Iodine

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 2008-08-31 to 2008-09-14

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

May 1981

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Certificate attached

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Iodine

EC Number:

231-442-4

EC Name:

Iodine

Cas Number:

7553-56-2

Molecular formula:

I2

IUPAC Name:

iodine

Specific details on test material used for the study:

Analysed Purity : 99.8%
Batch NO.: 182670986
Appearance/Colour/Odour : Prills, bluish-black with metallic luster coloured with pungent odour

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Animal Breeding Facility, Jai Research Foundation
- Age at study initiation: 10-11 weeks
- Weight at study initiation: Male 255-282 g, females 195-218 g.
- Fasting period before study: No
- Housing: Groups of five animals were housed in polypropylene rat cages each fitted with a stainless steel grid on top.
- Diet (e.g. ad libitum): ad libitum, except during exposure
- Water (e.g. ad libitum): ad libitum, except during exposure
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-23 °C
- Humidity (%): 64-66
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours darkness

Administration / exposure

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose/head only

Vehicle:

other: DMSO

Mass median aerodynamic diameter (MMAD):

3.58 µm

Geometric standard deviation (GSD):

3.15

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Inhalation equipment head/nose only exposure supplied by BIO-TOX Instrumentation International, New Delhi, India.
- Exposure chamber volume: 63.5 L
- Method of holding animals in test chamber: Exposure unit with port-holes to accommodate transparent rat exposure tubes
- Source and rate of air: Filtered air, 12-15 air changes per hour
- Method of conditioning air: Filter
- System of generating particulates/aerosols: Spray atomizer
- Method of particle size determination: Seven stage cascade impactor (Model No 02-150)
- Treatment of exhaust air: 1% sodium hydroxide solution, and moisture traps containing silica gel.
- Temperature, humidity, pressure in air chamber: 20.2-23.1 (°C), 43.7-50.5 (% RH), slight negative pressure


TEST ATMOSPHERE
- Brief description of analytical method used: Gravimetric concentration analysis. A suitable measured volume of air was drawn from the inhalation chamber at the level of the breathing zone at every one hour of exposure after equilibration of the chamber for 30 minutes). At the end of air sampling, glass microfibre papers with the test substance were weighed to determine the concentration of iodine aerosols.
- Samples taken from breathing zone: yes


VEHICLE
- Composition of vehicle (if applicable): dimethyl sulphoxide
- Concentration of test material in vehicle (if applicable): Stock solution 500 mg/L

TEST ATMOSPHERE
- Particle size distribution: See table 1
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): MMAD 3.58 µm, GSD 3.15

Analytical verification of test atmosphere concentrations:

yes

Remarks:

gravimetric analysis

Duration of exposure:

4 h

Concentrations:

4.588 mg/L and control

No. of animals per sex per dose:

5 males and 5 females in tested dose and control group

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Hourly intervals during the 4 h exposure period and at 1 h after the exposure on the day of exposure. Subsequently, twice a day for morbidity and mortality for a period of 14 days following exposure. Body weights recorded prior to exposure on day 0, day 7, 14 and at death.
- Necropsy of survivors performed: yes

Statistics:

As this study was conducted as a limit test, no statistical analyses was required. Body weight data was statistically analysed following Student's 't' test.

Results and discussion

Preliminary study:

A dose range finding study for test item was performed using four rats (2 males and 2 females) per group at the nominal concentration of 11.111 and 22.222 mg/L air and breathing zone concentration determined 2.626 and 4.629 mg/L air, respectively. 0 and 25% morality was observed in rats treated with 2.626 and 4.629 mg/L air respectively. As only 25% mortality was observed at maximum attainable concentration (4.629 mg/L air) hence, the main study was conducted as limit study at the nominal concentration of 22.222 mg/L air for group II.

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 4.588 mg/L air (analytical)

Exp. duration:

4 h

Remarks on result:

other: Maximum achievable concentration

Mortality:

3 rats from group II (1 male and 2 female died between day 1 and 3 post exposure). No mortality occurred in control group.

Clinical signs:

other: Toxic signs like lethargy, abdominal breathing, nasal discharge and nasal irritation were observed in the treatment group rats. The above symptoms were observed from 4 h during exposure and the surviving rats appeared normal from day 5 post exposure until

Body weight:

At the end of the observation period the mean weight of surviving rats belonging to the treatment group were comparable to that of the control group rats.

Gross pathology:

External examination of found dead and terminally sacrificed rats did not reveal any lesion of pathological significance. Visceral examination of the found dead rats from the treatment group revealed varying degree of lesions like lung congestion, lung haemorrhage. Terminally sacrificed rats belonging to both control and the treatment group did not reveal any lesion of pathological significance except, uterus distended (not correlated with the test substance).

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Remarks:

Migrated information

Conclusions:

Under testing conditions, the acute median lethal concentration (LC50) of test item was found to be greater than 4.588 mg /L air in Wistar rats.

Executive summary:

The study was performed to assess the acute inhalation toxicity (LC50) of test item in Wistar rats. The method followed was as per the Guideline of OECD No 403 (May 1981).

Based on the results obtained from the range finding study, two groups of rats, each consisting of five male and five females rats were used for the main study. Rats from group I were exposed to aerosols of dimethyl sulphoxide only and served as the control group. Rats from group II were exposed to breathing zone concentration of 4.588 mg/L of air. Rats from both groups were exposed for 4 hours followed by observation for a period of 14 days. No toxic sign and no mortality were observed in the rats of the control group (group I), whereas toxic signs like lethargy, abdominal breathing, nasal discharge and nasal irritation were observed in the treatment group rats. Percent mortality observed (both the sexes combined) was 30% at the maximum attainable breathing zone concentration of 4.588 mg/L of air. The incidence and severity of vascular changes observed in found dead rats of the treatment group could be correlated with treatment.

As 30% mortality was observed in the treatment group at the maximum achievable breathing zone concentration (4.588 mg/L air) of test item in present study, the acute median lethal concentration (LC50) of test item was found to be greater than 4.588 mg/L air.