Diphenyl sulphide

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

The reproductive toxicity study was predicted using OECD QSAR toolbox version 3.4 (2017) with respect to the descriptor log Kow; to evaluate the toxic effects of administration of Diphenyl sulphide (CAS No. 139-66-2) in rat by the oral route. No adverse effects was observed. Therefore, the no observed adverse effect level (NOAEL) of Diphenyl sulphide (CAS No. 139-66-2) for reproductive toxicity study was considered to be 705.03 mg/kg bw/day.

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 of test material (as cited in study report): Diphenyl sulphide
Molecular formula:C12H10S
Molecular weight:186.277 g/mol
Substance Type: Organic
Physical State: Liquid

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Route of administration:

oral: gavage

Type of inhalation exposure (if applicable):

not specified

Vehicle:

not specified

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

27 days

Frequency of treatment:

Daily

Details on study schedule:

not specified

Dose / conc.:

262 mg/kg bw/day

No. of animals per sex per dose:

Fifteen female controls and twelve females per treatment group

Control animals:

yes, sham-exposed

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:

not specified

Dermal irritation (if dermal study):

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

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Reproductive function: oestrous cycle:

not specified

Reproductive function: sperm measures:

not specified

Reproductive performance:

not specified

Key result

Dose descriptor:

NOAEL

Effect level:

262 mg/kg bw/day

Based on:

test mat.

Sex:

female

Basis for effect level:

reproductive performance

Remarks on result:

other: No effect observed

Critical effects observed:

not specified

System:

other: not specified

Organ:

not specified

Clinical signs:

not specified

Dermal irritation (if dermal study):

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

Reproductive function: oestrous cycle:

not specified

Reproductive function: sperm measures:

not specified

Reproductive performance:

not specified

Dose descriptor:

other: not specified

Based on:

not specified

Sex:

not specified

Remarks on result:

other: not specified

Critical effects observed:

not specified

System:

other: 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

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

Remarks on result:

other: not specified

Critical effects observed:

not specified

System:

other: not specified

Reproductive effects observed:

not specified

Treatment related:

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" )  and "d" )  and ("e" and ( not "f") )  )  and ("g" and ( not "h") )  )  and ("i" and ( not "j") )  )  and "k" )  and "l" )  and ("m" and "n" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Aromatic compound OR Thioether by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Aliphatic Sulfur, two aromatic attach OR Aromatic Carbon [C] OR Olefinic carbon [=CH- or =C<] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aryl OR Overlapping groups OR Sulfide by Organic Functional groups (nested) ONLY

Domain logical expression index: "d"

Similarity boundary:Target: c1ccccc1Sc1ccccc1
Threshold=50%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Group All log Kow > 9 by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as (!Undefined)Group CN Lipid Solubility < 0.4 g/kg by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Group C Vapour Pressure < 0.0001 Pa by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "k"

Similarity boundary:Target: c1ccccc1Sc1ccccc1
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "l"

Similarity boundary:Target: c1ccccc1Sc1ccccc1
Threshold=50%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "m"

Parametric boundary:The target chemical should have a value of log Kow which is >= 3.17

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.45

Conclusions:

The NOAEL was estimated to be 262 mg/kg bw when rats were orally exposed Diphenyl sulphide.

Executive summary:

In a prediction done by SSS (2018) using the OECD QSAR toolbox with log kow as the primary descriptor, the reproductive toxicity was estimated for Diphenyl sulphide. The NOAEL was estimated to be 262 mg/kg bw when rats were orally exposed Diphenyl sulphide.    

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

262 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

The data is Klimicsh 2 and from OECD QSAR toolbox version 3.4 (2018).

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, Diphenyl sulphide 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 Diphenyl sulphide along with the study available on structurally similar read across substance 1,1-Diphenylhydrazine (CAS no 530-50-7). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies.

In a prediction done by SSS (2018) using the OECD QSAR toolbox with log kow as the primary descriptor, the reproductive toxicity was estimated for Diphenyl sulphide. The NOAEL was estimated to be 262 mg/kg bw when rats were orally exposed Diphenyl sulphide.  

  

In another experimental study given by Hazardous Substances Data Bank (Hazardous Substances Data Bank (HSDB), Reviewed by SRP on 9/16/2004) on structurally similar read across substance 1,1-Diphenylhydrazine (CAS no 530-50-7), ICR/SIM female mice were treated with 1,1-Diphenylhydrazine in the concentration of 0 (Vehicle) and 525 mg/kg/day orally by gavage on gestation days 8-12. 2 mice died at 525 mg/kg bw. No significant effect on body weight of female mice was observed as compared to control. Similarly, No effect on Progeny counts or number of resorptions were observed in treated mice as compared to control. In addition, No effect on viability and body weight of pups on day 0 and 2 were observed as compared to control. Therefore, NOAEL was considered to be 525 mg/kg bw for P and F1 generation when ICR/SIM female mice were treated with 1,1-Diphenylhydrazine orally by gavage on gestation days 8-12.

Thus, based on the above study and predictions on Diphenyl sulphide and its read across substances, it can be concluded that NOAEL value is 262 mg/kg bw with no effect on reproduction. Thus, as per criteria of CLP regulation, Diphenyl sulphide 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

Thus, based on the above study and predictions on Diphenyl sulphide and its read across substances, it can be concluded that NOAEL value is 262 mg/kg bw with no effect on reproduction. Thus, as per criteria of CLP regulation, Diphenyl sulphide can be not classified for reproductive toxicity.