Registration Dossier

Ecotoxicological information

Long-term toxicity to aquatic invertebrates

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Administrative data

Endpoint:
long-term toxicity to aquatic invertebrates
Type of information:
experimental study planned (based on read-across)
Study period:
21 days
Justification for type of information:
Long-term toxicity testing on aquatic invertebrates (Annex IX, Section 9.1.5.; Test method: Daphnia magna reproduction test, EU C.20/OECD TG 211)

NON-CONFIDENTIAL NAME OF SUBSTANCE:
Name of the substance on which testing is proposed to be carried out: Cashew Nutshell Extract, Decarboxylated, Distilled (Distilled Grade) and Cashew Nutshell Extract, Decarboxylated, Distillation Residue (Distillation Residue Grade)
Name of the substance for which the testing proposal will be used [if different from tested substance]: Cashew Nutshell Extract, Decarboxylated (Technical Grade)

CONSIDERATIONS THAT THE GENERAL ADAPTATION POSSIBILITIES OF ANNEX XI OF THE REACH REGULATION ARE NOT ADEQUATE TO GENERATE THE NECESSARY INFORMATION [please address all points below]:

Available GLP and non-GLP studies
There is no existing reliable (GLP or non-GLP) data on the long-term toxicity testing of Cashew Nutshell Extract, Decarboxylated (Technical Grade). Therefore this is a standard information requirement for which data must be provided. The information on this endpoint is not available for the registered substance, but needs to be present in the registration dossier to meet the information requirements.
The current ecotoxicological dataset for Cashew Nutshell Extract, Decarboxylated, (Technical Grade) contains experimental short-term information for saltwater algae, invertebrates and fish which can be considered robust (Klimisch Code 2) because the studies used internationally recognised test guidelines which were carried out to Good Laboratory Practice (GLP). These short term toxicity tests were carried out using Water Accommodated Fractions and because of the low water solubility of Technical grade (0.2 mg/l) it is possible to state that there is no acute toxicity to aquatic organisms at the water solubility limit.

Historical human data
Historical human data is not relevant to the assessment of the long-term toxicity to aquatic invertebrates.

(Q)SAR
It was not possible to predict the long-term toxicity to aquatic invertebrates of the test substance Technical grade using the models in the OECD QSAR Toolbox because the logKow values of the constituents were outside the domain range for the specific model for the long-term toxicity to aquatic invertebrates endpoint.

In-vitro methods
The application of in vitro methods is not relevant to the assessment of the long-term toxicity to aquatic invertebrates.

Grouping and read-across
It is not proposed that a test will be carried out on the registered Cashew Nutshell Extract, Decarboxylated, (Technical grade), but rather that appropriate tests will be carried out on two source substances Cashew Nutshell Extract, Decarboxylated, Distilled (Distilled grade) and Cashew Nutshell Extract, Decarboxylated, Distillation Residue (Distillation Residue grade) with the required data for Technical grade being interpolated by read-across. In this context interpolation is “the estimation of a value for a member of the group using measured values from other members on both sides of that member within the defined group spectrum”.
The justification for the read-across approach results from the commonality of the constituents and functional groups in the three grades and the common modes of action for specific localised endpoints that are manifest in physico-chemical, environmental fate and toxicological properties that are similar or follow a regular pattern as a result of structural similarity. Further details on the justification for using the interpolation based read-across approach are given in the accompanying document “Report on the development of an updated grouping and read-across rationale for the three grades of processed Cashew Nutshell extract”. The following points are relevant:
• The three grades are manufactured using a common process in which the unprocessed cashew nutshell extract is heated to produce Cashew Nutshell Extract, Decarboxylated (Technical grade). Subsequent distillation does not result in the formation of any new constituents in the resulting Distilled and Distillation Residue grades, but rather changes in the proportion of certain constituents relative to those present in Technical grade.

• In all the three grades the proportions of three out of the five key constituents such as the low boilers, C17 phenolics and high boilers (cardol and 2-methylcardol) are similar. Whilst the lightest, lower molecular weight non-polymeric constituents (such as cardanol) and the highest molecular weight polymeric constituents vary between the grades Technical grade compositionally lies between Distilled and Distillation Residue grades.

• For all the physico-chemical parameters for which measured data are available the values estimated for the target substance Technical grade from the results generated in tests on the source substances Distilled and Distillation Residue grade are consistent with the actual measured values for Technical grade. The consistency of the estimated and measured values for these endpoints for Technical grade indicate that the read-across approach is appropriate and that reliable results can be generated by interpolation from the source substances (Distilled and Distillation Residue grades). In particular, there is consistency for the key physico-chemical parameters which are relevant to the long-term toxicity of the constituents of the three grades in aquatic organisms namely: water solubility and octanol-water partition coefficient (logKow). The three grades show consistent octanol-water partition coefficients (logKow >6.2 in all cases) and low water solubilities (0.2 to 0.3 mg/l).

• The environmental fate properties of aerobic biodegradation and soil absorption (log Koc) for the three grades of processed cashew nutshell extract follow a regular pattern as a result of structural similarity, supporting the interpolation-based read-across approach.
As compositionally Technical grade lies between Distilled and Distillation Residue grades testing of the source substances will provide data on the degree to which the differences in the chemical composition (in terms of the lower molecular weight cardanols and higher molecular weight polymeric constituents) affect long-term toxicity to aquatic species. The resulting read-across to Technical grade by interpolation is considered as an appropriate adaptation to the standard information requirements of Annex IX 9.1.5. of the REACH Regulation, in accordance with the provisions of Annex XI, 1.5 of the REACH Regulation. The use of data from two source substances (Distilled and Distillation Residue grades) to read-across to Technical grade is considered to provide greater confidence in the predicted data for the target substance.




Substance-tailored exposure driven testing
The application of substance-tailored exposure driven testing approach to this endpoint is not considered applicable.
CONSIDERATIONS THAT THE SPECIFIC ADAPTATION POSSIBILITIES OF ANNEXES VI TO X (AND COLUMN 2 THEREOF) OF THE REACH REGULATION ARE NOT ADEQUATE TO GENERATE THE NECESSARY INFORMATION:
Section 9.1 of Annex IX if REACH states that “Long-term toxicity testing shall be proposed by the registrant if the chemical safety assessment according to Annex I indicates the need to investigate further the effects on aquatic organisms. The choice of the appropriate test(s) depends on the results of the chemical safety assessment”.
The data generated for Technical grade will be used to refine the PNECwater values and confirm the Toxicity (T) element of the PBT assessment. This test is proposed rather than a long-term fish toxicity test (to address Annex IX – 9.1.6) to avoid unnecessary vertebrate testing. This approach is consistent with ECHA Guidance on information requirements and assessment: Chapter R.10: Dose (concentration)-response for environment which states that: “A long-term test has to be carried out for substances showing no toxicity in short-term tests if the log Kow >3 (or BCF >100) and if the PEClocal/regional is >1/100th of the water solubility. The long-term toxicity test should normally be a test on invertebrate (preferred species Daphnia) to avoid unnecessary vertebrate testing.”
The data from the long-term Daphnia study will be used to assess the risks posed by the test substance to the aquatic environment in different use scenarios based on the Risk Characterisation Ratios (RCRs) generated in a revised chemical safety assessment. If all of these RCRs are shown to be below 1, then the Consortium would not conduct a long-term fish study to avoid unnecessary vertebrate testing. However, if RCR values above one for the aquatic environment are indicated than the conduct of a long-term fish test such as the Fish Sexual Development Test (OECD TG 234) will be considered.
FURTHER INFORMATION ON TESTING PROPOSAL IN ADDITION TO INFORMATION PROVIDED IN THE MATERIALS AND METHODS SECTION:
It is proposed that the studies on the source substances Distilled and Distillation Residue grades would be carried out according to OECD Test Guideline 211 ‘Daphnia magna reproduction test’ and to GLP. The studies will assess the effect of chemicals on the reproductive output of the invertebrate Daphnia magna Straus. To this end, young female Daphnia will be exposed to the test substance added to water at a range of concentrations (at least five). For flow-through tests, 40 animals divided into four groups of 10 animals at each test concentration, will be used. The test duration will be 21 days. Reproductive output of the parent animals and the total number of living offspring produced per parent alive at the end of the test will be reported. The study report will also include: the daily counting of the offspring, the daily recording of the parent mortality, the weekly measurement of oxygen concentration, temperature, hardness and pH values and the determination of the concentrations of test substance. The testing will be supported by appropriate analytical confirmation of the exposure concentrations of key constituents such as cardanol and cardol. In addition chemical analysis to demonstrate attainment of equilibrium in WAF preparation and stability during the conduct of the test will be carried out using methods capable of identifying gross changes in the composition of WAFs with time such as ultra-violet (UV) spectroscopy or Total Peak Area. When designing the study the OECD Guidance Document on Aquatic Toxicity Testing of Difficult Substances and Mixtures, ENV/JM/MONO (2000)6 and ECHA Guidance on Information Requirements and Chemical Safety Assessment, Chapter R7b, Table R. 7.8-3 summarising aquatic toxicity testing of difficult substances will be consulted.

Data source

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 211 (Daphnia magna Reproduction Test)

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test organisms

Test organisms (species):
Daphnia magna

Study design

Test type:
flow-through
Water media type:
freshwater

Results and discussion

Applicant's summary and conclusion