Potassium aluminium silicate amorphous glass fibres

Repeated dose toxicity: oral

Administrative data

Endpoint:

repeated dose toxicity: oral, other

Remarks:

reproduction\developmental screening

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Fully GLP compliant and audited

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: OECD 421

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

silicon(4+) dialuminium(3+) dipotassium hexaoxidandiide

EC Number:

931-219-8

Molecular formula:

SinO(3n-1)2(n-1) polymeric anions ionically bonded to Al3+ and K2+ cations

IUPAC Name:

silicon(4+) dialuminium(3+) dipotassium hexaoxidandiide

Test material form:

solid - liquid: suspension

Remarks:

migrated information: dispersion

Details on test material:

- Name of test material (as cited in study report): Superwool 1400
- Substance type: Inorganic
- Physical state: Solid
- Analytical purity: >99%
- Impurities (identity and concentrations): trace impurities
- Purity test date: March 2011
- Lot/batch No.: BG-11-P19-2563
- Expiration date of the lot/batch: 31/12/2020
- Stability under test conditions: stable
- Storage condition of test material: room temperature, sealed container

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Margate, UK
- Age at study initiation: 10 to 12 weeks old
- Weight at study initiation: Males: 271.2 - 310.4g; Females: 172.1 - 201.7g;
- Fasting period before study: N/A
- Housing: Cages conforming to 'Code of practice for the housing and care of animals used in scientific procedures' (Home Office, London, 1989)
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25
- Humidity (%): 40 - 70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 26th January 2010 To: 6th April 2010

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: MC (Methyl cellulose)

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS: daily

VEHICLE
- Justification for use and choice of vehicle (if other than water): to ensure homogenous suspension of the substance for dosing as it is insoluble in water
- Amount of vehicle (if gavage): 10ml/kg

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Verification of composition at start and end of sampling carried out by XRF analysis, concentrations verified by gravimetric analysis of start and end samples.

Duration of treatment / exposure:

40 days to 55 days

Frequency of treatment:

daily dosing

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
250mg/kg/day
Basis:
other: nominal conc.

Doses / concentrations 2

Remarks:

Doses / Concentrations:
25mg/kg/day
Basis:
other: nominal conc.

No. of animals per sex per dose:

10

Control animals:

yes, concurrent vehicle

Details on study design:

- Dose selection rationale: The dose level for the test article was chosen after consultation with the Sponsor and based on the results of previous gavage studies on similar test articles and the physical properties of the test articles. Due to the potential risk of physical interference with gut motility, a high dose of between 50 and 100 mg/rat/day (250 mg/kg/day) was considered to be the limiting dose for this study.
A second dose of 25 mg/kg/day was adminstered to a second group of rats

Positive control:

None used

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily start and end (nominal) of the working day In addition, the animals were observed immediately on return to the home cage after dosing and at 0.5, 1, 2 and 4 hours post dose for signs of reaction to treatment for the first two weeks of dosing. As no signs were observed the animals were observed immediately on return to the home cage after dosing and at 0.5 and 1 hour post dose only from the start of the pairing period until the end of dosing.
- Cage side observations checked; ill health or overt toxicity. Any abnormalities of appearance or behaviour or other signs of reaction to treatment or ill health were recorded

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: weekly, at time of body weight examination Clinical signs for females during the gestation and lactation periods, were recorded more frequently that weekly due to days of body weight recording.

BODY WEIGHT: Yes
- Time schedule for examinations:
MALES : Day -7 (randomisation body weight check)
Weekly
Day of (prior to) necropsy
FEMALES: Day -7 (randomisation body weight check)
Weekly prior to pairing and until confirmation of mating
Days 0, 7, 14 and 20 of gestation
Days 1 and 4 post partum

FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
The food consumed by each cage of animals was determined weekly during the pre pairing periods.
Individual food intake of mated females was recorded on Days 0 to 6, 7 to 13 and 14 to 19 of gestation, and on Days 1 to 3 of lactation.

Sacrifice and pathology:

SACRIFICE
- Male animals: All surviving animals after assessment of females and offspring
- Maternal animals: All surviving animals 5 days post-partum

GROSS NECROPSY
- Gross necropsy consisted of external and internal examinations, including the cervical, thoracic, and abdominal viscera.

HISTOPATHOLOGY / ORGAN WEIGHTS
The tissues listed below were prepared for microscopic examination and weighed, respectively.
ovaries (with oviducts) testes
uterus epididymides
cervix seminal vesicles
vagina prostate
pituitary coagulating gland
gross lesions animal identification

Statistics:

Stastistical analysis used SAS

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

not examined

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:

no effects observed

Gross pathological findings:

no effects observed

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Details on results:

CLINICAL SIGNS AND MORTALITY (PARENTAL ANIMALS)
There was one death during the study; the cause of demise was a gavage injury, and not related to Superwool 1400 administration.
There were no clinical observations recorded that were considered to be related to administration with Superwool 1400.

BODY WEIGHT AND FOOD CONSUMPTION (PARENTAL ANIMALS)
There was no adverse effect of treatment on mean body weight or body weight gain in males or females. In males and females, there was no effect of treatment on mean food intake.

REPRODUCTIVE FUNCTION: ESTROUS CYCLE (PARENTAL ANIMALS)
the majority of females mated within one oestrous cycle.
There was no effect of treatment on fertility or fecundity indices

REPRODUCTIVE FUNCTION: SPERM MEASURES (PARENTAL ANIMALS)
Qualitative testis staging did not indicate any abnormalities in the integrity of the various cell types present within the different stages of the spermatogenic cycle.

REPRODUCTIVE PERFORMANCE (PARENTAL ANIMALS)
There was no effect of treatment on mating, the majority of females mated within one oestrous cycle.
There was no effect of treatment on fertility or fecundity indices.

ORGAN WEIGHTS (PARENTAL ANIMALS)
There was no adverse effect of treatment on adult male or female organ weights.

GROSS PATHOLOGY (PARENTAL ANIMALS)
there was no effect of treatment on adult male or females

HISTOPATHOLOGY (PARENTAL ANIMALS)
Macroscopic findings
Most tissues were macroscopically unremarkable and the findings seen were generally consistent with the usual pattern of findings in rats of this strain and age. There were no macroscopic findings suggestive of effects of the test articles.
Microscopic findings
Microscopic findings were generally infrequent, of a minor nature and consistent with the usual pattern of findings in rats of this strain and age. There were no microscopic findings in treated animals due to effects of the test articles.

Effect levels

Dose descriptor:

NOAEL

Effect level:

> 250 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: overall effects

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Administration of Superwool 1400 by oral gavage to male rats for at least 55 days and to female rats for at least 41 days at 250 mg/kg/day elicited no signs of adverse toxicity.
The no observed adverse effect level (NOAEL) for reproductive and developmental toxicity was considered to be at least 250 mg/kg/day for Superwool 1400

Executive summary:

The objective of the study was to provide a preliminary evaluation of the effects of the test article, Superwool 1400, on the reproductive/developmental toxicity in the rat.

Groups of 10 male and 10 female rats were given 25 or 250 mg/kg/day of Superwool 1400 orally, by gavage, for two weeks prior to pairing, during the pairing period and until Day 4 post-partum for the females and until the day before necropsy in Week 8 for the males. A similar group of 10 males and 10 females were given 1% (w/v) methylcellulose over the same period to act as controls.

There was one death during the study; the cause of demise was a gavage injury, and not related to Superwool 1400 administration.

There were no clinical observations recorded that were considered to be related to administration with Superwool 1400.

Mean body weight gains and food intake were unaffected by administration with Superwool 1400.

Mating data were unaffected by Superwool 1400 administration and there was no effect on mean uterine/implantation data or mean litter data.

Mean organ weights were unaffected by Superwool 1400 administration. At necropsy, macroscopic findings were unremarkable.

There were no microscopic findings or findings in the testis, suggestive of effects due to Superwool 1400 administration.

In conclusion, administration of Superwool 1400 by oral gavage to male rats for at least 54 days and to female rats for at least 41 days at 25 or 250 mg/kg/day elicited no signs of adverse toxicity.

The no-observed-adverse-effect-level (NOAEL) for repeated oral toxicity was considered to be at least 250 mg/kg/day.