Dysprosium and europium doped strontium dialuminium tetraoxide(monoclinic)

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

04 October to 15 November 1994

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study undertaken at a GLP accredited laboratory, to internationally accepted guidelines

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Report date:

1995

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)

Deviations:

yes

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Luminova

IUPAC Name:

Luminova

Details on test material:

- Name of test material (as cited in study report): LumiNova
- Substance type: Luminous
- Physical state: Powder
- Analytical purity: 100% w/w
- Lot/batch No.: NR-003-1
- Expiration date of the lot/batch: May 1996
- Stability under test conditions:
- Storage condition of test material: In the dark at room temperature in dry conditions.

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Laboratory animal supplier
- Age at study initiation: 5 weeks
- Weight at study initiation: males, 127.1 to 146.9 g and females, 113.0 to 129.5 g
- Fasting period before study: no data
- Housing: Individually in staniless stell cages with wire mesh floor.
- Diet: MF pelleted diet ad libitum
- Water: ad libitum
- Acclimation period: yes, no data.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 ± 2°C
- Humidity (%): 55 ± 10%
- Air changes (per hr): 10 - 15
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: To:

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS:

DIET PREPARATION
- Rate of preparation of diet (frequency): Weekly
- Mixing appropriate amounts with (Type of food):
- Storage temperature of food: no data

VEHICLE
- Justification for use and choice of vehicle (if other than water):
- Concentration in vehicle: 2.0, 0.4 and 0.1% w/v
- Amount of vehicle (if gavage): 10% w/v
- Lot/batch no. (if required): 147RTT, Fujisawa-astra
- Purity:

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

Test duration: 28 days

Frequency of treatment:

Dosing regime: 7 days/week

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
10 mg / kg / day
Basis:
nominal in diet

Doses / concentrations 2

Remarks:

Doses / Concentrations:
40 mg / kg / day
Basis:
actual ingested

Doses / concentrations 3

Remarks:

Doses / Concentrations:
200 mg / kg / day
Basis:
actual ingested

Doses / concentrations 4

Remarks:

Doses / Concentrations:
1000 mg / kg / day
Basis:
actual ingested

No. of animals per sex per dose:

Male: 6 animals at 0 mg/kg bw/day
Male: 6 animals at 10 mg/kg bw/day
Male: 6 animals at 40 mg/kg bw/day
Male: 6 animals at 200 mg/kg bw/day
Male: 6 animals at 1000 mg/kg bw/day
Female: 6 animals at 0 mg/kg bw/day
Female: 6 animals at 10 mg/kg bw/day
Female: 6 animals at 40 mg/kg bw/day
Female: 6 animals at 200 mg/kg bw/day
Female: 6 animals at 1000 mg/kg bw/day

Control animals:

yes, concurrent no treatment

Details on study design:

- Dose selection rationale: Decided from initial 14-day preliminary study.
- Rationale for animal assignment (if not random):
- Rationale for selecting satellite groups:
- Post-exposure recovery period in satellite groups: 14 days
- Section schedule rationale (if not random):

Positive control:

None

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Daily

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Daily

BODY WEIGHT: Yes
- Time schedule for examinations: Day 1, 2, 3, 5, 8, 10, 12, 14 and 15.

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: No

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes / No / No data
- Time schedule for examinations:

OPHTHALMOSCOPIC EXAMINATION: No
- Time schedule for examinations:
- Dose groups that were examined:

HAEMATOLOGY: Yes / No / No data
- Time schedule for collection of blood: At the end of the dosing and recovery period
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: no data

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: At the end of the dosing and recovery period
- Animals fasted: No data
- How many animals:No data

URINALYSIS: Yes / No / No data
- Time schedule for collection of urine: At the end of the dosing and recovery period
- Metabolism cages used for collection of urine: No data
- Animals fasted: No data

NEUROBEHAVIOURAL EXAMINATION: No
- Time schedule for examinations:
- Dose groups that were examined:
- Battery of functions tested: sensory activity / grip strength / motor activity / other:

OTHER:

Sacrifice and pathology:

GROSS PATHOLOGY: Yes (see attachment)
HISTOPATHOLOGY: Yes (see attachment)

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

There was death in one male but this was considered to be an administration error. Salivation was not considered toxicologically significant since this occurred sporadically just after administration.

Mortality:

mortality observed, treatment-related

Description (incidence):

There was death in one male but this was considered to be an administration error. Salivation was not considered toxicologically significant since this occurred sporadically just after administration.

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Description (incidence and severity):

Decreased food consumption was noted in males of 200 mg / kg group at Day 4 during the administration period, however, this change was not considered related to the treatment since there was no decrease in the 1000 mg / kg group.

Food efficiency:

not examined

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

not examined

Ophthalmological findings:

not examined

Haematological findings:

effects observed, treatment-related

Description (incidence and severity):

At the end of the recovery period there were significant differences in 1000 mg / kg group; however, these were considered to be accidental changes since these differences were not noted at the end of the administration period.

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

no effects observed

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Description (incidence and severity):

significant increase in male adrenal and female spleen weights at 1000 mg / kg.

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

not specified

Details on results:

Clinical observations: A single male animal died on day 13 of the study in the 200 mg/kg group. This death was not, however, considered to be treatment-related. No other signs of toxicity were observed.
Laboratory findings: No treatment-related changes were observed.
Effects in organs: Increases in absolute (but not relative) adrenal gland weight were noted in males from the 1000 mg/kg group at the end of the treatment period. There were, however, no abnormal histopathological findings associated with the weight increase.
No other treatment-related gross or microscopic findings were observed.

Effect levels

1

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male

Basis for effect level:

other: organ weights

2

Dose descriptor:

NOEL

Effect level:

200 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: organ weights

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Under the conditions of this study the results indicate that LumiNova should not be classified.