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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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

Toxic effect type:
dose-dependent

Effects on fertility

Description of key information

NOAEL (rat, male and female, oral) = 800 mg/kg bw/day

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
800 mg/kg bw/day
Study duration:
subacute
Species:
rat
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

In order to provide information on toxicity as well as any possible effects of the test item on male and female reproductive performance, a study was performed according to the OECD Guideline 421 (2016).The effects of the test item on male and female reproductive performance such as gonadal function, mating behaviour, conception, development of conceptus, parturition and early lactation of the offspring were investigated.

All doses (0, 50, 200 and 800 mg/kg/day) were administered orally, by gavage to 10 males and 10 females per dose group. The control group received softened water (by reverse osmosis). The dose volume was 10 ml/kg bodyweight. Males were treated for 2 weeks prior to pairing and during pairing with females until theday before necropsy, for a total of 28 or 29 days. Females were treated for 2 weeks prior to pairing, and thereafter during pairing, post coitum and post partum periods until Day 13 post partum (for at least 51 days). Four not pregnant females were dosed up to the day before necropsy.

The following investigations were performed: mortality check, clinical signs, body weight, food consumption, oestrous cycle, mating performance, litter data, sex ratios, macroscopic observations and organ weights.

Histopathological examination was performed on control and high dose groups, on allabnormalities detected during post mortem observation from all groups and on one found dead male.

The identification of the stages of the spermatogenic cycle was also performed in all males of the control and high dose groups. Thyroid hormone determination was performed in all parental males. Clinical signs were recorded in all pups. Thyroid weight and thyroid hormone determination of 1 pup/sex/litter (where possible) at Day 14 post partum were determined. All pups found dead in the cage were examined for external and internal abnormalities. All culled pups sacrificed at Day 4 post partum were subjected to an external examination. Sex was confirmed by internal gonads inspection. All live pups sacrifice on Day 14 post partum were examined for extenal abnormalities and sex confirmation by gonadal inspection. The presence of nipples/areolae was verified in male pups.

Mortality and fate of females

One male from the high dose group was found dead on Day 7 of the pre-mating phase of the study. No clinical signs were observed prior to death. On the basis of the macroscopic (dark fluid contents in the thoracic cavity and dark colour of lungs) and microscopic observation (essentially chronic inflammation and necrosis in the lungs with brown foreign material, test item like, and brown pigment-laden macrophages in the alveoli of the lungs), the cause of death was attributed to a misdosing.

Two females receiving 50 mg/kg/day and one female receiving 200 mg/kg/day were proved not pregnant at necropsy. In addition, one female receiving 800 mg/kg/day had unilateral total resorption in the left horn and was not pregnant in the right one. The number of females with live pups on Day 14 post partum was: 10 in the control, 8 in the low dose (50mg/kg/day), 9 in the mid-dose (200mg/kg/day) and 9 in the high dose group (800mg/kg/day).

Clinical signs

No relevant clinical signs were observed during the study. Staining observed in high dose group of both sexes and in females of mid-dose group was considered related to the colour of the test item.

Observations of the cage tray

Staining in the cage tray and red faeces generally observed in mid- and/or high dose groups were considered related to the colour of the test item which was eliminated by the animals.

Body weight and body weight gain

No relevant differences in body weight and body weight gain were noted between control and treated males and females throughout the study.

Food consumption

No effects on food consumption were observed in both sexes.

Thyroid hormone determination

Parental males

No changes in thyroid hormones were recorded in parental male animals of all treated groups.

Pups – Day 14 post partum

Changes observed in thyroid stimulating hormone of some female pups of the high dose group were considered of no toxicological relevance due to the absence of other related changes.

Oestrous cycle, reproductive parameters, pairing combination and mating performance

Oestrous cycle, pre-coital intervals, copulatory index and fertility index did not show intergroup differences.

Implantation, pre-birth loss data and gestation length of females

No significant differences were observed for these parameters between treated and control groups. All pregnant dams gave birth on Day 22 post coitum (mean value).

Litter data at birth, on Days 1 and 4 post partum (before culling) and on Day 13 post partum (after culling) and sex ratio of pups

Litter data at birth, on Days 4 and 13 post partum recorded on treated groups were comparable to those of the control group. Sex ratios at birth, on Days 4 and 14 post partum did not show differences between groups, when calculated as the percentage of males.

Clinical signs of pups

Pre-weaning clinical signs were comparable between treated and control groups.

Anogenital distance

No relevant differences were seen between the control and treated pups in anogenital distance.

Necropsy findings in decedent pups, in pups sacrificed on Days 4 and 14 post partum and nipple count

Necropsy findings in decedent pups and in pups sacrificed on Days 4 and 14 post partum did not reveal any treatment-related effect. No nipples were observed in male pups on Day 14 post partum.

Pups thyroid weight on Day 14 post partum

No differences were noted in thyroid weight between control and treated pups.

Terminal body weight and organ weights

Terminal body weight and organ weights did not show relevant differences between control and treated groups.

Macroscopic observations

No remarkable differences were noted at post mortem examination in treated animals sacrificed at the end of the study, when compared with controls.

Microscopic observations

No treatment-related changes were observed in treated animals sacrificed at the end of the study, when compared to the controls.

Effects on developmental toxicity

Description of key information

NOAEL (rat, male and female, oral) = 800 mg/kg bw/day

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
800 mg/kg bw/day
Study duration:
subacute
Species:
rat
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available

Justification for classification or non-classification

According to CLP Regulation (EC 1272/2008), 3.7 Reproductive toxicity section, reproductive toxicity includes adverse effects on sexual function and fertility in adult males and females, as well as developmental toxicity in the offspring.

The available experimental data are adequate for classification and labelling and the substance does not meet the criteria to be classified for reproductive toxicity, according to CLP Regulation (EC) No. 1272/2008.

Additional information