Disodium 8-hydroxynaphthalene-1,6-disulphonate

Endpoint summary

Description of key information

Prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, repeated dose oral toxicity was predicted for the test compound 8-hydroxynaphthalene-1,6-disulfonate ( 83732-80-3). The study assumed the use of male and female Wistar rats in chronic study of 90 days. No significant alterations were noted at the dose level of 568.57mg/Kg bw/day. The predicted No Observed Adverse Effect Level (NOAEL) for 8-hydroxynaphthalene-1,6-disulfonate is considered to be 568.57mg/Kg bw/day. Based on this value it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

chronic toxicity: oral

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:

Prediction is done using OECD QSAR Toolbox version 3.4and the supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: As mention below

Principles of method if other than guideline:

Not applicable

GLP compliance:

not specified

Limit test:

no

Specific details on test material used for the study:

- Name of test material (IUPAC name): Disodium 8-hydroxynaphthalene-1,6-disulfonate
- Molecular formula: C10H6Na2O7S2
- Molecular weight: 348.2624 g/mol
- Smiles notation: c1cc2cc(cc(c2c(c1)S(=O)(=O)[O-])O)S(=O)(=O)[O-].[Na+].[Na+]
- InChl: 1S/C10H8O7S2.2Na/c11-8-5-7(18(12,13)14)4-6-2-1-3-9(10(6)8)19(15,16)17;;/h1-5,11H,(H,12,13,14)(H,15,16,17);;/q;2*+1/p-2
- Substance type: Organic
- Physical state: Solid

Species:

rat

Strain:

Wistar

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

not specified

Details on oral exposure:

not specified

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

90 days

Frequency of treatment:

not specified

Remarks:

not specified

No. of animals per sex per dose:

not specified

Control animals:

not specified

Details on study design:

not specified

Positive control:

not specified

Observations and examinations performed and frequency:

not specified

Sacrifice and pathology:

not specified

Other examinations:

not specified

Statistics:

not specified

Clinical signs:

not specified

Mortality:

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

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Description (incidence and severity):

not specified

Details on results:

not specified

Dose descriptor:

NOAEL

Effect level:

568.571 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No significant effect were observed at this dose

Critical effects observed:

not specified

The prediction was based on dataset comprised from the following descriptors: NOAEL
Estimation method: Takes average value from the 6 nearest neighbours
Domain  logical expression:Result: In Domain

(((((("a" or "b" or "c" or "d" )  and ("e" and ( not "f") )  )  and "g" )  and "h" )  and "i" )  and ("j" and "k" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Naphthalene sulfonic acids, condensates by OECD HPV Chemical Categories

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  >> 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 AND Salt by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "e"

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

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Benzylamines-Acylation OR 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 >> 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 >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated esters OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated ketones OR SN1 OR SN1 >> Carbenium Ion Formation OR SN1 >> Carbenium Ion Formation >> Allyl benzenes 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 nitro OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine OR SN2 OR SN2 >> Direct Acting Epoxides and related OR SN2 >> Direct Acting Epoxides and related >> Epoxides OR SN2 >> SN2 at an sp3 Carbon atom OR SN2 >> SN2 at an sp3 Carbon atom >> Aliphatic halides by DNA binding by OECD

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Class 5 (Not possible to classify according to these rules) by Acute aquatic toxicity classification by Verhaar (Modified) ONLY

Domain logical expression index: "h"

Similarity boundary:Target: Oc1cc(S(=O)(=O)O{-}.[Na]{+})cc2cccc(S(=O)(=O)O{-}.[Na]{+})c12
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "i"

Similarity boundary:Target: Oc1cc(S(=O)(=O)O{-}.[Na]{+})cc2cccc(S(=O)(=O)O{-}.[Na]{+})c12
Threshold=10%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "j"

Parametric boundary:The target chemical should have a value of log Kow which is >= -4.66

Domain logical expression index: "k"

Parametric boundary:The target chemical should have a value of log Kow which is <= 6.25

Conclusions:

The predicted No Observed Adverse Effect Level (NOAEL) for disodium 8-hydroxynaphthalene-1,6-disulfonate ( 83732-80-3) is considered to be 568.57mg/Kg bw/day.

Executive summary:

Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, repeated dose oral toxicity was predicted for the test compound 8-hydroxynaphthalene-1,6-disulfonate ( 83732-80-3). The study assumed the use of male and female Wistar rats in chronic study of 90 days. No significant alterations were noted at the dose level of 568.57mg/Kg bw/day. The predicted No Observed Adverse Effect Level (NOAEL) for 8-hydroxynaphthalene-1,6-disulfonate is considered to be 568.57mg/Kg bw/day. Based on this value it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

568.57 mg/kg bw/day

Study duration:

chronic

Species:

rat

Quality of whole database:

K2 data from OECD QSAR 3.4.

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Repeated dose oral toxicity:

Prediction model based estimation and data available for the target chemical was reviewed to determine the toxic nature of 8-hydroxynaphthalene-1,6-disulfonate ( 83732-80-3) upon repeated exposure by oral, dermal and inhalation route of exposure. The studies are as mentioned below:

Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, repeated dose oral toxicity was predicted for the test compound 8-hydroxynaphthalene-1,6-disulfonate ( 83732-80-3). The study assumed the use of male and female Wistar rats in chronic study of 90 days. No significant alterations were noted at the dose level of 568.57mg/Kg bw/day. The predicted No Observed Adverse Effect Level (NOAEL) for 8-hydroxynaphthalene-1,6-disulfonate is considered to be 568.57mg/Kg bw/day. Based on this value it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation.

Another Repeated dose toxicity study was performed by S. A. CLODE et al.( Fd Chem. Toxic,1987) to determine the oral toxic nature of Amaranth dye(915-67-3). The data is taken from Read across substance. The read across substance share a high similarity in structure. So it is acceptable to tale data from analogous structure. In acombined repeated dose & carcinogenicity,Wistar male and female rats were treated withAmaranth dye in the concentration of 47, 242 and 1260 mg/kg bw/day for male and 49, 246 and 1260 mg/kg bw/day for female orally in fed.No significant effect on survival of treated rats were observed as compared to control.Significant decrease in body weight in male rats from week 4 to 73 and in female rat from 51 and 73 and increase in food consumption was observed in 1260 mg/kg bw/day treated rats as compared to control. Slight effect on body weight and food consumption was due to a reduction in the absorption or utilization of the nutrient. Average compound intake of male rats were 47, 242 and 1260 mg/kg bw/day and for female rats 49, 246 and 1260 mg/kg bw/day.Increase in water consumption was observed in 1260 mg/kg bw/day treated male rats as compared to control. Increased water loss was observed due to production of softer, moister faeces and a compensatory increase in water intake. Similarly, decreased in packed cell volume was observed at month 6 and 12 in male and at month 18 in female rats and slightly increased haemoglobin concentrations in female rats at termination of study and decrease in glutamic-oxalacetic transaminase activities in male and female rats but not significant in female rats were observed at 1260 mg/kg bw/day. Observed effect were not dose related or consistent between the sexes. Increase level of proteinin urine at 12 months in female was observed at 1260 mg/kg bw/day andSemi-quantitative analysis of urine for bilirubin and ketones was hindered at months 18 and 24 due to the contamination of the urine with amaranth which interfered with the colour reaction. Statistically significant increase in absolute and relative full and empty caecum weight were observed in male and female at 1260mg/kg bw/day andincrease in absolute and relative full caecum weight in male rats at 242mg/kg bw/day were observedas compared to control. The observed effect was not statistically significant as compared to control. In addition, Non-neoplastic transitional-cell hyperplasia of bladder, inflammatory cell infiltrate of the seminal vesicles and testicular interstitial-cell hyperplasia were observed in 47 mg/kg bw/day male and 1260 mg/kg bw/day treated male and female rats. Statistically significant increase in renal calcification and renal pelvic epithelial hyperplasia, lung oedema and haemorrhage, lymph-node haemorrhage and degenerative changes in the brain and nerve, degenerative and inflammatory changes in heart, inflammatory changes in thymus, aortic calcification and atrial thrombi were observed in 1260 mg/kg bw/day treated female rats. Statistically significant increase in neoplastic uterine polyps and vaginal fibromas were observed in 1260 mg/kg bw/day treated female rats. The observed effects were typical of this strain and occur in ageing rats. No effect on number of litters, number of pups per litter at day 18 and pup weight at day 18 were observed in treated rats as compared to control. Therefore, NOAEL was considered to be 1260 mg/kg body weight /day when Wistar male and female rats were treated with Amaranth dye orally in fed for 2 years.

 

Repeated inhalation study:

According to Annex IX of the REACH regulation, testing by the inhalation route is appropriate only if exposure of humans via inhalation is likely. Taking into account the low vapour pressure of the substance 8-hydroxynaphthalene-1,6-disulfonate ( 83732-80-3), which is reported as 1.22E-16Pa at 25 C. Also considering the particle size distribution of the substance the majority of the particles were found to be in the size of 150 micron to 53 micron which is much larger size range compared to the inhalable particulate matter. Thus, exposure to inhalable dust, mist and vapour of the chemical 8-hydroxynaphthalene-1,6-disulfonate is highly unlikely. Therefore this study is considered for waiver.

Repeated dermal study

The acute toxicity value for 8-hydroxynaphthalene-1,6-disulfonate(as provided in section 7.2.3) is 4668 mg/kg body weight. Also, given the use of the chemical; repeated exposure by the dermal route is unlikely since the use of gloves is common practice in industries. Thus, it is expected that 8-hydroxynaphthalene-1,6-disulfonate ( 83732-80-3) shall not exhibit 28 day repeated dose toxicity by the dermal route. In addition, there is no data available that suggests that 8-hydroxynaphthalene-1,6-disulfonate shall exhibit repeated dose toxicity by the dermal route. Hence this end point was considered for waiver.

Based on the data available for the target chemical and its prediction, 8-hydroxynaphthalene-1,6-disulfonate ( 83732-80-3) does not exhibit toxic nature upon repeated exposure by oral, inhalation and dermal route of exposure and hence is not likely to classify as per the criteria mentioned in CLP regulation.

Justification for classification or non-classification

Based on the data available for the target chemical and its read across, 8-hydroxynaphthalene-1,6-disulfonate ( 83732-80-3)does not exhibit toxic nature upon repeated exposure by oral, inhalation and dermal route of exposure and hence is not likely to classify as per the criteria mentioned in CLP regulation.