Diphenyl sulphide

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Experimental data from peer reviewed journal

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Materials and methods

Objective of study:

other: identification of metabolism products of Diphenyl sulphide

Test guideline

Qualifier:

according to guideline

Guideline:

other:

Principles of method if other than guideline:

Details of guidelines not available in the study report

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Diphenyl sulphide

EC Number:

205-371-4

EC Name:

Diphenyl sulphide

Cas Number:

139-66-2

Molecular formula:

C12H10S

IUPAC Name:

(phenylsulfanyl)benzene

Test material form:

other: Liquid

Details on test material:

CAS No: 139-66-2
IUPAC Name: diphenyl sulphide
Nature of the chemical: Organic

Radiolabelling:

no

Test animals

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

Male Wistar rats (230–280 g) were obtained from Charles River Laboratories (Wilmington, MA, USA). The animals were maintained in a controlled environment of constant temperature (20°C), 50% relative humidity and 12 h light–dark cycles for at least 4 days before use and allowed free access to food and water. The health of all animals was closely monitored throughout the study by determining weight gain or loss.

Administration / exposure

Route of administration:

oral: feed

Vehicle:

corn oil

Details on exposure:

Male Wistar rats in groups of four were pretreated with phenobarbitone (80 mg/kg/day in saline) intraperitoneally (i.p.), beta-naphthoflavone (100 mg/kg/day in corn oil, i.p.) or methimazole (50 mg/kg/day in saline) for three consecutive days. Rats in the control groups received an equivalent amount of the vehicles alone (1 mL/kg). On the fourth day, DPS (50 mg/kg in corn oil, 500 micro litre was administered orally to the appropriate group of rats pretreated with PB, beta-NF, methimazole, saline or corn oil.

The animals were placed individually in glass metabolic cages and urine samples, free of faeces, collected at 24 h intervals (0–24, 24– 48, 48–72 and 72–96 h)
into tubes supported in Dewar flasks containing liquid nitrogen to prevent nonenzymic degradation of metabolic products. The urine samples were stored at −20°C until analysis

Duration and frequency of treatment / exposure:

96 hours

Doses / concentrations

Remarks:

Doses / Concentrations:
50 mg/kg in corn oil

No. of animals per sex per dose / concentration:

4

Control animals:

yes

Results and discussion

Main ADME results

Main ADME results 1

Type:

absorption

Results:

No details available

Main ADME results 2

Type:

distribution

Results:

No details available

Main ADME results 3

Type:

metabolism

Results:

: DPS are oxidized to their corresponding sulphones, via a sulphoxide in rats. S-oxidation of these compounds, it is possible that other metabolic pathways may be relevant for the clearance of these simple sulphides.

Main ADME results 4

Type:

excretion

Results:

The low levels of the sulphoxides of these simple sulphides detected in urine suggest that the sulphoxides are short-lived in rats.

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

Diphenyl sulphoxide
Diphenyl sulphone

Any other information on results incl. tables

The above results are in agreement with previous studies that have demonstrated that sulphides show a tendency to be oxidized to sulphoxides, which are in turn converted to sulphones in vitro and in vivo.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): low bioaccumulation potential based on study results
In vivo administration of DPS in Male Wistar rats resulted in metabolism via S-oxidation to their corresponding sulphones, via a sulphoxide. These metabolites are eliminated through the urine. It appears that other modes of excretion may contribute to the overall elimination of these sulphides like lung and biliary excretion. Thus, it can be concluded that the chemical diphenyl sulphide (DPS) is not likely to bioaccumulate inside the living organisms and shall exhibit low bio-accumulation potential.

Executive summary:

In vivo administration of DPS in Male Wistar rats resulted in metabolism via S-oxidationto their correspondingsulphones, via a sulphoxide.These metabolites are eliminated through the urine.It appears that other modes of excretion may contribute to the overall elimination of these sulphides like lung and biliary excretion. Thus, it can be concluded that the chemical diphenyl sulphide (DPS) is not likely to bioaccumulate inside the living organisms and shall exhibit low bio-accumulation potential.