N,N'-dimethyldiphenylthiuram disulphide

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: according to OECD TG and GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

yes

Test type:

standard acute method

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:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

content 96.8 %
white powder
The test article was micronized in order to achieve the objective of test
average mass median aerodynamic diameter (MMAD): 4.1 µm

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: 2 month
- Weight at study initiation: 180-200 g
- Fasting period before study:
- Housing: before test : singly and during test in groups
- Diet ad libitum
- Water ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22
- Humidity (%): 40-60
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

inhalation

Type of inhalation exposure:

nose only

Vehicle:

clean air

Details on inhalation exposure:

generation and characterization of chamber atmosphere - mean vaöues
target concentration 5000 mg/m³
gravimetric concentration 5064 mg/m³
inlet air flow 28 l/min (concurrent control : air. 15 l/min)
exhaust air flow: 23.8 l/min (concurrent control: 12.8 l/min)
mean temperature 23.0°C (concurrent control: 23.7°C
mean rel humidity 8.4 % (concurrent control: 5 %)
Mass Median Aerodynamic Diameter(MMAD) 4.10 µm
Aerosol Mass < 3 µm: 38 %

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

ca. 4 h

Concentrations:

0 or 5000 µg/m³

No. of animals per sex per dose:

5 rats /sex and concentration

Control animals:

yes

Details on study design:

according to the respective guideline , 2 weeks pot exposure observation
To identify exposure related effects, comparisons with an appropriate vehicle control were performed. This control was exposed to an atmosphere using essentially similar exposure conditions as were used for the test substance.
body weight determination on dayys 1,3,7 and weekly thereafter
deaths were recorded
cöonical signs andappearannnce and behavior of each rat were recordedNecropsy was performed
andgross pathological changes were notet (if available)

Statistics:

yes

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5 064 mg/m³ air (analytical)

Exp. duration:

4 h

Mortality:

no rat died

Clinical signs:

other: no specific clinical signs were observed

Body weight:

Comparisons between the control and the exposure group revealed transient changes in body weights of no toxicological significance

Gross pathology:

-Animals sacrificed at the end of the observation period:
The macroscopic findings of extrapulmonary organs were essentially indistinguishable amongst expossusre and control groups.
The focal discoloration observed in 2 of 6 rats of the test groups are not considered to be pathodiagnostic of any adverse effects of the lung.

Other findings:

no further data

Applicant's summary and conclusion

Executive summary:

A study on acute inhalation toxicity of N,N'-dimethyldiphenylthiuram disulfide on rats has been conducted in accordance with OECD TG 403. A group of male and female rats was nose-only exposed to the dry powder aerosol of the test article at an actual concentration of 5064 mg/m³ The respirability of the aerosol was adequate to achieve the objective of the study, i.e. the average mass median aerodynamic diameter (MMAD) was 4.1 µm. The animals were obsreved post exposure for 14 days. Mortality did not occur. Apart from a minimal and transient decrease in body weights, which was considered to be of no toxicological significance, the exposure was tolerated without any pathodiagnostic effects suggestive of portal entry or systemic toxicity. The results can be summarized as follows: LC50 (rat) >5064 mg/m³ (Pauluhn 2012)