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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
toxicity to reproduction
Remarks:
other: effects on sperm parameters and estrous cycle
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: Meets generally accepted scientific standards, well documented and acceptable for assessment
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

Principles of method if other than guideline:
At the end of the exposure period (3 months), samples were collected for sperm count and motility from male animals exposed to 0, 2000, 10000 or 50000 ppm. In addition, vaginal cytology evaluations were performed on the last 12 days of the study from female animals.
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
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 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:
continuous
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
2000, 10000 or 50000 ppm
Basis:
nominal in diet
Remarks:
Doses / Concentrations:
160, 805 and 4243 mg/kg bw (males)
Basis:
other: average daily doses
Remarks:
Doses / Concentrations:
162, 780 and 4254 mg/kg bw (females)
Basis:
other: average daily doses
No. of animals per sex per dose:
10
Control animals:
yes, plain diet

Examinations

Parental animals: Observations and examinations:
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
Oestrous cyclicity (parental animals):
Evaluation of vaginal smears, cycle length and the number of cycles
Sperm parameters (parental animals):
testis weight, sperm count in testes, sperm count in epididymides, enumeration of cauda epididymal sperm reserve, sperm motility
Postmortem examinations (parental animals):
SACRIFICE
- Male and female animals: All surviving animals


HISTOPATHOLOGY / ORGAN WEIGHTS
Organ weights of liver, right kidney, heart, lungs, thymus and right testis

Results and discussion

Results: P0 (first parental animals)

Effect levels (P0)

Dose descriptor:
NOAEL
Remarks on result:
not determinable
Remarks:
no NOAEL identified Generation not specified (migrated information)

Overall reproductive toxicity

Reproductive effects observed:
not specified

Any other information on results incl. tables

Effects on systemic repeated dose toxicity after oral exposure are described in detail in section 7.5.1.

Reproductive organ weights were not affected.

Sperm parameters of exposed animals were similar of those of control animals. Evaluation of vaginal smears did not reveal any significant differences among the females in the amount of time spent in different estrous stages, the cycle length or the number of cycles. There was a significant increase in the number of females with regular cycles in the high dose group only.

Applicant's summary and conclusion