N,N'-dimethyldiphenylthiuram disulphide

Toxicity to reproduction: other studies

Administrative data

Endpoint:

toxicity to reproduction: other studies

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: guideline study and GLP

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: OECD TG 407

GLP compliance:

yes

Type of method:

in vivo

Test material

Test material information

Constituent 1

Reference substance name:

N,N'-dimethyldiphenylthiuram disulphide

EC Number:

234-196-6

EC Name:

N,N'-dimethyldiphenylthiuram disulphide

Cas Number:

10591-84-1

Molecular formula:

C16H16N2S4

IUPAC Name:

N-methyl-N-phenyl{[methyl(phenyl)carbamothioyl]disulfanyl}carbothioamide

Test material form:

other: white solid

Details on test material:

content: 99.7 %

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 5 weeks
- Weight at study initiation: males 152.4 g; females: 137.0 g
- Housing: in groups with 3 rats
- Diet ad libitum
- Water ad libitum
- Acclimation period: approximately 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22
- Humidity (%): 55
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: Solutol HS 15 / Ethanol / tap water (4:1:5)

Details on exposure:

The test item was administered by gavage in vehicle. the administration volume 10 ml/kg bw per day. The formulations were prepared as needed taking into account the analytically determined stability. The test item was administered as a suspension in vehicle.

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

28 days

Frequency of treatment:

once per day

Duration of test:

28 days

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 100, 300, 1000 mg/kg bw/day
Basis:

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Details on study design:

according to OECD TG 407

Statistics:

yes; Dunnett Exact Homogeneous Test, Dunnett exact Homogeneous test after logarithmic transformation, Bonferroni/Mann-Whitney U-test

Results and discussion

Effect levels

1

Dose descriptor:

other: LOAEL (general toxicity

Effect level:

ca. 100 mg/kg bw/day (nominal)

Sex:

male/female

Basis for effect level:

other: effects on hematology, spleen and kidney

2

Dose descriptor:

other: NOAEL (reproductive organs)

Effect level:

1 000 mg/kg bw/day (nominal)

Sex:

male/female

Basis for effect level:

other: no effects on reproductive organs

Observed effects

for general toxicity : see section 7.5.1. repeated dose toxicity:oral application
No effects on reproductive organs were detected including weights of prostate, seminal vesicle with coagulation glands, epididymides testes , ovaries /oviducts and histopathological examination

Applicant's summary and conclusion

Executive summary:

To examine N,N'-dimethylphenylthiuram disulfide for subacute oral toxicity according to OECD TG 407 and GLP, male and female Wistar rats received 0, 100, 300 and 1000 mg/kg bw/day dissolved in Solutol HS 15 / Ethanol / tap water (4 : 1 : 5) over a period of 28 days.

Survival was not affected by treatment. The only clinical observation was discolored feced at mid and high dose rats (both sexes). Compared to controls over the period of treatment, body weight development was reduced in high dose males by 9 % and in high dose females by 12 %. For General toxicity see section 7.5.1 (LOAEL 100 mg/kg bw/day)..No effects on reproductive organs were detected up to the highest test dose of 1000 mg/kg bw/day.