N,N'-dimethyldiphenylthiuram disulphide

Endpoint summary

Description of key information

Single oral application of the test item to rats yielded LD50 > 5000 mg/kg bw. 
 Single inhalation exposure against the test item for 4 hours yielded LC50 > 5000 mg/m³ 

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: reporting in brief but relevant information is available

Principles of method if other than guideline:

Single oral application by gavage of 5000 mg/kg bw dissolved in lutrol to 10 male Wistar rats; observation time: 14 days

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 160-180 g
- Housing: 5 /cage

Route of administration:

oral: gavage

Vehicle:

other: lutrol

Details on oral exposure:

single oral application by gavage

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

10

Control animals:

not specified

Details on study design:

Single oral application by gavage of 5000 mg/kg bw dissolved in lutrol to 10 male Wistar rats; observation time: 14 days LD 50 calcuation according to Fink and Hund Arneim.-forsch. 15, 624 (1965)

Statistics:

no further data

Sex:

male

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Remarks on result:

other: no mortality no clinical findings

Mortality:

0/10

Clinical signs:

other: no clinical findings

Gross pathology:

not examined

Other findings:

no further data

Executive summary:

Single oral application by gavage of 5000 mg/kg bw to 10 male rats caused no death and no clinical findings were observed during the 14 day-observation period. Thus, the LD50 was considered to be >5000 mg/kg bw (Loeser 1976)

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

5 000 mg/kg bw

Quality of whole database:

The only available reliable study on rats

Acute toxicity: via inhalation route

Link to relevant study records

Reference

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

yes

Test type:

standard acute method

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

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

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

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)

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating conc.

Value:

5 064 mg/m³ air

Quality of whole database:

The only available study is performed according to OECD Guidline and GLP and has Klimisch Score 1

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

oral exposure

Single oral application by gavage of 5000 mg/kg bw to 10 male rats caused no death and no clinical findings were observed during the 14 day-observation period. Thus, the LD50 was considered to be >5000 mg/kg bw (Loeser 1976)

inhalation exposure

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 for 4 hours 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 observed 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.

Thus, the results can be summarized as follows: LC50 (rat) >5064 mg/m³/4h (Pauluhn 2012)

dermal exposure

According to Regulation (EC) No 1907/2006 (REACh) ANNEX VIII column 2, in addition to the acute toxicty using the oral route , for substances other than gases, at least the acute toxicity data for one other route should be provided. This recommendation is fulfilled because there is an acute inhalation study available which was performed according to the respective guideline and GLP. Thus, there is no need to conduct an acute toxicity study using the dermal route..

Justification for selection of acute toxicity – oral endpoint
The only available reliable study on rats

Justification for selection of acute toxicity – inhalation endpoint
guideline study and GLP

Justification for selection of acute toxicity – dermal endpoint
According to Regulation (EC) No 1907/2006 (REACh) ANNEX VIII column 2, in addition to the acute toxicty using the oral route , for substances other than gases, at least the acute toxicity data for one other route should be provided. This recommendation is fulfilled because there is an acute inhalation study available which was performed according to the respective guideline and GLP. Thus, there is no need to conduct an acute toxicity study using the dermal route..

Justification for classification or non-classification

Based on the available data no classification or labelling is required.