Ammonium iodide

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

Toxicity to reproduction

Data available for the read across chemicals was reviewed to determine the reproductive toxicity Ammonium iodide (12027-06-4),Thus, Based on the data available for the read across chemical, No Observed Adverse Effect Level (NOAEL) was considered to be above 100mg/kg bw . Thus, comparing this value with the criteria of CLP regulation Ammonium iodide (12027-06-4)is not likely to classify as reproductive toxicant.

Link to relevant study records

Reference

Endpoint:

screening for reproductive / developmental toxicity

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

Reason / purpose for cross-reference:

read-across source

Qualifier:

equivalent or similar to guideline

Guideline:

other: As mentioned below

Principles of method if other than guideline:

WoE report is based on three reproductive toxicity study via oral route on rats,
1.The reproductive and developmental toxicity study of test chemical was performed on male and female rats.
2.The reproductive toxicity study of test chemical was performed on male and female wistar rats.
3.Long-Evans rats were fed test chemical at varying intervals of time after breeding. The effect on length of gestation, parturition time, lactation and survival of young was observed.

GLP compliance:

not specified

Limit test:

no

Justification for study design:

No data available

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 : [NH4+].[IH-]
- Inchl: 1S/HI.H3N/h1H;1H3
- Substance type: Inorganic
- Physical state: Solid crystalline powder (colorless to white)

Species:

rat

Strain:

other: Long-Evans (Study 1),Sprague-Dawley (Study 2),Wistar (Study 3)

Details on species / strain selection:

No data available

Sex:

male/female

Details on test animals or test system and environmental conditions:

1.
Details on test animals and env. conditions
TEST ANIMALS
- Source: Laboratory Supply Co., Indianapolis, IN
- Weight at study initiation: 200-240g
- Diet (e.g. ad libitum): Purina rat chow meal
- Acclimation period:5 days

Route of administration:

other: 1. feed ,2.drinking water,3. feed

Vehicle:

water

Details on exposure:

Study 1.
PREPARATION OF DOSING SOLUTIONS: Test material mixed with feed

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

Study 2.
Details on exposure
PREPARATION OF DOSING SOLUTIONS:
The test material mixed with Drinking water
DIET PREPARATION
- Rate of preparation of diet (frequency):No data available
- Mixing appropriate amounts with (Type of food )
- Storage temperature of food: No data available
VEHICLE
- Justification for use and choice of vehicle (if other than water): test material mixed with corn oil as it is not soluble in water
- Concentration in vehicle: 100or 1000mg/kg bw
- Amount of vehicle (if gavage): No data available
- Lot/batch no. (if required): No data available
- Purity: No data available

Study 3
PREPARATION OF DOSING SOLUTIONS:
Test material mixed with feed
DIET PREPARATION
- Rate of preparation of diet (frequency):No data
- Mixing appropriate amounts with (Type of food): Diet as Purina Laboratory Chow
- Storage temperature of food: no data

Details on mating procedure:

Study1.
- M/F ratio per cage: No data
- Length of cohabitation: No data
- Proof of pregnancy: [vaginal plug / sperm in vaginal smear] referred to as [day 0 / day 1] of pregnancy:day sperm were found was considered to
be day 0 of gestation

Study 2.
- M/F ratio per cage:1:1
- Length of cohabitation: No data
- Proof of pregnancy: [vaginal plug / sperm in vaginal smear] referred to as [day 0 / day 1] of pregnancy: day sperm were found was considered to be day 0 of gestation.

Study 3.
- M/F ratio per cage:1:1
- Length of cohabitation: No data
- After successful mating each pregnant female was caged (how): Individually

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

Study 1.
90 days ( Dietary treatments were given continuously
to both males and females for 14 days
before mating and for l-14 days during breeding, and
to females only during gestation (22 days) and lactation
(21 days).)
Study2.
3 days (Day 3 to day 5 of early pregnancy)
Study 3.
12 days

Frequency of treatment:

Daily

Details on study schedule:

No data available

Remarks:

Study1.F0: 0, 25,50,100mg/kg/day
F1: 0, 25,50,100mg/kg/day
Study2.100 or 1000mg/kg bw
Study3. 0 ,150 mg/kg bw (2500 ppm)

No. of animals per sex per dose:

Study3.
27 females

Control animals:

yes

Details on study design:

No data available

Positive control:

Study1.yes (5-azacytidine 2mg/kg )

Parental animals: Observations and examinations:

Study 1.
Parental animals observation and examinations
CAGE SIDE OBSERVATIONS: yes
DETAILED CLINICAL OBSERVATIONS: Yes
Time schedule: daily
BODY WEIGHT: Yes
Time schedule for examinations: Parental body weights were measured at weekly intervals except during breeding
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes food consumption
was measured on selected rats during all
phases of the experiment.
Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes / No / No data: No data available


Study 2.
Parental animals observation and examinations
CAGE SIDE OBSERVATIONS: yes
DETAILED CLINICAL OBSERVATIONS: Yes
Time schedule: daily
BODY WEIGHT: Yes
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: Yes
Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes / No / No data: No data available
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): daily fluid intake for each rat was determined
Time schedule for examinations:

Study3.
Observations were made for length of parturition time and number of young born dead and those born live.

Oestrous cyclicity (parental animals):

No data available

Sperm parameters (parental animals):

No data available

Litter observations:

Study 1.
STANDARDISATION OF LITTERS
Litters with fewer than eight live offspring were not kept beyond 1 day after birth. Litters of more than 12 were reduced to 12 by a random selection procedure that balanced the sex distribution as much as possible. At this time, two males and two females from each litter were designated for preweaning testing. In addition to these four, two other males and two other females from each litter were later designated for post-weaning testing

PARAMETERS EXAMINED
The following parameters were examined in [F1 / F2 / F3] offspring:
[all litters were examined and data collected on litter size, sex distribution, weight, and number of dead and/or malformed offspring.]
Study 3.
survival of young was observed.

Postmortem examinations (parental animals):

Study2.
Postmortem examinations (Parent Animal)
SACRIFICE : On Day 12 or 13, the mother was killed, the number of implantation sites noted and the weight of the sites determined.
Thyroid and adrenal weights were also measured.

Postmortem examinations (offspring):

Study1.
All pups not selected for mating were taken for necropsy at day 21 post partum or shortly thereafter; organ weights were recorded for brain, spleen and thymus.
Study 2.
SACRIFICE
On Day 9 or 10 of the post-partum pregnancy, the litter was removed, weighed and killed and the thyroid glands dissected out, pooled and weighed.

Statistics:

Study1.
Analysis of variance (ANOVA) was performed on the majority of data (general linear model), and Duncan's pairwise comparisons made between individual groups in the event of significant treatment F-ratios. Adjustments of Duncan's test for unequal group sizes were made sing the procedure of Kramer (1956). On all tests litter was used as the unit of analysis. On preweaning tests this was done by averaging scores together from all tested littermates. On post-weaning tests this was done by testing only one male and one female from each litter on each test. An exception was vaginal patency which was analysed as though it were a preweaning test. Frequency data were analysed using Fisher's test for uncorrelated proportions (Guilford, 1965).
Study3.
The data was subjected to statistical analysis.Method used included ANOVA were based upon analysis of variance.

Reproductive indices:

No data available

Offspring viability indices:

No data available

Clinical signs:

not specified

Dermal irritation (if dermal study):

not specified

Mortality:

mortality observed, treatment-related

Description (incidence):

Study 2.
In dose group 1000mg/kg bw,Three of nine rats died before the experiment was completed

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

Study 2.
In dose group 1000mg/kg bw,the body weight of the survivors were greatly reduced

Food consumption and compound intake (if feeding study):

no effects observed

Description (incidence and severity):

A reduction in male (P < 0.01), but not female, food consumption was found in the 0. 1% dose group prior to breeding, but this reduction resulted in only a marginal decrease in body weight (P < 0.09). No effects were found on maternal food consumption or body weight during gestation. Maternal food consumption was reduced during lactation in the 0.025% dose group but not dose related

Food efficiency:

not specified

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

no effects observed

Description (incidence and severity):

Study2.
The female rats in 100mg/kg bw dose group had normal fluid intake.

Ophthalmological findings:

no effects observed

Description (incidence and severity):

Study1.eye opening was unaffected by treatment.

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Reproductive function: oestrous cycle:

not specified

Reproductive function: sperm measures:

not specified

Reproductive performance:

no effects observed

Description (incidence and severity):

Study 1.no significant effects on parental mortality, fertility, pregnancy maintenance, or gestation length.
Study 2.In dose group 1000mg/kg bw,Failure of implantation was probably related to the poor general state of the mothers rather than to a specific effect of iodide.The female rats in 100mg/kg bw dose group maintained healthy litters and had a high rate of implantation.
Study 3.Gestation time for rats was not affected by iodine; however, prolonged parturition was observed in rats.No signs of the beginning of lactation were observed.

Dose descriptor:

NOAEL

Effect level:

100 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

clinical signs

mortality

body weight and weight gain

food consumption and compound intake

water consumption and compound intake

reproductive performance

Remarks on result:

other: overall no toxic effects observed

Dose descriptor:

LOAEL

Effect level:

150 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

female

Basis for effect level:

reproductive performance

Remarks on result:

other: prolonged parturition was observed in rats

Critical effects observed:

not specified

System:

other: not specified

Organ:

not specified

Treatment related:

not specified

Dose response relationship:

not specified

Relevant for humans:

not specified

Clinical signs:

not specified

Dermal irritation (if dermal study):

not specified

Mortality / viability:

mortality observed, treatment-related

Description (incidence and severity):

1.Test material produced significant increases in offspring mortality in the 0. I% group at birth and up to day 24 after birth. The 0.025% dose group, by contrast, showed reduced mortality up to day 24
2.there were many deaths among the litters at 1000mg/kg bw dose group.
3.Resulted in incidence of death in the neonates, with <10% of the young surviving for 3 days.

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

1.Test material produced a consistent decrease in offspring body weight throughout postnatal life which was generally dose-dependent
3.Weaning weight was significantly less than that of controls.

Food consumption and compound intake (if feeding study):

not specified

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:

not specified

Urinalysis findings:

not specified

Sexual maturation:

not specified

Organ weight findings including organ / body weight ratios:

no effects observed

Description (incidence and severity):

1.No change in thyroid weight was observed indicating that these doses were not overtly thyrotoxic

Gross pathological findings:

no effects observed

Description (incidence and severity):

1.external morphology among those born alive were not significantly altered.

Histopathological findings:

not specified

Other effects:

not specified

Behaviour (functional findings):

effects observed, treatment-related

Description (incidence and severity):

1.the doses of test material used here produced delayed early development of several indices of reflex ontogeny. These included delayed auditory startle response development, delayed olfactory orientation towards their home-cage scent, and delayed maturation of several aspects of swimming co-ordination. Physical milestones of development were not affected, nor were early measures of locomotor activity.

Developmental immunotoxicity:

not specified

Dose descriptor:

LOAEL

Generation:

F1

Effect level:

> 100 - < 1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

not specified

Basis for effect level:

viability

mortality

body weight and weight gain

organ weights and organ / body weight ratios

gross pathology

Remarks on result:

other: developmental effects observed

Critical effects observed:

not specified

System:

other: not specified

Organ:

not specified

Treatment related:

not specified

Dose response relationship:

not specified

Relevant for humans:

not specified

Reproductive effects observed:

not specified

Treatment related:

not specified

Relation to other toxic effects:

not specified

Dose response relationship:

not specified

Relevant for humans:

not specified

Conclusions:

The NOAEL for reproductive toxicity was considered to be 100 mg/kg bw/day as No effects on reproductive parameters were observed .When male and female rats were treated with Ammonium iodide (12027-06-4) orally.

Executive summary:

Reproductive toxicity study

Data available for the read across chemicals was reviewed to determine the reproductive toxicity of Ammonium iodide (12027-06-4). The studies are as mentioned below:

Study 1.

 The reproductive and developmental toxicity study of test material was performed in male and female Sprague-Dawley rats. The test material mixed with Purina rat chow meal in dose concentration0, 25,50, 100mg/kg/day. Dietary treatments were given continuously to both males and females for 14 days before mating and for l-14 days during breeding and to females only during gestation (22 days) and lactation (21 days). After weaning, the offspring were given dietary test material, at the level their parents had received, throughout the remainder of the experiment (up to 90 days of age for most animals). Negative control dams received no treatment. Positive-control dams were given two ip injections of 2 mg/kg of 5-azacytidine. On day 17 of gestation (day sperm were found was considered to be day 0 of gestation). Parental body weights were measured at weekly intervals except during breeding, and food consumption was measured on selected rats during all phases of the experiment. On the day following birth, all litters were examined and data collected on litter size, sex distribution, weight, and number of dead and/or malformed offspring.Pre weaning observations and post weaning observations were made.

The results indicate that test material at dietary doses of up to 100 mg/kg/day, produced only minor effects on parental weight gain and food consumption, and no significant effects on parental mortality, fertility, pregnancy maintenance, or gestation length. There was evidence suggesting that potassium iodide was embryotoxic. Litter size was significantly reduced, but birth weights and external morphology among those born alive were not significantly altered.

Test material produced a consistent decrease in offspring body weight throughout postnatal life which was generally dose-dependent. No change in thyroid weight was observed indicating that these doses were not overtly thyrotoxic. Behaviorally, the doses of potassium iodide used here produced delayed early development of several indices of reflex ontogeny. These included delayed auditory startle response development, delayed olfactory orientation towards their home-cage scent, and delayed maturation of several aspects of swimming co-ordination. Physical milestones of development were not affected, nor were early measures of locomotor activity. Hence The NOAEL for reproductive toxicity was considered to be 100 mg/kg bw/day as No effects on reproductive parameters were observed and LOAEL for developmental toxicity was considered to be 100mg/kg bw. When male and female Sprague-Dawley rats were treated with test material orally.

 

 

 Study 2.

 

 The reproductive toxicity study of test material was performed on female wistar rats. The test material dissolved in dose concentration 100 or 1000mg/kg bw in drinking water. Female rats caged singly with males and the date of post-partum mating determined by the finding of spermatozoa in the vaginal smear or a vaginal plug. On this day (Day 0 of pregnancy), the male was removed and the litter size reduced to nine and maintained at this number. On Day 9 or 10 of the post-partum pregnancy, the litter was removed, weighed and killed and the thyroid glands dissected out, pooled and weighed. On Day 12 or 13, the mother was killed, the number of implantation sites noted and the weight of the sites determined. Thyroid and adrenal weights were also measured.

 

The female rats in 100mg/kg bw dose group had normal fluid intake, maintained healthy litters and had a high rate of implantation. In dose group1000mg/kg bw ; none of the six rats had implantation sites at autopsy (, and the mothers were severely affected by this treatment. Three of nine rats died before the experiment was completed, the body weight and fluid intake of the survivors were greatly reduced and the adrenal glands enlarged, and there were many deaths among the litters whose body weights were low. Failure of implantation was probably related to the poor general state of the mothers rather than to a specific effect of test material. Hence The NOAEL for reproductive toxicity was considered to be 100 mg/kg bw/day as No effects on reproductive parameters were observed and LOAEL was considered to be 1000mg/kg bw. When female wistar rats were treated with test material orally.

 

Study 3

Study was conducted with rats to determine the effects of excess intake of test material. Females were bred to normal males, the test material was added to the diet during the latter portion of gestation and the females were permitted to litter normally. The effect of the treatment on gestation period, lactation and survival of the young was observed. Gestation time for rats was not affected; however, prolonged parturition was observed in rats. Female rats re-bred after removal from dietary iodine produced and nursed litters normally. Since LOAEL was considered 150 mg/kg bw, it is regarded that there is no reproductive toxicity at concentrations lower than 150 mg/kg bw when test material administered orally.

 

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

100 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

Data is Klimicsh 2 and from authoritative database

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

Reproductive toxicity study

Data available for the read across chemicals was reviewed to determine the reproductive toxicity of Ammonium iodide (12027-06-4). The studies are as mentioned below:

Study 1.

 

The reproductive and developmental toxicity study of test material was performed in male and female Sprague-Dawley rats. The test material mixed with Purina rat chow meal in dose concentration0, 25,50, 100mg/kg/day. Dietary treatments were given continuously to both males and females for 14 days before mating and for l-14 days during breeding and to females only during gestation (22 days) and lactation (21 days). After weaning, the offspring were given dietary test material, at the level their parents had received, throughout the remainder of the experiment (up to 90 days of age for most animals). Negative control dams received no treatment. Positive-control dams were given two ip injections of 2 mg/kg of 5-azacytidine. On day 17 of gestation (day sperm were found was considered to be day 0 of gestation). Parental body weights were measured at weekly intervals except during breeding, and food consumption was measured on selected rats during all phases of the experiment. On the day following birth, all litters were examined and data collected on litter size, sex distribution, weight, and number of dead and/or malformed offspring.Pre weaning observations and post weaning observations were made.

The results indicate that test material at dietary doses of up to 100 mg/kg/day, produced only minor effects on parental weight gain and food consumption, and no significant effects on parental mortality, fertility, pregnancy maintenance, or gestation length. There was evidence suggesting that potassium iodide was embryotoxic. Litter size was significantly reduced, but birth weights and external morphology among those born alive were not significantly altered.

Test material produced a consistent decrease in offspring body weight throughout postnatal life which was generally dose-dependent. No change in thyroid weight was observed indicating that these doses were not overtly thyrotoxic. Behaviorally, the doses of potassium iodide used here produced delayed early development of several indices of reflex ontogeny. These included delayed auditory startle response development, delayed olfactory orientation towards their home-cage scent, and delayed maturation of several aspects of swimming co-ordination. Physical milestones of development were not affected, nor were early measures of locomotor activity. Hence The NOAEL for reproductive toxicity was considered to be 100 mg/kg bw/day as No effects on reproductive parameters were observed and LOAEL for developmental toxicity was considered to be 100mg/kg bw. When male and female Sprague-Dawley rats were treated with test material orally.

 

 

 Study 2.

 

 

The reproductive toxicity study of test material was performed on female wistar rats. The test material dissolved in dose concentration 100 or 1000mg/kg bw in drinking water. Female rats caged singly with males and the date of post-partum mating determined by the finding of spermatozoa in the vaginal smear or a vaginal plug. On this day (Day 0 of pregnancy), the male was removed and the litter size reduced to nine and maintained at this number. On Day 9 or 10 of the post-partum pregnancy, the litter was removed, weighed and killed and the thyroid glands dissected out, pooled and weighed. On Day 12 or 13, the mother was killed, the number of implantation sites noted and the weight of the sites determined. Thyroid and adrenal weights were also measured.

 

The female rats in 100mg/kg bw dose group had normal fluid intake, maintained healthy litters and had a high rate of implantation. In dose group1000mg/kg bw ; none of the six rats had implantation sites at autopsy (, and the mothers were severely affected by this treatment. Three of nine rats died before the experiment was completed, the body weight and fluid intake of the survivors were greatly reduced and the adrenal glands enlarged, and there were many deaths among the litters whose body weights were low. Failure of implantation was probably related to the poor general state of the mothers rather than to a specific effect of test material. Hence The NOAEL for reproductive toxicity was considered to be 100 mg/kg bw/day as No effects on reproductive parameters were observed and LOAEL was considered to be 1000mg/kg bw. When female wistar rats were treated with test material orally.

 

Study 3

Study was conducted with rats to determine the effects of excess intake of test material. Females were bred to normal males, the test material was added to the diet during the latter portion of gestation and the females were permitted to litter normally. The effect of the treatment on gestation period, lactation and survival of the young was observed. Gestation time for rats was not affected; however, prolonged parturition was observed in rats. Female rats re-bred after removal from dietary iodine produced and nursed litters normally. Since LOAEL was considered 150 mg/kg bw, it is regarded that there is no reproductive toxicity at concentrations lower than 150 mg/kg bw when test material administered orally.

    Thus, Based on the data available for the read across chemical, No Observed Adverse Effect Level (NOAEL) was considered to be above 100mg/kg bw . Thus, comparing this value with the criteria of CLP regulation Ammonium iodide (12027-06-4)is not likely to classify as Reproductive toxicant.

 

Effects on developmental toxicity

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

Study duration:

subchronic

Species:

rat

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Justification for classification or non-classification

Thus, comparing this value with the criteria of CLP regulation Ammonium iodide (12027-06-4)is not likely to classify as Reproductive toxicant.