Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from 1997-06-04 to 1997-07-16
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report Date:
1997

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
adopted Februray 24, 1987
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Version / remarks:
92/69/EEC
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPP 81-1 (Acute Oral Toxicity)
Version / remarks:
edition November 1984
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Sodium Ascorbyl Phosphate
- Physical state: Solid (Powder); beige
- Analytical purity: 85.4 g/100 g (HPLC)
- Lot/batch No.: 28600/37-9
- Date of Manufacturing: 1997-05-02
- Storage condition of test material: room temperature
- Stability under test conditions: The stability of the test substance in aqua bidest. for a time period of 96 hours was confirmed by analysis

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
– Source: Dr. K. Thomae GmbH, Biberach, Germany
– Age at study initiation: young adult animals
– Weight at study initiation: animals of comparable weight; (150g – 300g) (+/- 20% of the mean weight)
- fasting period before study: the animals were given no feed at least 16 hours before administration, but water was available ad libitum.
- Housing: single housing. Typ of cage: stainless steel wire mesh cages, type DK-III (Becker & Co., Castrop-Rauxel, Germany).
– Bedding: No bedding in the cages, sawdust in the waste trays.
- Diet (e.g. ad libitum): Kliba-Labordiaet 343, Klingentalmühle AG; Kaiseraugst, Switzerland, ad Libitum.
- Water (e.g. ad libitum): tap water ad libitum per day.
- Acclimation period: acclimatization for at least 1 week


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24°C
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light): 12 hrs/12 hrs (6.00 A.M. - 6.00 P.M./ 6.00 P.M. - 6.00 A.M.)


IN-LIFE DATES: From: 1997-06-04 To: 1997-06-18

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 50 g/100 mL
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: AQUEOUS FORMULATION CORRESPONDS TO THE PHYSIOLOGICAL MEDIUM and test item is sufficient soluble in it.
- Purity: Aqua bidest


MAXIMUM DOSE VOLUME APPLIED:
10.00 mL/kg bw
Doses:
Single Dose: 5000 mg/kg bw
No. of animals per sex per dose:
5 male, 5 female
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: individual body weights shortly before application (day 0), weekly thereafter and at the end of the study (before fasting period). Recording of signs and symptoms several times on the day of administration, at least once each workday for the individual animals, a check for any dead or moribund animal was made twice each workday and once on Saturdays, Sundays and on public holidays.
- Necropsy of survivors performed: yes. Necropsy at the last day of the observation period. Withdrawal of food at least 16 hours before killing with CO2, then necropsy with grosspathology examination. Necropsy of all animals that died before as early as possible.
Statistics:
The binomial test (Snedecor G.W., Cochran W.G. (1989), statistical methods, 8th ED., Iowa State University Press/Ames) was used for LD50 determination.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Remarks on result:
other: 1% significance level
Mortality:
No mortality
Clinical signs:
Male animal symptoms: symptoms of the male animals (cageside observations):
impaired general state H0 – H5
poor general state H1 – H3
dyspnoea H0 – H5
apathy H1 – H3
staggering H0 –H5
piloerection H1 –H5
diarrhea H3 –H5
H: hour

number of the male animals showing symptoms: no. of animals: 5
impaired general state 5
poor general state 2
dyspnoea 5
apathy 2
staggering 5
piloerection 5
diarrhea 5

female animal symptoms: symptoms of the female animals (cageside observations):
impaired general state H0 – H3
dyspnoea H0 – H5
apathy H0 – H3
staggering H0 – H4
piloerection H1 – H5 diarrhea H1 – H5
H: hour

number of female animals showing symptoms: No. of animals: 5
impaired general state 5
poor general state 5
dyspnoea 5
apathy 5
staggering 5
piloerection 5
diarrhea 5
Body weight:
Mean body weight of the male animals
before application: Day0 191 g
after: Day7 263 g, Day13 301 g

Mean body weight of the female animals:
before application Day0 180 g
after: Day7 205 g, Day13 218 g


MEAN BODY WEIGHT OF THE FEMALE ANIMALS:
BEFORE APPLICATION: DAY0 180 g
AFTER: DAY7 205 g, DAY13 218 g
Gross pathology:
no particular findings

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information
Conclusions:
The acute oral toxicity of sodium ascorbyl phosphate was determined according to OECD guideline 401. The LD50 was >5000 mg/kg bw.