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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
fertility, other
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1956

Materials and methods

Principles of method if other than guideline:
Rats were fed with diets containing 1.2% citric acid (about 600 mg/kg bw/day). Exposure began 29 weeks prior to mating and continued for a few months after mating. The reproduction of the rats was investigated when they were 32 weeks old and had received the diets for 29 weeks. Eleven weeks later the same animals were mated again.
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): citric acid

Test animals

Species:
rat
Strain:
not specified
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Diet (e.g. ad libitum): Basal diet: Casein 6.0 %, Dried full milk 10.0 %, Whole wheat flour 34.5 %, Potato flour 33.0 %, Peanut oil 6.5 %, Cod liver oil 0.5 %, Linseed oil 0.5 %, Brewer's yeast 5.0 %, Ca2(PO4)2 1.9 %, Na2HPO4 . 2H20 0.8 %, KCl 0.9 %, MgCO3 0.2 %, Na-citrate 0.1 %, various salts 0.1 %.

Administration / exposure

Route of administration:
oral: feed
Vehicle:
not specified
Details on exposure:
Treated rats were fed diets containing 1.2% citric acid.
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
Several months. Exposure began 29 weeks prior to mating and continued for a few months after mating.
Frequency of treatment:
Daily
Doses / concentrations
Dose / conc.:
1.2 other: % in diet
Remarks:
1.2 % (ca. 600 mg/kg bw/day)
Basis: nominal in diet
No. of animals per sex per dose:
No data
Control animals:
not specified
Positive control:
No data

Examinations

Parental animals: Observations and examinations:
Fertility of female rats.
The reproduction of the rats was investigated when they were 32 weeks old and had received the diets for 29 weeks. Eleven weeks later the same animals were mated again.
Statistics:
The statistical methods used in the evaluation of the results have been described in detail. The bilateral tail probability (p), i.e. the probability that the difference found be accidental, was calculated in each instance. The difference was considered significant, whenever p was smaller than 0.05.

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
no effects observed
Dermal irritation (if dermal study):
not examined
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not specified
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
not specified
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Other effects:
not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
not examined
Reproductive performance:
no effects observed
Description (incidence and severity):
No reproductive effects were detected.

Effect levels (P0)

open allclose all
Key result
Dose descriptor:
NOAEL
Effect level:
600 mg/kg bw/day
Based on:
test mat.
Sex:
female
Basis for effect level:
reproductive performance
Remarks on result:
other: No adverse effect observed at the highest dose tested
Key result
Dose descriptor:
LOAEL
Effect level:
> 600 mg/kg bw/day
Based on:
test mat.
Sex:
female
Basis for effect level:
reproductive performance
Remarks on result:
other: No adverse effect observed at the highest dose tested

Target system / organ toxicity (P0)

Key result
Critical effects observed:
no

Results: F1 generation

General toxicity (F1)

Other effects:
not examined

Developmental immunotoxicity (F1)

Developmental immunotoxicity:
not examined

Effect levels (F1)

Remarks on result:
not measured/tested

Overall reproductive toxicity

Key result
Reproductive effects observed:
no

Any other information on results incl. tables

No reproductive effects were detected. The NOAEL for reproductive effects was 600 mg/kg bw/day. The LOAEL was higher than 600 mg/kg bw/day for the same effects.

Applicant's summary and conclusion

Conclusions:
No reproductive effects were detected. The NOAEL for reproductive effects was 600 mg/kg bw/day. The LOAEL was higher than 600 mg/kg bw/day for the same effects.
Executive summary:

A fertility test was carried out with Citric Acid on rats. Animals were fed diets containing 1.2% citric acid (about 600 mg/kg bw/day). Exposure began 29 weeks prior to mating and continued for a few months after mating. The reproduction of the rats was investigated when they were 32 weeks old and had received the diets for 29 weeks. Eleven weeks later the same animals were mated again.

No reproductive effects were detected. The NOAEL for reproductive effects was 600 mg/kg bw/day. The LOAEL was higher than 600 mg/kg bw/day for the same effects.