1,1'-(isopropylidene)bis[3,5-dibromo-4-(2,3-dibromo-2-methylpropoxy)benzene]

Sediment toxicity

Link to relevant study record(s)

Reference

Endpoint:

sediment toxicity: long-term

Type of information:

experimental study planned

Study period:

Dependent on ECHA approval of the present sediment toxicity testing proposal for AP 1300 S and, if a test shoul be performed, on the timing of the test itself to obtain the results.

Justification for type of information:

TESTING PROPOSAL ON VERTEBRATE ANIMALS

NON-CONFIDENTIAL NAME OF SUBSTANCE:

- Name of the substance on which testing is proposed to be carried out: AP 1300 S;
IUPAC name: 1,1'-(isopropylidene)bis[3,5-dibromo-4-(2,3-dibromo-2-methylpropoxy)benzene].

CONSIDERATIONS THAT THE GENERAL ADAPTATION POSSIBILITIES OF ANNEX XI OF THE REACH REGULATION ARE NOT ADEQUATE TO GENERATE THE NECESSARY INFORMATION:

- Available GLP studies: No studies on sediment toxicity are available for the considered substance.

- Available non-GLP studies: There are no non-GLP sediment toxicity studies available for the considered substance.

- Historical human/control data: NA.

- (Q)SAR: At our current knowledge, we are not aware of recognised validated (Q)SAR methods adequately covering this endpoint and resulting in a reliable prediction of sediment toxicity.

- In vitro methods: No reliable or recognised in vitro methods are available for this toxicity endpoint.

- Weight of evidence: There would be sufficient data available to develop a robust sediment toxicity weight of evidence approach.
Environmental distribution of AP1300 S has been evaluated by means of Level III Fugacity Model (EPIWEB 4.1) and the calculated mass amounts are:
• Air = 0.0699 %
• Water = 5.12 %
• Soil = 94.7 %
• Sediment = 0.0679 %
According to the distribution modelling estimation, the sediment compartment exposure to AP 1300 S is expected to be negligible. Moreover, direct environmental exposure to AP 1300 S is unlikely: after the application phase, the substance is incorporated into the product matrix and unavailable for exposure (see the paragraph “Substance-tailored exposure driven testing” of the testing proposal). Furthermore, even if on a worst-case AP 1300 S was indirectly released in the environment, low concentrations are expected and only a small fraction would be actually bioavailable due to its physicochemical properties (especially molecular size/weight > 700 g/mol and logKOW = 12.42) which lead to unlikely uptake, as confirmed by the toxicokinetic study conducted on Similar substance 01 (see section 7.1 of the present registration dossier).
Although exposure of the sediment compartment can reasonably be excluded, extensive literature research has been carried out to confirm that even in cases of accidental exposure no possible toxic effect on sediment organisms can arise.
Published data for sediment toxicity testing are available for Similar substance 02, as reported in paragraph “Grouping and read-across” of the present testing proposal. From these studies, after the results were converted in wet weight and normalised to a standard organic content of 5%, a NOEC of 27 mg/kg wet weight was derived. An assessment factor of 10 has been judged to be appropriate for long-term toxicity data for three species to derive a PNEC for freshwater sediment of 2.7 mg/kg wet weight, while an assessment factor of 50 has been considered to derive a PNEC for marine sediment of 0.54 mg/kg wet weight. Noteworthy how Similar substance 02 is a precursor/metabolite of AP 1300 S (and of Similar substance 01), therefore it is possible to consider these results as conservative compared to the parent substance: it is likely that because of the higher molecular weight, steric effects associated to the bulky bromine atoms, hindrance, and lower reactivity due to the covalent bond of the hydroxyl (OH) groups with brominated alkyl chains, AP 1300 S is unlikely to react with active sites of enzymes respect to the metabolite and as already stated it is less bioavailable.
To strengthen this assumption, a comparison among the terrestrial toxicity data existing for Similar substance 01 and Similar substance 02 has been made. Soil matrix is the most exposed environmental compartment and, based on the PNEC derived for Similar substance 02 for both sediment and soil, it is reasonable to say terrestrial organisms are also the most susceptible ones: a PNEC soil of 0.012 mg/kg wet weight was derived applying an assessment factor of 10 to the lowest reliable NOEC (0.12 mg/kg wet weight) obtained for earthworms. Since AP 1300 S, Similar substance 01 and Similar substance 02 are strongly adsorbing substances (logKoc>5 and logKow>5), uptake via sediment/soil ingestion is expected to be the most relevant exposure route and thus sediment/soil-dwelling organisms that feed on sediment/soil particles can be considered the most relevant source of information [Ref: “Chapter R.7b: Endpoint specific guidance” Version 4.0. June 2017. ECHA]
The results obtained for Similar substance 01 can be considered significant and more indicative of the actual toxicity of the considered substance since it has very similar physical-chemical properties and is predicted to have the same environmental fate of AP 1300 S. Testing has been carried out on earthworms (species: Eisenia fetida) to assess long-term terrestrial toxicity on macroorganisms: effects on biomass (weight change) and mortality were recorded after 28 days while effects on reproduction after 56 days. No increased mortality or influence on weight were determined and therefore EC50, LOEC and NOEC for these endpoints have been set at ≥ 1024 mg/kg soil dw; while reproduction rate was significantly decreased (-18% respect to control) at the maximum dose tested and thus NOEC for this endpoint was assumed to be 512 mg/kg soil dw. Therefore, the NOECs for Similar substance 01 are much higher than those derived from the same test organisms for Similar substance 02, and the same results are expected if AP 1300 S would be tested for terrestrial toxicity.
It is therefore realistic to state that AP 1300 S would have no effect on sediment-feeding organisms either, especially given that sediment-dwelling organisms would also be the most relevant test organisms for this compartment and the species suggested by the OECD guidelines are always part of the subclass Oligochaeta such as the terrestrial worms tested for Similar substance 01.

- Grouping and read-across: The possibility of performing a read across approach has been identified, based on structural similarity with other two brominated flame retardants sharing with the test item the presence of a tetrabromobisphenhyl moiety.
Similar substance 01, Tetrabromobisphenol A bis(2,3-dibromopropyl ether) [CAS Nr. 21850-44-5] is a monoconstituent substance with a halogenated biphenyl core and two propyl chains. The halogen substituents are disposed on the aliphatic chains (2 bromo each) and on the phenyl groups (2 each); in total there are eight bromine atoms. No test for sediment toxicity is currently available, since this environmental compartment has been judged to be neglected.
Similar substance 02, Tetrabromobisphenol A [CAS Nr. 79-94-7] is a monoconstituent substance with a biphenyl core substituted with 4 bromine atoms.
Four reliable and well documented sediment toxicity studies on Similar substance 02 have been performed on various species, covering different habitats and feeding modes: Chironomus sp. is a freshwater endobenthic suspension and deposit feeder; Hyalella azteca is a freshwater epibenthic detritivore and subsurface deposit feeder; Lumbriculus variegatus is an endobenthic freshwater sediment ingestor.
A test on Chironomus riparius has been performed according to OECD Guideline 218 at concentrations of 63, 125, 250, 500 and 1000 mg/kg dry weight and the investigated endpoints included abnormal behaviour, mean development time, percentage of emergence, emergence ratio and development rates. At the end of the study period (28 days) the following results were derived: EC50 (emergence) = 235 mg/kg dry wt; NOEC (abnormal behaviour) = 125 mg/kg dry wt; NOEC (mean development time) = 125 mg/kg dry wt; NOEC (mean emergence ratios) = 125 mg/kg dry wt; NOEC (mean development rate) = 125 mg/kg dry wt. Therefore, the overall NOEC for Similar substance 02 was estimated to be 125 mg/kg dry wt.
A test on Hyalella azteca has been performed based on USEPA (2000) ASTM standard E 1706-00 and USEPA OPPTS 850.1735 on artificial sediment with an organic carbon content of 5.7% at concentrations of 63, 125, 250, 500 and 1000 mg/kg dry weight. The results at 28 days were NOEC (survival) = 250 mg/kg dry wt and NOEC (growth, mean individual dry weight) ≥ 1000 mg/kg dry wt. Thus, based on the survival endpoint were determined NOEC = 250 mg/kg dry wt and LOEC = 500 mg/kg dry wt.
Two tests on Lumbriculus variegatus have been performed based of ASTM E 1706-95b Guideline and USEPA Series 850 Ecological Effects Test Guideline OPPTS No. 850.1735, respectively with sediments of 2.5% and 5.9% organic carbon content and at concentrations of 90, 151, 250, 254, 426, 715 and 1200 mg/kg dry weight. This study investigated mortality/reproduction (number of organisms at the end of study period) and growth (dry weight). At 28 days with sediments of 2.5% organic carbon content the following results were found: NOEC (mortality) 90 mg/kg dry wt; EC50 (mortality) = 294 mg/kg dry wt (95% confidence interval 140-391 mg/kg dry wt); at 28 days with 5.9% organic carbon content the results were the following: NOEC (mortality) = 254 mg/kg dry wt; EC50 (mortality) = 405 mg/kg dry wt (95% confidence interval 314-869 mg/kg dry wt); NOEC (growth) = 254 mg/kg dry wt. [Ref: “Risk assessment of 2,2’,6,6’-Tetrabromo-4,4’-Isopropylidene Diphenol (Tetrabromobisphenol-A)”, Final Environmental Rar, February 2008].

- Substance-tailored exposure driven testing: The percentage of substance AP 1300 S within the polymers is typically low and once it is incorporated within the matrix in the form of an article it is unavailable for exposure. Moreover, as stated in the document “Describing uses of additives in plastic material for articles and estimating related exposure Practical Guide for Industry” published by ECHA (2020), a qualitative argumentation for negligible release/exposure from articles can be derived in case the below benchmarks are simultaneously fulfilled:
Molecular weight > 700 g/mol → AP 1300 S = 971.67 g/mol
LogKOW > 9 → AP 1300 S = 12.42
Low water solubility (< 0.01 mg/L) → AP 1300 S = 1.259x10-11 mg/l
Low vapor pressure (< 10-4 Pa) → AP 1300 S = 8.48x10-13 Pa
Meeting the substance all above requirements, its potential release from articles in which is incorporated during their service life is irrelevant or very low and therefore environmental exposure is not likely to occur or, on a worst-case scenario, it can be expected only in indirect and small concentrations.

- Approaches in addition to above [if applicable]: Not applicable.
- Other reasons [if applicable]: None identified.

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:

- According to Reach Regulation Annex X, column 2, section 9.5.1: Long-term toxicity testing shall be proposed by the registrant if the results of the chemical safety assessment indicates the need to investigate further the effects of the substance and/or relevant degradation products on sediment organisms. The choice of the appropriate test(s) depends on the results of the chemical safety assessment.
The tests carried out on Similar substance 02 resulted in a lowest NOEC of 90 mg/kg dry wt for Lumbriculus variegatus with sediments of 2.5% organic carbon content and these results can be considered as conservatives compared to the findings expected for AP 1300 S (as outlined in the paragraph “Grouping and read-across”); moreover other evidences are consistent with the non-toxic behaviour of the considered substance (see paragraph “Weight of evidence”). These data enable us to exclude the relevance of the sediment compartment and thus that further testing is needed.

FURTHER INFORMATION ON TESTING PROPOSAL IN ADDITION TO INFORMATION PROVIDED IN THE MATERIALS AND METHODS SECTION:

- Details on study design / methodology proposed [if relevant]: If a test were to be conducted, it is our opinion that it should be carried out according to the OECD 225 directive: Sediment-Water Lumbriculus Toxicity Test Using Spiked Sediment. This method is designed to assess the effects of prolonged exposure to sediment-associated chemicals on the reproduction and the biomass of the endobenthic oligochaete Lumbriculus variegatus: as previously stated, due to its physicochemical properties (logKoc>5 and logKow>5), AP 1300 S is a strongly adsorbing substance and therefore uptake via sediment ingestion is expected to be the most relevant exposure route and thus sediment-dwelling organisms that feed on sediment particles, like Oligochaetes which are sediment ingestors, can be considered the most relevant source of information.

Qualifier:

according to guideline

Guideline:

OECD Guideline 225 (Sediment-Water Lumbriculus Toxicity Test Using Spiked Sediment)

GLP compliance:

yes

Test organisms (species):

Lumbriculus variegatus

Description of key information

Environmental distribution of AP1300 S has been evaluated by means of Level III Fugacity Model (EPIWEB 4.1) and the calculated mass amounts are:
• Air = 0.0699 %
• Water = 5.12 %
• Soil = 94.7 %
• Sediment = 0.0679 %
According to the distribution modelling estimation, the sediment compartment exposure to AP 1300 S is expected to be negligible. Moreover, direct environmental exposure to AP 1300 S is unlikely: after the application phase, the substance is incorporated into the product matrix and unavailable for exposure and even if on a worst-case AP 1300 S was indirectly released in the environment, low concentrations are expected and only a small fraction would be actually bioavailable due to its physicochemical properties (especially molecular size/weight > 700 g/mol and logKOW = 12.42) which lead to unlikely uptake, as confirmed by the toxicokinetic study conducted on Similar substance 01 (see section 7.1 of the present registration dossier). 
Although exposure of the sediment compartment can reasonably be excluded, extensive literature research has been carried out and confirmed that even in cases of accidental exposure no possible toxic effect on sediment organisms can arise. On the basis of the available information, there is sufficient data to develop a robust sediment toxicity weight of evidence approach proving the negligible exposure of this environmental compartment and the non-toxicity of the substance for sediment organisms.