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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
publication
Title:
Absence of toxic effects in F344/N rats and B6C3F1 mice following subchronic administration of chromium picolinate monohydrate.
Author:
Rhodes, M.C. et al.
Year:
2005
Bibliographic source:
Food and Chemical Toxicology 43, 21-29

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity in Rodents)
Deviations:
yes
Remarks:
limited measurements and examinations
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Chromium picolinate monohydrate, TCI America
- Analytical purity: 99%

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Taconic Laboratory Animals and Services
- Age at study initiation: 6 weeks
- Weight at study initiation: 92 g (male), 93 g (female)
- Housing: 5 per cage
- Acclimation period: 11 - 14 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.6 - 23.9
- Humidity (%): 35 - 65
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: feed
Vehicle:
other: diet (irradiated NTP-2000 open formula diet)
Details on oral exposure:
DIET PREPARATION
- Rate of preparation of diet (frequency): four times throughout the study
- Storage temperature of food: room temperature, protected from light (stability of the test substance under these conditions was at least 42 days)
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
93 days
Frequency of treatment:
ad libitum
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
80; 240; 2000; 10,000 or 50,000 ppm
Basis:
nominal in diet
Remarks:
Doses / Concentrations:
7, 19, 160, 805 and 4243 mg/kg bw (males)
Basis:
other: average daily doses
Remarks:
Doses / Concentrations:
6, 19, 162, 780 and 4254 mg/kg bw (females)
Basis:
other: average daily doses
No. of animals per sex per dose:
10 in core study and 10 per sex and dose and time point in special study (hematology and clinical chemistry analyses on days 3 and 21)
Control animals:
yes, plain diet

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: No data


DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: weekly


BODY WEIGHT: Yes
- Time schedule for examinations: day 1, weekly throughout the study and at sacrifice


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: No, food consumption was measured by cage covering a 7-day period
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data


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


OPHTHALMOSCOPIC EXAMINATION: No


HAEMATOLOGY: Yes
- Time schedule for collection of blood: on days 3, 21 and 93 (terminal sacrifice)
- Anaesthetic used for blood collection: Yes, CO2/O2
- Animals fasted: No data
- How many animals: 10
- Parameters checked: erythrocyte count, hemoglobin, packed cell volume, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelet count, reticulocyte count, nucleated red blood cell count, total leukocyte count, differential leukocyte counts, red blood cell morphology and platelet morphology


CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: on days 3, 21 and 93 (terminal sacrifice)
- Animals fasted: No data
- How many animals: 10
- Parameters checked: sorbitol dehydrogenase, alkaline phosphatase, creatine kinase, creatinine, total protein, albumin, blood urea nitrogen, total bile acids and alanine aminotransferase


URINALYSIS: No


NEUROBEHAVIOURAL EXAMINATION: No
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
Organ weights of liver, right kidney, heart, lungs, thymus and right testis
HISTOPATHOLOGY: Yes
complete (no further details given)
Statistics:
analysis of variance followed by the parametric multiple comparison procedures of Dunnett and Williams (organ and body weight), Kruskal-Wallis analysis of variance (hematology and clinical chemistry), Jonckheere's test (dose-response analysis), Cochran-Armitage and Fisher's exact test (prevalence of nonneoplastic lesions)

Results and discussion

Effect levels

Dose descriptor:
NOAEL
Effect level:
>= 2 015 mg/kg bw/day (nominal)
Sex:
male/female
Basis for effect level:
other: overall effects NOAEL converted from the tri-picolinate monohydrate to the basic acetate monohydrate

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

No deaths occured.

No significant compound-related affects on body weight, body weight gain and food consumption were observed.

Administration of the test substance did not produce clinical signs of toxicity. However, the feces of high dose animals had a reddish colour, probably because of the reddish-colour of the test substance.

There were no statistically significant hematological and clinical chemistry changes observed.

Absolute organ weights showed slight alterations in exposed animals. Male heart and liver weights showed negative trends (not dose-related, 9% less than controls in high dose group). Female right kidney weights were significantyl increased in all dosed animals (up to 12% greater than controls). These effects were, however, not considered treatment-related.

Histopathological lesions were considered spontaneous or incidental and not related to the test substance.

Effects on reproduction are described in section 7.8.

Applicant's summary and conclusion