Dodecairon strontium nonadecaoxide

Toxicity to reproduction

Administrative data

Endpoint:

screening for reproductive / developmental toxicity

Remarks:

based on test type (migrated information)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2010-07-26 to 2010-10-22

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Data generated according to generally valid testing guideline.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)

Deviations:

yes

Remarks:

Minor deviations which do not significantly impact the validity of the study

GLP compliance:

yes (incl. QA statement)

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Dodecairon strontium nonadecaoxide

EC Number:

234-685-4

EC Name:

Dodecairon strontium nonadecaoxide

Cas Number:

12023-91-5

Molecular formula:

Fe12O19.Sr

IUPAC Name:

dodecairon(3+) strontium(2+) nonadecaoxidandiide

Details on test material:

- Name of test material (as cited in study report): Strontiumhexaferrite ("Manipermpulver")
- Analytical purity: 100 % industrial strontiumferrite
- Impurities (identity and concentrations): see section 1.2 of the IUCLid5.2-file
- Composition of test material, percentage of components: see section 1.2 of the IUCLID5.2-file
- Lot/batch No.: S16/179/08
- Expiration date of the lot/batch: 12/2999
- Stability under test conditions: stable
- Storage condition of test material: air-conditioned romm temperature, non-sterile

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:National University of Singapore, Centre for Animal resources (CARE), 7 Perahu road, Singapore 718836
- Age at study initiation: (P) x wks: 7 - 9
- Weight at study initiation: (P) Males: 314-374 g; Females: 209 -271 g
- Fasting period before study: no data
- Housing: OptimMIICE Caging IVC Systems for Rats
- Use of restrainers for preventing ingestion (if dermal): not applicable
- Diet (e.g. ad libitum): PicoLab Rodent Diet 20 5053 at libitum
- Water (e.g. ad libitum): Tap water ad libitum through plastic bottle
- Acclimation period: 5 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 - 22 °c
- Humidity (%): 30 - 70 5

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on exposure:

PREPARATION OF DOSING SOLUTIONS: The limit dose of 1000 mg/kg b.w. daily was selected. Dosing was via food and in water.

DIET PREPARATION
no data

VEHICLE
not applicable

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

Dosing of both sexes began 2 weeks prior to mating, and was kept during the 14-day mating period. Dosing of Males was terminated when 14-day mating period was completed (28 days in total), while dosing of females was continued throughout the study until day 4 post-partum.

Frequency of treatment:

The dose was given to the parental males and females daily, seven days per week continuously until their termination days, respectively.

Details on study schedule:

- Age at mating of the mated animals in the study: 8 - 10 weeks

Doses / concentrations

Remarks:

Doses / Concentrations:
300 mg/ml, suspended
Basis:
nominal in water
The dose level of 1000 mg/kg b.w. was administered in the concnetration of 300 mg/l in water

No. of animals per sex per dose:

12 male, 12 female

Control animals:

yes, concurrent vehicle

Details on study design:

- Dose selection rationale: According to OECD Guideline for the testing of Chemicals 421, the limit dose is normally used for the test substances that do not produce observable toxic effects and if toxicity is not expected. No severe toxicity was expected to the test item based on the product information provided by the sponsor. In addition, the LD50 cut-off value of the test item in acute oral toxicity study was more than 5000 mg/kg body. Therefore, the limit dose of 1000 mg/kg body weight daily was selected for this study.
- Rationale for animal assignment (if not random): random
- Other:

Positive control:

12 male, 12 female

Examinations

Parental animals: Observations and examinations:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: once a day thoughout dosing (1 week) and observation period (22 d)
- Cage side observations checked in table: Yes. Not included in IUCLID5.2-file

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Daily

BODY WEIGHT: Yes
- Time schedule for examinations: Daily

FOOD CONSUMPTION AND COMPOUND INTAKE:
- 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: no

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes
- Time schedule for examinations: Daily

OTHER:

Oestrous cyclicity (parental animals):

Observed and included in test study if exceptional

Sperm parameters (parental animals):

Parameters examined in [all/P/F1/F2] male parental generations: none
testsis weight determined after 28 d (endpoint day)

Litter observations:

STANDARDISATION OF LITTERS
- Performed on day 4 postpartum: yes
- If yes, maximum of 18 pups/litter, of which 17 alive (1 post-implantation loss)

PARAMETERS EXAMINED
The following parameters were examined in F1 offspring: number and sex of pups, stillbirths, live births, runts, postnatal mortality, presence of gross anomalies, weight gain, visual abnormalities

GROSS EXAMINATION OF DEAD PUPS: yes, for external and internal abnormalities; possible cause of death was not determined for pups born or found dead.

Postmortem examinations (parental animals):

SACRIFICE
- Male animals: All surviving animals, as soon as possible after the last litters in each generation were produced.
- Maternal animals: All surviving animals, as soon as possible.

GROSS NECROPSY
- Gross necropsy consisted ofmacroscopic findings

HISTOPATHOLOGY / ORGAN WEIGHTS
Male: weight of testis, weight of epididymis, microscopic histological examination of testis and epididymis.
Fenale: Microscopic histological examination of ovaries

Postmortem examinations (offspring):

SACRIFICE
- The F1 offspring not selected as parental animals.
- These animals were subjected to postmortem examinations (macroscopic and/or microscopic examination) as follows: Necropsy findings

GROSS NECROPSY
- Gross necropsy consisted of body weight, organ weight

HISTOPATHOLOGY / ORGAN WEIGTHS
Macroscopic findings

Statistics:

Not described in detail

Reproductive indices:

gestation lenght, number of implantation

Offspring viability indices:

Live births, post-implanttaion loss, litter size on day 4-post partum, number of abnormal pups, numbere of runts

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:

no effects observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Organ weight findings including organ / body weight ratios:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Other effects:

not examined

Description (incidence and severity):

Test substance intake: Strontium ferrite does not accumulate in the body (blood).

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:

no effects observed

Reproductive function: sperm measures:

no effects observed

Description (incidence and severity):

Weight of testis, epididymis and ovaries

Reproductive performance:

no effects observed

Details on results (P0)

No parent animal was found dead prior to endpoint day.
Toxic response (including fertility, gestation) of parent animals and reversal: No adverse effect was observed on all the parent animals of both test and control groups throughout the observation period.

Effect levels (P0)

Dose descriptor:

NOAEL

Effect level:

> 1 000 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: Not applicable - no adverse effects observed

Remarks on result:

not determinable

Remarks:

no NOAEL identified

Results: P1 (second parental generation)

Effect levels (P1)

Remarks on result:

not determinable

Results: F1 generation

General toxicity (F1)

Clinical signs:

no effects observed

Mortality / viability:

no mortality observed

Body weight and weight changes:

no effects observed

Sexual maturation:

no effects observed

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings:

no effects observed

Details on results (F1)

No toxic effect was observed on reproduction of parent animals, offspring and post-natal growth of pups.

Effect levels (F1)

Remarks on result:

not determinable

Results: F2 generation

Effect levels (F2)

Remarks on result:

not determinable

Overall reproductive toxicity

Reproductive effects observed:

not specified

Any other information on results incl. tables

No adverse effects were observed.

Applicant's summary and conclusion

Conclusions:

Based on the above study,

a) No parent animal died during the dosing and observation period

b) No adverse effect was observed on all the parent animals of both test and control groups throughout the observation period

c) No toxic effect was observed on reproduction of parent animals, offspring and post-natal growth of pups

d) No treatment-related necropsy finding was observed on the parent animals

e) No treatment-related microscopic finding was observed on the ovaries, testes and epididymides of the parent animals in both test and control groups. All findings observed were considered to re-present normal background changes in animals of this strain and age.

Hence, based on the above results, administrating the test item repeatedly at 1000 mg/kg body weight through oral route (28-day for male parents and up to post-partum Day 4 for female parents), the test item does not produce reproductive / developmental toxicity to Sprague Dawley (SD) rats.

Executive summary:

The reproductive / developmental toxicity of strontium ferrite was investigated in a screening study according to OECD guideline 421. The limit doese of 1000 mg/kg b.w. was administered to 12 male and 12 female rats (Spargue Dawley). The control group consisted of 12 animals each. Clinical observations were made for each animal of F1, toxic effects on reproducation, offspring and post-natal growth were examined.

Based on the study,

a) No parent animal died during the dosing and observation period

b) No adverse effect was observed on all the parent animals of both test and control groups throughout the observation period

c) No toxic effect was observed on reproduction of parent animals, offspring and post-natal growth of pups

d) No treatment-related necropsy finding was observed on the parent animals

e) No treatment-related microscopic finding was observed on the ovaries, testes and epididymides of the parent animals in both test and control groups. All findings observed were considered to re-present normal background changes in animals of this strain and age.

Hence, based on the above results, administrating the test item repeatedly at 1000 mg/kg body weight through oral route (28-day for male parents and up to post-partum Day 4 for female parents), the test item does not produce reproductive / developmental toxicity to Sprague Dawley (SD) rats.

It can be concluded that strontium ferrite does not produce reproductive / developmental toxicity.