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Administrative data

Key value for chemical safety assessment

Effects on fertility

Additional information

No assessment of reproductive hazard has been undertaken at this tonnage threshold. This is due to the following considerations:

 

1) The substance was not found to be harmful to reproductive developmental processes in a developmental study on a closely related analogue. No abnormalities of offspring were noted in this study at the maximum dose tested (2000 mg/kg/day).  Full justification for the use of this study is provided.

 

2) The substance was negative in mutagenicity assays involving animal cells, and did not have any effects at the highest dose thresholds noted.

3) Repeat-dose studies with oral treatment in rats did not reveal any tumorigenic properties which could be related to the administration of the test substance. Histopathological evaluation of reproductive organs from the 28-day study indicated no effects.Consequently, the substance is considered not to have the potential to cause reproductive effects.

4) The substance has been notified originally under the 7th Amendment, and has been in use for a number of years without effects associated with reproductive toxicity being noted.  

As such, on animal welfare grounds it is not considered appropriate to conduct a further developmental screening test at this level of registration, as the evidence indicates that there is no associated potential teratogenic effect associated with the substance. 


Short description of key information:
It is considered that assessment of fertility effects is not scientifically justifiable at this level of registration. A developmental study on a structural analogue is available for the substance, and this is offered in section 7.8.2 of the registration dossier, and demonstrated no effects. No effects were seen on reproductive organs in the repeat dose study on the substance, and the category of substance (disperse dye) is not known for reproductive toxicity effects. Also, the substance has been notified originally under the 7th Amendment, and has been in use for a number of years without effects associated with reproductive toxicity being noted. On the basis of animal welfare it is proposed that the developmental study in conjunction with the lack of effects noted in the other toxicity studies is suitable to address this endpoint. An assessment of reproductive effects can be carried out at the next tonnage threshold.

Effects on developmental toxicity

Effect on developmental toxicity: via oral route
Dose descriptor:
NOAEL
2 000 mg/kg bw/day
Additional information

This study is read across to the structural analogue C.I. Disperse Blue 79:1, which is considered structurally equivalent to the substance to be registered. Justification for this read across is detailed within section 7.8.2.

Timed-pregnant CD (Sprague-Dawley) rats, 25 sperm-positive females per group, were exposed to the test chemical, C. I. Disperse Blue 79:1, by gavage once daily, on gestational days (gd)6 through 15 at doses of 0.0, 500.0, 1000.0 or 2000.0 mg/kg/day in corn oil. The dosing volume was 10.0 ml/kg and was adjusted based on each animal's most recent body weight. Clinical obser­ vations were taken daily, twice daily during the dosing period, and maternal body weights were taken on gd 0, 6, 9, 12, 15, 18 and 20. Food consumption was measured for the intervals gd 0-6, 6-9, 9-12, 12-15, 15-18 and 18-20. At scheduled sacrifice on gd 20, the dams were evaluated for body weight, liver and gravid uterine weight. Ovarian corpora lutea were counted and the status

of uterine implantation sites (i.e., resorptions, dead fetuses, live fetuses) was recorded. All fetuses were dissected from the uterus, counted, weighed, sexed and examined for external abnormalities. Approximately one-half of the live fetuses in each litter were examined for visceral malformations and variations. These fetuses were decapitated and the heads fixed in Bouin's solution; serial free-hand sections of the heads were examined for soft tissue craniofacial malformations and variations. All fetuses in each litter were eviscerated, fixed in alcohol, and stained with alizarin red S/alcian blue. Intact fetuses were examined for skeletal malformations and variations.

Pregnancy rate was unexpectedly low (44-56%) and approximately equivalent across all groups. No females died, aborted, delivered early or were removed from study. Two litters at 500 mg/kg/day were fully resorbed; all remaining pregnant animals had one or more live fetuses on gd 20. The numbers of lit­ ters evaluated were 11 -14 per group. Maternal body weights and weight gains were equivalent across all groups for all timepoints; corrected gestational weight gain was statistically equivalent across all groups. No maternal clinical signs appeared treatment related except for green, dark and/or dark green feces at 500.0, 1000.0 and 2000.0 mg/kg/day. Maternal food consumption exhibited no treatment-related differences for any intervals evaluated. All gestational parameters were equivalent across all groups including pre- and post implantation loss and fetal body weights/litter. There were no treatment­ related increased incidences of individual or pooled external, visceral, skeletal or total fetal malformations or variations.

In conclusion, C. I. Disperse Blue 79:1 administered by gavage during major organogenesis in CD (Sprague-Dawley) rats resulted in no demonstrable maternal or developmental toxicity at any dose tested. The "no observable adverse effect level (NOAEL) for maternal and developmental toxicity of C. I. Disperse Blue 79:1 in rats is therefore at least 2000.0 mg/kg/day under the conditions of this study.

Justification for classification or non-classification

The above study has been ranked reliability 1 according to the Klimish et al system. This ranking was deemed appropriate because the study was conducted to GLP and in compliance with agreed protocols. Sufficient dose ranges and numbers are detailed; hence it is appropriate for use based on reliability and animal welfare grounds.

The above results triggered no classification under the Dangerous Substance Directive (67/548/EEC) and the CLP Regulation (EC No 1272/2008). No classification for reproductive effects is therefore required.

Additional information