mancozeb (ISO); manganese ethylenebis(dithiocarbamate) (polymeric) complex with zinc salt  

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1997-10-23 to 1997-11-07

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1997

Report date:

1997

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

12th May 1981

GLP compliance:

yes (incl. QA statement)

Test type:

traditional method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Complexation products of manganese and zinc with ethylenebis(dithiocarbamate)

EC Number:

616-995-5

Cas Number:

8018-01-7

Molecular formula:

(x+y)[C4H6N2S4]2- + xMn2+ + yZn2+, x:y ranges between 1:0.062 to 1:0.12 (mean 1:0.091)

IUPAC Name:

Complexation products of manganese and zinc with ethylenebis(dithiocarbamate)

Test material form:

solid: particulate/powder

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Breeding facility, Jai Research Foundation, India
- Weight at study initiation: 112.0 g - 148.0 g
- Housing: Group-housed (5 animals of same sex per cage) in solid floor polypropylene rat cage with clean paddy husk bedding
- Diet: Rat pellet feed (Amrut brand) ad libitum (MF: Nav Maharashtra Chakan Oil Mills Limited, 43, Shaniwar Peth, Pune-411 030, Maharashtra, India)
- Water: Pure drinking water filtered through Aquaguard water filter system ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): between 21 ± 1.38 and 24 ± 1.38
- Humidity (%): 66 ± 5.44
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

other: inhalation: dust aerosol

Type of inhalation exposure:

head only

Vehicle:

air

Remark on MMAD/GSD:

The size of generated respirable particle was found in between 6 to 10 microns because 94.90% of the particles were collected at the Effective Cut-off Diameter (particle size 6 to 10 microns) . Therefore the particle size distribution curve was not plotted and the mass median aerodynamic diameter could not be evaluated.

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Dynamic inhalation equipment consisting of an inhalation chamber, air compressor, gas flow meter, dust generator system, rotameter, Andersen personal cascade impactor, Humitherm, Oxygen monitor and rat confinement cages.
- Exposure chamber volume:
Dynamic inhalation equipment: 3 main parts: inlet, exposure and outlet chambers. Each part is 30 cm in height and 30 cm in internal diameter. The total capacity of the chamber is 63.5 L
- Method of holding animals in test chamber: in rat confinement cages accommodated in the port-holes of the inhalation chamber.
- Source and rate of air (airflow): air inflow rate: 20 L/min and outflow rate 21.04 L/min
- Method of conditioning air:
- System of generating particulates/aerosols:
The test item was used as such and loaded into powder filling funnel once every 30 minutes during the exposure period. The regulated quantity of the test item fell on the vibrating funnel through the rotary wheel feeder which in turn filled uniform cavities (holes) on the circular rotating dosage disc. The test item from the cavities was sucked with the help of compressed air venturi dust aerosol ejector and aerosolised. The test item dust aerosol thus generated was directed into the nose only inhalation exposure chamber with the conducting pipe. Uniform distribution of the test item aerosol inside the inhalation chamber was ensured with help of placing a baffle plate at the end of conducting pipe.
- Method of particle size determination: by using Andersen Personal Cascade Impactor (6 stage)
- Temperature, humidity, oxygen concentration in air chamber: The mean chamber temperature and relative humidity during the exposure were 24 ± 0.95°C and 65.6 ± 7.80%, respectively. The mean chamber oxygen concentration was 20.9 ± 0.08%.

TEST ATMOSPHERE
A known quantity of the test item was used as such and loaded in to powder filling funnel. The nominal concentration of the test item was calculated using the following formula:

N.C = (Test substance carrying capacity of dosage disc (mg) / Air flow rate through dust generator venturi (L)) x ( r.p.m of dosage disc) = mg/L air

The test substance carrying capacity of dosage disc was found to be 471.5 mg at 1 revolution per minute (r.p.m) of the dosage disc. The the test item was evaluated at the nominal concentration of 23.57 mg/L air. To measure the breathing zone concentration, a measured volume of air was drawn from the inhalation chamber at the level of breathing zone every one hour of exposure and determined by the gravimetric method.

- Time needed for equilibrium of exposure concentration before animal exposure : 10 min


TEST ATMOSPHERE
The size of generated respirable particle was found in between 6 to 10 microns because 94.90% of the particles were collected at the Effective Cut-off Diameter (particle size 6 to 10 microns). Therefore the particle size distribution curve was not plotted and the mass median aerodynamic diameter could not be evaluated.

Analytical verification of test atmosphere concentrations:

no

Duration of exposure:

4 h

Concentrations:

0 and 1.766 mg/L air

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: The toxicity symptoms and mortality were observed at 1, 2, 3 and 4 h during exposure and once daily up to 14 days from the day of the exposure. Individual body weights were recorded prior to dosing and on day 7 and 14.
- Necropsy of survivors performed: yes
- Clinical signs including body weight : The toxic symptom observed in the treated group during exposure was abdominal breathing and nasal irritation in treated group only. The animals in both treated and control groups showed a gain in body weight during the study.
- Other examinations performed: clinical signs, body weight

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 1.766 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

There was no mortality in any group.

Clinical signs:

other: abdominal breathing and nasal irritation in treated group

Body weight:

The animals in both treated and control groups showed a gain in body weight during the study.

Gross pathology:

At the end of the experimental period the animals from the control and treated groups were sacrificed by cervical dislocation and subjected to thorough necropsy examination.
External examination of carcasses of both control and treated groups did not reveal any external findings of significance.
In control group, vascular pathology in lung revealed focal emphysema (1 male), mild congestion (1 female) and necrotic patches (1 female) while kidney revealed mild paleness in one male animal.
In treated group, lung revealed emphysema in six animal (3 male + 3 female), haemorrhages in 3 animals (2 male + 1 female). Liver showed congestion in 2 female animals. The vascular pathology in kidney showed cystic foci. Whereas, adrenal in two animals (1 male + 1 female) revealed slightly hyperaemia.
In sum, it may be concluded that the lesions recorded in lung and kidney of control group were having mild intensity of toxic effect and.it may considered as incidental. Whereas, in treated group, vascular lesions met in lung, liver, kidney and adrenal showed effect of the toxic substance by inhalation route as evidenced by the result of this study.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute inhalation toxicity (LC50) value to rat was found to be more than the maximum achieved concentration of the test item dust aerosol viz.,1.766 mg/L of air at breathing zone.

Executive summary:

This study was undertaken to assess the acute inhalation toxicity (LC50) of the test item to rat. The method followed was as per the guidelines of Organization for Economic Co-operation and Development (OECD) for testing of chemicals No. 403 (adopted 12th May 1981) "Acute Inhalation Toxicity".

This study was carried out using inhalation equipment (head only exposure) supplied by Bio-Tox Instrumentations International, New Delhi, India. Two groups of rats each comprising 5 males and 5 females were taken up for the study. One group was exposed to the maximum achieved concentration the test item dust aerosol viz., 1.766 mg/L of air and another control group was exposed to only compressed air without test item dust for a duration of 4 h continuously and observed for 14 days. No mortality was observed in both the groups. The surviving animals were subjected to necropsy 14 days after the exposure. Animals sacrificed at termination of the study revealed mild toxicity by inhalation route at the concentration level tested.

The acute inhalation toxicity (LC50) value to rat was found to be more than the maximum achieved concentration of the test item dust aerosol viz., 1.766 mg/L of air at breathing zone.