A dried sludge product resulting from the treatment process of domestic wastewater. The exact processes followed for the production of the dried sludge are: Preliminary + secondary treatment of the wastewater stream, thickening, dehydration and drying of the excess sludge.

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study planned

Justification for type of information:

Testing Proposal for Prenatal developmental toxicity study (OECD 414):

Name of the substance on which testing is proposed to be carried out: Dried Sludge From Domestic Wastewater

According to EU/1907/2006 a Prenatal developmental toxicity study (one species) is required to be conducted based on Annex IX. A testing proposal for prenatal developmental toxicity study (oral route as the most appropriate route of exposure) is made since all the general adaptation possibilities of Annex XI of the REACH Regulation are not adequate to generate the necessary information (see below):

- Available GLP studies
Based on Annex IX of the REACH regulation, a Prenatal developmental toxicity study (one species) is required. No GLP studies are available in relation to the reproductive toxicity properties of the Dried Sludge from Domestic Wastewater or any other similar substance and subsequently there is no adequate data in order to fulfill the specific endpoint’s requirements based on already existing GLP data.

- Available non-GLP studies
No non-GLP study that can fulfill the requirement of Prenatal Developmental Toxicity Test are available.

- Historical human/control data
No historical human data, such as epidemiological studies on exposed populations, accidental or occupational exposure data and clinical studies are available for the dried sludge from domestic waste. More specifically, none of the following types of human data are available:
• Analytical epidemiology studies on exposed populations
• Descriptive or correlation epidemiology studies
• Case reports describe a particular effect in an individual or a group of individuals exposed to the substance
• Controlled studies in human volunteers
• Information from occupational surveillance
• Postmarketing surveillance data
• Meta-analysis

- (Q)SAR
In general, based on ECHA's Guidance R7a. there are a large number of potential targets/mechanisms associated with reproductive toxicity which, on the basis of current knowledge, cannot be adequately covered by a battery of QSAR models. QSAR approaches are currently not well fitted-for-purpose for reproductive toxicity and consequently no firm recommendations can be made concerning their routine use in a testing strategy in this area. Thus, the possibility to use (Q)SAR models for the prediction of prenatal developmental toxicity is limited.
Furthermore, QSAR models heavily rely on the chemical structure of the examined substance. However, the composition of Dried Sludge from Domestic Wastewater has not been fully identified (approximately 20% remains unknown) and the identified part is expressed in terms of grouping into generic substance categories (proteins, lipids, inorganic content etc.). As a result, QSAR models cannot be used in the specific case to fulfill the requirement of prenatal developmental toxicity study.

- In vitro methods
According to ECHA's Guidance R7a in vitro methods may be used complementary so as to support read-across or a weight of evidence approach. However, none of these two approaches can be applied in our case due to the complex composition of the substance and subsequently in vitro testing won’t be adequate so as to fulfill the requirement of a prenatal developmental toxicity study.

- Grouping and read-across
Considering the technical difficulties that the specific UVCB substance entails (highly insoluble, abundancy of components), the identification was conducted on the basis of identifying general group categories, such as proteins, lipids, inorganic content, water etc.). Subsequently, being technically impossible to identify specific compounds, no grouping can be made based on similar physicochemical toxicological, and ecotoxicological properties of substances and no data from other studies could be exploited so as to fulfill the prenatal developmental toxicity requirement.

- Weight of evidence
A weight of evidence approach cannot be adopted since no read across, Q(SAR) model, adequate in vitro methods or human historical data are available so as to support the specific strategy.

- Substance-tailored exposure driven testing
Testing in accordance with Section 8.7.2. of Annex IX could have been avoided based on the exposure scenario developed and by fulfilling the criteria of point 3.2.a. of Annex XI of REACH Regulation. However, there are no available scientific data that could be used so as to derive a relevant DNEL for the prenatal developmental toxicity in order fulfill the second criteria of the endpoint 3.2.a.

Furthermore, the substance is not incorporated in an article nor strictly controlled conditions as set out in Article 18(4)(a) are implemented, so as to take advantage of either the endpoint 3.2.b or 3.2.c.

Finally, no adaptation can be made based on column 2 “Specific rules for adaptation from column 1”.

The OECD 414 is proposed to be conducted so as to fulfill the requirement of the prenatal developmental toxicity study as it provides a focused evaluation of potential effects on prenatal development.

Materials and methods

Test guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

Test material

Test material information

Constituent 1

Reference substance name:

A dried sludge product resulting from the treatment process of domestic wastewater. The exact processes followed for the production of the dried sludge are: Preliminary & secondary treatment of the wastewater stream, thickening, dehydration and drying of the excess sludge.

EC Number:

943-834-9

Molecular formula:

Not applicable for UVCB substances

IUPAC Name:

A dried sludge product resulting from the treatment process of domestic wastewater. The exact processes followed for the production of the dried sludge are: Preliminary & secondary treatment of the wastewater stream, thickening, dehydration and drying of the excess sludge.

Test animals

Species:

rat

Categories Display