Registration Dossier

Skin Irritation:

The target chemical can be considered to be irritating to skin and it can be further classified under the category “Category 2” as per CLP regulation.

Eye Irritation:

The target chemical was considered to be irritating to eyes and it can be further classified under the category “Category 2” as per CLP regulation.

Reference

Endpoint:

skin irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Remarks:

Experimental data from various test chemicals

Justification for type of information:

Data for the target chemical is summarized based on data from various test chemicals

Reason / purpose for cross-reference:

read-across: supporting information

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

according to guideline

Guideline:

other: Refer below principle

Principles of method if other than guideline:

WoE for the target chemical is summarized based on data from various test chemicals

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material: Ammonium iodide
- IUPAC name: Ammonium iodide
- Molecular formula: H4IN
- Molecular weight: 144.939 g/mole
- Smiles Notation : [NH4+].[IH-]
- InChl: 1S/HI.H3N/h1H;1H3
- Substance type: Inorganic
- Physical state: Solid crystalline powder (colorless to white)

Species:

rabbit

Strain:

other: 2. New Zealand White 3. No data

Details on test animals or test system and environmental conditions:

2. Details on test animal
TEST ANIMALS
- Source: Rich-Glo-farms (U.S.D.A. 74-AA-29), El Campo, Texas
- Housing: The animals were housed in galvanized steel cages placed over trays lined with aspen bedding.
- Diet: Purena Complete Rabbit Chow, Lot #197C , ad libitum
- Water: City of Houston Tap Water, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 72 - 76 degree F
- Humidity (%): Relative humidity from 40 to 60 %.
- Air changes (per hr): air conditioned rooms

Type of coverage:

occlusive

Preparation of test site:

clipped

Remarks:

intact, abraded

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

2. 0.5 gram of crystalline test chemical
3. 500 mg

Duration of treatment / exposure:

2/3. 24 hours

Observation period:

2. 48, 72 and 96 hours
3. 24 hours

Number of animals:

2. 6
3. No data

Details on study design:

2. TEST SITE
- Area of exposure: intact and abraded back skin
- % coverage: double layered 1 square inch gauze pad
- Type of wrap if used: polyethylene wrapper was placed over the bandages and wound around the t runk. The wrapper was secured with masking tape.

SCORING SYSTEM: The skin reactions were scored according to the method of Draize.

3. No data

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

24 h

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Remarks:

2 / 3

Irritant / corrosive response data:

2. Abraded(12tests) : Score(2)X7,(3)X5 /0 /0
Unabraded(12tests): Score(2)X7,(3)X5 /0 /0
The test chemical was moderately irritant to skin.

3. Signs of irritation observed

2. The backs of 6 rabbits were clipped free of hair in an area of about 15 X 12 square cm. The backs of the animals were divided into quadrants. The animals were abraded in a 2 square mm cross-hatch pattern on the tattoo side by drawing a lancet across the skin, being careful not to penetrate the dermis. Two-one square inch areas on each rabbit were tested. Two unabraded additional 1 square inch sites on each rabbit were also tested.The animals were placed in a restraining box and replaced in their individual cages. Water was available to the animals during the test. After 24 hours the animals were released from their restraints and the bandages were removed. All bandages were stuck to the skin by the test materials but peeled away with no skin removed. The remaining test materials was brushed of the skin but was not otherwise removed.

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

The test chemical induced irritation on the skin of rabbits and hence it is likely to classify as "Skin irritant Category 2"

Executive summary:

Data available for the various test chemicals was reviewed to determine the toxic nature of the test chemical. The studies are as mentioned below:

The dermal irritation potential of the test chemical was assessed in rabbits according to Federal Register, vol.43, no 163-Tuesday, Aug.22, 1978 Guidelines. 6 New Zealand White rabbits were used for the study. The backs of 6 rabbits were clipped free of hair in an area of about 15 X 12 square cm. The backs of the animals were divided into quadrants. The animals were abraded in a 2 square mm cross-hatch pattern on the tattoo side by drawing a lancet across the skin, being careful not to penetrate the dermis. Two-one square inch areas on each rabbit were tested. Two unabraded additional 1 square inch sites on each rabbit were also tested. 0.5 gram of crystalline test chemical were placed in a double layered 1 square inch gauze pad and affixed to the four test sites on each animal with adhesive tape. The gauze was moistened with about 1 mL of distilled-deionized water and a polyethylene wrapper was placed over the bandages and wound around the trunk. The wrapper was secured with masking tape.The animals were placed in a restraining box and replaced in their individual cages. Water was available to the animals during the test. After 24 hours the animals were released from their restraints and the bandages were removed. All bandages were stuck to the skin by the test materials but peeled away with no skin removed. The remaining test materials was brushed of the skin but was not otherwise removed.The skin reactions were scored according to the method of Draize. Redness was observed at all 7 sites on the abraded and intact skin of rabbits after 24 hours of exposure. Hence the test chemical was considered to be moderately irritating to skin.

The above study is further supported by another study performed as per standard Draize test to determine the irritation potential of the test chemical in rabbits. 500 mg of the undiluted test chemical was applied to the rabbit skin and observed for signs of irritation till 24 hours. The test chemical was moderately irritating to rabbit skin after 24 hours of exposure.

Based on the data available data and applying the weight of evidence approach, it can be concluded that the target chemical will also tend to behave in a similar manner. Therefore the target chemica can be considered to be irritating to skin and it can be further classified under the category “Category 2” as per CLP regulation.

Endpoint conclusion:

adverse effect observed (irritating)

Reference

Endpoint:

eye irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Remarks:

Experimental data from various test chemicals

Justification for type of information:

Data for the target chemical is summarized based on data from various test chemicals

Reason / purpose for cross-reference:

read-across: supporting information

Reason / purpose for cross-reference:

read-across: supporting information

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

according to guideline

Guideline:

other: Refer below principle

Principles of method if other than guideline:

WoE for the target chemical is summarized based on data from various test chemicals

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material: Ammonium iodide
- IUPAC name: Ammonium iodide
- Molecular formula: H4IN
- Molecular weight: 144.939 g/mole
- Smiles Notation : [NH4+].[IH-]
- InChl: 1S/HI.H3N/h1H;1H3
- Substance type: Inorganic
- Physical state: Solid crystalline powder (colorless to white)

Species:

rabbit

Strain:

other: 2. New Zealand White 3. No data 4. Vienna White

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

2. 0.1 g
3. 100 mg/ undiluted
4. 50 mg of the powdered substance

Duration of treatment / exposure:

2. single exposure
3. 24 hours
4. single exposure

Observation period (in vivo):

2. 1, 24, 48 and 72 hours after treatment and on Day 8
3. No data
4. 10 min, 1 and 24hrs, 72 hours till day 8

Duration of post- treatment incubation (in vitro):

no data available

Number of animals or in vitro replicates:

2. 6
3. No data
4. No data

Details on study design:

no data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 1 h

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Remarks:

2

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

24 h

Reversibility:

not specified

Remarks on result:

probability of weak irritation

Remarks:

3

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

72 h

Reversibility:

fully reversible within: 8 days

Remarks on result:

probability of moderate irritation

Remarks:

4

Irritant / corrosive response data:

2. Signs of irritation observed
4. After 10min, 1 and 24hrs, clear signs of inflammation with redness, swelling and cloudy corneal opac ity were observed. All effects were still observable 72 hours after exposure, but were not visible by the end of the eight day observation period

Other effects:

2. A well– defined appearance to the conjunctival blood vessels, iridial congestion, a moderate or slig ht discharge and slight chemosis were observed in all rabbits one hour after treatment. No corneal lesions were observed. The observed changes resolved within 3 days after treatment and all eyes were normal on Day 8.

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

On the basis of available studies for the various test chemicals, the weight of evidence approach was applied to assess the ocular irritation potential of Ammonium Iodidie. The test chemicals was considered to be irritating to eyes.

Executive summary:

Data available for the various test chemicals was reviewed to determine the toxic nature of the test chemical. The studies are as mentioned below:

A study was performed according to US EPA Pesticide Assessment Guidelines, 1982 to assess the ocular irritation potential of the test chemical. 0.1 g undiluted test chemical was instilled in to the eyes of 6 New Zealand White rabbits and observed for effects. The treated eyes were assessed 1, 24, 48 and 72 hours after treatment and on Day 8. A well– defined appearance to the conjunctival blood vessels, iridial congestion, a moderate or slight discharge and slight chemosis were observed in all rabbits one hour after treatment. No corneal lesions were observed. The observed changes resolved within 3 days after treatment and all eyes were normal by 8 days.The test chemical was considered to be slightly irritating to rabbit eyes.

This is supported by another standard Draize test was conducted to determine the irritation potential of the test chemical. Rabbit eyes were exposed to 100mg of the undiluted test chemical for 24 hours and observed for effects. Exposure to 100mg of the undiluted test chemical for 24 hours showed moderate signs of irritation. Hence, the chemical was considered to be irritating to eyes.

Another ocular irritation potential study was performed to determine the toxic nature of the test chemical using rabbits. 50 mg of the powdered substance was administered in to the eyes of Vienna White rabbits and observed for signs of irritation. The reactions were observed after 10min, 1 and 24hrs, 72 hours of exposure till day 8. After 10min, 1 and 24hrs, clear signs of inflammation with redness, swelling and cloudy corneal opacity were observed. All effects were still observable 72 hours after exposure, but were not visible by the end of the eight day observation period. The chemical was considered to be irritating to the eyes of Vienna White rabbits.

On the basis of available studies for the various test chemicals, the weight of evidence approach was applied to assess the ocular irritation potential of the test chemical. Therefore the target chemical was considered to be irritating to eyes and it can be further classified under the category “Category 2” as per CLP regulation.

Endpoint conclusion:

adverse effect observed (irritating)

Endpoint conclusion:

no study available

Data available for the various test chemicals was reviewed to determine the toxic nature of the test chemical. The studies are as mentioned below:

Skin Irritation:

The dermal irritation potential of the test chemical was assessed in rabbits according to Federal Register, vol.43, no 163-Tuesday, Aug.22, 1978 Guidelines. 6 New Zealand White rabbits were used for the study. The backs of 6 rabbits were clipped free of hair in an area of about 15 X 12 square cm. The backs of the animals were divided into quadrants. The animals were abraded in a 2 square mm cross-hatch pattern on the tattoo side by drawing a lancet across the skin, being careful not to penetrate the dermis. Two-one square inch areas on each rabbit were tested. Two unabraded additional 1 square inch sites on each rabbit were also tested. 0.5 gram of crystalline test chemical were placed in a double layered 1 square inch gauze pad and affixed to the four test sites on each animal with adhesive tape. The gauze was moistened with about 1 mL of distilled-deionized water and a polyethylene wrapper was placed over the bandages and wound around the trunk. The wrapper was secured with masking tape.The animals were placed in a restraining box and replaced in their individual cages. Water was available to the animals during the test. After 24 hours the animals were released from their restraints and the bandages were removed. All bandages were stuck to the skin by the test materials but peeled away with no skin removed. The remaining test materials was brushed of the skin but was not otherwise removed.The skin reactions were scored according to the method of Draize. Redness was observed at all 7 sites on the abraded and intact skin of rabbits after 24 hours of exposure. Hence the test chemical was considered to be moderately irritating to skin.

The above study is further supported by another study performed as per standard Draize test to determine the irritation potential of the test chemical in rabbits. 500 mg of the undiluted test chemical was applied to the rabbit skin and observed for signs of irritation till 24 hours. The test chemical was moderately irritating to rabbit skin after 24 hours of exposure.

Based on the data available data and applying the weight of evidence approach, it can be concluded that the target chemical will also tend to behave in a similar manner. Therefore the target chemical can be considered to be irritating to skin and it can be further classified under the category “Category 2” as per CLP regulation.

Eye Irritation:

A study was performed according to US EPA Pesticide Assessment Guidelines, 1982 to assess the ocular irritation potential of the test chemical. 0.1 g undiluted test chemical was instilled in to the eyes of 6 New Zealand White rabbits and observed for effects. The treated eyes were assessed 1, 24, 48 and 72 hours after treatment and on Day 8. A well– defined appearance to the conjunctival blood vessels, iridial congestion, a moderate or slight discharge and slight chemosis were observed in all rabbits one hour after treatment. No corneal lesions were observed. The observed changes resolved within 3 days after treatment and all eyes were normal by 8 days.The test chemical was considered to be slightly irritating to rabbit eyes.

This is supported by another standard Draize test was conducted to determine the irritation potential of the test chemical. Rabbit eyes were exposed to 100mg of the undiluted test chemical for 24 hours and observed for effects. Exposure to 100mg of the undiluted test chemical for 24 hours showed moderate signs of irritation. Hence, the chemical was considered to be irritating to eyes.

Another ocular irritation potential study was performed to determine the toxic nature of the test chemical using rabbits. 50 mg of the powdered substance was administered in to the eyes of Vienna White rabbits and observed for signs of irritation. The reactions were observed after 10min, 1 and 24hrs, 72 hours of exposure till day 8. After 10min, 1 and 24hrs, clear signs of inflammation with redness, swelling and cloudy corneal opacity were observed. All effects were still observable 72 hours after exposure, but were not visible by the end of the eight day observation period. The chemical was considered to be irritating to the eyes of Vienna White rabbits.

On the basis of available studies for the various test chemicals, the weight of evidence approach was applied to assess the ocular irritation potential of the test chemical. Therefore the target chemical was considered to be irritating to eyes and it can be further classified under the category “Category 2” as per CLP regulation.

Based on the available data for the various test chemicals and applying the weight of evidence approach, it can be concluded that the target chemical will also tend to behave in a similar manner as that of the test chemicals. Therefore the target chemical was considered to be irritating to eyes and it can be further classified under the category “Category 2” as per CLP regulation.