Tetrakis(phenylmethyl)thioperoxydi(carbothioamide)

Endpoint summary

Description of key information

Acute toxicity data indicate no acute toxicity. In rats the oral LD50 was >5000 mg/kg bw (EU Method B1, GLP compliant). Inhalation exposure in rats resulted in a LC50 >5.03 mg/L (OECD 403, GLP compliant).

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

Study period:

December 23, 1987to March 14, 1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Guideline study performed in compliance with GLP, available as unpublished report, no restrictions, fully adequate for assessment.

Qualifier:

according to guideline

Guideline:

other: Directive EEC 84/449, Annex V, B.1

Deviations:

no

Principles of method if other than guideline:

Directive 84/449/EEC was replaced by Directive 92/69/EEC and REGULATION (EC) No 440/2008.
Equivalent to OECD 401

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Strain: Wistar CrL: (Wi) BR (outbred, SPF quality)

Route of administration:

oral: gavage

Vehicle:

methylcellulose

Details on oral exposure:

VEHICLE
- Concentration in vehicle: Substance delivered in 1% aqueous methyl cellulose.

MAXIMUM DOSE VOLUME APPLIED: The dose volume was 10 ml/kg bodyweight on each occasion, instead of twice 7.5 ml/kg as mentioned in the study protocol. This was not considered to have adversely affected the outcome .of the study.

Doses:

The dose level was 5000 mg/kg bodyweight and was administered as two doses of 2500 mg/kg within 24 hours.

No. of animals per sex per dose:

Based on the absence of mortality observed in the pilot study, one group of animals, comprising 5 males and 5 females was dosed with a total oral dose of test substance at 5000 mg/kg bodyweight (2500 mg/kg twice within 24 hours)

Control animals:

no

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

Male: 5000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 5000 mg/kg bw; Number of animals: 5; Number of deaths: 0

Clinical signs:

other: Signs of toxicity related to dose levels: No signs of systemic toxicity were observed during the observation period.

Gross pathology:

Effects on organs:
No effects on organs were found after sacrifice on day 15.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions used in this study, it is concluded that the oral LD50 value of TBzTD in the rat exceeds 5000 mg/kg bodyweight for both males and females.

Executive summary:

One group of Wistar rats, comprising 5 males and 5 females, received a total oral dose of Tetrabenzylthiuram disulfide at 5000 mg/kg. bodyweight (2500 mg/kg twice within 24 hours).

No mortality occurred and no signs of toxicity were observed during the 14 day observation period.

Post-mortem examination of all animals at the end of the study did not reveal any changes that were considered to have arisen as a result of treatment.

Since no mortality occurred, the oral LD50 value for both males and females was noted as exceeding 5000 mg/kg bodyweight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

GLP compliant, guideline study, available as unpublished report, no restrictions, fully adequate for assessment

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

Study period:

May 10, 1988 to July 7, 1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Guideline study performed in compliance with GLP, available as unpublished report, no restrictions, fully adequate for assessment.

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

(1981)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

- Substance: TETRABENZYLTHIURAM DISULFIDE
- Appearance: Powder (creamy, solid)
- Stability: At room temperature, protected from light.
- Protective measures: Gloves, goggl es and face mask were suffi cient to assure personnel health and safety.

Physical form of substance: Solid
Mass median aerodynamic diameter (for liq.+solid aerosol): MMAD has not been calculated. 47.7% of particles =< 3 um.
Cumulative particel size: Percent Effective cutoff diameter 4.0 < 0.325 4.2 0.325 4.7 0.715 6.3 1.06 11.0 1.60 26.8 2.13 47.7 3.0 100 4.6
- Batch: RB 67+65+77
- Purity: Technical pure product

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Wistar rat, KFM-HAN, outbred, SPF quality

Route of administration:

inhalation: dust

Vehicle:

air

Details on inhalation exposure:

Nose-only

Duration of exposure:

4 h

Statistics:

The LOGIT-Model could not be applied to these data.

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.03 mg/L air

Exp. duration:

4 h

Mortality:

Male: .78 mg/L; Number of animals: 5; Number of deaths: 0
Male: 5.03 mg/L; Number of animals: 5; Number of deaths: 0
Female: .78 mg/L; Number of animals: 5; Number of deaths: 0
Female: 5.03 mg/L; Number of animals: 5; Number of deaths: 0

Clinical signs:

other: Signs of toxicity related to dose levels: At the concentration of 5.03 mg/l, some excitement was noted during exposure. Slight breathing difficulty (males and females) and piloerection (males only) were noted just after exposure.

Gross pathology:

Effects on organs:
No abnormal observations were made in any animals of any groups.

Interpretation of results:

GHS criteria not met

Conclusions:

The acute 4-hour inhalation toxicity of TETRABENZYLTHIURAM DISULFIDE in rats of both sexes observed over a period of 15 days was estimated to be: Greater than 5.03 mg/L air

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

5 030 mg/m³ air

Quality of whole database:

GLP compliant, guideline study, available as unpublished report, no restrictions, fully adequate for assessment

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In an acute oral toxicity study performed in accordance with Directive EEC 84/449, Annex V; B.1 and in compliance with GLP, one group of Wistar rats, comprising 5 males and 5 females, received a total oral dose of Tetrabenzylthiuram disulfide at 5000 mg/kg bw (2500 mg/kg twice within 24 hours). No mortality occurred and no signs of toxicity were observed during the 14-day observation period. Post-mortem examination of all animals at the end of the study did not reveal any changes that were considered to have arisen as a result of treatment. Since no mortality occurred, the oral LD50 value for both males and females was noted as exceeding 5000 mg/kg bodyweight.

In an acute inhalation toxicity study performed in accordance with OECD 403 and in compliance with GLP, two group of Wistar rats, comprising 5 males and 5 females were exposed to Tetrabenzylthiuram disulfide. Animals were exposed to 0.78 and 5.03 mg/L dust via nose-only exposure. No mortality occurred. At the concentration of 5.03 mg/L, some excitement was noted during exposure and slight breathing difficulty (males and females) and piloerection (males only) were noted just after exposure. Post-mortem examination of all animals at the end of the study did not reveal any changes that were considered to have arisen as a result of treatment. Since no mortality occurred, the inhalation LD50 value for both males and females was noted as exceeding 5.03 mg/L air.

Justification for classification or non-classification

Based on the results of the acute oral and inhalation study, the substance does not need to be classified according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.