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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information

Under the conditions of the test (OECD TG 421, GLP), the systemic NOAEL is determined to be 150 mg/kg food, corresponding to 9.76 mg/kg bw based dose related effects on organ weights (liver and kidneys) in males. In females no adverse systemic effects were seen.

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Study duration:
subacute
Species:
rat
Quality of whole database:
The study is sufficiently adequate to cover the fertility endpoint.
Additional information

In a reproscreening study (OECD TG 421, GLP) test substance was given orally in the diet to Wistar rats at 0, 150, 600 or 1875 mg/kg food during a premating period of 2 weeks and during mating (1 week), gestation and lactation until postnatal day 4. Doses were selected based in a 2-week dose-range finding study with the test substance in rats. The control group received the vehicle only (diet).


Results:


Clinical signs: Daily clinical observations during the premating, gestation and lactation period did not reveal any treatment-related changes in the animal’s appearance, general condition or behaviour. Mean body weight of male animals of the high dose group were slightly (<10%) but statistically significantly decreased during the dosing period and the mean body weight gain of these animals was statistically significantly decreased between days 7-14, 21-28 and 0-28.


A slightly, but statistically significant decrease in food consumption was observed in the male and female animals of the high dose group during the first week of the study, most probably related to the palatability of the diets containing a high concentration of the test substance. Since the effect on body weight gain in the male animals could only be partly explained by the lower food consumption during the first week of the dosing period, the effects on body weight gain of the high dose males were considered treatment related.


Organ effects: In males increased relative liver weight was seen: 9, 20 and 31% in the low, mid and high dose respectively of which the high dose may be considered adverse but not histopathology was performed and makes it difficult to assess its adversity. In females the increase was only 9% at the high dose and not considered adverse.


In males increased relative kidney weight were seen: 7, 14 and 22%, in the low, mid and high dose, respectively. In females this increase was 6%. In males, histopathology showed an increase in basophilic tubili: 3, 6, 6 and 12/12 animals, reaching statistical significance at the high dose. This high dose effects are considered adverse. Specific assessment of alpha-2u-microglobulins did not demonstrate treatment-related differences.


In females of all dose groups no effects on liver or kidney weigh were observed.


Fertility: No treatment related effects were observed in reproduction indices, except for a statistically significant increase in pre-implantation 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.


Developmental: No treatment-related effects on pups were observed.


Conclusion: 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. 


 


Justification for selection of Effect on fertility via oral route:
A reproscreening study is available and conducted according to OECD-guideline and under GLP conditions, which is adequate for covering this endpoint.

Effects on developmental toxicity

Description of key information

Under the conditions of the test (OECD TG 421, GLP), The NOAEL for fertility and developmental toxicity was determined to be 1875 mg/kg food, corresponding to 115.24 mg/kg bw/d for males and 121.83 mg/kg bw/d for females, respectively. The lower value will be used for the risk assessment.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Study duration:
subacute
Species:
rat
Quality of whole database:
The study is partly adequate to cover the developmental toxicity endpoint. A test proposal for an OECD TG 414 study is added, in order to fulfill the REACH information requirements.
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

The executive summary is the same as for Toxicity to reproduction, (OECD 421, GLP) see above. 



Justification for selection of Effect on developmental toxicity: via oral route:
A prenatal developmental toxicity study (OECD TG 414) is proposed according to OECD-guideline and under GLP conditions, which is adequate for covering this endpoint.

Justification for classification or non-classification

Based on the results of the available Repeated dose and Reproductive toxicity studies the substance does not have to be classified for reproductive toxicity (fertility and developmental toxicity) according to EU CLP (EC 1272/2008 and its amendments).

Additional information