4-chlororesorcinol

Endpoint summary

Description of key information

4-chlororesorcinol is likely to exhibit the Acute toxicity via oral route.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Data is from peer reviewed journal

Qualifier:

according to guideline

Guideline:

other:

Principles of method if other than guideline:

The acute oral toxicity studies in rats were performed to evaluate the toxic effect of 4-chlororesorcinol present as a constituent in hair dyes.

GLP compliance:

not specified

Test type:

standard acute method

Species:

rat

Strain:

other: CFY

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 90-122 g
- Fasting period before study: overnight

Route of administration:

oral: gavage

Vehicle:

other: 0.5% aqueous gum tragacanth

Details on oral exposure:

Details on exposure
VEHICLE
- Concentration in vehicle: 10%
DOSAGE PREPARATION (if unusual): The test material was prepared as an aqueous solution or suspension in 0.5% aqueous gum tragacanth. Each preparation contained 0.05% anhydrous sodium sulphite and the pH was adjusted to 7.0 ± 0-2 with 0-1N-NaOH or 0-1 N-HCl.
-CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: In a preliminary dose finding test, the freshly prepared solution or suspension was administered to groups of two male and two female rats by oral intubation in a range of dosage volumes, to locate the approximate median lethal oral dose (LD50). Atfer these preliminary range-finding tests had given a rough approximation of the LD50, larger groups of rats (five males and five females) were used in order to locate the median lethal dose more precisely. A logarithmic dosage interval of 1.6 was used for each material.

Doses:

10%

No. of animals per sex per dose:

Total 10 animals
five males and five females

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 14 days
- Necropsy of survivors performed: Yes
- Other examinations performed: clinical signs of toxicity, mortality and macroscopic examination to identify target organs

Statistics:

The LD50 and its 95% confidence limits were calculated from the mortality data either by the method of Litchfield & Wilcoxon (1949) or by that of Weil (1952).

Sex:

male/female

Dose descriptor:

LD50

Effect level:

369 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Showed salivation, ataxia, fine body tremors, and changes in respiratory rate, dieresis and diarrhea.

Mortality:

50% Mortality was observed.

Clinical signs:

other: Signs of reaction to treatment, observed shortly after dosing with compounds, included lethargy and piloerection.

Gross pathology:

Animals that died as a result of treatment revealed changes including darkening of the liver and kidneys, darkening or pallor of the spleen, haemorrhage of the lungs and intestines, and injection of the intestinal and mesenteric blood vessels.
Autopsy of the survivors at the end of each experiment did not reveal any abnormalities indicative of residual systemic effects.

Interpretation of results:

Toxicity Category IV

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral median lethal dose (LD50) of 4-chlororesorcinol in CFY male and female rats is found to be 369 (314-433) mg/kg bw.

Executive summary:

Acute oral toxicity study was conducted on male and female CFY strain rats to study the toxic nature of the test material 4-chlororesorcinol.

 

The dose selected was on the basis of the preliminary dose range finding study conducted to find the approximate median lethal oral dose (LD50).

 

After these preliminary range-finding tests had given a rough approximation of the LD50, larger groups of rats (five males and five females) were used in order to locate the median lethal dose more precisely. A logarithmic dosage interval of 1.6 was used for each material.

 

14 days study was conducted, the animals were checked for death and signs of toxicity. Died rats were examined macroscopically in an attempt to identify the target organs, and animals surviving to the end of the experiment were similarly examined at that time to detect any possible residual damage. There was no microscopic examination of the various tissues and organ systems.

 

The observations suggest theacute oral median lethal dose (LD50) of 4-chlororesorcinol in CFY male and female rats to be 369 (314-433) mg/kgbw. Thus considering the CLP criteria for classification, the substance 4-chlororesorcinol is likely to be classified as Acute Toxic Category IV.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

369 mg/kg bw

Quality of whole database:

The data is K2 level as the data has been obtained from publication.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

other justification

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

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:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Principles of method if other than guideline:

The prediction is done using QSAR toolbox version 3.3

GLP compliance:

not specified

Test type:

standard acute method

Species:

rabbit

Strain:

not specified

Sex:

male

Type of coverage:

not specified

Vehicle:

water

Duration of exposure:

max 24 hours

No. of animals per sex per dose:

4 males

Control animals:

other: yes, untreated animals for assessment of body weight gain in treatment groups

Sex:

male

Dose descriptor:

LD50

Effect level:

3 437.57 mg/kg bw

Based on:

test mat.

The prediction was based on dataset comprised from the following descriptors: LD50
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") )  )  )  and ("v" and "w" )  )

Domain logical expression index: "a"

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

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Aryl AND Aryl halide AND Phenol by Organic Functional groups

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aryl halide 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 Aromatic Carbon [C] AND Chlorine, aromatic attach [-Cl] AND Chlorine, olefinic attach [-Cl] 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 Aromatic compound AND Aryl chloride AND Aryl halide AND Halogen derivative AND Hydroxy compound AND Phenol 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 Acylation OR Acylation >> Direct Addition of an Acyl Halide OR Acylation >> Direct Addition of an Acyl Halide >> Acyl halide OR Acylation >> Isocyanates and Isothiocyanates OR Acylation >> Isocyanates and Isothiocyanates >> Isothiocyanates OR Acylation >> P450 Mediated Activation to Acyl Halides OR Acylation >> P450 Mediated Activation to Acyl Halides >> 1,1-Dihaloalkanes OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Benzylamines-Acylation OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Formamides OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Thiazolidinediones 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 esters 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 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 >> Benzylamines-Schiff base 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 Schiff base formers >> Direct Acting Schiff Base Formers >> Mono aldehydes OR SN1 OR SN1 >> Carbenium Ion Formation OR SN1 >> Carbenium Ion Formation >> Allyl benzenes OR SN1 >> Carbenium Ion Formation >> Diazoalkanes OR SN1 >> Carbenium Ion Formation >> Hydrazine OR SN1 >> Carbenium Ion Formation >> N-Nitroso (alkylation) 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 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 >> Tertiary 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 >> Halogenated polarised alkenes OR SN2 >> Epoxidation of Aliphatic Alkenes >> Phenoxy polarised alkenes OR SN2 >> Nitrosation-SN2 OR SN2 >> Nitrosation-SN2 >> Nitroso-SN2 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: "h"

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

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Aryl AND Aryl halide AND Phenol by Organic Functional groups

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Aryl halide 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 Aromatic Carbon [C] AND Chlorine, aromatic attach [-Cl] AND Chlorine, olefinic attach [-Cl] 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 Aromatic compound AND Aryl chloride AND Aryl halide AND Halogen derivative AND Hydroxy compound AND Phenol by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "m"

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

Domain logical expression index: "n"

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, non cyclic structure OR Non binder, without OH or NH2 group OR Strong binder, NH2 group OR Strong binder, OH group OR Very strong binder, OH group OR Weak binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "o"

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

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Aryl AND Aryl halide AND Phenol by Organic Functional groups

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Aryl halide 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 Aromatic Carbon [C] AND Chlorine, aromatic attach [-Cl] AND Chlorine, olefinic attach [-Cl] 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 Aromatic compound AND Aryl chloride AND Aryl halide AND Halogen derivative AND Hydroxy compound AND Phenol 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 Protein binding by OECD

Domain logical expression index: "u"

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 Acylation >> Direct Acylation Involving a Leaving group >> Acyl halides (including benzyl and carbamoyl deriv.) OR Acylation >> Direct Acylation Involving a Leaving group >> Sulphonyl halides OR Acylation >> Isocyanates and Related Chemicals OR Acylation >> Isocyanates and Related Chemicals >> Isothiocyanates OR Acylation >> Isocyanates and Related Chemicals >> Thiocyanates-Acylation OR Acylation >> Ring Opening Acylation OR Acylation >> Ring Opening Acylation >> alpha-Lactams OR Acylation >> Ring Opening Acylation >> beta-Lactones-Acylation OR Michael addition OR Michael addition >> Polarised Alkenes OR Michael addition >> Polarised Alkenes >> Polarised alkene - aldehydes OR Michael addition >> Polarised Alkenes >> Polarised alkene - amides OR Michael addition >> Polarised Alkenes >> Polarised alkene - cyano OR Michael addition >> Polarised Alkenes >> Polarised alkene - esters OR Michael addition >> Polarised Alkenes >> Polarised alkene - ketones OR Michael addition >> Polarised Alkenes >> Polarised alkene - nitro OR Michael addition >> Polarised Alkenes >> Polarised alkene - pyridines OR Michael addition >> Polarised Alkenes >> Polarised alkene - sulfonate OR Michael addition >> Quinones and Quinone-type Chemicals OR Michael addition >> Quinones and Quinone-type Chemicals >> Benzoquinones OR Michael addition >> Quinones and Quinone-type Chemicals >> Pyranones (and related nitrogen chemicals) OR Michael addition >> Quinones and Quinone-type Chemicals >> Quinone-diimine OR Michael addition >> Quinones and Quinone-type Chemicals >> Quinone-imine OR Schiff Base Formers OR Schiff Base Formers >> Direct Acting Schiff Base Formers OR Schiff Base Formers >> Direct Acting Schiff Base Formers >> 1-2-Dicarbonyls OR Schiff Base Formers >> Direct Acting Schiff Base Formers >> 1-3-Dicarbonyls OR Schiff Base Formers >> Direct Acting Schiff Base Formers >> Mono-carbonyls OR SN2 OR SN2 >> Epoxides and Related Chemicals OR SN2 >> Epoxides and Related Chemicals >> Epoxides OR SN2 >> Ring Opening SN2 Reaction OR SN2 >> Ring Opening SN2 Reaction >> beta-Lactones-SN2 OR SN2 >> SN2 reaction at a sp2 carbon atom OR SN2 >> SN2 reaction at a sp2 carbon atom >> Polarised alkenes with a halogen leaving group OR SN2 >> SN2 reaction at a sulphur atom OR SN2 >> SN2 reaction at a sulphur atom >> Disulfides OR SN2 >> SN2 reaction at a sulphur atom >> Thiocyanates-SN2 OR SN2 >> SN2 reaction at a sulphur atom >> Thiols OR SN2 >> SN2 reaction at sp3 carbon atom OR SN2 >> SN2 reaction at sp3 carbon atom >> Alkyl diazo OR SN2 >> SN2 reaction at sp3 carbon atom >> Alkyl halides OR SN2 >> SN2 reaction at sp3 carbon atom >> Allyl acetates and related chemicals OR SN2 >> SN2 reaction at sp3 carbon atom >> alpha-Haloalkenes (and related cyano, sulfate and sulfonate subs. chem.) OR SN2 >> SN2 reaction at sp3 carbon atom >> alpha-Halobenzyls (and related cyano, sulfate and sulphonate subs. chem.) OR SN2 >> SN2 reaction at sp3 carbon atom >> alpha-Halocarbonyls OR SN2 >> SN2 reaction at sp3 carbon atom >> beta-Halo ethers OR SN2 >> SN2 reaction at sp3 carbon atom >> Phosphonates OR SNAr OR SNAr >> Nucleophilic aromatic substitution OR SNAr >> Nucleophilic aromatic substitution >> Activated halo-benzenes OR SNAr >> Nucleophilic aromatic substitution >> Activated halo-pyridines OR SNAr >> Nucleophilic aromatic substitution >> Halo-pyrimidines OR SNAr >> Nucleophilic aromatic substitution >> Halo-triazines by Protein binding by OECD

Domain logical expression index: "v"

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

Domain logical expression index: "w"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.24

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based on the QSAR prediction done for acute toxicity of 4-chlororesorcinol via dermal route, the LD50 value is estimated to be 3437.57 mg/kg bw on rabbits. Thus it can be concluded that 4-chlororesorcinol is considered to be not classified as per criteria of CLP regulation.

Executive summary:

Based on the QSAR prediction done for acute toxicity of 4-chlororesorcinol via dermal route, the LD50 value is estimated to be 3437.57 mg/kg bw on rabbits. Thus it can be concluded that 4-chlororesorcinol is considered to be not classified as per criteria of CLP regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

3 437.57 mg/kg bw

Quality of whole database:

The K2 level data is predicted using the OECD QSAR toolbox version 3.3

Additional information

Acute toxicity oral:

Acute oral toxicity study was conducted on male and female CFY strain rats to study the toxic nature of the test material 4-chlororesorcinol. The acute oral median lethal dose (LD50) of 4-chlororesorcinol in CFY male and female rats is found to be 369 (314-433) mg/kg bw.

Acute Toxicity Inhalation: Vapour pressure of test substance 4-Chlororesorcinol is found to be 0.0012 mm Hg at 25 °C. This value is equivalent to 0.1599 Pascal at 25°C. Considering this low vapour pressure values, this end point was considered for waiver

Acute toxicity dermal:

Based on the QSAR prediction done for acute toxicity of 4-chlororesorcinol via dermal route, the LD50 value is estimated to be 3437.57 mg/kg bw on rabbits. Thus it can be concluded that 4-chlororesorcinol is considered to be not classified as per criteria of CLP regulation.

Justification for selection of acute toxicity – oral endpoint
The acute oral median lethal dose (LD50) of 4-chlororesorcinol in CFY male and female rats is found to be 369 (314-433) mg/kg bw.

Justification for selection of acute toxicity – inhalation endpoint
Vapour pressure of test substance 4-Chlororesorcinol is found to be 0.0012 mm Hg at 25 °C. This value is equivalent to 0.1599 Pascal at 25°C.
Considering this low vapour pressure values, this end point was considered for waiver

Justification for selection of acute toxicity – dermal endpoint
Based on the QSAR prediction done for acute toxicity of 4-chlororesorcinol via dermal route, the LD50 value is estimated to be 3437.57 mg/kg bw on rabbits. Thus it can be concluded that 4-chlororesorcinol is considered to be not classified as per criteria of CLP regulation.

Justification for classification or non-classification

The available study indicates that the substance 4-Chlororesorcinol is likely to be classified as Acute Oral Toxic Category IV according to CLP regulation.