Iodine

Acute Toxicity: dermal

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Materials and methods

Test guideline

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

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

Details on test material:

- Name of test material (as cited in study report): Iodine
- Substance type: Iodine ACS/USP/BP grade
- Physical state: Solid, grey balls
- Analytical purity: over 99%
- Impurities (identity and concentrations): Inorganic salts, none relevant
- Composition of test material, percentage of components: over 99%
- Isomers composition: Not applicable
- Purity test date: Not available
- Lot/batch No.: #22682
- Expiration date of the lot/batch: Not applicable
- Stability under test conditions: Stable
- Storage condition of test material: Room temperature and humidity
- Other:

Test animals

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

Administration / exposure

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.

Results and discussion

Effect levels

Effect levels 1

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Effect levels 2

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.

Applicant's summary and conclusion

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.