Iodine

Endpoint summary

Description of key information

Acute oral toxicity: 315 mg/kg (rats)

Acute inhalation toxicity: >4.588 mg/L air (rats)

Acute dermal toxicity: 1425  mg/kg bw (rabbits)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Data waiving:

other justification

Justification for data waiving:

the study does not need to be conducted because a study on acute toxicity by the inhalation route is available

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Remarks:

Handbook data

Qualifier:

no guideline followed

Principles of method if other than guideline:

Handbook data, no info presented

GLP compliance:

not specified

Species:

mouse

Route of administration:

oral: unspecified

Sex:

not specified

Dose descriptor:

LD50

Effect level:

1 425 mg/kg bw

Based on:

element

Conclusions:

The acute oral median lethal dose (LD50) for potassium iodide in mice was 1425 mg iodide /kg bw.

Executive summary:

The acute oral median lethal dose (LD50) for potassium iodide in mice was 1425 mg iodide /kg bw.

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Remarks:

Handbook data

Qualifier:

no guideline followed

Principles of method if other than guideline:

Handbook data, no info presented

GLP compliance:

not specified

Species:

rat

Route of administration:

oral: unspecified

Sex:

not specified

Dose descriptor:

LD50

Effect level:

3 320 mg/kg bw

Based on:

element

Conclusions:

The acute oral median lethal dose (LD50) for potassium iodide in rats was 3320 mg iodide /kg bw.

Executive summary:

The acute oral median lethal dose (LD50) for potassium iodide in rats was 3320 mg iodide /kg bw.

Reference 4

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Remarks:

Data set by U.S. Environmental Protection Agency

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

GLP compliance:

not specified

Specific details on test material used for the study:

Purity: 99.5%

Species:

rat

Route of administration:

oral: unspecified

Sex:

not specified

Dose descriptor:

LD50

Effect level:

315 mg/kg bw

Based on:

test mat.

Conclusions:

LD50 is 315 mg/kg to rats.

Executive summary:

The acute oral LD50 of iodine (99.5% a.i.) is 315 mg/kg to rats.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

315 mg/kg bw

Quality of whole database:

2 (reliable with restrictions)

Acute toxicity: via inhalation route

Link to relevant study records

Reference

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

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

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

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

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.

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.

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).

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

4 588 mg/m³ air

Quality of whole database:

1 (reliable without restriction)

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 2005-11-30 to 2006-01-17

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Version / remarks:

August 1998

Deviations:

yes

Remarks:

4-h systemic observations for the 500 mg/kg dose level were inadvertently not recorded. This did not affect the outcome of the study since the animals appeared normal at the 2-h and day 1 of the observation periods.

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Millbrook Breeding Labs, Amherst, MA
- Age at study initiation: approximately 3 months old
- Weight at study initiation: 2.3-3.3 kg males and 2.7-3.3 kg for females
- Fasting period before study: None
- Housing: 1 animal per cage (suspended wire cages)
- Diet (e.g. ad libitum): Fresh purina Rabbit Chow daily
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): Temperature was controlled, but no data presented
- Humidity (%): No data
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12 h light/dark cycle

Type of coverage:

occlusive

Vehicle:

water

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal area of the trunk
- % coverage: 10% of the body weight
- Type of wrap if used: surgical gauze patch and plastic with non-irritating tape


REMOVAL OF TEST SUBSTANCE
- Washing (if done): gently washing with distilled water
- Time after start of exposure: 24 hours


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): dose level 2000 mg/kg: 5.4-6.6 (g); 1000 mg/kg: 2.3-2.5 (g); 500 mg/kg: 1.35-1.60 (g)
- For solids, paste formed: yes


VEHICLE
- Amount(s) applied (volume or weight with unit): 0.25-1.0 mL

Duration of exposure:

24-h

Doses:

2000, 1000, 500 mg/kg bw

No. of animals per sex per dose:

At 2000 mg/kg bw five males and five females, at 1000 mg/kg bw five males, and at 500 mg/kg bw five males

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Toxicity: 1,2 and 4 hours postdose and once daily for 14 days. Mortality: twice daily for 14 days. Body weights: pretest, weekly and at study/termination.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology, other: dermal irritation

Statistics:

LD50, 95% confidence limits according to Litchfield, J.T., Jr. & Wilcoxon, F. F., JPET 96:99, 1949.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Sex:

male

Dose descriptor:

LD50

Effect level:

1 425 mg/kg bw

95% CL:

> 996 - < 2 038

Mortality:

2000 mg/kg bw: one of five males and three of five females survived
1000 mg/kg bw: four of five males survived
500 mg/kg bw: all five males survived

Clinical signs:

other: 2000 mg/kg bw Predeath: few feces, emaciation, soiling of the anogenital area, lethargy and nose/mouth area stained brown. In the survivors: instances of few faeces and soiling of the anogenital area. 1000 mg/kg bw Predeath: diarrhoea and soiling of the

Gross pathology:

2000 mg/kg bw:
Dead animals: abnormalities of the treated skin, lungs, kidneys, liver, stomach, intestines, peritoneal cavity and spleen. Soiling of the anogenital cavity, emacination, brown staining of the nose/mouth area and excess fluid in the abdominal cavity.
Survivors: abnormalities of the spleen, kidneys, intestines, treated skin, thymus, pancreas and testicle, as well as soiling of the anogenital area.
1000 mg/kg bw:
dead animals: abnormalities of the treated skin, lungs, liver, kidneys, intestines, spleen and stomach, as well as brown staining of the nose/mouth area and soiling of the anogenital area.
Survivors: abnormalities of the treated skin, spleen, kidneys, thymus and pancreas.
500 mg/kg bw
Abnormalities of the treated skin, pancreas, thymus and spleen.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Under testing conditions, the dermal LD50 of iodine in male rabbits is 1425 mg/kg bw. It appeared that females are not markedly more sensitive to the substance and the LD50 in females is greater than 2000 mg/kg bw.

Executive summary:

To determine the potential for toxicity of iodine when applied dermally, the substance was tested following set forth in US EPA Health Effects Testing Guidelines, OPPTS 870.1200, final guideline, August 1998.

Five healthy male and healthy female New Zealand White rabbits were dosed dermally with iodine at 2000 mg/kg bw. Since compound related mortality occurred at this level, five additional males were dosed at 1000 mg/kg bw and five males were dosed at 500 mg/kg bw. The test article was kept in contact with the skin for 24 h. Animals were observed for toxicity and mortality at 1, 2 and 4 hours postdose and daily for 14 days. Body weights and gross pathology were examined in all animals.

The dermal LD50 and 95% confidence limits of iodine in male rabbits is 1425 (996 -2038) mg/kg bw. It appeared that females are not markedly more sensitive to the substance and the LD50 in females is greater than 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 425 mg/kg bw

Quality of whole database:

2 (reliable with restrictions)

Additional information

Iodine is classified under Regulation (EC) 1272/2008 (Annex VI Table 3.2.) as Acute Tox. 4 (H332, H312).

Tests results are in line with the current classification of the substance, although in the case of acute inhalation toxicity, the LC₅₀ is expected to be slightly over the threshold. Based of the fact that 30% of animals died at the maximum achievable concentration, the result is considered as a borderline case. However, after taking into account the current harmonized classification the LC₅₀ is set at 4.588 mg/L air.

Two authority reviews have published values for the acute oral toxicity of iodine:

- 315 mg/kg (rats) by the United States Environmental Protection Agency, and

- 1840 mg/kg (rats) by the United Nations.

As this information has come from recognised reliable sources, the primary information sources cited have not been revisited as suggested in the Guidance for the implementation of REACH- Guidance on information requirements and chemical safety assessment: Chapter R3: Information gathering. Furthermore, in accordance with Column 2 of REACH Annex VII, study for acute oral toxicity need not be conducted if an acute toxicity study by the inhalation route is available.

Based on the most conservative value, for classification and labelling purposes, the acute oral toxicity of iodine is set at 315 mg/kg.

References:

- United Nations. 2008. Committee of experts on the transport of dangerous goods and on the globally harmonized system of classification and labelling of chemicals. Sub-committee of experts on the transport of dangerous goods. Thirty-third session. Geneva, 30 June-9July 2008. Item 4 of the provisional agenda. Listing, classification and packing. New entry for iodine, raw in class 8. Submitted by the expert from Germany.

- United States Environmental Protection Agency. 2006. Reregistration eligibility decision for iodine and iodophor complexes.

Justification for classification or non-classification

Iodine has a harmonized EC classification under CLP Regulation 1272/2008. The acute oral toxicity of iodine (in rats) is set at 315 mg/kg.