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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
2006
Report Date:
2006

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: OECD Guideline but not TG indicated.
Principles of method if other than guideline:
The study was conducted in compliance with the good laboratory practices (US FDA, 1987), and in accordance with OECD guidelines (OECD, 1987) at Product Safety Laboratories (Dayton, NJ, USA). One group of males and one group of females were assigned to one of the four treatments: control (distilled water), low dose (30 mg test product/kg/day), intermediate dose (300 mg test product/kg/day), or high dose (1000 mg
test product/kg/day). The human exposure to the test substance, based on the label recommendation found in the dietary ‘‘supplement facts’’ panel, was up to 30 mg/kg/day. Thus, the dose levels selected for this study corresponded to 0, 1, 10, and 33 times the expected human exposure level. The highest level (33 times) is considered as a regulatory limit dose for rats and was expected to exhibit some evidence of toxicity. A NOAEL was expected at 300 mg/kg/day.
The individual doses of the test product were determined based on each animal body weight and prepared within 2 h of administration as a 0.6% (low), 6.0% (intermediate), and 20% (high) w/v solution in distilled water. All doses were volumetrically equal (100 mL) and administered orally using a stainless steel ball-tipped gavage needle attached to a syringe.
The dose administration was performed at the same time each day (± 2 h) for 92 (males) or 93 (females) consecutive days. The control animals received distilled water at the same volume (100 mL) as the test groups.
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
The test product was a patented preparation of hydrolyzed chicken sternal cartilage (BioCell Collagen II; USA Patents 6025.327; 6323319;
6780841) supplied by BioCell Technology, LLC (Anaheim, CA, USA).
The test product was a food grade (nutraceutical) powder containing minimum 60% collagen type II, 20% chondroitin sulfate, 10% hyaluronic
acid and 1% other proteoglycans as well as 0.1% lipid, and 8% ash IBC Labs (2004)

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
90 days
Frequency of treatment:
dayly
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
20% (high) w/v
Basis:
nominal in water
Remarks:
Doses / Concentrations:
6.0% w/v (intermediate)
Basis:
nominal in water
Remarks:
Doses / Concentrations:
0.6% w/v (low)
Basis:
nominal in water
No. of animals per sex per dose:
40 males and 40 females total.
10 males and 10 females per dose
Control animals:
yes

Results and discussion

Effect levels

Key result
Dose descriptor:
NOAEL
Effect level:
> 1 000 mg/kg bw/day (nominal)
Sex:
male/female
Basis for effect level:
mortality

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

There was no mortality, adverse effects or clinical signs of toxicity during the study associated with the treatment.

One male from the intermediate dose group was euthanized on day 38 after the animal was found moribund. Postmortem analysis revealed a red discharge from the animal’s eyes and nose, nasal swelling, crooked or broken teeth, and minimal stomach content. These symptoms indicated an injury sustained in the cage and were not related to the treatment.

Male and female animals treated with the test substance had an average body weight and average body weight gain comparable to those from the control group.

Applicant's summary and conclusion

Conclusions:
A GLP, OCDE Guideline study indicates a NOAEL higher that 1.000 mg/Kw bw