Ziram

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

until 10 Mar 1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EPA OPP 81-1 (Acute Oral Toxicity)

Version / remarks:

not specified

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Ziram

EC Number:

205-288-3

EC Name:

Ziram

Cas Number:

137-30-4

Molecular formula:

C6H12N2S4Zn

IUPAC Name:

ziram

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, France
- Age at study initiation: 4 - 6 weeks
- Weight at study initiation: 142 - 158 g
- Fasting period before study: Rats were fasted the night before dosing.
- Housing: Five rats per cage of similar sex were housed in metal cages with wire mesh floors.
- Diet: Standard laboratory rodent diet (Biosure LAD 1), ad libitum
- Water: Tap water, ad libitum
- Acclimation period: 15 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 - 24
- Humidity (%): 62
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 1% w/v

MAXIMUM DOSE VOLUME APPLIED: 20.0 mL/kg bw

DOSAGE PREPARATION:
Rats were dosed via gavage. Individual doses were calculated based on the animal’s body weight recorded just prior to dosing at a dose volume of 20 mL/kg bw. Rats were fasted the night before dosing and approximately 4 h after dosing.

CLASS METHOD
- Rationale for the selection of the starting dose: A trial test was carried out to establish a dosing regimen for the main study. Groups of 2 male and female rats were orally dosed at 200 and 800 mg/kg bw.

Doses:

250, 400, 640 mg/kg bw

No. of animals per sex per dose:

5/sex/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All animals were observed for mortality, general condition and clinical signs (time, onset, severity and recovery) soon after dosing and at frequent intervals for the remainder of Day 1 (a period of 6 h) and two times a day on subsequent days for 14 days. Individual body weights were recorded prior to dosing (Day 1), on Day 8 and the day of necropsy.
(Day 15 or day of death).
- Necropsy of survivors performed: On Day 15, all surviving animals were euthanised by cervical dislocation. Gross pathological examinations, including external examination and opening of the abdominal and thoracic cavities, were conducted on all animals in the study.

Statistics:

The acute median lethal oral dose (LD50) to male and female rats was calculated using probit analysis.

Results and discussion

Preliminary study:

The results of the preliminary study indicated that the acute medium lethal oral dose to male rats for the test substance was approximately 800 mg/kg bw and for females between 200 and 800 mg/kg bw. Therefore, in the main study oral doses of 250, 400 and 640 mg/kg bw were used.

Effect levels

Effect levels 1

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

267 mg/kg bw

Based on:

test mat.

95% CL:

113 - 393

Effect levels 2

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

381 mg/kg bw

Based on:

test mat.

95% CL:

227 - 594

Effect levels 3

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

320 mg/kg bw

Based on:

test mat.

95% CL:

176 - 422

Mortality:

There were deaths amongst males and females dosed at all dose levels. Deaths occurred from Day 2 to Day 3.
250 mg/kg bw: 1 male and 2 females
400 mg/kg bw: 3 males and 4 females
640 mg/kg bw: 4 males and 5 females

Clinical signs:

other: pilo-erection, abnormal body carriage (hunched posture), abnormal gait (waddling), lethargy, decreased respiratory rate, ptosis, pallor of the extremities and diarrhoea

Body weight:

other body weight observations

Remarks:

Slightly low body weight gains were recorded for one male and one female dosed at 250 mg/kg bw and one male dosed at 640 mg/kg bw on Day 8. All other rats achieved anticipated body weight gains throughout the study.

Gross pathology:

Autopsy of rats revealed no macroscopic abnormalities.

Applicant's summary and conclusion

Interpretation of results:

other: According to the classification criteria of the CLP Regulation (EU) No. 1272/2008, classification for acute oral toxicity Category 3 (H301) is warranted.

Conclusions:

The GLP-compliant study was performed in accordance with EPA OPP 81-1. The test substance was administered by gavage to CD rats at dose levels of 250, 400 and 640 mg/kg bw. Under the conditions chosen, the acute oral LD50 value was determined to be 381 mg/kg bw for male and 267 mg/kg bw for female rats. According to criteria of the CLP Regulation (EU) No. 1272/2 008, classification of the test substance for acute oral toxicity category 3 (H301) is warranted.