Merbromin

Endpoint summary

Description of key information

Acute oral toxicity:

LD50 was estimated to be 360 mg/kg bw when mice were orally exposed with disodium [2,7-dibromo-9-(2-carboxylatophenyl)-6-oxido-3-oxo-3H-xanthen-5-yl]mercurol.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute 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:

Data is predicted using OECD QSAR toolbox version 3.3 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 3.3

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

- Name of test material: disodium [2,7-dibromo-9-(2-carboxylatophenyl)-6-oxido-3-oxo-3H-xanthen-5-yl]mercurol
- Common name : Merbromin
- Molecular formula: C20H8Br2HgNa2O6
- Molecular weight: 750.6552 g/mol
- Smiles notation: c1ccc2c(c1)C(=O)OC23c4cc(c(cc4Oc5c3cc(c(c5[Hg]O)[O-])Br)[O-])Br.[Na+].[Na+]
- InChl: 1S/C20H9Br2O5.Hg.2Na.H2O/c21-13-5-11-17(7-15(13)23)26-18-8-16(24)14(22)6-12(18)20(11)10-4-2-1-3-9(10)19(25)27-20;;;;/h1-7,23-24H;;;;1H2/q;3*+1;/p-3
- Substance type: Organic
- Physical state: Solid

Species:

mouse

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

not specified

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

not specified

Doses:

360 mg/kg bw

No. of animals per sex per dose:

45

Control animals:

not specified

Details on study design:

not specified

Statistics:

not specified

Preliminary study:

not specified

Sex:

not specified

Dose descriptor:

LD50

Effect level:

360 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50 % mortality observed

Mortality:

not specified

Clinical signs:

not specified

Body weight:

not specified

Gross pathology:

not specified

Other findings:

not specified

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" )  and ("e" and ( not "f") )  )  and ("g" and ( not "h") )  )  and "i" )  and ("j" and ( not "k") )  )  and ("l" and ( not "m") )  )  and ("n" and ( not "o") )  )  and ("p" and ( not "q") )  )  and ("r" and ( not "s") )  )  and "t" )  and "u" )  and ("v" and "w" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Alkenyl halide OR Aryl OR Aryl halide OR Carboxylic acid OR Chromene OR Cyclo conjugated system OR Cycloketone OR Fused carbocyclic aromatic OR Oxoxanthene OR Phenol OR Unsaturated heterocyclic fragment OR Xanthene by Organic Functional groups ONLY

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Alkenyl halide OR Aryl OR Aryl halide OR Carboxylic acid OR Overlapping groups OR Oxoxanthene OR Phenol by Organic Functional groups (nested) ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aromatic Carbon [C] OR Bromine, aromatic attach [-Br] OR Bromine, olefinic attach [-Br] OR Carbonyl, olefinic attach [-C(=O)-] OR Carbonyl, one aromatic attach [-C(=O)-] OR Ketone in a ring, olefinic aromatic attach OR Mercury [-Hg-] OR Miscellaneous sulfide (=S) or oxide (=O) OR Olefinic carbon [=CH- or =C<] OR Oxygen, one aromatic attach [-O-] OR Oxygen, two olefinic attach [-O-] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Anion OR Aromatic compound OR Aryl bromide OR Aryl halide OR Carbonic acid derivative OR Carboxylic acid derivative OR Carboxylic acid salt OR Cation OR Halogen derivative OR Heterocyclic compound OR Organometallic compound by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "e"

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

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds OR AN2 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds >> alpha, beta-Unsaturated Aldehydes OR AN2 >> Schiff base formation OR AN2 >> Schiff base formation >> alpha, beta-Unsaturated Aldehydes OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide Side Chain OR Radical OR Radical >> Radical mechanism by ROS formation (indirect) or direct radical attack on DNA OR Radical >> Radical mechanism by ROS formation (indirect) or direct radical attack on DNA >> Organic Peroxy Compounds OR SN1 OR SN1 >> Alkylation after metabolically formed carbenium ion species OR SN1 >> Alkylation after metabolically formed carbenium ion species >> Polycyclic Aromatic Hydrocarbon Derivatives OR SN2 OR SN2 >> Alkylation, direct acting epoxides and related OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines 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 >> Polycyclic Aromatic Hydrocarbon Derivatives by DNA binding by OASIS v.1.3

Domain logical expression index: "g"

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

Domain logical expression index: "h"

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 >> Formamides 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 >> Arenes 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 SN1 OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Primary (unsaturated) heterocyclic amine by DNA binding by OECD

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as High (Class III) by Toxic hazard classification by Cramer (original) ONLY

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Alkali Earth AND Halogens AND Non-Metals AND Transition Metals by Groups of elements

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Alkaline Earth OR Metalloids OR Metals OR Rare Earth by Groups of elements

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Group 1 - Alkali Earth Li,Na,K,Rb,Cs,Fr AND Group 12 - Trans.Metals Zn,Cd,Hg AND Group 14 - Carbon C AND Group 16 - Oxygen O AND Group 17 - Halogens Br AND Group 17 - Halogens F,Cl,Br,I,At by Chemical elements

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Group 15 - Nitrogen N by Chemical elements

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Group 1 - Alkali Earth Li,Na,K,Rb,Cs,Fr AND Group 12 - Trans.Metals Zn,Cd,Hg AND Group 14 - Carbon C AND Group 16 - Oxygen O AND Group 17 - Halogens Br AND Group 17 - Halogens F,Cl,Br,I,At by Chemical elements

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Group 17 - Halogens Cl OR Group 17 - Halogens F by Chemical elements

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Aliphatic bromide   [-Br] AND Aromatic bromide   [-Br] AND Aromatic ether  [-O-aromatic carbon] AND Aromatic-H AND Benzene AND -C=CH  [alkenyl hydrogen] AND Ketone   [-C-C(=O)-C-] AND Number of fused 6-carbon aromatic rings AND Number of fused acyclic rings by Bioaccumulation - metabolism alerts

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Unsubstituted aromatic (3 or less rings) by Bioaccumulation - metabolism alerts

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Aliphatic bromide   [-Br] AND Aromatic bromide   [-Br] AND Aromatic ether  [-O-aromatic carbon] AND Aromatic-H AND Benzene AND -C=CH  [alkenyl hydrogen] AND Ketone   [-C-C(=O)-C-] AND Number of fused 6-carbon aromatic rings AND Number of fused acyclic rings by Bioaccumulation - metabolism alerts

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Carbon with 4 single bonds & no hydrogens by Bioaccumulation - metabolism alerts

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Anion AND Aromatic compound AND Aryl bromide AND Aryl halide AND Carbonic acid derivative AND Carboxylic acid derivative AND Carboxylic acid salt AND Cation AND Halogen derivative AND Heterocyclic compound AND Organometallic compound by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Aromatic Carbon [C] AND Bromine, aromatic attach [-Br] AND Bromine, olefinic attach [-Br] AND Carbonyl, olefinic attach [-C(=O)-] AND Carbonyl, one aromatic attach [-C(=O)-] AND Ketone in a ring, olefinic aromatic attach AND Mercury [-Hg-] AND Miscellaneous sulfide (=S) or oxide (=O) AND Olefinic carbon [=CH- or =C<] AND Oxygen, one aromatic attach [-O-] AND Oxygen, two olefinic attach [-O-] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "v"

Parametric boundary:The target chemical should have a value of log Kow which is >= -7.19

Domain logical expression index: "w"

Parametric boundary:The target chemical should have a value of log Kow which is <= -0.573

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

LD50 was estimated to be 360 mg/kg bw when mice were orally exposed with disodium [2,7-dibromo-9-(2-carboxylatophenyl)-6-oxido-3-oxo-3H-xanthen-5-yl]mercurol.

Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for disodium [2,7-dibromo-9-(2-carboxylatophenyl)-6-oxido-3-oxo-3H-xanthen-5-yl]mercurol. The LD50 was estimated to be 360 mg/kg bw when mice were orally exposed with disodium [2,7-dibromo-9-(2-carboxylatophenyl)-6-oxido-3-oxo-3H-xanthen-5-yl]mercurol.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

360 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from OECD QSAR toolbox

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral toxicity:

In different studies, disodium [2,7-dibromo-9-(2-carboxylatophenyl)-6-oxido-3-oxo-3H-xanthen-5-yl]mercurol has been investigated for acute oral 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 disodium [2,7-dibromo-9-(2-carboxylatophenyl)-6-oxido-3-oxo-3H-xanthen-5-yl]mercurol along with the study available on structurally similar read across substance Peracetic acid (CAs no 79-21-0) and Cobaltous acetate (CAS no 71-48-7. 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 acute oral toxicity was estimated for disodium [2,7-dibromo-9-(2-carboxylatophenyl)-6-oxido-3-oxo-3H-xanthen-5-yl]mercurol. The LD50 was estimated to be 360 mg/kg bw when mice were orally exposed with disodium [2,7-dibromo-9-(2-carboxylatophenyl)-6-oxido-3-oxo-3H-xanthen-5-yl]mercurol.

In another experimental study summarized by U.S. National Library of Medicine (ChemIDplusA TOXNET DATABASE Lite Browse Advanced, 2017) on structurally similar read across substance Peracetic acid (CAs no 79-21-0), rat were treated with Peracetic acid in the concentration of 1832.6 mg/kg bw orally. 50 % mortality was observed at 1832.6 mg/kg. Therefore, LD50 was considered to be 1832.6 mg/kg bw when rat were treated with Peracetic acid orally

Further supported by experimental study summarized by U.S. National Library of Medicine (ChemIDplusA TOXNET DATABASE Lite Browse Advanced, 2017) on structurally similar read across substance Cobaltous acetate (CAS no 71-48-7), rat were treated with Cobaltous acetate in the concentration of 503 mg/kg bw orally. 50 % mortality was observed at 502 mg/kg. Lungs, Thorax or Respiration Dyspnea and Somnolence (General Depressed Activity) were observed in treated rat. Therefore, LD50 was considered to be 503 mg/kg bw when rat were treated with Cobaltous acetate orally. 

Thus, based on the above studies and predictions on disodium [2,7-dibromo-9-(2-carboxylatophenyl)-6-oxido-3-oxo-3H-xanthen-5-yl]mercurol and its read across substances, it can be concluded that LD50 value is less than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, disodium [2,7-dibromo-9-(2-carboxylatophenyl)-6-oxido-3-oxo-3H-xanthen-5-yl]mercurol can be classified as category IV of acute oral toxicity.

Justification for classification or non-classification

The substance will be classified as per the harmonized classification (Acute tox 2 - oral, Acute tox 1 - skin and Acute tox 2 - Inhalation) for the group entry 080-004-00-7.