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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study is done according to OECD TG 421 under GLP
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: OECD TG 421
Deviations:
no
GLP compliance:
yes (incl. certificate)
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Wistar
Details on test animals and environmental conditions:
See 7.8.1

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on exposure:
see IUCLID 7.8.1
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
see IUCLID 7.8.1
Details on mating procedure:
see IUCLID 7.8.1
Duration of treatment / exposure:
see IUCLID 7.8.1
Frequency of treatment:
see IUCLID 7.8.1
Duration of test:
see IUCLID 7.8.1
Doses / concentrations
Remarks:
Doses / Concentrations:
see IUCLID 7.8.1
Basis:

Results and discussion

Results: maternal animals

Effect levels (maternal animals)

Dose descriptor:
NOAEL
Effect level:
>= 120 mg/kg bw/day (actual dose received)
Based on:
test mat.
Basis for effect level:
other: developmental toxicity

Results (fetuses)

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Cashmeran is not a developmental toxic substance. No effects were seen at 120 mg/kg bw
Executive summary:

A reproscreening study in accordance with OECD 421 was performed to determine the reprotoxic/developmental toxic potential of Cashmeran. Cashmeran was given orally in the diet to Wistar rats at 0, 150, 600 or 1875 mg Cashmeran/kg food during a premating period of 2 weeks and during mating (1 week), gestation and lactation until postnatal day 4. The homogeneity, stability and content of the test substance in the diets were confirmed by analysis.

No treatment-related changes in appearance, general condition or behaviour of the animals were observed. Mean body weight and body weight change were slightly decreased in the high dose group of the male animals. Also, food consumption was slightly decreased in this dose group, in both male and female animals. The effects on body weight could only partly be explained by the decrease in food consumption, therefore, this effect was considered to be treatment-related.

Increased organ weights (kidney and liver) were observed in male rats at the mid- and high-dose. At the low dose level also an increase was observed, however, this increase was considered to be minimal. No treatment-related effects on organ weight were observed in females. Histopathologically, an increased incidence of basophilic tubules was observed at the low-, mid- and high-dose. In the low- and mid-dose this increase was considered not toxicologically relevant due to the high incidence in the control and absence of increase in severity. Specific assessment of alpha-2u-microglobulins did not demonstrate treatment-related differences. Therefore it was concluded that no histopathological changes were observed that could explain the increased kidney weights in the treated animals.

No treatment related effects were observed in reproduction indices, except for a statistically significant increase in pre-implantion loss in the highest dose group. However, as this effect was mainly due to 2 females in this group and the mean pre-implantation loss was within the historical control range, this effect was considered to be not related to treatment. No treatment-related effects on pups were observed.

Based on the results, the NOAELparental is considered to be 150 mg/kg food, corresponding to an overall intake of 9.76 mg/kg bw/d for males. No effects were observed on fertility and the development. Therefore, the NOAELfertility/developmental toxicity is 1875 mg/kg food, corresponding to 115.24 mg/kg bw/d for males and 121.83 mg/kg bw/d for females. Based on these results, Cashmeran is considered to be not reprotoxic/toxic for the development.