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Key value for chemical safety assessment

Effects on fertility

Description of key information

According to REACH Annex VIII Section 8.7.1 Column 2 a screening for reproductive/developmental toxicity (OECD 421 or 422) does not need to be conducted, if a prenatal developmental toxicity study (Annex IX, 8.7.2) is available.  For Direct Blue 264 (CAS 68411-04-1) a GLP prenatal developmental toxicity study after repeated oral administration in Wistar rats with Direct Blue 264 (CAS 68411-04-1) according to TG OECD 414 is available. Therefore, the requirements of REACH Annex VIII Section 8.7.1 Column 2 are fulfilled and no screening for reproductive/developmental toxicity (OECD 421 or 422) must be conducted.

According to REACH Annex VIII Section 8.7.3 Column 1 an Extended One-Generation Reproductive toxicity study is required, if the available repeated dose toxicity studies indicate adverse effects on reproductive organs or tissues or reveal other concerns in relation with reproductive toxicity. In a ‘90-Day Repeated Dose Oral Toxicity Study in Wistar Rats with Direct Blue 264 including Fertility Parameters’ there were neither macroscopic lesions nor histological changes in this study that could be attributed to the treatment with the test item. The following male and female reproductive organs were histopathological examined: testes, prostate and seminal vesicles with coagulating glands as a whole, epididymides, ovaries, uterus with cervix and vagina.  At histopathological evaluation, the testes were checked on completeness of cell populations, completeness of stages and degenerative changes. No treatment-related effects on the testicular histomorphology were observed. Further, no treatment-related effect on interstitial cell structure was noticed. Thus, the histopathological NOEL (no observed effect level) may be established at 1000 mg/kg bw (the highest dose tested). In an OECD Guideline 414 (Prenatal Developmental Toxicity Study) in Wistar pregnant female rats with Direct Blue 264 at dose levels of 250, 500, and 1000 mg/kg body weight per day administered on gestation days 5 to 19, no effects of Direct Blue 264 on pregnant females and foetuses were found at dose levels up to 1000 mg/kg body weight/day. The NOAEL (No Observed Adverse Effect Level) for both maternal toxicity and foetal toxicity of Direct Blue 264 in this study is considered to be 1000 mg/kg body weight/day (the highest dose tested). Therefore, an Extended One-Generation Reproductive toxicity study is not required based on REACH Annex IX Section 8.7.3 Column 1.

Effect on fertility: via oral route
Endpoint conclusion:
no study available
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available

Effects on developmental toxicity

Description of key information

In an OECD TG 414 study possible adverse effects on pregnant females and embryo-foetal development were assessed, which could arise from repeated exposure of Direct Blue 264 via oral administration (gavage) to female rats during gestation days 5 to 19. Nulliparous and non-pregnant females were mated with males (2:1 ratio) and divided into four groups based on their body weights on the day of sperm positive vaginal smears (GD 0). The 4 groups comprised 25 female Wistar rats in the control (C), the low dose (LD), the medium dose (MD) and the high dose (HD) groups. The following doses were evaluated: 0 (control), 250, 500 or 1000 mg/kg body weight/day.

All clinical signs observed in terminally sacrificed females were incidental or non- adverse in nature.

No treatment-related effect on body weight development, food consumption, prenatal data parameters, litter data parameters, thyroid weight and hormones, foetal anogenital distance and gross pathology of terminally sacrificed females was observed up to highest dose tested. Furthermore, no treatment-related and toxicologically relevant external, visceral or craniofacial findings were observed in the HD group.

No effects of Direct Blue 264 on pregnant females and foetuses were found at dose levels up to 1000 mg/kg body weight/day. The NOAEL (No Observed Adverse Effect Level) for both maternal toxicity and foetal toxicity of Direct Blue 264 in this study is considered to be 1000 mg/kg body weight/day (the highest dose tested).

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
GLP guideline study.
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

Additional information

No data.

Justification for classification or non-classification

In a ‘90-Day Repeated Dose Oral Toxicity Study in Wistar Rats with Direct Blue 264 including Fertility Parameters’ there were neither macroscopic lesions nor histological changes in this study that could be attributed to the treatment with the test item. The following male and female reproductive organs were histopathological examined: testes, prostate and seminal vesicles with coagulating glands as a whole, epididymides, ovaries, uterus with cervix and vagina.  At histopathological evaluation, the testes were checked on completeness of cell populations, completeness of stages and degenerative changes. No treatment-related effects on the testicular histomorphology were observed. Further, no treatment-related effect on interstitial cell structure was noticed. Thus, the histopathological NOEL (no observed effect level) may be established at 1000 mg/kg bw (the highest dose tested). In an OECD Guideline 414 (Prenatal Developmental Toxicity Study) in Wistar pregnant female rats with Direct Blue 264 at dose levels of 250, 500, and 1000 mg/kg body weight per day administered on gestation days 5 to 19, no effects of Direct Blue 264 on pregnant females and foetuses were found at dose levels up to 1000 mg/kg body weight/day. The NOAEL (No Observed Adverse Effect Level) for both maternal toxicity and foetal toxicity of Direct Blue 264 in this study is considered to be 1000 mg/kg body

According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification is not justified.