[No public or meaningful name is available]

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:

23 September 1996

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

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

Version / remarks:

7 days study "in the sense of the OECD 407 directive"

Deviations:

yes

Remarks:

7 days instead of 28 days study

GLP compliance:

yes (incl. QA statement)

Remarks:

quality assurance statement included

Test material

Test material information

Constituent 1

Reference substance name:

Chondroitin disaccharide deltadi-4S sodium salt

Cas Number:

136144-56-4

Molecular formula:

C14H19NO14S•2Na

IUPAC Name:

Chondroitin disaccharide deltadi-4S sodium salt

Constituent 2

Reference substance name:

α-deltaUA-[1→3]-GalNAc-6S = α-[4-deoxy-L-threo-hex-4-enopyranosyluronic acid] sodium salt-[1→3]-N-acetyl-D-galactosamine-6-sulphate

Cas Number:

136132-72-4

Molecular formula:

C14H19NO14S•2Na

IUPAC Name:

α-deltaUA-[1→3]-GalNAc-6S = α-[4-deoxy-L-threo-hex-4-enopyranosyluronic acid] sodium salt-[1→3]-N-acetyl-D-galactosamine-6-sulphate

Constituent 3

Reference substance name:

unknown metal constituents

IUPAC Name:

unknown metal constituents

Constituent 4

Reference substance name:

Chloride

Cas Number:

16887-00-6

Molecular formula:

Cl

IUPAC Name:

Chloride

Constituent 5

Reference substance name:

Ethanol

EC Number:

200-578-6

EC Name:

Ethanol

Cas Number:

64-17-5

Molecular formula:

C2H6O

IUPAC Name:

Ethanol

Constituent 6

Reference substance name:

unknown constituent

Molecular formula:

unknown

IUPAC Name:

unknown constituent

Constituent 7

Reference substance name:

Glucuronic acid

EC Number:

229-486-4

EC Name:

Glucuronic acid

Cas Number:

6556-12-3

Molecular formula:

C6H10O7

IUPAC Name:

(2S,3S,4S,5R,6R)-3,4,5,6-Tetrahydroxyoxane-2-carboxylic acid / (2S,3S,4S,5R,6R)-3,4,5,6- Tetrahydroxyoxane-2-carboxylic acid

Constituent 8

Reference substance name:

(2R,3S,5R)-3-amino-6-(hydroxyméthyl)oxane-2,4,5-triol

Cas Number:

7535-00-4

Molecular formula:

C6H13NO5

IUPAC Name:

(2R,3S,5R)-3-amino-6-(hydroxyméthyl)oxane-2,4,5-triol

Constituent 9

Reference substance name:

group of unknown constituents

Molecular formula:

unknown

IUPAC Name:

group of unknown constituents

Test material form:

solid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Details on species / strain selection:

Male and female, approximately 45 days old, male weight 200-220 g and female weight 160-180 g

Sex:

male/female

Details on test animals or test system and environmental conditions:

Acclimatization for 7 days; air-conditionned room; temperature of 20°C and humidity of 55%; regulated light/dark cycle (lighting from 7 a.m to 7 p.m).
Drinking water ad libitum and sterilized food pellets.

Administration / exposure

Route of administration:

oral: gavage

Details on route of administration:

intubation

Vehicle:

water

Remarks:

deionized water

Details on oral exposure:

gastric intubation
20 mL/kg administered volume using 5 or 10 mL syringues fitted with a stainless steel cannula

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

7 days

Frequency of treatment:

Daily

Doses / concentrations

Dose / conc.:

3 750 mg/kg bw/day (nominal)

No. of animals per sex per dose:

5 per sex, 1 dose

Control animals:

yes

Details on study design:

similar with OECD 407 protocol

Positive control:

no

Examinations

Observations and examinations performed and frequency:

Observations twice daily for 7 days, especially for the 6 hours following the administration, except on saturday and sunday:
Body weight, food and water consumption, clinical signs (symptoms, lethality), haemtology and blood chemistry, post mortem observations (organ weight, liver and kidney micropical anatomy examination)

Sacrifice and pathology:

Animals were killed 24 hours after the last treatment by exsanguination.

Other examinations:

not specified

Statistics:

ANOVA (variance analysis) and DUNNET's test if necessary to test the homogeneity of body weights before treatment, body weight values, clinical biology and organ weights values.

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 specified

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

no effects observed

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Description (incidence and severity):

In males, urea was significantly lower in treated animals when compared with control group but was considered of no clinical significance.
In females, treated animals exhibited a glycemia significantly lower than that of controls, this difference was very weak and remained in a physiological range.

Urinalysis findings:

not examined

Behaviour (functional findings):

not specified

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

effects observed, non-treatment-related

Description (incidence and severity):

The only abnormality consisted in gastric ulcer like lesions found in several control and treated animals.

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

effects observed, non-treatment-related

Description (incidence and severity):

Hepatic microgranulomas were observed in 9 control animals and 10 treated animals.
Periportal inflammation was associated with hepatic microgranulomas in 1 male control and in 2 female treated animals.
Test substance as the cause of this alteration could not be ascertained.

Histopathological findings: neoplastic:

not examined

Other effects:

not specified

Details on results:

Results comparable between treated animals and controls.
Most parameters of treated animals were unchanged, remained in a physiological range or were modified in a similar way as in controls.

Effect levels

Key result

Dose descriptor:

NOAEL

Effect level:

ca. 3 750 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: highest dose tested

Target system / organ toxicity

Key result

Critical effects observed:

no

Lowest effective dose / conc.:

3 750 mg/kg bw/day (actual dose received)

System:

hepatobiliary

Organ:

kidney

liver

Treatment related:

no

Dose response relationship:

no

Relevant for humans:

yes

Applicant's summary and conclusion

Conclusions:

The test substance was non toxic after repeated exposure by oral route during 7 days at 3750 mg/kg bw/d (only dose tested).

Executive summary:

Non toxic in male and female rats after repeated exposure by oral route during 7 days at 3750 mg/kg bw/d, only dose tested, protocol similar to OECD 407