Registration Dossier

Toxicological information

Repeated dose toxicity: oral

Currently viewing:

Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study in conformance with requirements of the standard repeated dose toxicity testing protocols, assessment taken from EU-RAR.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996

Materials and methods

Principles of method if other than guideline:
Study in conformance with requirements of the standard repeated dose toxicity testing protocols.
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
synthetic cryolite
purity: 96%

Test animals

Species:
rat
Strain:
other: Crl:CD(SD)BR
Sex:
male/female

Administration / exposure

Route of administration:
oral: feed
Duration of treatment / exposure:
90 days
Frequency of treatment:
continuously
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
50, 5000, and 50000 ppm
Basis:
nominal in diet
Remarks:
Doses / Concentrations:
3.8, 399.2, and 4172.3 mg/kg bw/day in males; 4.5, 455.9, and 4758.1 mg/kg bw/day in females
Basis:

No. of animals per sex per dose:
40
Control animals:
yes

Results and discussion

Results of examinations

Details on results:
At 50000 ppm male and female rats exhibited reduced body weights and decreases in haemoglobin and haematocrit. At necropsy the stomach of male and female rats receiving ≥5000 ppm exhibited thickened walls, dark contents, raised focal areas, glandular thickened walls, non-glandular light focal areas, glandular dark focal areas and red glandular areas. Microscopical examination revealed submucosal lymphoid foci, hyperplasia, hyperkeratosis/acanthosis, erosion/ulcerations, mucosal atrophy and chronic submucosal inflammation. Fluoride accumulated in bones and teeth at all dose levels. The LOAEL for fluoride accumulation for male and female rats was 50 ppm, representing 3.8/4.5 mg/kg bw/day. The NOAEL for this effect could not be determined in this study. The LOAEL for lesions observed in the stomach was 5000 ppm (399.2 mg/kg bw/day in males and 455.9 mg/kg bw/day in females). The NOAEL for stomach effects in rats was 50 ppm, representing 3.8 mg/kg bw/day in males and 4.5 mg/kg bw/day in females.

Effect levels

open allclose all
Dose descriptor:
LOAEL
Effect level:
3.8 other: mg/kg bw/day
Sex:
male
Basis for effect level:
other: fluoride accumulation in bones and teeth
Dose descriptor:
LOAEL
Effect level:
4.5 other: mg/kg bw/day
Sex:
female
Basis for effect level:
other: fluoride accumulation in bones and teeth

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion