Phosphorodithioic acid, O,O-di-C1-14-alkyl esters, zinc salts

Endpoint summary

Description of key information

Acute oral toxicity:

LD50 was estimated to be 2154 mg/kg bw when female rats were orally exposed with Phosphorodithioic acid, O,O-di-C1-14-alkyl esters, zinc salts. 

Acute inhalation toxicity: 

LC50 was considered to be > 5,000 mg/m3 when rats were exposed with Phosphorodithioic acid, O,O-di-C1-14-alkyl esters, zinc salts by inhalation.

Acute dermal toxicity:

LD50 was estimated to be 6965 mg/kg bw when New Zealand White male rabbit were dermally exposed with Phosphorodithioic acid, O,O-di-C1-14-alkyl esters, zinc salts. 

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 (IUPAC name): Dialkyl(C1-C14)dithiophosphoric acid, zinc salt
- Common name: Phosphorodithioic acid, O,O–di–C1–14–alkyl esters, zinc salts
- Molecular formula: C28H60O4P2S4Zn
- Molecular weight: 716.38 g/mol
- Smiles notation: [Zn+2].CCCCCCCOP(=S)([S-])OCCCCCCC.CCCCCCCOP(=S)([S-])OCCCCCCC
- InChl: 1S/2C14H31O2PS2.Zn/c2*1-3-5-7-9-11-13-15-17(18,19)16-14-12-10-8-6-4-2;/h2*3-14H2,1-2H3,(H,18,19);/q;;+2/p-2
- Substance type: Organic
- Physical state: liquid

Species:

rat

Strain:

not specified

Sex:

female

Details on test animals or test system and environmental conditions:

not specified

Route of administration:

oral: gavage

Vehicle:

other: sunflower oil

Details on oral exposure:

not specified

Doses:

2154 mg/kg bw

No. of animals per sex per dose:

10 females

Control animals:

not specified

Details on study design:

not specified

Statistics:

not specifiednot specified

Preliminary study:

not specified

Sex:

female

Dose descriptor:

LD50

Effect level:

2 154 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50 % mortality observed

Mortality:

not specified

Clinical signs:

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

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Zinc metal and salts by OECD HPV Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Soluble complexes of Zinc by US-EPA New Chemical Categories

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Alkoxy AND Thiophosphate by Organic Functional groups

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Alkoxy AND Overlapping groups AND Thiophosphate by Organic Functional groups (nested)

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Miscellaneous sulfide (=S) or oxide (=O) AND Phosphite, aliphatic attach [-O-P] AND Sulfur, phosphorus attach [-S-] AND Thio-phosphorus [S=P] AND Zinc [Zn] by Organic functional groups (US EPA)

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Anion AND Cation by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "g"

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

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >>  Michael-type addition, quinoid structures OR AN2 >>  Michael-type addition, quinoid structures >> Quinones OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation >> Geminal Polyhaloalkane Derivatives OR AN2 >> Shiff base formation for aldehydes OR AN2 >> Shiff base formation for aldehydes >> Geminal Polyhaloalkane Derivatives OR AN2 >> Shiff base formation for aldehydes >> Haloalkane Derivatives with Labile Halogen OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Amino Anthraquinones OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide Side Chain OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines OR Non-covalent interaction >> DNA intercalation >> Quinones OR Radical OR Radical >> Generation of reactive oxygen species OR Radical >> Generation of reactive oxygen species >> Thiols OR Radical >> Generation of ROS by glutathione depletion (indirect) OR Radical >> Generation of ROS by glutathione depletion (indirect) >> Haloalkanes Containing Heteroatom OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Amino Anthraquinones OR Radical >> Radical mechanism via ROS formation (indirect) >> Diazenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Haloalcohols OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitro Azoarenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Quinones OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR SN1 OR SN1 >> Carbenium ion formation OR SN1 >> Carbenium ion formation >> Alpha-Haloethers OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Amino Anthraquinones OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Fused-Ring Primary Aromatic Amines OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitro Azoarenes OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitrobiphenyls and Bridged Nitrobiphenyls OR SN2 OR SN2 >> Acylation involving a leaving group  OR SN2 >> Acylation involving a leaving group  >> Geminal Polyhaloalkane Derivatives OR SN2 >> Acylation involving a leaving group  >> Haloalkane Derivatives with Labile Halogen OR SN2 >> Acylation involving a leaving group after metabolic activation OR SN2 >> Acylation involving a leaving group after metabolic activation >> Geminal Polyhaloalkane Derivatives OR SN2 >> Alkylation by epoxide metabolically formed after E2 reaction OR SN2 >> Alkylation by epoxide metabolically formed after E2 reaction >> Haloalcohols 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 cyclization OR SN2 >> Alkylation, direct acting epoxides and related after cyclization >> Nitrogen Mustards OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Haloalkane Derivatives with Labile Halogen OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Haloalkanes Containing Heteroatom OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation >> Geminal Polyhaloalkane Derivatives OR SN2 >> SN2 at sp3-carbon atom OR SN2 >> SN2 at sp3-carbon atom >> Alpha-Haloethers by DNA binding by OASIS v.1.3

Domain logical expression index: "i"

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

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as 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 >> 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 Schiff base formers OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  >> Ethylenediamines (including piperazine) 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 >> Aromatic phenylureas OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine OR SN1 >> Nitrenium Ion formation >> Unsaturated heterocyclic azo OR SN2 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 >> Phosphates by DNA binding by OECD

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Non binder, MW>500 by Estrogen Receptor Binding

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Non binder, impaired OH or NH2 group OR Non binder, non cyclic structure OR Non binder, without OH or NH2 group OR Strong binder, OH group OR Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OASIS v1.3

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides 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 >> Conjugated systems with electron withdrawing groups  OR Nucleophilic addition OR Nucleophilic addition >> Addition to carbon-hetero double bonds OR Nucleophilic addition >> Addition to carbon-hetero double bonds >> Ketones OR SNAr OR SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds OR SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds >> Activated aryl and heteroaryl compounds by Protein binding by OASIS v1.3

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as No superfragment by Superfragments ONLY

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Inclusion rules not met by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Ketones OR Quaternary organic ammonium compounds OR Sulfonic acids or their salts by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "r"

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

Domain logical expression index: "s"

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

Domain logical expression index: "t"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.225

Domain logical expression index: "u"

Parametric boundary:The target chemical should have a value of log Kow which is <= 25.2

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

LD50 was estimated to be 2154 mg/kg bw when female rats were orally exposed with Phosphorodithioic acid, O,O-di-C1-14-alkyl esters, zinc salts.

Executive summary:

In an prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for Phosphorodithioic acid, O,O-di-C1-14-alkyl esters, zinc salts. The LD50 was estimated to be 2154 mg/kg bw when female rats were orally exposed with Phosphorodithioic acid, O,O-di-C1-14-alkyl esters, zinc salts. 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 151 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from OECD QSAR toolbox

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Data is from Haz-Map, Databases

Qualifier:

according to guideline

Guideline:

other: as below

Principles of method if other than guideline:

Acute inhalation toxicity study of Phosphorodithioic acid, O,O-di-C1-14-alkyl esters, zinc salts in rats

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Specific details on test material used for the study:

- Name of test material (IUPAC name): Dialkyl(C1-C14)dithiophosphoric acid, zinc salt
- Common name: Phosphorodithioic acid, O,O–di–C1–14–alkyl esters, zinc salts
- Molecular formula: C28H60O4P2S4Zn
- Molecular weight: 716.38 g/mol
- Smiles notation: [Zn+2].CCCCCCCOP(=S)([S-])OCCCCCCC.CCCCCCCOP(=S)([S-])OCCCCCCC
- InChl: 1S/2C14H31O2PS2.Zn/c2*1-3-5-7-9-11-13-15-17(18,19)16-14-12-10-8-6-4-2;/h2*3-14H2,1-2H3,(H,18,19);/q;;+2/p-2
- Substance type: Organic
- Physical state: liquid

Species:

rat

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

not specified

Route of administration:

inhalation

Type of inhalation exposure:

not specified

Vehicle:

not specified

Analytical verification of test atmosphere concentrations:

not specified

Concentrations:

5,000 mg/m3

No. of animals per sex per dose:

not specified

Control animals:

not specified

Details on study design:

not specified

Statistics:

not specified

Preliminary study:

not specified

Sex:

not specified

Dose descriptor:

LC50

Effect level:

> 5 000 mg/m³ air

Based on:

test mat.

Remarks on result:

other: No mortality observed

Mortality:

No mortality were observed in treated rats at 5,000 mg/m3

Clinical signs:

other: not specified

Body weight:

not specified

Gross pathology:

not specified

Other findings:

not specified

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

LC50 was considered to be > 5,000 mg/m3 when rats were exposed with Phosphorodithioic acid, O,O-di-C1-14-alkyl esters, zinc salts by inhalation.

Executive summary:

In a acute inhalation toxicity study,rats were treated with Phosphorodithioic acid, O,O-di-C1-14-alkyl esters, zinc salts in the concentration of5,000 mg/m³by inhalation.No mortality was observed in treated rats at5,000 mg/m³. Therefore,LC50 was considered to be>5,000 mg/m³when rats were exposed with Phosphorodithioic acid, O,O-di-C1-14-alkyl esters, zinc salts by inhalation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

5 000 mg/m³ air

Quality of whole database:

Data is Klimisch 2 and from Haz-Map database

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

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 (IUPAC name): Dialkyl(C1-C14)dithiophosphoric acid, zinc salt
- Common name: Phosphorodithioic acid, O,O–di–C1–14–alkyl esters, zinc salts
- Molecular formula: C28H60O4P2S4Zn
- Molecular weight: 716.38 g/mol
- Smiles notation: [Zn+2].CCCCCCCOP(=S)([S-])OCCCCCCC.CCCCCCCOP(=S)([S-])OCCCCCCC
- InChl: 1S/2C14H31O2PS2.Zn/c2*1-3-5-7-9-11-13-15-17(18,19)16-14-12-10-8-6-4-2;/h2*3-14H2,1-2H3,(H,18,19);/q;;+2/p-2
- Substance type: Organic
- Physical state: liquid

Species:

rabbit

Strain:

New Zealand White

Sex:

male

Details on test animals or test system and environmental conditions:

not specified

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

not specified

Duration of exposure:

24 hours

Doses:

6965 mg/kg bw

No. of animals per sex per dose:

6

Control animals:

yes, concurrent no treatment

Details on study design:

not specified

Statistics:

not specified

Preliminary study:

not specified

Sex:

male

Dose descriptor:

LD50

Effect level:

6 965 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50 % mortality observed

Mortality:

not specified

Clinical signs:

other: 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" or "e" or "f" )  and ("g" and ( not "h") )  )  and "i" )  and ("j" and ( not "k") )  )  and ("l" and ( not "m") )  )  and ("n" and "o" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Zinc metal and salts by OECD HPV Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Soluble complexes of Zinc by US-EPA New Chemical Categories

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Alkoxy AND Thiophosphate by Organic Functional groups

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Alkoxy AND Overlapping groups AND Thiophosphate by Organic Functional groups (nested)

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Miscellaneous sulfide (=S) or oxide (=O) AND Phosphite, aliphatic attach [-O-P] AND Sulfur, phosphorus attach [-S-] AND Thio-phosphorus [S=P] AND Zinc [Zn] by Organic functional groups (US EPA)

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Anion AND Cation by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Non binder, MW>500 by Estrogen Receptor Binding

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Non binder, impaired OH or NH2 group OR Non binder, non cyclic structure OR Non binder, without OH or NH2 group OR Strong binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as No superfragment by Superfragments ONLY

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as No alert found by in vivo mutagenicity (Micronucleus) alerts by ISS

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as 1-phenoxy-benzene OR H-acceptor-path3-H-acceptor by in vivo mutagenicity (Micronucleus) alerts by ISS

Domain logical expression index: "l"

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

Domain logical expression index: "m"

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

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is >= 9.51

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is <= 16.6

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

LD50 was estimated to be 6965 mg/kg bw when New Zealand White male rabbit were dermally exposed with Phosphorodithioic acid, O,O-di-C1-14-alkyl esters, zinc salts.

Executive summary:

In an prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated for Phosphorodithioic acid, O,O-di-C1-14-alkyl esters, zinc salts. The LD50 was estimated to be 6965 mg/kg bw when New Zealand White male rabbit were dermally exposed with Phosphorodithioic acid, O,O-di-C1-14-alkyl esters, zinc salts. 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

6 965 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from OECD QSAR toolbox

Additional information

Acute oral toxicity:

In different studies, Phosphorodithioic acid, O,O-di-C1-14-alkyl esters, zinc salts 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 Phosphorodithioic acid, O,O-di-C1-14-alkyl esters, zinc salts along with the study available on structurally similar read across substance zinc bis(O,O–diisooctyl) bis(dithiophosphate) (CAS no 28629-66-5) and zinc bis[O,O–bis(2–ethylhexyl)] bis(dithiophosphate)) (CAS no 4259-15-8). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies.

In an prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for Phosphorodithioic acid, O,O-di-C1-14-alkyl esters, zinc salts. The LD50 was estimated to be 2154 mg/kg bw when female rats were orally exposed with Phosphorodithioic acid, O,O-di-C1-14-alkyl esters, zinc salts. 

In a experimental study given by Toxic Substances Control Act Test Submissions (TSCATS) (United States Environmental Protection Agency (EPA) 2006), Charles River male rats were treated with Phosphorodithioic acid, O,O-di-C1-14-alkyl esters, zinc salts in the concentration of 1350, 2025, 3038, 4556, 5000 and 6834 mg/kg bw orally by gavage and observed for 14 days. All animals died within 6-22 hours at 6834 mg/kg bw, 7 animals died within 3-4 days at 5000 mg/kg bw, 4 animals died within 2-3 days at 4556 mg/kg bw, 2 animals died in 3 days at 3038 mg/kg bw, 1 animals died in 3 days at 2025 mg/kg bw and no mortality were observed in treated rats at 1350 mg/kg bw. Hypoactivity, ptosis, ruffed fur, muscular weakness and Diarrhea were observed in treated rats. Slightly reddened lungs were observed in dead animals and no gross pathological changes were observed in terminally sacrificed rats. Therefore, LD50 was considered to be 3195 mg/kg bw when CD male rats were treated with Phosphorodithioic acid, O,O-di-C1-14-alkyl esters, zinc salts orally by gavage.

Further it is supported by experimental study summarized by U S National Library of Medicine (Hazardous Substance DataBank [HSDB], U S National Library of Medicine, last updated 2008) on structurally similar read across substance zinc bis(O,O–diisooctyl) bis(dithiophosphate) (CAS no 28629-66-5), rats were treated with zinc bis(O,O–diisooctyl) bis(dithiophosphate) in the concentration of 3100 mg/kg bw orally. 50 % mortality observed at 3100 mg/kg bw. Therefore, LD50 was considered to be 3100 mg/kg bw when rats were treated with zinc bis(O,O–diisooctyl) bis(dithiophosphate) orally.

This is supported by experimental study summarized by European Chemicals Bureau (IUCLID Data set, European Commission – European Chemicals Bureau, 18–FEB–2000) on structurally similar read across substance zinc bis(O,O–diisooctyl) bis(dithiophosphate) (CAS no 28629-66-5), Wistar male rats were treated with zinc bis(O,O–diisooctyl) bis(dithiophosphate) in the concentration of 320, 560, 1000, 1780, 3160 and 5620 mg/kg bw orally by gavage.No mortality were observed in treated rats at 320, 560, 1000 and 1780 mg/kg bw.One animal died in the 3160 mg/kg group. All animals died in 5620 mg/kg group. Lethargy, piloerection and diarrhea were the most frequently observed toxic signs. All sacrificed rats were normal at necropsy. Necropsy findings in the animals that died prior to study termination included heart, lung and gastrointestinal abnormalities. Therefore,LD50 was considered to be3760 mg/kg bw when Wistar male rats were treated with zinc bis(O,O–diisooctyl) bis(dithiophosphate) orally by gavage.

This is again supported by experimental study summarized by European Chemicals Bureau (IUCLID Data set, European Commission – European Chemicals Bureau, 18–FEB–2000) on structurally similar read across substance zinc bis[O,O–bis(2–ethylhexyl)] bis(dithiophosphate)) (CAS no 4259-15-8), rats were treated with zinc bis[O,O–bis(2–ethylhexyl)] bis(dithiophosphate)) in the concentration of 3100mg/kg bw orally by gavage. 50 % mortality observed at 3100 mg/kg bw. Therefore,LD50 was considered to be3100 mg/kg bw when rats were treated with zinc bis[O,O–bis(2–ethylhexyl)] bis(dithiophosphate)) orally by gavage.

Thus, based on the above studies and predictions on Phosphorodithioic acid, O,O-di-C1-14-alkyl esters, zinc salts and its read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Phosphorodithioic acid, O,O-di-C1-14-alkyl esters, zinc salts can be classified as category V of acute oral toxicity.

Acute inhalation toxicity: 

In different studies, Phosphorodithioic acid, O,O-di-C1-14-alkyl esters, zinc salts has been investigated for acute inhalation toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments and estimated data in rodents for Phosphorodithioic acid, O,O-di-C1-14-alkyl esters, zinc salts along with the study available on structurally similar read across substance zinc bis(O,O–diisooctyl) bis(dithiophosphate) (CAS no 28629-66-5) and zinc bis[O,O–bis(2–ethylhexyl)] bis(dithiophosphate)) (CAS no 4259-15-8). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies.

In a experimental study given by U.S.National Library of Medicine (HazMap, Databases, 2017), rats were treated with Phosphorodithioic acid, O,O-di-C1-14-alkyl esters, zinc salts in the concentration of 5,000 mg/m3 by inhalation. No mortality was observed in treated rats at 5,000 mg/m3. Therefore, LC50 was considered to be > 5,000 mg/m3 when rats were exposed with Phosphorodithioic acid, O,O-di-C1-14-alkyl esters, zinc salts by inhalation.

In another experimental study given by Toxic Substances Control Act Test Submissions (TSCATS) (United States Environmental Protection Agency (EPA) 2006), In a acute inhalation toxicity study, Albino rats, mice and guinea pigs were treated with Phosphorodithioic acid, O,O-di-C1-14-alkyl esters, zinc salts in the concentration of 0 and 8.16 mg/L by Vapour inhalation and observed for 14 days. No mortality was observed in treated rats, mice and guinea pigs at 8.16 mg/L. Lacrimation, salivation, ptosis, and dyspnea were observed in treated rats and mice. Lacrimation was observed in treated Guinea Pigs. Which were recovered within 16 hours in all animals. No change in body weight of treated rats, mice and guinea pigs was observed in 14 days. No gross pathological changes were observed in treated rats, mice and guinea pigs. Therefore, LC50 was considered to be > 8.16 mg/L when Albino rats, mice and guinea pigs were exposed with Phosphorodithioic acid, O,O-di-C1-14-alkyl esters, zinc salts by Vapour inhalation.

 

Further supported by experimental study given by European Chemicals Bureau (European Commission – European Chemicals Bureau, 18–FEB–2000),rats were treated with zinc bis(O,O–diisooctyl) bis(dithiophosphate) in the concentration of 0.52 mg/kg bw by vapor inhalation for 6 hours.One male and one female rat died during the post exposure period. Nasal discharge and variable incidence of dypnea in males and females which commenced during the first hour of exposure at a high incidence. Macroscopic abnormalities were mainly seen in the lungs. Therefore,LC50 was considered to be> 0.52 mg/L when rats were exposed with zinc bis(O,O–diisooctyl) bis(dithiophosphate) by vapor inhalation for 6 hours.

Thus, based on the above studies and predictions on Phosphorodithioic acid, O,O-di-C1-14-alkyl esters, zinc salts and its read across substances, it can be concluded that LD50 value is greater than 5,000 mg/m3 bw. Thus, comparing this value with the criteria of CLP regulation, Phosphorodithioic acid, O,O-di-C1-14-alkyl esters, zinc salts can be classified as category V of acute inhalation toxicity.

Acute dermal toxicity:

In different studies, Phosphorodithioic acid, O,O-di-C1-14-alkyl esters, zinc salts has been investigated for acute dermal 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 rabbits for Phosphorodithioic acid, O,O-di-C1-14-alkyl esters, zinc salts along with the study available on structurally similar read across substance zinc bis(O,O–diisooctyl) bis(dithiophosphate) (CAS no 28629-66-5) and zinc bis[O,O–bis(2–ethylhexyl)] bis(dithiophosphate)) (CAS no 4259-15-8). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies.

In an prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated for Phosphorodithioic acid, O,O-di-C1-14-alkyl esters, zinc salts. The LD50 was estimated to be 6965 mg/kg bw when New Zealand White male rabbit were dermally exposed with Phosphorodithioic acid, O,O-di-C1-14-alkyl esters, zinc salts. 

In a experimental study given by Toxic Substances Control Act Test Submissions (TSCATS) (United States Environmental Protection Agency (EPA) 2006), male and female rabbits were treated with Phosphorodithioic acid, O,O-di-C1-14-alkyl esters, zinc salts in the concentration of 200 and 3160 mg/kg bw applied on abraded skin and observed for 14 days. No mortality were observed in treated rabbits at 3160 mg/kg bw. Hypo-activity were observed in treated rabbits at 3160 mg/kg bw. The observed reaction was subside within 4 hours. In one male rabbit weight loss was observed during first week of treatment at 3160 mg/kg bw, which was resumed normal during second week. One female rabbit lost weight throughout 14 day of treatment. Moderate irritation were observed at 200 mg/kg bw and severe irritation at 3160 mg/kg bw in treated rabbits. Red well-defined erythema and sever edema at 24 hours, moderate to severe desquamation and fissuring at day 7 and mild to moderate desquamation at day 14 were observed in 200 mg/kg bw treated rabbits. Beet red erythema, sever edema and second degree burns at 24 hour, escharosis fissuring and hemorrhaging at day 7 and escharosis, necrosis and sever desquamation at day 14 were observed in 3160 mg/kg bw treated rabbits. No gross pathological changes were observed in treated rabbits. Therefore, LD50 was considered to be 3160 mg/kg bw when male and female rabbits were exposed with Phosphorodithioic acid, O,O-di-C1-14-alkyl esters, zinc salts on abraded skin.

Further it is supported by experimental study summarized by European Chemicals Bureau (IUCLID Data set, European Commission – European Chemicals Bureau, 18–FEB–2000) on structurally similar read across substance zinc bis(O,O–diisooctyl) bis(dithiophosphate) (CAS no 28629-66-5), rabbits were treated with zinc bis(O,O–diisooctyl) bis(dithiophosphate) in the concentration of 3000 mg/kg bw applied on clipped unabraded skin and observed for 14 days. No mortality were observed in treated rabbits at 3000 mg/kg bw. Therefore, LD50 was considered to be 3000 mg/kg bw when rabbits were exposed with zinc bis(O,O–diisooctyl) bis(dithiophosphate) on unabraded skin.

This is again supported by experimental study summarized by European Chemicals Bureau (IUCLID Data set, European Commission – European Chemicals Bureau, 18–FEB–2000) on structurally similar read across substance zinc bis[O,O–bis(2–ethylhexyl)] bis(dithiophosphate)) (CAS no 4259-15-8), rabbits were treated with zinc bis[O,O–bis(2–ethylhexyl)] bis(dithiophosphate)) in the concentration of 5000 mg/kg bw by dermal application. No mortality observed at 5000 mg/kg bw. Therefore, LD50 was considered to be 5000 mg/kg bw when rabbits were treated with zinc bis[O,O–bis(2–ethylhexyl)] bis(dithiophosphate)) by dermal application.

Thus, based on the above studies and predictions on Phosphorodithioic acid, O,O-di-C1-14-alkyl esters, zinc salts and its read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Phosphorodithioic acid, O,O-di-C1-14-alkyl esters, zinc salts can be classified as category V of acute dermal toxicity.

Justification for classification or non-classification

Based on the above studies and predictions on Phosphorodithioic acid, O,O-di-C1-14-alkyl esters, zinc salts and its read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Phosphorodithioic acid, O,O-di-C1-14-alkyl esters, zinc salts can be classified as category V of acute oral, inhalation and dermal toxicity.