Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information

Since there were no histopathology effects on reproductive organs observed in a subchronic study and developmental toxicity studies did not indicate disturbances of fertility and reproductive performance, the test does not need to be conducted in accordance with Annex IX (8.7.3) of the REACH legislation.

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subchronic
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

Since no available data on the target substance is available, experimental data on Similar Substance 01 is taken into account. Justification for Read Across is given in Section 13 of IUCLID.

A subchronic oral toxicity study was performed with Similar Substance 01 according to the OECD Guideline 408. Ten male and ten female rats were orally (gavage) dosed with 125, 350 and 1000 mg/kg bw in 1 % Carboxymethylcellulose in water, for 90 days. Five male and five female rats were in the recovery group included in the 28 -day post exposure recovery group (control and 1000 mg/kg bw dose group). The animals were observed for clinical signs, mortality and food consumption behaviour. Haematological, opthalmoscopic, clinical chemistry and urine analysis were performed. All animals were submitted to full necropsy procedure and specific organ and tissues were weighed and were subjected to histopathological examinations. Some of the tissues subjected to histopathologic examinations were the mammary gland, prostate, seminal vesicles, testes and uterus (horn + cervix).

No histopathology effects on reproductive organs were observed (up tp the highest tested dose of 1000 mg/kg bw/day) during the subchronic study that could indicate disturbances of fertility and reproductive performance.

NOAEL = 1000 mg/kg bw/day (actual dose received)

Effects on developmental toxicity

Description of key information

Evaluation of the potential of the substance to cause developmental toxicity was done by considering experimental data on Similar Substance 01. Justification for Read Across is given in Section 13 of IUCLID.

The test substance was tested for teratogenicity in rats, mice, hamsters, rabbits. The studies performed are adequate in design to conclude an absence of a hazard. Tested concentrations were up to 1600 mg/kg bw (except in the study with rabbits, where up to 1000 mg/kg bw were tested). No indication of teratogenicity was recorded in any of these studies. In the study with rabbits, high mortality occurred in all tested groups and this study is considered inadequate for hazard assessment.

The study design of these studies is similar to the OECD guideline 414. The studies pre-date GLP requirements: no purity or physical/chemical properties reported, no numerical values reported for temperature and humidity, acclimatization period not reported, concentrations and stability were not verified, and no statistics were performed. It is noted in the reports that the studies were part of a project with more than 40 substances and that statistics would be performed once all studies had been completed.

The administration of up to 1600 mg/kg bw/day of the test material to pregnant rats and mice for 10 consecutive days had no clearly discernible effect on nidation or on maternal or foetal survival. The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ from the number occurring spontaneously in the sham-treated controls.

The administration of up to 1600 mg/kg bw/day to pregnant hamsters for 5 consecutive days had no clearly discernible effect on nidation or on maternal or fetal survival. The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ from the number occurring spontaneously in the sham-treated controls.

The maternal NOAEL was determined to be 1600 mg/kg bw/day (highest tested dose).

 

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 600 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

Toxicity to reproduction: other studies

Description of key information

No teratogenic effects observed to the developing chicken embryo

Additional information

Similar Substance 01 was evaluated for its toxic and teratogenic potential to the developing chicken embryo under four sets of conditions. It was administered in sesame oil as the solvent by the two routes at two stages of embryonic development: via the air cell at pre-incubation (0 hours) and at 96 hours of incubation, and via the yolk at 0 hours and at 96 hours. Groups of 10 or more eggs were treated under these 4 conditions at several dose levels until a total of 90 -100 eggs/level was reached for all levels allowing some to hatch. Groups of comparable size were treated with the solvent at corresponding volumes and untreated controls were also included in each experiment. After treatment, all eggs were candled daily and non-viable embryos removed. Surviving embryos were allowed to hatch. All hatched chicks and non-viable embryos were examined carefully for abnormalities (internally and externally) as well as for toxic responses (such as oedema, haemorrhage, hypopigmentation of the down and other disorders such as feather abnormalities, significant groivth retardation, cachexia, ataxia or other nerve disorder; structural abnormality of the head, viscera, limbs, or body skeleton) and accidental deaths. At hatchings, 3 chicks were removed at random from each level including control for skeletal clearing, weighing and fixing of bursa, spleen, liver and kidney. Tissues were processed, blocked in paraffin, sectioned, affixed to slides, and stained. These sections were examined for internal damage to the tissues.

Justification for classification or non-classification

The substance did not cause any developmental or reproduction adverse effects in the animals tested.

On the basis of the available data, the substance is not considered to be classified for reproductive toxicity under the CLP Regulation (EC) No. 1272/2008.