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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
toxicity to reproduction
Remarks:
other: Chronic
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)

Data source

Reference
Reference Type:
publication
Title:
Comparative subacute toxicity for rabbits of citric, fumaric, and tartaric acids
Author:
Packman EW, Abbott DD and Harrisson JWE
Year:
1963
Bibliographic source:
Toxicology and applied pharmacology 1963; 5 (2): 163-167.

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
no data
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
not specified
Details on test material:
No further information on test material idendity are available.

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male

Administration / exposure

Route of administration:
oral: feed
Type of inhalation exposure (if applicable):
not specified
Details on exposure:
Sodium salts of tartaric acids was incorporated into the diets of the test animals.
The diets and water were provided ad libitum throughout the test period.
Details on mating procedure:
no data
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
150 days
Frequency of treatment:
no data
Details on study schedule:
no data
Doses / concentrations
Remarks:
Doses / Concentrations:
7.7%
Basis:
no data
No. of animals per sex per dose:
Sixty rabbits (male), randomly divided into 4 groups of 15 animals each.
Control animals:
yes
Details on study design:
The mary purpose of the study was to acquire additional information relating to the safety of sodium tartratee when fed at high dietary levels to rabbits and to investigate the effects on the rabbit's testes.
Positive control:
no data

Examinations

Parental animals: Observations and examinations:
Each animal was examined daily, and food intake and body weights were recorded at weekly intervals.
- growth and survival
- blood and urine studies
- organ weights
- pathology
At the conclusion of the study (150 days), all surviving animals were sacrificed, and gross and histologic studies were carried out.
For organ weights: mean ± standard deviation, expressed as g/kg bw.
Oestrous cyclicity (parental animals):
no data
Sperm parameters (parental animals):
no data
Litter observations:
no data
Postmortem examinations (parental animals):
no data
Postmortem examinations (offspring):
no data
Statistics:
no data
Reproductive indices:
no data
Offspring viability indices:
no data

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
effects observed, treatment-related
Body weight and weight changes:
effects observed, treatment-related
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Other effects:
effects observed, treatment-related

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
effects observed, treatment-related
Description (incidence and severity):
3 animals exhibited small testes, and 1 control animal showed calcification of the right testicle. The smaller gonads appeared to be related to an inguinal position
Reproductive performance:
not specified

Effect levels (P0)

Dose descriptor:
NOAEL
Based on:
test mat.
Sex:
male
Basis for effect level:
other: No significant toxic effeet oceurred in rats fed diets containing 7.7% of sodium tartrate
Remarks on result:
not determinable
Remarks:
no NOAEL identified Generation: no data (migrated information)

Results: F1 generation

General toxicity (F1)

Clinical signs:
not specified
Mortality / viability:
not specified
Body weight and weight changes:
not specified
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings:
not specified

Overall reproductive toxicity

Reproductive effects observed:
not specified

Any other information on results incl. tables

The following organs were weighed at autopsy: adrenals, bladder, brain, heart, kidneys, liver, lung, prostate, spleen, stomach, testes, and thyroid. The histologic changes observed in the experimental groups were similar to those seen in the control group. Mild focal pyelonephritis, moderate congestion, mild hyperplasia of tubular epithelium, and occasionai protein casts and hyaline droplet' degeneration were noted in the kidneys, while livers of rabbits in ali groups exhibited pericholangitis, bile duct proliferation, and dilatation as well as moderate congestion. These changes are not unusual in rabbits and are not to be attributed to the experimental feeding.

Examination of the testes revealed that the seminiferous tubules, the interstitial cells, and spermatogenesis were normal in all groups. Slight peritubular fibrosis and mild stromal hyalinization were observed in each group after 150 days of feeding.

Applicant's summary and conclusion

Conclusions:
No significant differences attributable to the experimental feeding could be found in any case; either grossly or microscopically. Thus, the rabbit does not appear to be affected by the inclusion of these substances in the diet for a period of 150 days.
It must be noted that the rabbits' testes are generally small, diffuse, easily dehydrated, and subject to variation in size and position. This species, therefore, is not ideai for the study of testicular pathology.
Executive summary:

The effects of sodium tartrate when fed to rabbits for 150 days at concentrations equivalent to 5.0% of the organic acid in the diet were investigated. Particular attention was given to the possible appearance of testicular toxicity. No significant gross or histopathologic changes attributable to the experimental feeding could be found in any case.