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Administrative data

Description of key information

NOAEL in male rats 521 mg/kg bw/day (based on the chronic study on OB 3a-MSA)

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
521 mg/kg bw/day
Study duration:
chronic
Species:
rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The substance under registrationOB 3b-Abelongs to the category of Stilbene Fluorescent Whitening Agents.

As for the standard requirements of this registration, the repeated dose toxicity potential is assessed throughCombined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening (OECD 422).

Currently, a study on 3b-A is still in progress. The preliminary results of dose range finding at 100, 300, 1000 mg/Kg bw/day indicates very little effects only at the highest tested dose of 1000 mg/Kg bw/day.

Following oral exposure by gavage, the similar substances show no toxicological adverse effects, even on the reproduction parameters, therefore, considering the high structural similarity and the comparable physicochemical/toxicokinetic profile between this category of substances, their studies are used to cover the endpoint of OB 3b-A.Details on the Read Across approach for category are reported in a document attached in IUCLID section 13.

Recently, a Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening (OECD 422), following GLP’s principles, was performed onOB 4-MSAat doses of 80, 250 and 750 mg/kg/bw.

No toxicologically adverse effects of the test item on growth of animals, food consumption and health condition of animals were detected in both sexes.

During the biometry of organs, statistically significantly increased relative weight of testes and statistically insignificantly increased absolute and relative weight of pituitary gland in males were found out. Examination of sperm motility and morphology did not show any significant changes. During pathological inspection of reproductive organs, no changes were detected in animals of both sexes. During histopathological examination, only spontaneous change in prostate gland (chronic inflammation) was found out. The findings, which related to previous gravidity in uterus (presence of hemosiderin and focal accumulation of lipophages and siderophages in the mesometrium) were found out in females. These findings were not related to the treatment of the test item.

In females the number of implantation sites was increased. One female with abort was detected. The fertility parameters were not changed compared to control group.

All changes in reproductive parameters observed in parental males and females at all dose levels were considered to be of no toxicological significance.The NOAEL was therefore established as 750mg/kg body weight/day.

A further Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening is available and was carried out onOB 3a-A(Na), with the same conditions and doses as the one performed for OB 4-MSA.

Repeated oral administration of the test item, to rats by gavage did not cause any mortality (except one male from the dose level 250 mg/kg/day). This death was accidental and not treatment-related.

The body weight of parental males and females was not affected by the test item administration.

Evaluation of the absolute and relative weight of reproductive organs of male and female, as well as the weight of pituitary and thyroid gland, did not reveal any statistically significant differences in organ weight.

Test item treatment did not affect male ability to produce sperm that can fertilise eggs and ability of females to become pregnant. 

No adverse effect of the test item treatment was observed during examination of thyroxine and rat thyroid stimulating hormone blood concentration in males. 

Histological examination did not reveal negative effect of the test item on collected organs of reproductive organs (pituitary and thyroid gland). Spermatogenesis in the testes of the high dose administered males was without any pathological findings. Epididymides of both control and high dose males were without any pathological findings. Sporadic findings were of spontaneous origin. The administration of test item did not cause pathological changes in the organs. Examination of sperm motility and morphology in treated parental males did not show any differences in comparison with the control males. The administration of test item did not cause damage of sperms.

The number of implantations was comparable between treated and control groups. The test item did not affect the number of pups and their development.

Under test condition, the NOAEL (No Observed Adverse Effect Level) value was established as 750mg/kg body weight/day.

Justification for classification or non-classification

According to the CLP Regulation (EC 1272/2008), 3.9 Specific target organ toxicity - repeated exposure section, substances are classified as specific target organ toxicants following repeated exposure by the use of expert judgement, on the basis of the weight of all evidence available, including the use of recommended guidance values which take into account the duration of exposure and the dose/concentration which produced the effect(s), and are placed in one of two categories, depending upon the nature and severity of the effect(s) observed.

Classification in Category 2 is applicable, when significant toxic effects observed in a 90-day repeated-dose study conducted in experimental animals are seen to occur within the guidance value ranges as:

- oral (rat): 10 < C ≤ 100 mg/kg bw/day

The guidance values refer to effects seen in a standard 90-day toxicity study conducted in rats.

The No Observed Adverse Effect Level was established at 521 mg/kg bw/day, on the basis of the results from a chronic study on rats.

In conclusion, the available experimental data are adequate for classification and labelling and the substance is not classified for repeated dose toxicity according to the CLP Regulation (EC 1272/2008).