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.

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study planned

Justification for type of information:

Testing Proposal for Repeated Dose Toxicity (Oral):

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

According to EU/1907/2006 a sub-chronic repeated dose toxicity study (90-days) is required to be conducted for substances that are to be registered in the tonnage band 100 or higher. A testing proposal for repeated dose toxicity (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 sub-chronic repeated dose toxicity study (90-days) is required for the specific tonnage band. No such study is available for the dried sludge from domestic wastewater. Acute toxicity studies (GLP) have been conducted (oral, dermal) as required by Annexes VII-VIII but this information is not adequate so as to fulfill the requirements of Annex IX. Furthermore, no short-term toxicity study (28 days) has been conducted. Based on column 2 of the endpoint 8.6.2. of Annex IX of the REACH Regulation, a sub-chronic toxicity study (90-days) requirement can be waived if a reliable short-term toxicity study (28 days) is available showing severe toxicity effects. However, since no 28-days toxicity study is available for the substance and based on the acute toxicity studies (no toxicity effects observed), it was decided to submit a testing proposal for a sub-chronic toxicity study (90-days), so as to avoid conducting two in-vivo studies (90-days and 28-days) for the same endpoint.

- Available non-GLP studies
No non-GLP study that can fulfill the requirement of Sub-Chronic Repeated Dose 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. the possibility to use (Q)SAR models for the prediction of repeated dose toxicity is limited. This limitation is due to the complexity of the systemic interactions and effects involved in repeated dose toxicity studies. This complexity is difficult to predict with computational tools. Therefore, the use of (Q)SAR models should be seen in the context of Weight-of-Evidence considerations, where screening and mechanistic information (including the prediction of target organs and metabolites) from (Q)SARs can support available in vivo studies. However no in-vivo studies are available regarding the specific endpoint. Furthermore, (Q)SAR 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, (Q)SAR models cannot be used in the specific case to fulfill the requirement of long-term toxicity study.

- In vitro methods
According to ECHA's Guidance R7a no available alternatives to animal testing are considered adequate to be used on their own for detecting toxicity after repeated exposure. 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.

- 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 repeated dose 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 8.6.2. 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, acute toxicity studies results are not adequate so as to compute a DNEL appropriate for the 90-days Repeated Dose Toxicity so as to 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, considerations based on the specific adaptation possibilities of annexes VI to X (column 2 included) of the REACH Regulation are not adequate to generate the necessary information since neither a reliable short-term (28 days) toxicity study (showing severe toxicity effects) nor a reliable chronic toxicity study are available.

The OECD Guidelines 408 (Repeated Dose 90-day Oral Toxicity Study in Rodents) is proposed to be conducted so as to fulfill the requirement of the repeated dose 90-day toxicity study. This study was chosen taking into account that oral is the most appropriate route of administration. More specifically based on the granulometry of the substance, the dried sludge from domestic wastewater is not inhalable and no skin contact in production and use is likely to occur if the Personal Protective Measures are implemented.

Materials and methods

Test guideline

Guideline:

OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)

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:

mouse

Results and discussion

Effect levels

Effect level:

>= 2 000 CFU/kg bw (total dose)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

clinical biochemistry