Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information

The study does not need to be conducted because (i) the substance is of low toxicological activity (no evidence of toxicity seen in any of the tests available), (ii) it can be proven from toxicokinetic data that no systemic absorption occurs via relevant routes of exposure (e.g. plasma/blood concentrations below detection limit using a sensitive method and absence of the substance and of metabolites in urine, bile or exhaled air) and (iii) there is no or no significant human exposure. Bioavailability drives toxicity. The absence of any measureable bioavailability at even the limit dose for either ferro- or silicomanganese slag, reinforced bythe absence of any toxicity in the OECD 408 90 day gavage study (including neurotox) with the ferro- or silico- manganese slag, or the OECD 414 developmental toxicity study (maternal or fetal) with the ferromanganese slag, demonstrates with satisfactory certainty that there will be no effects seen in any reproductive toxicity studies with the slags. Neither a mulitigeneration study either the extended one generation (OECD 433) or 2 generation (OECD 416) are therefore scientifically justifiable on the basis of the absence of any absorption of toxicologically relevant metals from these materials. See the attached justification.

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

OECD 414 study in the rat

The maternal and foetal NOAEL were both considered to be 1000 mg/kg/day.

Requirement for an OECD 414 Developmental Toxicity Study in a Second Species

A pre-natal developmental toxicity study on a second species is part of the standard information requirements as laid down in Annex X, section 8.7.2. for substances registered for 1000 tonnes or more per year. The Registrant has taken into account the outcome of the pre-natal developmental toxicity on a first species (rat) and all other relevant available data and has concluded that the conditions are not met for adaptations according to Annex X, 8.7. column 2, or according to Annex XI. As such, a testing proposal for a pre-natal developmental toxicity study on a second species (rabbit) has been included in this registration update.

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:
The study was conducted in accordance with standardised guidelines under GLP conditions. The quality of the database is therefore considered to be high. The study was awarded a reliability score of 1.
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

An assessment of the influence of the material on embryo-foetal survival and development when administered during the organogenesis and foetal growth phases of pregnancy in the rat was carried out in accordance with the standardised guidelines OECD 414, EU Method B.31, US EPA OPPTS 870.3700 and JMAFF 12 Nohsan No. 8147 under GLP conditions.

Three groups of 20 females received the test material at doses of 100, 330 or 1000 mg/kg/day by oral gavage administration, from Day 6 to 19 after mating. A similarly constituted Control group received the vehicle, corn oil, at the same volume dose as treated groups. Animals were killed on Day 20 after mating for reproductive assessment and foetal examination.

Clinical observations, body weight and food consumption were recorded. Adult females were examined macroscopically at necropsy on Day 20 after mating and the gravid uterus weight recorded. All foetuses were examined macroscopically at necropsy and subsequently by detailed internal visceral examination or skeletal examination.

There were no unscheduled deaths, no signs associated with dosing, no adverse treatment related clinical signs, effects on body weight or food consumption and no findings detected at necropsy of the dams.

All animals receiving the test material were pregnant. There was no effect on embryo-foetal survival growth or development. High placental weights (up to 111 % of control) were recorded attaining statistical significance at the 330 and 1000 mg/kg/day dose levels, but the differences were considered not to be adverse at the degree observed.

Under the conditions of this study, the test material was well tolerated and the maternal NOAEL was considered to be 1000 mg/kg/day. There was no adverse effect on embryo-foetal survival, development or growth, therefore the foetal NOAEL was considered to be 1000 mg/kg/day.

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No 1272/2008, the substance does not require classification with respect to toxicity to reproduction.