Ziram

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

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 81-3 (Acute inhalation toxicity)

Version / remarks:

not specified

Deviations:

not specified

GLP compliance:

yes

Test type:

traditional 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, Portage, USA
- Age at study initiation: 6 - 8 weeks
- Weight at study initiation: approximately 200 g
- Housing: Animals were housed in groups of 5 per sex in polypropylene cages.
- Diet: Rodent standard diet (Biosure LAD 1), ad libitum
- Water: Tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 — 24 °C, except on 3 occasions when temperatures of 17 °to 17.5 °C were recorded
- Humidity (%): 28 - 65
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

inhalation: dust

Type of inhalation exposure:

whole body

Vehicle:

air

Mass median aerodynamic diameter (MMAD):

>= 1.3 - <= 2.7 µm

Geometric standard deviation (GSD):

>= 2.01 - <= 4.3

Remark on MMAD/GSD:

For detail on MMAD, please refer to Table 1 under "Any other information on results incl. tables".

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: The whole-body exposure chambers used were of square section and were fitted with pyramidal tops. The chambers were made of perspex.
- Exposure chamber volume: 120 L
- Method of holding animals in test chamber: For exposure, the rats were held in cages of stainless steel mesh partitioned to provide 10 individual animal compartments.
- Source and rate of air (airflow): clean, dried, compressed air; flow rate of 25 L/min
- System of generating particulates/aerosols: A Wright dust generator was used to produce a test atmosphere containing the test substance. For all test groups the test atmosphere produced by the generator was passed through a glass elutriation column to reduce, by sedimentation, the amount of non-respirable particulate in the test atmosphere.
- Method of particle size determination: The particle size was determined by using an Andersen mini sampler. The collected material was weighed to determine the particle size distribution.
- Temperature, humidity: 22.0 - 24.3 °C, 41 - 57%

TEST ATMOSPHERE
- Brief description of analytical method and equipment used: Five air samples, of 2.5 - 5 min duration, were taken from the chamber during each exposure. The samples were taken from a port in the wall of the chamber at the same level as, and near to, the breathing zone of the rats. Each air sample was withdrawn, at 4 L/min, through a weighed glass fibre filter mounted in an open-face filter holder. The volume of each air sample was measured with a wet-type gas meter.
- Time needed for equilibrium of exposure concentration before animal exposure : 11 min

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

0.020, 0.029, 0.047, 0.098 and 0.145 mg/L air

No. of animals per sex per dose:

5/sex/dose

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All rats were observed continuously for signs of reaction to the test substance during exposure and at least twice daily throughout the observation period. All rats were weighed daily from the day of delivery until the end of the observation period.
- Necropsy of survivors performed: At the end of the 14-day observation period, the surviving rats were anaesthetised by intraperitoneal injection of pentobarbitone sodium and killed by exsanguination. All rats were subjected to a detailed macroscopic examination. The lungs were removed, dissected clear of surrounding tissue and weighed in order to calculate the lung weight to body weight ratio. The lungs were infused with, and preserved in, buffered 10% formalin together with samples of the liver and kidneys for possible macroscopic examination.
- Other examinations performed: The amount of food and water consumed by each cage of rats was measured daily from the day following arrival. The daily mean intakes of food and water for each rat were calculated from the recorded data.

Statistics:

Data were analysed statistically by the log probit method.

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male

Dose descriptor:

LC50

Effect level:

0.08 mg/L air

Based on:

test mat.

Remarks:

corresponding to 6.72 mg/kg bw

95% CL:

>= 0.052 - <= 0.828

Exp. duration:

4 h

Remarks on result:

other: corresponding to 6.72 mg/kg bw

Effect levels 2

Key result

Sex:

female

Dose descriptor:

LC50

Effect level:

0.06 mg/L air

Based on:

test mat.

Remarks:

corresponding to 5.04 mg/kg bw

95% CL:

>= 0.043 - <= 0.077

Exp. duration:

4 h

Remarks on result:

other: corresponding to 5.04 mg/kg bw

Effect levels 3

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

0.07 mg/L air

Based on:

test mat.

95% CL:

>= 0.059 - <= 0.081

Exp. duration:

4 h

Remarks on result:

other: corresponding to 5.88 mg/kg bw

Mortality:

0.020 mg/L: 0/5 males and 0/5 females
0.029 mg/L: 0/5 males and 0/5 females
0.047 mg/L: 0/5 males and 4/5 females
0.098 mg/L: 2/5 males and 4/5 females
0.145 mg/L: 5/5 males and 4/5 females

Clinical signs:

other: during exposure: partial closing of the eyes, irregular respiration rate, sallivation, pilo-erection and reduced activity; during observation period: abnormal respiration, a dark appearance of the eyes, lethargy and death (surviving animals recovered)

Body weight:

There were moderate to marked decreases of body weight or reductions in the rate of body weight gain for up to 2 days following exposure in all dose groups. Subsequently, weight gain for rats that survived exposure to the test material was similar to that of the control rats.

Gross pathology:

There were no macroscopic abnormalities in the control animals and in the rats that survived exposure to the test substance.
In the animals that died during the study, the ratio of lung to body weight was increased. In addition, the lungs of the majority of the rats that died were congested. A frothy fluid in the trachea, occasional swollen appearance of the lungs and gas-filled stomachs were found in a proportion of the desendentrats.

Any other information on results incl. tables

Table 1: Summary of chamber atmosphere conditions

Group	Meana chieved concentration of the test substance [mg/L air]		Particle size
	Mean	Variation [%]	MMAD [µm]	SD	≤5.5 µm [%]
Control	-	-	-	-	-
Treatment groups	0.020	45	2.7*	2.01	82.7
	0.029	66	1.8	3.43	83.7
	0.047	36	1.3	3.22	92.7
	0.098	26	1.4	3.02	90.6
	0.145	79	2.3	4.30	76.4

MMAD:Mass median aerodynamic diameter
SD: Geometric standard deviation
* In view of the small amount of material collected in the sample for this group, the calculated MMAD and SD should be interpreted with caution. The fact that there was no measureable amount collected on the filter will have caused the calculated MMAD to be larger than the true value.

Food consumption

Food consumption was reduced for up to 2 days following exposure to the test material.

 

Water consumption
Water consumption was reduced for up to 2 days following exposure. There were some instances of high water consumption during the observation period for female rats exposed to the test substance.

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 2 (H330) is warranted.

Conclusions:

The study was performed according to EPA OPP 81-3 (acute inhalation toxicity) and GLP. In this test, five male and female rats were exposed (whole-body) to the test substance at exposure levels of 0.020, 0.029, 0.047, 0.098 and 0.145 mg/L of air for 4 h. Under the conditions of the test, the acute inhalation LC50 value was determined to be 0.08 mg/L air for male and 0.06 mg/L air for female rats. According to criteria of the CLP Regulation (EU) No. 1272/2008, classification of the test item for acute inhalation toxicity category 2 (H330) is warranted.