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Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Additional information

This study was conduced to provide initial information concerning possible effects of Vegeflux Soy on reproduction and/or developmental when administered orally, by gavage, to male and female rats using an OECD 421 protocol (according to GLP).

The Wistar rats, 48 adult males and 48 adult females were divided to four groups.Vegeflux Soy was administered at doses of 200, 500 and 1000 mg.kg-1in olive oil; the control group of rats received the vehicle at an equivalent volume. The administered dose was calculated on the current body weight. Fixed application volume 0.5mL/100g body weight was administered.

The males were treated 42 days: 14 days before the mating procedure, 14 days during the mating procedure, and 14 days after the mating procedure. The females were exposed to effect of Vegeflux Soy 41 – 51 days: 14 days before the mating procedure, at most 14 days during the mating process, 22 - 24 days the gestation, and 4 days during the lactation.

All animals were weighted weekly. The litters were weighted 24 hours after the birth and on day 4 post-parturition. All animals were monitored for the signs of toxicity during the application of the test substance. During study clinical observation and food consumption were recorded. After finishing of the test all animals were sacrificed and moved to the histological evaluation. The results were elaborated in form of tables.

 

There was no test article-related mortality of animals during the study. There were no clinical signs of toxicity in all animals during observation period. The temporary occurrence of alopecia and smooth stool in animals were registered. The lethargy in three males (one male in each tested group except control group) was registered, too. These incidences were not being indicated relation to the test article treatment.

The body weight of all animals moderately increased during the study. There were not significant differences between of all tested groups and the control groups. The food consumption in all animals was adequate.

After 8th day of beginning mating procedure two males were replaced (one in dose group 500mg.kg-1, and one in dose group 1000mg.kg-1). The length of pregnancy in all females was 22 – 23 days (in one female of dose group 500mg.kg-1 - 24 days).

Pup body weigh, external observation and necropsy data were comparable among the groups.  In litters of all dose levels were not found any abnormal pups. 

Copulation and fertility indices, precoital intervals, gestation lengths and pregnancy rates were comparable among the groups and no signs of prolonged delivery or unusual nesting behaviours were noted.

The indices of reproductive parameters in all dose groups against control group and number of corpora lutea and implantation sites in all females were stable.

At termination of study in males of control and highest dose groups left of epididymis for examination of sperm parameters were used. Sperm comparative concentration, motility and morphology were monitored. These parameters in highest dose group against control group were comparable.

Detailed histological examination was performed on reproduction organs of the males and females control and highest dose groups. We have not seen pathological changes related to the effect of Vegeflux Soy.  

In all animals the kidney and liver were evaluated as the possible target organs, too. In females of control and highest dose group pathological changes related to the effect of test article were not observed. In males significant increase of liver relative weight in highest dose group, and degenerative (but not necrotic) changes (nephropathy) of kidneys in all dose groups against control group were observed.

The NOAEL (No-Observed-Adverse-Effect Level) for reproduction/developmental parameters of males and females determined in this study is > 1000mg.kg-1 bw/day, excluding the findings of male rat nephropathy.


Short description of key information:
NOAEL (reproduction/developmental parameters of males and females) > 1000mg/kg bw/day (OECD 421, GLP, rat, gavage)

Effects on developmental toxicity

Description of key information
NOAEL (reproduction/developmental parameters of males and females) > 1000mg/kg bw/day (OECD 421, GLP, rat, gavage)
Additional information

See section on fertility.

Justification for classification or non-classification

Based on the classification criteria of Annex VI Directive 67/548/EEC or UN/EU GHS, and given the absence of signs of toxicity up to the highest dose of 1000 mg/kg bw/d administered in rats by gavage in a reproduction screening study (OECD 421, GLP), no classification for reproductive and developmental toxicity is warranted according to the criteria of Annex VI Directive 67/548/EEC or UN/EU GHS.