaturated) heterocyclic amine OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine OR SN1 >> Nitrenium Ion formation >> Secondary aromatic amine OR SN1 >> Nitrenium Ion formation >> Unsaturated heterocyclic azo OR SN1 >> Nitrenium Ion formation >> Unsaturated heterocyclic nitro OR SN2 OR SN2 >> Direct Acting Epoxides and related OR SN2 >> Direct Acting Epoxides and related >> Aziridines OR SN2 >> Direct Acting Epoxides and related >> Epoxides OR SN2 >> Epoxidation of Aliphatic Alkenes OR SN2 >> Epoxidation of Aliphatic Alkenes >> Phenoxy polarised alkenes OR SN2 >> P450 Mediated Epoxidation OR SN2 >> P450 Mediated Epoxidation >> Coumarins OR SN2 >> P450 Mediated Epoxidation >> Thiophenes-SN2 OR SN2 >> Ring opening SN2 Reaction OR SN2 >> Ring opening SN2 Reaction >> Lactones OR SN2 >> SN2 at an sp3 Carbon atom OR SN2 >> SN2 at an sp3 Carbon atom >> Aliphatic halides OR SN2 >> SN2 at an sp3 Carbon atom >> Phosphonic esters by DNA binding by OECD

Domain logical expression index: "ac"

Parametric boundary:The target chemical should have a value of log Kow which is >= 1.03

Domain logical expression index: "ad"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.52

Conclusions:
The NOAEL value of 3 diethylaminop phenol in Sprague-Dawley rat in 90 days study was observed at dose concentration of 419 mg/kg bw/day nominal
Executive summary:

The NOAEL for 3-diethylaminophenol is estimated to be 419mg/kg bw/dayfor rat in90 daysusing the toolbox version 3.2. The data is estimated to be based on the data summarized below

CAS no.

End point

Value

Species

Doses

Duration

Effects

Remarks

108-39-4

NOAEL

824 mg/kg /day

Rattus Norvegicus

100 to 1000mg/kg/day

28 days

no treatment related effect observed on enzymes

 

108-68-9

NOAEL

30 mg/kg /day

Rat

0, 30, 100, 300mg/kg/day

28 days

No adverse effect observed

 

108-95-2

NOAEL

153mg/kg /day

Rat

0, 2500,5000 ppm

1.97 yrs

multiple effects not observed

 

108-46-3

NOAEL

494 mg/kg /day

Mus musculus

28 to 420 mg/kg/day

13 weeks

No change in organ weight

 

108-73-6

NOAEL

976mg/kg /day

Rat

30 to 1000 mg/kg/day

28 days

Change in body weight

 

 

All the values when equalized to 90 days duration by using conversion factor of 3 and the Species are also converted by using conversion factor , the values are summarized as follows

CAS no.

End point

Value

Species

Duration

108-39-4

NOAEL

274.66 mg/kg/day

Rat

90 days

108-68-9

NOAEL

10 mg/kg /day

Rat

90 days

108-95-2

NOAEL

306 mg/kg /day

Rat

90 days

108-46-3

NOAEL

864.5 mg/kg /day

Rat

90 days

108-73-6

NOAEL

325.33 mg/kg /day

Rat

90 days

 

Thus the calculated NOEL of analogues for 90 days for the species rat is within the range of 10 – 864.5 mg/kg bw /day. Thus the predicted NOEL value is (calculated to be)356.098mg/kg bw/d with 90 days for rat (harmonized using assessment factors) falls within the domain using Log Kow as the descriptor and justified to be used as NOEL for further DNEL calculation for the purpose of risk assessment. Also it does not impact the classification of the substance thus the predicted value considered to be acceptable.

Justified to be used as NOEL for the purpose of weight of evidence
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
419 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
K2 data from QSAR model considered reliable by OECD

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records
Reference
Endpoint:
sub-chronic toxicity: inhalation
Type of information:
(Q)SAR
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Justification for type of information:
QSAR prediction: migrated from IUCLID 5.6
Qualifier:
according to guideline
Guideline:
other: estimated data
Principles of method if other than guideline:
Prediction is done using QSAR Toolbox version 2.3.
GLP compliance:
no
Species:
rat
Strain:
Wistar
Sex:
not specified
Route of administration:
inhalation
Type of inhalation exposure:
not specified
Vehicle:
not specified
Analytical verification of doses or concentrations:
not specified
Dose descriptor:
LOEL
Effect level:
26.912 other: mg/kg/day
Based on:
test mat.
Sex:
not specified
Basis for effect level:
other: lowest adverse effect level
Critical effects observed:
not specified

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

(("a" and ("b" and ( not "c") ) ) and ("d" and "e" ) )

Domain logical expression index: "a"

Similarity boundary:Target: c1(O)cc(N(CC)CC)ccc1
Threshold=50%,
Dice(Atom pairs;Topologic torsions;Atom centered fragments;Path;Cycles)

Domain logical expression index: "b"

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 Aliphatic Nitrogen, one aromatic attach [-N] AND Amino, aliphatic attach [-N<] AND Aromatic Carbon [C] AND Hydroxy, aromatic attach [-OH] AND Olefinic carbon [=CH- or =C<] AND Oxygen, one aromatic attach [-O-] by Organic functional groups (US EPA)

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Acetylenic Carbon [#C] OR Aliphatic Nitrogen, two aromatic attach [-N-] OR Chlorine, aromatic attach [-Cl] OR Chlorine, olefinic attach [-Cl] OR Isocyanate, aromatic attach [-N=C=O] OR Miscellaneous sulfide (=S) or oxide (=O) OR Nitro, aromatic attach [-NO2] OR Nitrogen, two or tree olefinic attach [>N-] by Organic functional groups (US EPA)

Domain logical expression index: "d"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.154

Domain logical expression index: "e"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.61

Conclusions:
Repeated dose toxicity LOEL (Lowest observed effect level) of 3-diethylaminophenol to rat by the inhalation route was estimated at a dose concentration of 26.91227 mg/kg/day.
Executive summary:

Repeated dose toxicity LOEL (Lowest observed effect level) of 3-diethylaminophenol to rat by the inhalation route was estimated at a dose concentration of 26.91227 mg/kg/day. This indicates that 3-diethylaminophenol shall not exhibit toxic effect to rat by the inhalation route below the above mention dose.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
26.912
Study duration:
subchronic
Species:
rat
Quality of whole database:
K2 data from QSAR model considered reliable by OECD

Repeated dose toxicity: dermal - systemic effects

Link to relevant study records
Reference
Endpoint:
chronic toxicity: dermal
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Qualifier:
according to guideline
Guideline:
other:
Principles of method if other than guideline:
The potential carcinogenicity and toxicity of several commonly used cutaneous agents of which one is resocersinol were studied in female Swiss mice by administering repeated applications of the chemical on the skin for the life-span of the animals
GLP compliance:
not specified
Limit test:
no
Species:
mouse
Strain:
Swiss
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Eppley colony
- Age at study initiation: Seven-week-old
- Weight at study initiation: no data
- Fasting period before study: no data
- Housing: plastic cages with commercial bedding
- Diet (e.g. ad libitum):commercial diet Wayne, Allied Mills, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

IN-LIFE DATES: From: To:
Type of coverage:
open
Vehicle:
acetone
Details on exposure:
TEST SITE
- Area of exposure: dorsal skin between the flanks
- % coverage: l-inch square area
- Type of wrap if used: no data
- Time intervals for shavings or clipplings: shaved regularly.

REMOVAL OF TEST SUBSTANCE
- Washing (if done):no data
- Time after start of exposure:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.02 ml
- Concentration (if solution): 5, 25,50 %
- Constant volume or concentration used: no data
- For solids, paste formed: no data
Duration of treatment / exposure:
life time
Frequency of treatment:
twice a week
Remarks:
Doses / Concentrations:
0,5,25,50% (8333.33, 41666.6, 83333.3 mg/kg bw/day)
Basis:
nominal per unit area
No. of animals per sex per dose:
50/dose group
Control animals:
yes, concurrent vehicle
Positive control:
7,12-dimethylbenzanthracene
Sacrifice and pathology:
The animals were checked weekly, and all lesions, as well as tumors, were recorded. Animals were allowed to die spontaneously or were killed when moribund. Complete autopsies were performed on all animals. The skin from all animals, all grossly observed tumors and other lesions in the lungs, livers, kidneys, etc., from treated as well as control groups were studied histologically. Formalin-fixed paraffin-embedded specimens were cut and stained with hematoxylin-eosin and other stains when needed.
Statistics:
The statistical significance of the results was evaluated using the methods presented by Armitage
Clinical signs:
no effects observed
Dermal irritation:
effects observed, treatment-related
Mortality:
no mortality observed
Body weight and weight changes:
not examined
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Gross pathological findings:
not examined
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Histopathological findings: neoplastic:
effects observed, treatment-related
Details on results:
Animals treated with resorcinol showed skin lesions with ulceration, inflammation and hyperplasia. Two skin tumors were seen, 1 on the back and 1 on the ear as well as 1 subcutaneous fibrosarcoma.
Dose descriptor:
LOAEL
Effect level:
8 333.33 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
female
Basis for effect level:
other: skin lesions with ulceration, inflammation and hyperplasia was observed
Critical effects observed:
not specified
Conclusions:
The LOAEL of resorcinol in female swiss mice in a life time study was observed at dose concentration of 8333.33 mg/kg bw/day
Executive summary:

50 female swiss mice were applied resorcinol at dose concentration of 0,5,25,50% (8333.33, 41666.6, 83333.3 mg/kg bw/day) (0.02 ml) were dropped on the dorsal skin between the flanks twice a week on a l-inch square area which was shaved regularly. The animals

were checked weekly, and all lesions, as well as tumors, were recorded. Animals treated with resorcinol showed skin lesions with ulceration, inflammation and hyperplasia. Two skin tumors were seen, 1 on the back and 1 on the ear as well as 1 subcutaneous fibrosarcoma. Hence the LOAEL was considered to be 8333.33 mg/kg bw/day.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LOAEL
8 333.33 mg/kg bw/day
Study duration:
chronic
Species:
mouse
Quality of whole database:
K2 level data from relaible journal toxicology and applied pharmocology

Additional information

Repeated dose toxicity : Oral :

Based on the various studies available with Klimish rating 2 and 4 for the target as well as read across substances for CAS NO 91-68-9, also from category based on organic functional group along with similar mechanistic approach and having structural similarities defined by QSAR toolbox. The results for target as well as analogues are summarized as follows

 

Sr. No

End point

Value

Species

Route

Effects

Remarks

1

NOAEL

419 mg/ kg bw/day

rat

Oral

Change in body weight

Predicted data for target chemical

 

2

NOAEL (female)

 

 

 

 

 

 

 

 

NOAEL (male)

27.5 mg/Kg bw /d

 

 

 

 

 

 

 

 

 

110 mg/Kg bw /d

 

 

 

Rat

Oral

hyperexcitability at doses at and greater than 55 mg/kg bw along with tachypnea at 110 and 450 mg/kg bw. Decreased absoluteand relative thymus weights were observed at 450 mg/kg bw.

hyperexcitability and tachypnea at 225 mg/kg bw.

Data from study report for CAS NO 108-46-3

3

NOAEL (male)

 

 

 

 

 

 

 

 

 

 

NOAEL (female)

 

75 mg/kg bw/d

 

 

 

 

 

 

 

 

 

 

150 mg/kg bw/d

 

 

Rat

 

 

 

Oral

 

 

 

 

 

 

prostration and tremors at 150 mg/kg bw. 80% mortality at 600 mg/kg bw, 20% mortality at 300 mg/kg bw and absence of any other significant differences when compared to controls.

 

 

prostration and tremors at 300 mg/kg bw. Complete mortality at 600 mg/kg bw; no other significant findings.

Data from study report for CAS NO 108-46-3

4

NOAEL (male)

 

 

 

 

 

 

 

 

 

 

NOAEL (female)

 

65 mg/kg bw/d

 

 

 

 

 

 

 

 

 

 

32 mg/kg bw/d

 

 

Rat

 

 

 

Oral

 

 

 

 

 

 

increased absolute liver weights at 130 and 260 mg/kg/bw. Tremors were observed at 520 mg/kg bw. Absolute and relative adrenal gland weights were significantly increased in all surviving male doses groups.

 

increased absolute and relative liver weights at 65 mg/kg/bw. Tremors were observed at 520 mg/kg bw.

Data from study report for CAS NO 108-46-3

5

NOAEL (male)

 

 

 

 

225 mg/kg bw/d

Rat

Oral

dyspnea, prostration, and tremors occuring at the highest dose of 420 mg/kg bw. Mortality at 420 mg/kg bw.

Data from study report for CAS NO 108-46-3

 

Based on the studies summarized in the above table it can be observed that NOAEL values was found to be in the range of 27.5 - 419 mg/Kg bw/ d. The effects observed on these doses was listed as follows

·        Change in body weight

·        hyperexcitability at doses at and greater than 55 mg/kg bw along with tachypnea at 110 and 450 mg/kg bw. Decreased absoluteand relative thymus weights were observed at 450 mg/kg bw.

·        hyperexcitability and tachypnea at 225 mg/kg bw.

·        prostration and tremors at 150 mg/kg bw. 80% mortality at 600 mg/kg bw, 20% mortality at 300 mg/kg bw and absence of any other significant differences when compared to controls.

·        prostration and tremors at 300 mg/kg bw. Complete mortality at 600 mg/kg bw; no other significant findings.

·        increased absolute liver weights at 130 and 260 mg/kg/bw. Tremors were observed at 520 mg/kg bw. Absolute and relative adrenal gland weights were significantly increased in all surviving male doses groups.

·        increased absolute and relative liver weights at 65 mg/kg/bw. Tremors were observed at 520 mg/kg bw.

·        dyspnea, prostration, and tremors occuring at the highest dose of 420 mg/kg bw. Mortality at 420 mg/kg bw.

Thus based on above values it can be concluded that substance CAS NO 91-68-9 is expected to show the similar toxicological effect based on the effects observed on the other category members. Since no effective dose value (NOAEL) is 27.5 mg/Kg bw/d thus based on this value it can be concluded that substance CAS NO 91-68-9 is considered to be not toxic to repeated dose via oral route for the above mentioned dose. Also there are no known evidence of adverse effect to Human of CAS NO 91-68-9 as well as mechanistic trigger does not indicates any concern of CAS NO 91-68-9 on toxicity to human.

Repeated dose toxicity : Inhalation :

Based on the various studies available with Klimish rating 2 and 4 for the target as well as read across substances for CAS NO 91-68-9, also from category based on organic functional group along with similar mechanistic approach and having structural similarities defined by QSAR toolbox. The results for target as well as analogues are summarized as follows

 

Sr. No

End point

Value

Species

Route

Effects

Remarks

1

LOEL

26.91227 mg/kg/day

rat

Inhalation

-

Predicted data for target chemical

 

2

LOAEL

 

1000 mg/m3

 

 

 

Rat

Inhalation mist

Systemic effect observed

Data from study report for CAS NO 108-46-3

 

Based on the studies summarized in the above table it can be observed that LOEL values was found to be in the range of 26.91227mg/kg bw/day - 1000 mg/m3. The effects observed on these doses was listed as follows

·        Systemic effect observed

 

Thus based on above values it can be concluded that substance CAS NO 91-68-9 is expected to show the similar toxicological effect based on the effects observed on the other category members. Since Low effective dose value (LOEL) is 26.91227mg/Kg bw/d thus based on this value it can be concluded that substance CAS NO 91-68-9 is considered to be not toxic to repeated dose via inhalation route below the above mentioned dose. Also there are no known evidence of adverse effect to Human of CAS NO 91-68-9 as well as mechanistic trigger does not indicates any concern of CAS NO 91-68-9 on toxicity to human. Repeated dose toxicity dermal:

50 female swiss mice were applied resorcinol at dose concentration of 0,5,25,50% (8333.33, 41666.6, 83333.3 mg/kg bw/day) (0.02 ml) were dropped on the dorsal skin between the flanks twice a week on a l-inch square area which was shaved regularly. The animals

were checked weekly, and all lesions, as well as tumors, were recorded. Animals treated with resorcinol showed skin lesions with ulceration, inflammation and hyperplasia. Two skin tumors were seen, 1 on the back and 1 on the ear as well as 1 subcutaneous fibrosarcoma. Hence the LOAEL was considered to be 8333.33 mg/kg bw/day.

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:

The NOAEL value of 3 diethylaminop phenol in Sprague-Dawley rat in 90 days study was observed at dose concentration of 419 mg/kg bw/day nominal This indicates that 3-diethylaminophenol shall not exhibit toxic effect to rat by the oral route below the above mention dose.

Justification for selection of repeated dose toxicity inhalation - systemic effects endpoint:

Repeated dose toxicity LOEL (Lowest observed effect level) of 3-diethylaminophenol to rat by the inhalation route was estimated at a dose concentration of 26.91227 mg/kg/day. This indicates that 3-diethylaminophenol shall not exhibit toxic effect to rat by the inhalation route below the above mention dose.

Justification for selection of repeated dose toxicity dermal - systemic effects endpoint:

50 female swiss mice were applied resorcinol at dose concentration of 0,5,25,50% (8333.33, 41666.6, 83333.3 mg/kg bw/day) (0.02 ml) were dropped on the dorsal skin between the flanks twice a week on a l-inch square area which was shaved regularly. The animals  were checked weekly, and all lesions, as well as tumors, were recorded. Animals treated with resorcinol showed skin lesions with ulceration, inflammation and hyperplasia. Two skin tumors were seen, 1 on the back and 1 on the ear as well as 1 subcutaneous fibrosarcoma. Hence the LOAEL was considered to be 8333.33 mg/kg bw/day.

Justification for classification or non-classification