Ammonium iodide

Endpoint summary

Description of key information

Repeated dose toxcity: Oral

The data available for the read across chemicals was reviewed to determine the toxic nature of Ammonium iodide upon repeated exposure by oral route. The studies are as mentioned below:

15 weeks repeated dose oral toxicity study was performed to determine the toxic nature of the read across chemical. The study was performed using 8-10/group Wistar rats for 15 weeks. The test chemical at dose level of 0 or 10 mg/Kg bw was dissolved in sterile distilled water to produce iodide water. Blood was collected for thyroid function analysis prior to removal of the thyroid. The thyroid gland was further removed for microscopic examination.Iodide had no effect on reverse T3. Macroscopically the thyroid gland appeared small and white in colour. The Wistar rats on iodide water gave similar results to the Wistar controls. Under EM examination the follicles appeared intact with cuboidal cells. The colloid was evenly stained with regular microvilli at the apical surface. Nuclei were regularly shaped with evenly stained chromatin. Both ER and mitochondria appeared normal. Lysosomes were present in greater numbers than in the control groups. Tissue damage and apoptosis were not observed in this group, nor were inclusion bodies. Follicular architecture in the Iodide treated groups was essentially normal. Lysosomes were increased and there was no lymphocytic infiltration. Based on the observations made, No Observed Adverse Effect Level (NOAEL) for the test chemical using Wistar rats for 15 weeks repeated oral toxicity study is considered to be 10 mg/Kg bw.

In another study, 70 days repeated dose oral toxicity study was performed to determine the toxic nature of the another test chemical. The study was performed using male Sprague dawley rats. The test chemical was mixed with feed and used at dose level of 0 or 12300 ppm (0 or 684 mg/Kg bw). The treated animals were observed for clinical signs, changes in body weight and food consumption, urinalaysis, organ weight changes and were subjected to gross pathology and histopathology. This substance had no effect on clinical signs, body weights, food consumption or necropsy findings. The urine pH was approximately 6.0 compared to a pH of 7.56 or greater in the control group, and the concentration of urinary calcium was increased. However no crystals were found in the urine. The other urinary chemistries (the concentration of magnesium, creatinine, phosphate, protein, and osmolality) were unchanged.This substance had no effect on necropsy findings and the kidney weights in all groups were similar at both 11 and 21 weeks.Examination by light microscopy during week 11 showed no urothelial changes in the bladders in the bladders from controls and test group. Focal superficial necrosiswas evident in the test group. The changes in the bladder of animals administered NH4Cl were minimal, except for two rats with focal, small areas of superficial cell necrosis, proliferation, and prominant vascularity. Cortical inflammation, with andwithout tubular proliferation, was present in all groups at at week 11 and 21. A slight incidence of urothelial hyperplasia was also noted. There was no evidence of hyperplasia or other lesions in the stomach of control or treated group. Based on the observations made, the No observed adverse effect level (NOAEL) for the test chemical is considered to be 684 mg/Kg bw when male Sprague Dawley rats were exposed to the test chemical for 70 days.

Based on the data available for the strcuturally and functionally similar read across chemical, Ammonium iodide is not likely to be toxic atleast in the dose range of 10-684 mg/Kg bw.

Repeated dose toxicity: Inhalation

Ammonium iodide has a vapour pressure of 1 mmHg at 210.9°C and particle size distribution of 52-107 micron, so the potential for the generation of inhalable vapours is very low. Also the normal conditions of use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be highly unlikely and therefore this end point for repeated dose toxicity by inhalation route is considered for waiver.

Repeated dose toxicity: Dermal

The acute dermal toxicity value for Ammonium iodide (as provided in section 7.2.3) is >2000 mg/kg body weight. The substance was also found to be not irritating and not sensitizing to the skin. Based on these considerations, the end point for repeated dermal toxicity is considered as waiver.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

chronic toxicity: oral

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 of read across substances

Justification for type of information:

Data for the target chemical is summarized based on the structurally similar read across chemicals

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

other: Refer below principle

Principles of method if other than guideline:

WoE report is based on twochronic repeated dose toxicity study via oral route on rats,
1. 15 weeks repeated dose oral toxicity study was performed to determine the toxic nature of test chemical
2. 70 days repeated dose oral toxicity study was performed to determine the toxic nature of the test chemical

GLP compliance:

not specified

Limit test:

no

Species:

rat

Strain:

other: Wistar (Study 1) and Sprague Dawley rats (Study 2)

Details on species / strain selection:

No data

Sex:

male

Details on test animals or test system and environmental conditions:

2. TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc. (Kingston NY)
- Age at study initiation: 6 weeks
- Weight at study initiation: No data
- Fasting period before study:
- Housing: Rats were housed individually in suspended stainless steel wire-mesh cages
- Diet (e.g. ad libitum): Purina Mills Certified Rodent Lab Chow, St. Louis, MO ad libitum
- Water (e.g. ad libitum): Water ad libitum
- Acclimation period: 12 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 47C
- Humidity (%): 55 ± 15%
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): a 12-h light/dark

IN-LIFE DATES: From: To: No data

Route of administration:

other: Drinkng water (Study 1) and Feed (Study 2)

Details on route of administration:

No data

Vehicle:

other: sterile drinkinf water (Study 1) and feed (Study 2)

Details on oral exposure:

Study 1:
PREPARATION OF DOSING SOLUTIONS: The test chemical at dose level of 0 or 10mg/Kg bw was dissolved in sterile distilled water to produce iodide water

DIET PREPARATION
- Rate of preparation of diet (frequency): No data
- Mixing appropriate amounts with (Type of food): No data
- Storage temperature of food: No data

VEHICLE
- Justification for use and choice of vehicle (if other than water): Sterile drinking water
- Concentration in vehicle: 0 or 10 mg/Kg/day
- Amount of vehicle (if gavage): No data
- Lot/batch no. (if required): No data
- Purity: No data

Study 2:
PREPARATION OF DOSING SOLUTIONS: The test chemical was mixed with feed at dose level of 0 or 12300 ppm (0 or 384 mg/Kg bw)

DIET PREPARATION
- Rate of preparation of diet (frequency): No data
- Mixing appropriate amounts with (Type of food): No data
- Storage temperature of food: No data

VEHICLE
- Justification for use and choice of vehicle (if other than water):Feed (Purina Mills Certified Rodent Lab Chow)
- Concentration in vehicle: 0 or 12300 ppm (0 or 384 mg/Kg bw)
- Amount of vehicle (if gavage): No data
- Lot/batch no. (if required): No data
- Purity: No data

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

No data

Duration of treatment / exposure:

1. 15 weeks
2. 70 days (10 weeks)

Frequency of treatment:

1. Daily
2. Daily

Remarks:

0 or 10 mg/Kg bw (Study 1)

Remarks:

0 or 12300 ppm (0 or 384 mg/Kg bw) (Study 2)

No. of animals per sex per dose:

1.
Total: 17
0 mg/Kg/bw: 8
10 mg/Kg/bw: 9

2.
Total: 30 males
0 mg/Kg bw: 20 males
10 mg/Kg bw: 10 males

Control animals:

yes, concurrent vehicle

Details on study design:

1. No data
2.
- Dose selection rationale: No data
- Rationale for animal assignment (if not random): They were randomized into treatment groups and a control group using a weight stratification method (INSTEM Computer Systems, Stone, Staffordshire, UK) and started on test diet
- Rationale for selecting satellite groups: No data
- Post-exposure recovery period in satellite groups: No data
- Section schedule rationale (if not random): No data

Positive control:

No data

Observations and examinations performed and frequency:

Study 1.
CAGE SIDE OBSERVATIONS: No data
- Time schedule: No data
- Cage side observations checked in table [No.?] were included. No data

DETAILED CLINICAL OBSERVATIONS: No data
- Time schedule: No data

BODY WEIGHT: No data
- Time schedule for examinations: No data

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data
- Time schedule for examinations: No data

OPHTHALMOSCOPIC EXAMINATION: No data
- Time schedule for examinations: No data
- Dose groups that were examined: No data

HAEMATOLOGY: No data
- Time schedule for collection of blood: No data
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: No data
- Parameters checked in table [No.?] were examined. No data

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: No data
- Animals fasted: No data
- How many animals: No data
- Parameters checked in table [No.?] were examined. Total thyroxine (T4) and total tri-iodothyronine (T3) were analysed, Thyrotrophin (TSH), Reverse T3

URINALYSIS: No data
- Time schedule for collection of urine: No data
- Metabolism cages used for collection of urine: No data
- Animals fasted: No data
- Parameters checked in table [No.?] were examined. No data

NEUROBEHAVIOURAL EXAMINATION: No data
- Time schedule for examinations: No data
- Dose groups that were examined: No data
- Battery of functions tested: sensory activity / grip strength / motor activity / other: No data

OTHER: No data

Study 2.
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Weekly
- Cage side observations checked in table [No.?] were included.

DETAILED CLINICAL OBSERVATIONS: No data
- Time schedule: No data

BODY WEIGHT: Yes
- Time schedule for examinations: Once per week

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes, Once per week
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data
- Time schedule for examinations: No data

OPHTHALMOSCOPIC EXAMINATION: No data
- Time schedule for examinations: No data
- Dose groups that were examined: No data

HAEMATOLOGY: No data
- Time schedule for collection of blood: No data
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: No data
- Parameters checked in table [No.?] were examined. No data

CLINICAL CHEMISTRY: No data
- Time schedule for collection of blood: No data
- Animals fasted: No data
- How many animals: No data
- Parameters checked in table [No.?] were examined. No data

URINALYSIS: Yes
- Time schedule for collection of urine: During the beginning of weeks 11 and 21
- Metabolism cages used for collection of urine: No data
- Animals fasted: No data
- Parameters checked in table [No.?] were examined. pH, total protein, creatinine, calcium, phosphorus, magnesium, and osmolalitym, the presence of insoluble material. The urine was centrifuged, the supernatant removed, and the remaining pellet wicked to remove additional urine. The pellet was dried in a speed vacuum for 2 h, reconstituted with 10 ml deionized water, placed on a 0.22-mm Millipore filter, and vacuum dried before being placed on an aluminum stub for analysis by scanning electron microscopy with an attached energy dispersive spectrometer.

NEUROBEHAVIOURAL EXAMINATION: No data
- Time schedule for examinations: No data
- Dose groups that were examined: No data
- Battery of functions tested: sensory activity / grip strength / motor activity / other: No data

OTHER: No data

Sacrifice and pathology:

Study 1.
GROSS PATHOLOGY: Yes, thyoid gland was examined

HISTOPATHOLOGY: Yes, After washing out red blood cells, the thyroid gland was removed and stored in Karnovsky fixative (2.5% glutaraldehyde, 2.5% pure formalin in 0.1M MOPS buffer, pH7.4) for 3 h and then cut into 1mm3 blocks. Both lobes were diced and processed using a Polaron E9000 EM Tissue Processor. On average 20 diced sections were prepared from each rat thyroid gland and 6 were selected randomly for block preparation. For histological assessment sections were cut at 0.5 mm thickness and stained with methylene blue; they were photographed using Kodak Technical Pan Film (black and white; magnification X 399). For EM assessment resin-embedded ultra-thin sections were stained with uranyl acetate and lead citrate and examined using a Phillips EM 201S transmission electron microscope. Photographs of sections were recorded on Kodak SO-281 electron microscope film (35mm) and developed in Kodak D19 developer. The observed changes were graded by two of the authors (VP and LM) independently without knowledge of the treatment groups. The changes were graded as follows: (a) follicular disruption, ER dilatation and lymphocytic infiltration: 0, none observed; 1, low; 2, moderate; 3, marked; (b) lysosomal numbers: 1, low; 2, moderate; 3, marked; (c) lipofuscinogenesis: 1, low; 2, moderate; 3, marked.

Study 2.
GROSS PATHOLOGY: Yes, rats were killed during week 11 and 21 by p administration of Nembutal. One hour prior to sacrifice the rats were given bromodeoxyuridine. At necropsy, the bladder and stomach were inflated with Bouin’s fixative in situ and placed in the same fixative. The kidneys were removed, weighted, and placed in formalin. Approximately 1 h after fixation the bladder and stomach were rinsed in 70% ethanol, and the bladder was weighed and divided in half longitudinally.

HISTOPATHOLOGY: Yes, bladder was cut into four strips longitudinally and processed with a slice of the forestomach and glandular stomach for embedding in paraffin and microscopic histopathology after hematoxylin and eosin staining. The bladder was evaluated according to criteria described by Cohen (1983) into the categories of simple hyperplasia and papillary and nodular hyperplasia. The evaluation also included examination of toxicity, acute and chronic inflammation, fibrosis, and squamous metaplasia. Sections of both kidneys were processed for histopathologic evaluation in the same manner. A slide of the bladder from all rats euthanized at 21 weeks was stained by Masson’s trichrome method to evaluate the presence of fibrosis

Other examinations:

No data

Statistics:

1. The thyroid function results are expressed as means±S.E. Analysis of difference was performed using analysis of variance (ANOVA) followed by Scheffes test for significance of differences among multiple experimental groups.

2. Data for urinary pH and labeling indices were analyzed by Student’s t test (unpaired). All other urine chemistry values, body weight, and food consumption data were compared by a one-way variance analysis (ANOVA) (Snedecor and Chochran, 1967) followed by Dunnett’s test (Dunnett, 1955, 1964). Analysis of variance followed by Duncan’s multiple range test (Duncan, 1955) was used to analyze tissue weights. Histologic results, when analyzed statistically, where compared using Fisher’s exact test. Scanning electron microscopy results were examined using a nonparametric one-way analysis with x2 performed with software
from INSTEM Computer Systems (Staffordshire, UK), SAS Institute Inc. (Cary, NC), or Jandel Scientific (Corte Madera, CA). A p value ≤0.05 was considered statistically significant.

Clinical signs:

no effects observed

Description (incidence and severity):

2. This substance had no effect on clinical signs

Mortality:

not specified

Body weight and weight changes:

no effects observed

Description (incidence and severity):

2. This substance had no effect on body weights

Food consumption and compound intake (if feeding study):

no effects observed

Description (incidence and severity):

2. This substance had no effect on food consumption

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

no effects observed

Description (incidence and severity):

1. Iodide had no effect on reverse T3

Urinalysis findings:

no effects observed

Description (incidence and severity):

2. The urine pH was approximately 6.0 compared to a pH of 7.56 or greater in the control group, and the concentration of urinary calcium was increased. However no crystals were found in the urine. The other urinary chemistries (the concentration of magnesium, creatinine, phosphate, protein, and osmolality) were unchanged.

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

no effects observed

Description (incidence and severity):

2. Kidney weights in all groups were similar at both 11 and 21 weeks

Gross pathological findings:

no effects observed

Description (incidence and severity):

1. Macroscopically the thyroid gland appeared small and white in colour.
2. This substance had no effect on necropsy findings

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

no effects observed

Description (incidence and severity):

1. In the 15-week-old Wistar rat controls fed sterile water, the thyroid follicles were morphologically intact, microvilli were regular in shape at the apical surface and the colloid was evenly stained. Nuclei were regular in shape with evenly stained chromatin and regular nucleoli. Under higher magnification the ER was of normal appearance and mitochondria also appeared normal with oval and rod shapes present. Lysosomes were present with low numbers of lipofuscin bodies. There was no evidence of tissue damage, apoptosis or inclusion bodies.

The Wistar rats on iodide water gave similar results to the Wistar controls. Under EM examination the follicles appeared intact with cuboidal cells. The colloid was evenly stained with regular microvilli at the apical surface. Nuclei were regularly shaped with evenly stained chromatin. Both ER and mitochondria appeared normal. Lysosomes were present in greater numbers than in the control groups. Tissue damage and apoptosis were not observed in this group, nor were inclusion bodies.

Folicular architecture in the Iodide treated groups was essentially normal. Lysosomes were increased and there was no lymphocytic infiltration.

2. Examination by light microscopy during week 11 showed no urothelial changes in the bladders in the bladders from controls and test group. Focal superficial necrosis was evident in the test group. The changes in the bladder of animals administered NH4Cl were minimal, except for two rats with focal, small areas of superficial cell necrosis, proliferation, and prominant vascularity.

Cortical inflammation, with and without tubular proliferation, was present in all groups at at week 11 and 21. A slight incidence of urothelial hyperplasia was also noted. There was no evidence of hyperplasia or other lesions in the stomach of control or treated group.

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Details on results:

No data

Dose descriptor:

NOAEL

Effect level:

> 10 - <= 684 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male

Basis for effect level:

other: No significant effects were noted at the mentioned dose level

Critical effects observed:

not specified

Conclusions:

The test chemical Ammonium iodide is not likely to be toxic atleast in the dose range of 10-684 mg/Kg bw.

Executive summary:

The data available for the read across chemicals was reviewed to determine the toxic nature of Ammonium iodide upon repeated exposure by oral route. The studies are as mentioned below:

15 weeks repeated dose oral toxicity study was performed to determine the toxic nature of the read across chemical. The study was performed using 8-10/group Wistar rats for 15 weeks. The test chemical at dose level of 0 or 10 mg/Kg bw was dissolved in sterile distilled water to produce iodide water. Blood was collected for thyroid function analysis prior to removal of the thyroid. The thyroid gland was further removed for microscopic examination.Iodide had no effect on reverse T3. Macroscopically the thyroid gland appeared small and white in colour. The Wistar rats on iodide water gave similar results to the Wistar controls. Under EM examination the follicles appeared intact with cuboidal cells. The colloid was evenly stained with regular microvilli at the apical surface. Nuclei were regularly shaped with evenly stained chromatin. Both ER and mitochondria appeared normal. Lysosomes were present in greater numbers than in the control groups. Tissue damage and apoptosis were not observed in this group, nor were inclusion bodies. Follicular architecture in the Iodide treated groups was essentially normal. Lysosomes were increased and there was no lymphocytic infiltration. Based on the observations made, No Observed Adverse Effect Level (NOAEL) for the test chemical using Wistar rats for 15 weeks repeated oral toxicity study is considered to be 10 mg/Kg bw.

In another study, 70 days repeated dose oral toxicity study was performed to determine the toxic nature of the test chemical. The study was performed using male Sprague dawley rats. The test chemical was mixed with feed and used at dose level of 0 or 12300 ppm (0 or 684 mg/Kg bw). The treated animals were observed for clinical signs, changes in body weight and food consumption, urinalaysis, organ weight changes and were subjected to gross pathology and histopathology. This substance had no effect on clinical signs, body weights, food consumption or necropsy findings. The urine pH was approximately 6.0 compared to a pH of 7.56 or greater in the control group, and the concentration of urinary calcium was increased. However no crystals were found in the urine. The other urinary chemistries (the concentration of magnesium, creatinine, phosphate, protein, and osmolality) were unchanged.This substance had no effect on necropsy findings and the kidney weights in all groups were similar at both 11 and 21 weeks.Examination by light microscopy during week 11 showed no urothelial changes in the bladders in the bladders from controls and test group. Focal superficial necrosiswas evident in the test group. The changes in the bladder of animals administered NH4Cl were minimal, except for two rats with focal, small areas of superficial cell necrosis, proliferation, and prominant vascularity. Cortical inflammation, with andwithout tubular proliferation, was present in all groups at at week 11 and 21. A slight incidence of urothelial hyperplasia was also noted. There was no evidence of hyperplasia or other lesions in the stomach of control or treated group. Based on the observations made, the No observed adverse effect level (NOAEL) for the test chemical is considered to be 684 mg/Kg bw when male Sprague Dawley rats were exposed to the test chemical for 70 days.

Based on the data available for the strcuturally and functionally similar read across chemical, Ammonium iodide is not likely to be toxic as per the criteria mentioned in CLP regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

684 mg/kg bw/day

Study duration:

chronic

Species:

rat

Quality of whole database:

Data is from peer revewed publications

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records

Reference

Endpoint:

repeated dose toxicity: inhalation, other

Data waiving:

other justification

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Quality of whole database:

Waiver

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Link to relevant study records

Reference

Endpoint:

repeated dose toxicity: dermal, other

Data waiving:

other justification

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Quality of whole database:

Waiver

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Repeated dose toxcity: Oral

The data available for the read across chemicals was reviewed to determine the toxic nature of Ammonium iodide upon repeated exposure by oral route. The studies are as mentioned below:

15 weeks repeated dose oral toxicity study was performed by Pitsiavas et al (European Journal of Endocrinology, 1997) to determine the toxic nature of read across chemical Sodium iodide (RA CAS no 7681 -82 -5). The study was performed using 8-10/group Wistar rats for 15 weeks.Sodium iodide at dose level of 0 or 10 mg/Kg bw was dissolved in sterile distilled water to produce iodide water. Blood was collected for thyroid function analysis prior to removal of the thyroid. The thyroid gland was further removed for microscopic examination.Iodide had no effect on reverse T3. Macroscopically the thyroid gland appeared small and white in colour. The Wistar rats on iodide water gave similar results to the Wistar controls. Under EM examination the follicles appeared intact with cuboidal cells. The colloid was evenly stained with regular microvilli at the apical surface. Nuclei were regularly shaped with evenly stained chromatin. Both ER and mitochondria appeared normal. Lysosomes were present in greater numbers than in the control groups. Tissue damage and apoptosis were not observed in this group, nor were inclusion bodies. Follicular architecture in the Iodide treated groups was essentially normal. Lysosomes were increased and there was no lymphocytic infiltration. Based on the observations made, No Observed Adverse Effect Level (NOAEL) for sodium iodide using Wistar rats for 15 weeks repeated oral toxicity study is considered to be 10 mg/Kg bw.

In another study by Arnold et al (Fundamental and Applied Toxicology, 1977) 70 days repeated dose oral toxicity study was performed to determine the toxic nature of read across chemical ammonium chloride (RA CAS no 12125 -02 -9). The study was performed using male Sprague dawley rats. The test chemical was mixed with feed and used at dose level of 0 or 12300 ppm (0 or 684 mg/Kg bw). The treated animals were observed for clinical signs, changes in body weight and food consumption, urinalaysis, organ weight changes and were subjected to gross pathology and histopathology. This substance had no effect on clinical signs, body weights, food consumption or necropsy findings. The urine pH was approximately 6.0 compared to a pH of 7.56 or greater in the control group, and the concentration of urinary calcium was increased. However no crystals were found in the urine. The other urinary chemistries (the concentration of magnesium, creatinine, phosphate, protein, and osmolality) were unchanged.This substance had no effect on necropsy findings and the kidney weights in all groups were similar at both 11 and 21 weeks.Examination by light microscopy during week 11 showed no urothelial changes in the bladders in the bladders from controls and test group. Focal superficial necrosiswas evident in the test group. The changes in the bladder of animals administered NH4Cl were minimal, except for two rats with focal, small areas of superficial cell necrosis, proliferation, and prominant vascularity. Cortical inflammation, with andwithout tubular proliferation, was present in all groups at at week 11 and 21. A slight incidence of urothelial hyperplasia was also noted. There was no evidence of hyperplasia or other lesions in the stomach of control or treated group. Based on the observations made, the No observed adverse effect level (NOAEL) for ammonium chloride is considered to be 684 mg/Kg bw when male Sprague Dawley rats were exposed to the test chemical for 70 days.

Based on the data available for the strcuturally and functionally similar read across chemical, Ammonium iodide is not likely to be toxic atleast in the dose range of 10-684 mg/Kg bw.

Repeated dose toxicity: Inhalation

Ammonium iodide has a vapour pressure of 1 mmHg at 210.9°C and particle size distribution of 52-107 micron, so the potential for the generation of inhalable vapours is very low. Also the normal conditions of use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be highly unlikely and therefore this end point for repeated dose toxicity by inhalation route is considered for waiver.

Repeated dose toxicity: Dermal

The acute dermal toxicity value for Ammonium iodide (as provided in section 7.2.3) is >2000 mg/kg body weight. The substance was also found to be not irritating and not sensitizing to the skin. Based on these considerations, the end point for repeated dermal toxicity is considered as waiver.

Based on the data available for the target chemical and its read across, Ammonium iodide is not likely to be toxic upon repeated exposure by oral rouote as per the criteria mentioned in CLP regulation.

Justification for classification or non-classification

Based on the data available for the target chemical and its read across, Ammonium iodide (CAS no 12125 -02 -9) is not likely to be toxic upon repeated exposure by oral rouote as per the criteria mentioned in CLP regulation.