Bismuth bromide iodide oxide

Toxicity to reproduction

Administrative data

Endpoint:

one-generation reproductive toxicity

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1984

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Developmental toxicity and psychotoxicity of potassium iodide in rats: a case for the inclusion of behaviour in toxicological assessment.

Author:

Vorhees CV, Butcher RE, Brunner RL

Year:

1984

Bibliographic source:

Food and Chemical Toxicology, Vol 22 (12): 963-970

Materials and methods

Principles of method if other than guideline:

Potassium iodide was fed to male and female rats before and during breeding, to females only during gestation and lactation, and to their offspring after weaning (day 21 after birth) through to day 90, at levels of 0, 0.025, 0.05 or 0.1% (w/w) of the diet. The screening test battery of Cincinnati Psychoteratogenicity for rats as the method for assessing the psychotoxic potential of potassium iodide was used to investigate the hazard effects to parents and developmental toxic effects to embryo and offspring in 90 days.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Potassium iodide

EC Number:

231-659-4

EC Name:

Potassium iodide

Cas Number:

7681-11-0

Molecular formula:

IK

IUPAC Name:

potassium iodide

Details on test material:

Food grade potassium iodide (Mallinckrodt Inc.) was purchased from the Tab Chemical Company, Chicago, IL.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

Potassium iodide was fed to male and female rats before and during breeding, to females only during gestation and lactation, and to their offspring after weaning (day 21 after birth) through to day 90, at levels of 0, 0.025, 0.05 or 0.1% (w/w) of the diet. The screening test battery of Cincinnati Psychoteratogenicity for rats as the method for assessing the psychotoxic potential of potassium iodide was used to investigate the hazard effects to parents and developmental toxic effects to embryo and offspring in 90 days.

Frequency of treatment:

Daily in feed

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0.025 other: % in diet

Doses / concentrations 2

Dose / conc.:

0.05 other: % in diet

Doses / concentrations 3

Dose / conc.:

0.1 other: % in diet

No. of animals per sex per dose:

Not specified

Control animals:

yes, concurrent no treatment

Positive control:

A separate group of dams (positive controls) were given 4 mg/kg bw ip of the anti-mitotic/cytotoxic drug 5-azacytidine on day 17 of gestation.

Examinations

Parental animals: Observations and examinations:

CAGE SIDE OBSERVATIONS: Yes
BODY WEIGHT: Yes
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): yes

Litter observations:

All offspring were reared by their natural dams and were evaluated blind with respect to treatment in a battery of standardized behavioural tests between 3 and 90 days of age. The following parameters were further examined: litter size, birth weight, external malformations, offspring mortality, body weight and weight gain, brain and thyroid weight.

Postmortem examinations (offspring):

Brain and thyroid weights were determined.

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:

no effects observed

Mortality:

not specified

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

not specified

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

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Immunological findings:

not examined

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 / performance (P0)

Reproductive function: oestrous cycle:

not specified

Reproductive function: sperm measures:

not specified

Reproductive performance:

no effects observed

Details on results (P0)

KI produced no significant reductions in parental body weight or food consumption

Effect levels (P0)

Key result

Dose descriptor:

NOAEL

Effect level:

0.1 other: % in diet

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no adverse effects observed at the highest tested dose

Remarks on result:

not determinable due to absence of adverse toxic effects

Target system / organ toxicity (P0)

Critical effects observed:

no

Results: F1 generation

General toxicity (F1)

Clinical signs:

not specified

Mortality / viability:

mortality observed, treatment-related

Description (incidence and severity):

KI significantly increased offspring mortality at the highest dose.

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

KI produced decreased weight gain at the two highest doses throughout the first 90 days after birth.

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

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

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Sexual maturation:

not examined

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Description (incidence and severity):

In rats killed on day 90 after birth KI reduced brain and body weight at a dose of 0.1% of the diet, and reduced body but not brain weight at a dose of 0.05% of the diet. No significant effect was found on absolute or relative thyroid weight at 90 days of age.

Gross pathological findings:

not specified

Histopathological findings:

not specified

Other effects:

effects observed, treatment-related

Description (incidence and severity):

Functionally, KI delayed auditory startle at the two highest doses, delayed olfactory orientation to the home-cage scent at the middle dose and decreased female running-wheel activity at all dose levels.

Developmental neurotoxicity (F1)

Behaviour (functional findings):

effects observed, treatment-related

Description (incidence and severity):

Functionally, KI delayed auditory startle at the two highest doses, delayed olfactory orientation to the home-cage scent at the middle dose and decreased female running-wheel activity at all dose levels.

Developmental immunotoxicity (F1)

Developmental immunotoxicity:

not examined

Effect levels (F1)

Key result

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

0.025 other: % in diet

Based on:

test mat.

Sex:

male/female

Basis for effect level:

mortality

body weight and weight gain

Target system / organ toxicity (F1)

Key result

Critical effects observed:

yes

Lowest effective dose / conc.:

0.05 other: % in diet

System:

endocrine system

Organ:

thyroid gland

Overall reproductive toxicity

Key result

Reproductive effects observed:

yes

Lowest effective dose / conc.:

0.05 other: % in diet

Treatment related:

yes

Relation to other toxic effects:

reproductive effects in the absence of other toxic effects

Dose response relationship:

yes

Relevant for humans:

not specified

Applicant's summary and conclusion

Conclusions:

In the study with rats, in which potassium iodide was administered in diet at 0.025%, 0.05% and 0.1% to male and female rats before and during breeding, to females only during gestation and lactation, and to their offspring after weaning (day 21 after birth) through to day 90, the NOAEL for developmental toxicity was 0.025% in diet, based on decreased body weight and weight gain and delayed auditory startle at the two top dose levels. The NOAEL for parental toxicity was 0.1% in diet.

Executive summary:

Potassium iodide (KI) was fed to male and female rats before and during breeding, to females only during gestation and lactation, and to their offspring after weaning (day 21 after birth) through to day 90, 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 bw ip of the anti-mitotic/cytotoxic drug 5-azacytidine on day 17 of gestation. All offspring were reared by their natural dams and were evaluated blind with respect to treatment in a battery of standardized behavioural tests between 3 and 90 days of age. KI produced no significant reductions in parental body weight or food consumption, though it significantly reduced litter size and increased offspring mortality at the highest dose, and decreased weight gain at the two highest doses throughout the first 90 days after birth. Functionally, KI delayed auditory startle at the two highest doses, delayed olfactory orientation to the home-cage scent at the middle dose and decreased female running-wheel activity at all dose levels. In rats killed on day 90 after birth KI reduced brain and body weight at a dose of 0.1% of the diet, and reduced body but not brain weight at a dose of 0.05% of the diet. No significant effect was found on absolute or relative thyroid weight at 90 days of age. Several additional behavioural effects were observed in the low-dose KI group, but because these effects were not dose-dependent, they were not regarded as reliable. 5-Azacytidine produced evidence of substantially greater developmental toxicity than KI. It was concluded that KI produced evidence of developmental toxicity consistent with a picture of impaired thyroid function. The parental NOEL value for potassium iodide in rats was 0.1% in diet, while the NOAEL for offspring was0.025% in diet.