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Diss Factsheets

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information

NOAEL was estimated to be 725 mg/kg bw when rats were orally exposed with 4-hydroxy-6-(methylamino)naphthalene-2-sulfonic acid.  

Thus, as per criteria of CLP regulation, 4-hydroxy-6-(methylamino)naphthalene-2-sulfonic acid can be not classified for reproductive toxicity.   

Link to relevant study records
Reference
Endpoint:
toxicity to reproduction
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
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: 4-hydroxy-6-(methylamino)naphthalene-2-sulfonic acid
InChI: 1S/C11H11NO4S/c1-12-8-3-2-7-4-9(17(14,15)16)6-11(13)10(7)5-8/h2-6,12-13H,1H3,(H,14,15,16)
Smiles: CNc1ccc2cc(cc(c2c1)O)S(=O)(=O)O
- Molecular formula (if other than submission substance):C11H11NO4S
- Molecular weight (if other than submission substance):253.2769 g/mol
- Substance type:Organic
Species:
rat
Strain:
Wistar
Sex:
male/female
Route of administration:
oral: gavage
Type of inhalation exposure (if applicable):
not specified
Remarks on MMAD:
not specified
Vehicle:
corn oil
Details on exposure:
not specified
Details on mating procedure:
not specified
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
54 days
Frequency of treatment:
Daily
Dose / conc.:
725 mg/kg bw/day
No. of animals per sex per dose:
80 animals (40 males and 40 females)
Control animals:
yes, concurrent vehicle
Details on study design:
not specified
Positive control:
not specified
Parental animals: Observations and examinations:
not specified
Oestrous cyclicity (parental animals):
not specified
Sperm parameters (parental animals):
not specified
Litter observations:
not specified
Postmortem examinations (parental animals):
not specified
Postmortem examinations (offspring):
not specified
Statistics:
not specified
Reproductive indices:
not specified
Offspring viability indices:
not specified
Clinical signs:
no effects observed
Dermal irritation (if dermal study):
not specified
Mortality:
not specified
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
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
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified
Reproductive function: oestrous cycle:
not examined
Reproductive function: sperm measures:
not examined
Reproductive performance:
not specified
Dose descriptor:
NOAEL
Effect level:
725 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
clinical signs
body weight and weight gain
food consumption and compound intake
reproductive performance
Remarks on result:
other: No effect observed
Critical effects observed:
not specified
System:
other: not specified
Organ:
not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified
Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality / viability:
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
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings:
not specified
Other effects:
not specified
Behaviour (functional findings):
not specified
Developmental immunotoxicity:
not specified
Dose descriptor:
other: not specified
Generation:
other: not specified
Based on:
not specified
Sex:
not specified
Basis for effect level:
other: not specified
Remarks on result:
other: not specified
Critical effects observed:
not specified
System:
other: not specified
Organ:
not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified
Reproductive effects observed:
not specified
Treatment related:
not specified
Relation to other toxic effects:
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" )  and ("e" and ( not "f") )  )  and ("g" and ( not "h") )  )  and ("i" and "j" )  )

Domain logical expression index: "a"

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

Domain logical expression index: "b"

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

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as AN2 AND AN2 >> Michael-type addition to quinoid structures  AND AN2 >> Michael-type addition to quinoid structures  >> N-Substituted Aromatic Amines AND AN2 >> Michael-type addition to quinoid structures  >> Substituted Phenols by Protein binding by OASIS v1.4

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Acid moiety AND Phenols by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Not known precedent reproductive and developmental toxic potential by DART scheme v.1.0

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Known precedent reproductive and developmental toxic potential OR Non-steroid nucleus derived estrogen receptor (ER) and androgen receptor (AR) OR Non-steroid nucleus derived estrogen receptor (ER) and androgen receptor (AR) >> 4-alkylphenol-like derivatives (2b-3) by DART scheme v.1.0

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Benzene/ Naphthalene sulfonic acids (Less susceptible) Rank C by Repeated dose (HESS)

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Phenols (Mucous membrane irritation) Rank C by Repeated dose (HESS)

Domain logical expression index: "i"

Parametric boundary:The target chemical should have a value of log Kow which is >= -4.26

Domain logical expression index: "j"

Parametric boundary:The target chemical should have a value of log Kow which is <= 6.97

Conclusions:
NOAEL was estimated to be 725 mg/kg bw when rats were orally exposed with 4-hydroxy-6-(methylamino)naphthalene-2-sulfonic acid.
Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the reproductive toxicity was estimated for 4-hydroxy-6-(methylamino)naphthalene-2-sulfonic acid. The NOAEL was estimated to be 725 mg/kg bw when rats were orally exposed with 4-hydroxy-6-(methylamino)naphthalene-2-sulfonic acid.  

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
725 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
Data is Klimisch 2 and from OECD QSAR toolbox
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

Reproductive toxicity:

In different studies, 4-hydroxy-6-(methylamino)naphthalene-2-sulfonic acid has been investigated for reproductive toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments and estimated data in rodents, i.e. most commonly in rats for 4-hydroxy-6-(methylamino)naphthalene-2-sulfonic acid along with the study available on structurally similar read across substance 2-Naphthalenecarboxylic acid, 3-hydroxy-4-[(4- methyl-2- sulfophenyl)azo]-,calcium salt (CAS no 5281-04-9). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies.

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the reproductive toxicity was estimated for 4-hydroxy-6-(methylamino)naphthalene-2-sulfonic acid. The NOAEL was estimated to be 725 mg/kg bw when rats were orally exposed with 4-hydroxy-6-(methylamino)naphthalene-2-sulfonic acid.  

In another experimental study given by United States Environmental Protection Agency (High Production Volume Information System (HPVIS)| OPPT | US EPA, 2017) on structurally similar read across substance 2-Naphthalenecarboxylic acid, 3-hydroxy-4-[(4- methyl-2- sulfophenyl)azo]-,calcium salt (CAS no 5281-04-9), male and female rats treated with 2-Naphthalenecarboxylic acid, 3-hydroxy-4-[(4- methyl-2- sulfophenyl)azo]-,calcium salt in the concentration of 0, 100, 300 and 1000 mg/kg orally by gavage 56 Days. No effect on mating performance, duration of gestation and sex distribution were observed in treated rats. In addition, No effect on pup viability, body weight and gross anomalies were observed. Therefore, NOAEL was considered to be 1000 mg/kg bw for P and F1 generation when male and female rats were treated with 2-Naphthalenecarboxylic acid, 3-hydroxy-4-[(4- methyl-2- sulfophenyl)azo]-,calcium salt orally by gavage 56 Days. 

Thus, based on the above study and predictions on 4-hydroxy-6-(methylamino)naphthalene-2-sulfonic acid and its read across substances, it can be concluded that NOAEL value is 725 mg/kg bw with no effect on reproduction. Thus, as per criteria of CLP regulation, 4-hydroxy-6-(methylamino)naphthalene-2-sulfonic acid can be not classified for reproductive toxicity. 

Effects on developmental toxicity

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the above study and predictions on 4-hydroxy-6-(methylamino)naphthalene-2-sulfonic acid and its read across substances, it can be concluded that NOAEL value is 725 mg/kg bw with no effect on reproduction. Thus, as per criteria of CLP regulation, 4-hydroxy-6-(methylamino)naphthalene-2-sulfonic acid can be not classified for reproductive toxicity.   

Additional information