Tetramethylthiuram monosulphide

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

April-September 1987

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1987

Report date:

1987

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EPA OPP 81-3 (Acute inhalation toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Thiram

EC Number:

205-286-2

EC Name:

Thiram

Cas Number:

137-26-8

Molecular formula:

C6H12N2S4

IUPAC Name:

[disulfanediylbis(carbonothioylnitrilo)]tetramethane

Constituent 2

Reference substance name:

tetramethylthiuram disulfide

IUPAC Name:

tetramethylthiuram disulfide

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): thiram technical
- Physical state: fine white powder
- Analytical purity: 99.5%
- Lot/batch No.: M.5.1841; G3380
- Storage condition of test material: room temperature
- Median particle size: 5.61 µm

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:Harlan Sprague-Dawley, Inc. Hoston, Texas, USA
- Age at study initiation: yound adult
- Weight at study initiation: 242-350g (male), 178-219g (female)
- Fasting period before study:no data
- Housing: 1-3 per cage, males separate from females
- Diet (e.g. ad libitum): Purina Formulab Chow #5008 ad libitum
- Water (e.g. ad libitum):tap water ad libitum
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data
Temperature and humidity were recorded at 30 minutes intervals during the exposure period from a Taylor wet hygrometer located in the exposure room.

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

other: dried filtered air

Details on inhalation exposure:

The arerosol was generated by passing a stream of dry, filtered air though either two (for the lower exposure concentration) or four (for the higher exposure concentration) glass flasks containing the test material.The concentrated aerosol was then diluted with dried and filtered air and drawn into the exposure cahmber. Air flow into the chamber was maintained through the use of a calibrated critical orifice. Air flow was recorded at 30 minute intervals during the exposure period. The air flow was sufficient to ensure adequate oxygen content of the exposure atmosphere. Temperature and humidity were recorded at 30 minutes intervals during the exposure period from a Taylor wet hygrometer located in the exposure room.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

determined gravimetrically twice per hour (Anderson cascade impactor)

Duration of exposure:

4 h

Concentrations:

Nominal concentrations: 6.9, 14.1, 32.03 mg/L
Analytical concentrations: 2.06, 3.36, 5.04 mg/L (gravimetric)

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

Observations for mortality and pharmacologic and/or toxicologica effects were made frenquently on the day of exposure and at least one daily thereafter for 14 days (day of exposure considered Day 0). Individual body weights were recorded just prior to the inhalation exposure and on Days 7 and 14 or a time of discovery after death. A gross necropsy examination was conducted on each animal at termination of the study or at the time of discovery after death.

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

4.42 mg/L air (analytical)

Based on:

test mat.

95% CL:

3.09 - 6.32

Exp. duration:

4 h

Remarks on result:

other: LC50 calculated

Effect levels 2

Key result

Sex:

male

Dose descriptor:

LC50

Effect level:

> 5.04 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: One male died at each dose

Effect levels 3

Key result

Sex:

female

Dose descriptor:

LC50

Effect level:

3.464 mg/L air (analytical)

Based on:

test mat.

95% CL:

2.98 - 4.03

Exp. duration:

4 h

Remarks on result:

other: LC50 calculated

Mortality:

2.06 mg/L: one male died, no female died (10%)
3.36 mg/L: one male and two females died (30%)
5.04 mg/L: one male and five females died (60%)

Clinical signs:

other: Clinical signs were observed at all doses. Prominent in-life observations included activity decrease, constricted pupils, gasping, nasal discharge, piloerection, polyurea, ptosis and salivation.

Body weight:

A decrease of body weight was observed.

Gross pathology:

Treatment related gross necropsy findings: lacrimation, nasal discharge, polyuria, salivation, discoloration of the contents of the stomach, stomach distended with gaz, discoloration of lungs and variations thereof.

Other findings:

no

Applicant's summary and conclusion

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute inhalation LC-50 with 95% confidence limits afor actual thiram technical when administered undiluted as an aerosol to abino rats were calculated: the males LC50 was higher than 5.04 mg/L, the female LC50 was equal to 3.46 [2.96 -4.03] mg/L , and the combined LC50 was equal to 4.42 [3.09 -6.32] mg/L.

Executive summary:

An acute inhalation toxicity study was conducted on male and female albino rats using test material thiram technical.

The animals were exposed for 4 hours to an aerosol generated from the undiluted test material (fine powder). Five males and five females were exposed to the following levels: 2.06, 3.36 and 5.04 mg/L. One male exposed to 2.06 mg/L died during the study. One male and two females exposed to 3.36 mg/L doed during the study. One male and five females exposed to 5.04 mg/L died during the study. The acute inhalation LC-50 with 95% confidence limits afor actual thiram technical when administered undiluted as an aerosol to abino rats were calculated: the males LC50 was higher than 5.04 mg/L, the female LC50 was equal to 3.46 [2.96 -4.03] mg/L , and the combined LC50 was equal to 4.42 [3.09 -6.32] mg/L. Prominent in-life observations included activity decrease, constricted pupils, gasping, nasal discharge, piloerection, polyurea, ptosis and salivation. Moreover a decrease of body weight was observed in treated animals. Treatment related gross necropsy findings: lacrimation, nasal discharge, polyuria, salivation, discoloration of the contents of the stomach, stomach distended with gaz, discoloration of lungs and variations thereof.