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Administrative data

Key value for chemical safety assessment

Effects on fertility

Link to relevant study records
Reference
Endpoint:
one-generation reproductive toxicity
Remarks:
based on test type (migrated information)
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Qualifier:
according to
Guideline:
other:
Principles of method if other than guideline:
Potassium iodide (KI) was fed to male and female rats before and during breeding, to females only during gestation and lactation, at levels of 0, 0.025, 0.05 or 0.1% (w/w) of the diet. Dams in a fifth group (positive controls) were given 4 mg/kg ip of the anti-mitotic/cytotoxic drug 5-azacytidine on day 17 of gestation. The rats were evaluated for effects.
GLP compliance:
not specified
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Laboratory Supply Co., Indianapolis, IN
- Weight at study initiation: 200-240 g
- Diet (e.g. ad libitum): Purina rat chow meal
- Acclimation period: 5 days
Route of administration:
oral: feed
Vehicle:
other: Purina rat chow meal
Details on exposure:
The newborn offspring were exposed through lactating females until weaning
Details on mating procedure:
- Proof of pregnancy: The day on which sperm were found was considered to be day 0 of gestation
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
Males: 28 days
Females: 71 days
Frequency of treatment:
Daily
Details on study schedule:
Males: 14 days before mating and for 1-14 days during breeding
Females: 14 days before mating and for 1-14 days during breeding; during gestation (22 days) and lactation (21 days).
Remarks:
Doses / Concentrations:
0, About 23,45 and 90 mg/kg bw /day
Basis:
nominal in diet
0, 0.025, 0.05 or 0.1% (w/w)
No. of animals per sex per dose:
no data available
Control animals:
yes, concurrent vehicle
Positive control:
Dams were given two i.p. injections of 2 mg/kg of S-azacytidine on day 17 of gestation.
Parental animals: Observations and examinations:
BODY WEIGHT: Yes
- Time schedule for examinations: 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.

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
The potassium iodide doses, calculated from food consumption measurements, for the 0.025% potassium iodide group were 22, 22 and 34 mg/kg/day prior to breeding, during gestation and during lactation, respectively, for females; for the 0.05% potassium iodide group they were 46, 44 and 66mg/kg/day; and for the 0.1% potassium iodide group they were 93, 92 and 140 mg/kg/day respectively.
Litter observations:
PARAMETERS EXAMINED
The following parameters were examined in [F1 / F2 / F3] offspring:
Incisor eruption was observed daily from day 8 until all incisors were visible. Eye opening was observed daily from day 10 until both eyes were fully open in all rats.Testicular development was checked each day from day 10 until both testes could first be seen as two small nodules in the scrotum.
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.
The reduction in weight in the 90 mg/kg group was 7.7% on day 14 and 7.3% on day 21, for males and females combined. The reduction in weight in the 45 mg/kg group was 12.5% on day 14 and 6.8% on day 21, males and females combined.
Statistics:
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 un-equal group sizes were made using the procedure of Kramer.
Clinical signs:
not examined
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
minor effects on parental weight gain and food consumption
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
minor effects on parental weight gain and food consumption
Organ weight findings including organ / body weight ratios:
not examined
Histopathological findings: non-neoplastic:
not examined
Other effects:
not examined
Reproductive function: oestrous cycle:
not examined
Reproductive function: sperm measures:
not examined
Reproductive performance:
no effects observed
Description (incidence and severity):
no significant effects on parental mortality, fertility, pregnancy maintenance, or gestation length
Dose descriptor:
LOEL
Effect level:
ca. 90 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: see 'Remark'
Clinical signs:
no effects observed
Description (incidence and severity):
Upper and lower incisor eruption and eye opening were unaffected by treatment.
Mortality / viability:
mortality observed, treatment-related
Description (incidence and severity):
Potassium iodide produced significant increases in offspring mortality in the 90 mg/kg group at birth and up to day 24 after birth.
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Potassium iodide decreased preweaning body weights in both the 90 and 45 mg/kg groups
Sexual maturation:
no effects observed
Description (incidence and severity):
Testicular development was unaffected by treatment.
Organ weight findings including organ / body weight ratios:
no effects observed
Description (incidence and severity):
No significant effect was found on absolute or relative thyroid weight at 90 days of age.
Gross pathological findings:
not examined
Histopathological findings:
not examined
Reflex behaviour:
• KI delayed auditory startle at the two highest doses by 1 day but did not significantly affect surface-righting or negative geotaxis behaviour.
• The 45mg/kg and 90 mg/kg potassium iodide groups showed delayed olfactory orientation towards their home-cage scent, but only in the 45mg/kg group the delay was significant
Dose descriptor:
LOEL
Generation:
F1
Effect level:
ca. 45 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Decreased pre-weaning body weights, delay in auditory startle and delayed olfactory orientation from the home-cage scent
Reproductive effects observed:
not specified
Conclusions:
The LOEL value for potassium iodide administered in diet to Sprague-Dawley rats is found to be about 90 mg/kg/day (0.1%)
At this dose level, KI produced no significant reductions in parental body weight or food consumption, though it significantly reduced litter size and increased offspring mortality.

For the F1 generation, the LOEL value was found to be about 45 mg/kg/day (0.05%) based on the effect of decreased pre-weaning body weights in the offspring, delay in auditory startle and delayed olfactory orientation from the home-cage scent.
Executive summary:

The effect of ingestion of potassium iodide by parents on the behavioural competence of developing animals is studied.

 

Potassium iodide (KI) was administered in diet to male and female Sprague-Dawley rats before and during breeding, to females only during gestation and lactation, at levels of 0, about 23,45 and 90 mg/kg bw [0, 0.025, 0.05 or 0.1% (w/w)]. Dams in a positive control group were given 4 mg/kg ip of the anti-mitotic/cytotoxic drug 5-azacytidine on day 17 of gestation.

 

The LOEL value for potassium iodide in rats is found to be about 90 mg/kg/day (0.1%). At this dose level, KI did not produce any significant reduction in parental body weight or food consumption, though it significantly reduced litter size and increased offspring mortality.

 

The LOEL value for potassium iodide is found to be about 45 mg/kg/day (0.05%) for the F1 generation based on the effect of decreased pre-weaning body weights in the offspring, delay in auditory startle and delayed olfactory orientation from the home-cage scent. Overall, the data in this experiment support the view that potassium iodide at doses of up to 0.1% in the diet of growing rats produces evidence of developmental toxicity.
Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LOAEL
45 mg/kg bw/day
Study duration:
chronic
Species:
rat
Quality of whole database:
The data is K2 level as the data has been obtained from the experimental study from the reliable journal .Based upon this available data it is expected that the test chemical Calcium iodate does not exhibit reproductive toxicity
Additional information

Toxicity to reproduction:

Based on the various studies available with Klimish rating 2 for the target as well as read across substances for CAS NO 7789-80-2, also from category based on organic functional group along with similar mechanistic approach and having structural similarities defined by QSAR toolbox. The results for target as well as analogues are summarized as follows

 

Sr. No

End point

Value

Species

Effects

Remarks

1

LOAEL

150 mg/kg bw

Rat

Effects observed on the following parameters :

Gestation time

Parturition

No signs of the beginning of lactation were observed.

Publication data for CAS NO 7681-82-5

2

LOEL

(Parental)

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

LOEL

(developmental)

90 mg/kg bw/day

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

45 mg/kg bw/day

rat

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 as it significantly reduced litter size and increased offspring mortality, but birth weights and external morphology among those born alive were not significantly altered.

 

Decreased pre-weaning body weights, delay in auditory startle and delayed olfactory orientation from the home-cage scent

Publication data for CAS NO 7681-11-0

3

LOAEL

1332 mg/kg bw/day

Rat

Decreased body weight (females and litters)

Reduced fluid intake

Enlarged adrenal glands

Prevented blastocyst implantation

Publication data for CAS NO 7681-11-0

 

Based on the studies summarized in the above table it can be observed that LOAEL values is expected to be in range of 45 - 1000 mg/kg bw/day .The effects observed on these doses was listed as follows

 

 

·        Effects observed on the following parameters: Gestation time, Parturition No signs of the beginning of lactation was observed.

·        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 as it significantly reduced litter size and increased offspring mortality, but birth weights and external morphology among those born alive were not significantly altered.

·        Decreased body weight (females and litters), Reduced fluid intake, Enlarged adrenal glands, Prevented blastocyst implantation

 

Thus based on above discussion it can be concluded that substance CAS NO 7789-80-2 is expected to show the similar toxicological effect based on the effects observed on the other category members.Since the Low effective dose value (LOAEL) is 45 mg/Kg bw/d thus based on this value it can be concluded that substance CAS NO 7789-80-2 is considered to be not toxic to reproduction below this dose level. Also there are no known evidence of adverse effect to Human of CAS NO 7789-80-2 as well as mechanistic trigger does not indicates any concern of CAS NO 7789-80-2 on toxicity to human.

 

 


Short description of key information:
The test chemical Calcium iodate does not exhibit reproductive toxicity

Justification for selection of Effect on fertility via oral route:
The effect of ingestion of potassium iodide by parents on the behavioural competence of developing animals is studied.
 
Potassium iodide (KI) was administered in diet to male and female Sprague-Dawley rats before and during breeding, to females only during gestation and lactation, at levels of 0, about 23,45 and 90 mg/kg bw [0, 0.025, 0.05 or 0.1% (w/w)]. Dams in a positive control group were given 4 mg/kg ip of the anti-mitotic/cytotoxic drug 5-azacytidine on day 17 of gestation.
 
The LOEL value for potassium iodide in rats is found to be about 90 mg/kg/day (0.1%). At this dose level, KI did not produce any significant reduction in parental body weight or food consumption, though it significantly reduced litter size and increased offspring mortality.
 
The LOEL value for potassium iodide is found to be about 45 mg/kg/day (0.05%) for the F1 generation based on the effect of decreased pre-weaning body weights in the offspring, delay in auditory startle and delayed olfactory orientation from the home-cage scent. Overall, the data in this experiment support the view that potassium iodide at doses of up to 0.1% in the diet of growing rats produces evidence of developmental toxicity.

Effects on developmental toxicity

Description of key information
The developmental toxicity TDLo (Lowest published toxic dose) of calcium iodate was observed at dose concentration of 2700 mg/kg diet in human by the oral route. This indicates that calcium iodate, shall not exhibit toxic effects to human by the oral route upto the above mentioned dose.
Link to relevant study records
Reference
Endpoint:
developmental toxicity
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Justification for type of information:
QSAR prediction: migrated from IUCLID 5.6
Qualifier:
according to
Guideline:
other:
Principles of method if other than guideline:
Data is predicted using QSAR Toolbox version 2.3
GLP compliance:
no
Species:
other: Human
Strain:
other: not applicable
Route of administration:
oral: unspecified
Type of inhalation exposure (if applicable):
not specified
Vehicle:
not specified
Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
no data
Duration of treatment / exposure:
no data
Frequency of treatment:
no data
Duration of test:
no data
Remarks:
Doses / Concentrations:
no data
Basis:
no data
No. of animals per sex per dose:
no data
Control animals:
not specified
Dose descriptor:
other: TDLo
Effect level:
2 700 mg/kg diet
Based on:
test mat.
Basis for effect level:
other: developmental toxicity
Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no data
Abnormalities:
not specified
Developmental effects observed:
not specified

The prediction was based on dataset comprised from the following descriptors: TDLo
Estimation method: Taking average value from the 5 nearest neighbours


("a" and "b" )

Domain logical expression index: "a"

Parametric boundary:The target chemical should have a value of log Kow which is >= -7.18

Domain logical expression index: "b"

Parametric boundary:The target chemical should have a value of log Kow which is <= -7.18

Conclusions:
The developmental toxicity TDLo (Lowest published toxic dose) of calcium iodate was observed at dose concentration of 2700 mg/kg diet in human by the oral route.
Executive summary:

The developmental toxicity TDLo (Lowest published toxic dose) of calcium iodate was observed at dose concentration of 2700 mg/kg diet in human by the oral route. This indicates that calcium iodate, shall not exhibit toxic effects to human by the oral route below the above mention dose.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
2 700 mg/kg bw/day
Species:
other: human
Quality of whole database:
The data is K2 level as the data has been obtained from QSAR model considered by OECD.
Additional information

Developmental Toxicity:

Based on the various studies available with Klimish rating 2 for the read across substances for CAS NO 7789-80-2 based on the category approach of organic functional group along with similar mechanistic approach and having structural similarities defined by QSAR toolbox. This data is combined with the prediction done using the QSAR toolbox for the target chemical based on similar category approach, the results is summarized as follows

 

Sr. No

End point

Value

Species

Route

Effects

Remarks

1

TDLo

2700 mg/kg diet

Human

oral

Specific Developmental Abnormalities - endocrine system.

Predicted data of target chemical

2

LOAEL

150 mg/kg bw

Rat

oral feed

Effects observed on the following parameter :

Mortality and on survival of animals

Weaning weights

 

Data from publication for CAS NO 7681-82-5

3

LOAEL

1300 mg/kg bw.day

Humans

Oral

developmental effects, prenatal-post natal hypothyroidism, later hyperthyroidism, metal retartdation

Data from publication for CAS NO 7681-82-5

4

NOAEL

(Parental)

 

 

 

NOAEL

(Developmental)

160 mg/kg/bw/day

 

 

 

160 mg/kg/bw/day

Hamster

Oral feed

No effect on survival

 

 

 

No effect on reproduction and lactation

Data from publication for CAS NO 7681-11-0

 

 

Based on the studies summarized in the above table it can be observed that LOAEL values is expected to be in range of 130 - 2700 mg/kg bw/day and the NOAEL was observed at 160 mg/kg bw/day .The effects observed on these doses was listed as follows

 

·        Effects observed on the following parameter : Mortality and on survival of animals Weaning weights

·        developmental effects, prenatal-post natal hypothyroidism, later hyperthyroidism, metal retartdation was also observed

·        No effect on survival, reproduction and lactation observed

 

Thus based on above discussion it can be concluded that substance CAS NO 7789-80-2 is expected to show the similar toxicological effect based on the effects observed on the other category members. Since the Low effective dose value (LOAEL) is 150 mg/Kg bw/d thus based on this value it can be concluded that substance CAS NO 7789-80-2 is considered to be not toxic to reproduction as well as developmental effects below this dose level. Also there are no known evidence of adverse effect to Human of CAS NO 7789-80-2 as well as mechanistic trigger does not indicates any concern of CAS NO 7789-80-2 on toxicity to human. 

 

 


Justification for selection of Effect on developmental toxicity: via oral route:
The developmental toxicity TDLo (Lowest published toxic dose) of calcium iodate was observed at dose concentration of 2700 mg/kg diet in human by the oral route. This indicates that calcium iodate, shall not exhibit toxic effects to human by the oral route below the above mention dose.

Justification for classification or non-classification

The above studies suggest that the substance calcium iodate will not be classified in reproductive toxicity category as per the C & L criteria set by EU