Thiophanate-methyl

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

30 September 1986 - 04 March 1987

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1987

Report date:

1987

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

yes

Test type:

traditional method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Thiophanate-methyl

EC Number:

245-740-7

EC Name:

Thiophanate-methyl

Cas Number:

23564-05-8

Molecular formula:

C12H14N4O4S2

IUPAC Name:

methyl N-{[2-({[(methoxycarbonyl)amino]methanethioyl}amino)phenyl]carbamothioyl}carbamate

Test material form:

solid: particulate/powder

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Japan, Inc. (Atsugi, Kanagawa, Japan)
- Age at study initiation: 7 weeks old
- Weight at study initiation: males: 183 ± 5 g, females: 146 ± 8 g (at the start of the experiment)
- Housing: Group-housed (5 animals per cage) in stainless steel mesh cage (34 x 34 x 21 cm), which was placed for 4 hours in whole-body exposure chambers.
- Diet: standardised pelleted dry diet, MF (Oriental Yeast Co., Ltd.), ad libitum; no food during exposure
- Water: tap water ad libitum; no water during exposure
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24.5 - 25.7
- Humidity (%): 51 - 85.9
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:

inhalation: dust

Type of inhalation exposure:

whole body

Vehicle:

clean air

Mass median aerodynamic diameter (MMAD):

>= 3.7 - <= 4.5 µm

Geometric standard deviation (GSD):

>= 0.2 - <= 0.9

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: inhalation apparatus with pre-filter and dust generator
- Exposure chamber volume: 590 L
- Method of holding animals in test chamber: whole body exposure, cages were placed in the exposure camber for 4 hours
- Source and rate of air: 127 - 130 L/min
- System of generating particulates/aerosols: dust generator
- Method of particle size determination: Measurements of particle size of dust were carried out twice an hour during exposure. The constant volume (28 - 84 L) of dust was taken from the sample port of the chamber and led to Andersen Sampler (Dylec Co., Ltd.). The particles of each size were caught on each filter paper in the sampler. The actual concentration was determined by means of weighing the papers with the particles of each size range.
- Treatment of exhaust air: exhaust air was taken out from the bottom of the exposure chamber and discarded through shower cleaner and filters
- Temperature, humidity, pressure in air chamber: temperature: 24.5 - 25.7 °C, humidity: 51.1 - 85.9%,

TEST ATMOSPHERE
- Brief description of analytical method used: Measurements of actual concentration of dust were carried out twice an hour during exposure. The constant volume (28 - 84 L) of dust was taken from the sample port of the chamber and led to Andersen Sampler (Dylec Co., Ltd.). The particles of each size were caught on each filter paper in the sampler. The particle size distribution was determined by means of weighing the papers with the particles of each size range.
- Samples taken from breathing zone: no

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

nominal concentrations: 1.9, 3.8, 5.6, 7.6 and 9.4 mg/L
acutal concentrations: 0.5, 1.0, 1.5, 1.6 and 1.9 mg/L

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations: 1 hour and 3 hours after exposure, and at least once a day for 14 days thereafter; weighing: prior to exposure and on the 1st, 2nd, 3rd, 7th and 14th days of the observation period
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male

Dose descriptor:

LC50

Effect level:

1.7 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Effect levels 2

Key result

Sex:

female

Dose descriptor:

LC50

Effect level:

1.9 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

No deaths occurred in the control and the lower dosed groups (0, 0.5, 1.0 and 1.5 mg/L) in males. In females no deaths occurred in the control and the 0.5, 1.5 and 1.6 mg/L groups . In males, all animals of the 1.9 mg/L group died at the 1st day (One rat died during the exposure). In females, death occurred at the 1st and 2nd days in the 1.0 and 1.9 mg/L groups. Mortalities in the male groups of 1.0, 1.5, 1.6 and 1.9 mg/L were 0, 0, 0 and 100%, respectively, and those in the female groups of 0.5, 1.0, 1.5, 1.6 and 1.9 mg/1 were 0, 20, 0, 0 and 60%, respectively.

Clinical signs:

other: No toxic signs appeared in the control groups in either sex. Decreased motor activity, low sensitivity, hypotonia, ventral position, incontinence of urine, ataxia, ptosis, tremor and convulsion were observed in the dosed groups.

Remarks:

These toxic signs appeared within 1 day after the exposure. However, all toxic signs disappeared within 3 days after the exposure.

Body weight:

Body weight decrease and growth depression were observed in almost all female rats of all dosed groups and male rats in the 1.5 and 1.6 mg/L groups within 3 days after the exposure, however, their body weights increased thereafter. Net gains in treated animals were less than gains recorded in control animals.

Gross pathology:

In the gross necropsy, dark reddish lung was found in one dead rat. But, there were no significant changes in the other rats which died or survived until the termination of the observation period.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The LC50 value of the test item was determined to be 1.7 mg/L for males and 1.9 mg/L for females.

Executive summary:

An acute inhalation toxicity study was performed in male and female Crj:CD(SD) rats. The animal were divided into 9 dosed and 2 control groups, each group consisted of 5 rats, and the former groups were exposed to the test item and the latter to air only for 4 hours. The mean actual concentrations of the test item were 1.9, 1.6, 1.5 and 1.0 mg/L in males and females. The particle size of the test item was almost identical among the dosed groups (mean mass median diameters were 3.7 - 4.5 µm and most of the particles were smaller than 10 µm in diameter). The toxic signs observed in the rats exposed to the test item were decreased motor activity, low sensitivity, ataxia, ptosis, incontinence of urine, tremor, convulsion, hypotonia and ventral position. Body weight decrease and growth depression were observed for 1 - 3 days after the exposure in many rats of the dosed groups, however, their body weights increased thereafter. The mortalities in the 1.9, 1.6, 1.5 and 1.0 mg/L groups of males were 100, 0, 0 and 0% and those in the 1.9, 1.6, 1.5, 1.0 and 0.5 mg/L groups of females were 60, 0, 0, 20 and 0%. Dark reddish lung was found in one dead rat. The LC50 value of the test item was determined to be 1.7 mg/L for males and 1.9 mg/L for females.