Reaction mass of 2-methylbutyl salicylate and pentyl salicylate

Long-term toxicity to aquatic invertebrates

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

long-term toxicity to aquatic invertebrates

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

Final Report not yet issued. Study Protocol issued 17 January, 2017.

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Justification for type of information:

The source substance is a mono-constituent substance, HEXYL SALICYLATE (EC 228-408-6, CAS 6259-76-3). The typical concentration is 99 %. The Source Substance is a Carboxylic Acid-Ester.

The source and target substances share close structural similarity and are both Carboxylic Acid-Esters. The presence of the impurity in the target substance is not expected to impair any significant impact on toxicity and observed effects in aquatic toxicity studies, since this is also a structural isomer.

The basic structures of the target and source substance are illustrated on Table 1. Both substances are Carboxylic Acid-Esters, the source having the molecular formula of C13H18O3 and the target C12H16O3. The slight structural difference and greater hydrophobicity of the source substance com-pared to the target substance represents an over-conservative assumption. This has been taken in to account in this assessment, and, the corresponding influence on the aquatic toxicity properties char-acterised, herein.

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

EPA OPPTS 850.1300 (Daphnid Chronic Toxicity Test)

Version / remarks:

2016

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 211 (Daphnia magna Reproduction Test)

Version / remarks:

02 October, 2012

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

HEXYL SALICYLATE :
- Lot No. : PE00193366
- Purity : 99.6%
- Expiry Date : 22 December 2018 (all exyperimental and analytical work had been completed by 02 March, 2018)

Analytical monitoring:

yes

Details on sampling:

Test solution samples were collected from each replicate test chamber of each treatment and control group three and two days prior to the start of exposure to confirm concentrations after conditioning the diluter system for three and four days, respectively. Samples of the stock solutions being delivered to the test system were collected for analysis two days prior to the start of exposure to verify proper delivery of the test material. Test solution samples also were collected from each replicate test chamber in each treatment and control group at the beginning of the test, approximately weekly during the test, and at the end of the test to measure concentrations of the test substance. Samples were collected from mid-depth, placed in 40 mL Teflon® centrifuge tubes. Immediately after sampling, two drops of 10% phosphoric acid and 1.00 mL of saturated sodium chloride in HPLC water was added to the individual centrifuge tubes. The samples were processed immediately for analysis.

Due to a high recovery from the sample collected on Day 7 of the test from the 175 µg a.i./L treatment group, an additional sample was collected from this treatment group on Day 11 of the test. Inspection of the test system after the high recovery was obtained revealed no apparent causes as to why the measured recovery in the 175 µg a.i./L treatment group was slightly higher on Day 7 than it was on the pretest and Day 0 analytical intervals.

Vehicle:

yes

Remarks:

Stock solutions prepared per exposure level in Di-Methyl Formamide as co-solvent. The concentration of co-solvent in the final exposure solutions was 0.05 mL/L.

Details on test solutions:

Five exposure solution concentration levels as well as two Controls - 1 x Solvent control and a Negative Control.

Individual stock solutions were prepared for each of the five concentrations tested, and were prepared every seven days during the test. All test solution concentrations were adjusted to 100% active ingredient during preparation, based on the reported test substance purity (99.6%). At each preparation, a 250 mL primary stock solution was prepared by mixing a calculated amount (~1.76 g) of test substance into HPLC-grade dimethylformamide (DMF) at a nominal concentration of 7.0 mg a.i./mL. The primary stock solution was sonicated for approximately 15 minutes and inverted to mix. The primary stock appeared clear and colorless, with no visible precipitates observed. Four secondary stock solutions (124 mL each) were prepared in DMF at nominal concentrations of 0.44, 0.88, 1.76, and 3.5 mg a.i./mL by proportional dilution of the primary stock. The secondary stock solutions were mixed by inversion, and appeared clear and colorless, with no visible precipitates observed.

Nominal Time-Weighted Mean Measured
Negative Control < LOQ
Solvent Control < LOQ
22 µg a.i./L 10 µg a.i./L
44 µg a.i./L 22 µg a.i./L
88 µg a.i./L 37 µg a.i./L
175 µg a.i./L 79 µg a.i./L
350 µg a.i./L 140 µg a.i./L

It is worth noting that the relatively low measured exposure concentrations with respect to Nominal test concebntrations, may be due to the low recovery rates obtained in the sample work-up methods. As such, it is highly likely that the daphnids were actually exposed to significantly higher test concentrations of HEXYL SALICYLATE than those determined and reported analytically.

Test organisms (species):

Daphnia magna

Details on test organisms:

The cladoceran, Daphnia magna, was selected as the test species for this study. Daphnids are representative of an important group of aquatic invertebrates and were selected for use in the test based upon past history of use in the laboratory. Daphnid neonates used in the test were less than 24 hours old and were obtained from cultures maintained by EAG Laboratories of Easton, Maryland. Identification of the species was verified by the supplier of the original stock culture.

Adult daphnids were cultured in water from the same source and at approximately the same temperature as used during the test. During the 2 week period immediately preceding the test, water temperatures in the cultures ranged from 19.3 to 20.6ºC, measured with a hand-help digital thermometer. The pH of the water ranged from 8.0 to 8.5, measured with a Thermo Orion Benchtop 4 Star Plus pH meter, and dissolved oxygen concentrations were 8.1 mg/L (> =89% of saturation), measured with a Thermo Orion Benchtop 3 Star Plus dissolved oxygen meter.

During culture and testing, daphnids were fed a mixture of yeast, cereal grass media, and trout chow (YCT), supplemented with a vitamin stock solution and a suspension of the freshwater green alga, Raphidocelis subcapitata. Daphnids were fed two or three times per day through Day 6 of the test and then were fed four times per day until the last day of the test. At each feeding, each test chamber was fed 0.80 mL of YCT, 1.50 mL of algae and 0.50 mL of vitamin solution. This amount of feed is equal to a range of 0.6 to 0.7 mg C/daphnid/day. While this amount of feed exceeds the OECD guideline recommended amount of 0.1 to 0.2 mg C/daphnid/day, an excess amount was fed in order to maintain sufficient feed in the flow-through system to support acceptable reproduction rates. The concentrations of selected organic and inorganic constituents in the YCT were measured at least annually.

The five adult daphnids used to supply neonates for the test were held for 21 days prior to collection of the juveniles for testing, and had each produced at least one previous brood. Adult daphnids in the culture had produced an average of at least three young per adult per day over the 7 day period prior to the test. The adults showed no signs of disease or stress and no ephippia were produced during the holding period. To initiate the test, the juvenile daphnids were collected from the cultures and indiscriminately transferred one or two at a time to transfer chambers until each chamber contained 5 daphnids. Each group of neonates then was impartially assigned to a control or treatment group and the neonates were transferred to the test compartments to initiate the test. All transfers were made below the water surface using wide-bore pipettes.

Test type:

flow-through

Water media type:

freshwater

Limit test:

no

Total exposure duration:

21 d

Hardness:

130 mg CaCO3/L

Test temperature:

Range 18.9 - 20.3 °C

pH:

Range pH 8.0 - 8.3

Dissolved oxygen:

Range : 5.5 - 9.1 mg O2/L

Conductivity:

Range : 317 - 376 microS/cm

Nominal and measured concentrations:

Nominal Time-Weighted Mean Measured
Negative Control < LOQ
Solvent Control < LOQ
22 µg a.i./L 10 µg a.i./L
44 µg a.i./L 22 µg a.i./L
88 µg a.i./L 37 µg a.i./L
175 µg a.i./L 79 µg a.i./L
350 µg a.i./L 140 µg a.i./L

It is worth noting that the relatively low measured exposure concentrations with respect to Nominal test concebntrations, may be due to the low recovery rates obtained in the sample work-up methods. As such, it is highly likely that the daphnids were actually exposed to significantly higher test concentrations of HEXYL SALICYLATE than those determined and reported analytically

Details on test conditions:

Test Apparatus
The toxicity test was conducted using an exposure system consisting of a continuous-flow diluter used to deliver each concentration of the test substance, a solvent control, and a negative control (dilution water) to test chambers. Syringe pumps (Harvard Apparatus, Holliston, Massachusetts) were used to deliver test substance stock solutions or solvent to impartially assigned mixing chambers where the stocks or solvent were mixed with dilution water prior to delivery to the test chambers. The flow of dilution water into each mixing chamber was controlled using rotameters. After mixing, the test solution in each mixing chamber was pumped into the appropriate replicate test chamber using a peristaltic pump (Cole Parmer Instrument Company, Chicago, Illinois). The peristaltic pumps were calibrated to deliver 11 volume additions of test solution in each test chamber per day.

The syringe pumps used to deliver stock solutions or solvent to the mixing chambers were calibrated prior to the test. The peristaltic pumps used to deliver test solutions to the test chambers, and the rotameters used to control the flow of dilution water to the mixing chambers, were calibrated prior to the test and calibrated/verified approximately weekly during the test. Delivery of test solutions to the test chambers was initiated six days prior to the introduction of the test organisms to the test water in order to achieve equilibrium of the test substance. The general operation of the exposure system was checked visually at least once on the first and last days of the test and at least two times per day during the test.

The delivery system and the test chambers were placed in a temperature-controlled environmental chamber to maintain the target water temperature throughout the test period. Test chambers were 7 L glass aquaria filled with approximately 6.5 L of test water. The volume in the test chambers was maintained by an overflow port on the side of the test chamber. Each test chamber contained one test compartment. Test compartments were 300 mL glass beakers, approximately 6.5 cm in diameter and 12 cm in height. Nylon mesh screens covered two holes on opposite sides of each test compartment to permit test solution to flow in and out of the compartment. The depth of the test solution in a representative compartment was approximately 8 cm, while the depth of water in a representative test chamber was approximately 16 cm. All test chambers were labeled with the project number, test concentration and replicate designation. The delivery system and test chambers were cleaned periodically during the test when needed.

Environmental Conditions
Ambient laboratory light was used to illuminate the test systems. Fluorescent light bulbs that emit wavelengths similar to natural sunlight were controlled by an automatic timer to provide a photoperiod of 16 hours of light and 8 hours of darkness. A 30 minute transition period of low light intensity was provided when lights went on and off to avoid sudden changes in lighting. Light intensity was measured at the water surface of one representative test chamber at the beginning of the test using a SPER Scientific Model 840006 light meter.

The target test temperature during the test was 20 ± 1°C. Temperature was measured in each test chamber at the beginning of the test, approximately weekly during the test, and at the end of the test using a digital thermometer. Temperature also was monitored continuously in one negative control test chamber using a minimum/maximum thermometer, which was calibrated prior to exposure initiation with a digital thermometer.

Dissolved oxygen was measured in one replicate test chamber of each treatment and control group at the beginning of the test, approximately three times per week during the test, and at the end of the test. Measurements of pH were made in one replicate test chamber of each treatment and control group at the beginning of the test, approximately weekly during the test, and at the end of the test. Measurements typically rotated between the four replicates in each treatment or control group at each measurement interval. Dissolved oxygen was measured using a Thermo Orion Star A213 Benchtop RDO/DO meter, and measurements of pH were made using a Thermo Orion Dual Star pH/ISE meter

Hardness, alkalinity and specific conductance were measured in alternating replicates of the negative control (dilution water) and the highest test concentration at the beginning of the test, approximately weekly during the test, and at the end of the test. Hardness and alkalinity were measured by titration based on procedures in Standard Methods for the Examination of Water and Wastewater (4). Specific conductance was measured using a Thermo Orion Star A122 portable conductivity meter. Total organic carbon (TOC) in the dilution water at the beginning and end of the test was measured using a Shimadzu Model TOC-VCSH total organic carbon analyzer, based on procedures in Standard Methods for the Examination of Water and Wastewater.

Biological Observations
Observations of each first-generation daphnid were made daily during the test. At these times, the numbers of immobile daphnids were recorded along with any clinical signs of toxicity (e.g., inability to maintain position in the water column, uncoordinated swimming or cessation of feeding). Those daphnids that were not able to swim within 15 seconds after gentle agitation of the test vessel were considered to be immobilized (even if they could still move their antennae). Immobilization was used as a surrogate for death. Therefore, dead animals were counted as immobile. The presence of eggs in the brood pouch, aborted eggs, males or ephippia also was recorded daily. With the onset of reproduction, neonates produced by the first-generation daphnids were counted and then discarded every Monday, Wednesday, and Friday during the test. The body length and the dry weight of each surviving first-generation daphnid were measured at the end of the test.

Reference substance (positive control):

no

Duration:

21 d

Dose descriptor:

NOEC

Effect conc.:

79 µg/L

Nominal / measured:

meas. (TWA)

Conc. based on:

test mat.

Basis for effect:

growth

Remarks on result:

other: Based on dry weight

Duration:

21 d

Dose descriptor:

NOEC

Effect conc.:

140 µg/L

Nominal / measured:

meas. (TWA)

Conc. based on:

test mat.

Basis for effect:

growth

Remarks on result:

other: Based on total length

Duration:

21 d

Dose descriptor:

EC10

Effect conc.:

99 µg/L

Nominal / measured:

meas. (TWA)

Conc. based on:

test mat.

Basis for effect:

reproduction

Remarks on result:

other: Live neonates produced per reproductive day

Key result

Duration:

21 d

Dose descriptor:

EC10

Effect conc.:

50 µg/L

Nominal / measured:

meas. (TWA)

Conc. based on:

test mat.

Basis for effect:

mortality

Details on results:

After 21 days of exposure, survival in the negative control and solvent control groups was 90.0 and 85.0%, respectively. According to Fisher’s Exact test, there were no statistically significant differences observed in percent survival between the negative control and solvent control (p > 0.05), therefore, the percent survival of the control data were pooled for comparison with the treatment data.

At test termination, survival in the pooled control and the 10, 22, 37, 79, and 140 µg a.i./L treatment groups was 87.5, 85.0, 100, 100, 60.0, and 65.0%, respectively. Fisher’s Exact test indicated that the decrease in survival in the 79 and 140 µg a.i./L treatment groups were statistically significant.

Daphnids in the 10, 22, and 37 treatment groups that survived to test termination generally appeared normal. There were sporadic observations of daphnids floating on the surface of the test solution in these treatment groups early on in the test. However, these observations were infrequent and were not concentration-responsive, and therefore were not considered to be treatment-related. There appeared to be an increased prevalence of daphnids that appeared lethargic, discolored, or small in stature in the 79 and 140 µg a.i./L treatment groups, in comparison to organisms in the controls.

Reproduction
The first day of brood production in the negative and solvent control replicates and in all Hexyl Salicylate (CAS #6259-76-3) treatment replicates, with the exception of one replicate of the 79 µg a.i./L treatment group, was Day 7 or 8 of the test, indicating that there was no apparent delay in the onset of production at any Hexyl Salicylate (CAS #6259-76-3) concentration tested. There were observations of immobile neonates and aborted eggs produced in the control groups and treatment groups throughout the test (Appendix 12). However, the number of immobile neonates and aborted eggs in the 10, 22, and 37 µg a.i./L treatment groups were comparable to the controls and therefore were not considered to be treatment-related. There was an increased prevalence of immobile neonates and aborted eggs in the 79 and 140 µg a.i./L treatment groups, in comparison to the controls. No males or ephippia were produced during the test.

The production rate of the first brood, the mean number of live young produced per reproductive day, the mean number of live young produced per adult at the beginning of the test and the mean number of live young produced per adult alive at test termination in the negative control was 0.1487, 15.8 young per day, 223 young per adult, and 250 young per adult, respectively. The production rate of the first brood, the mean number of live young produced per reproductive day, the mean number of live young produced per adult at the beginning of the test, and the mean number of live young produced per adult alive at test termination in the solvent control was 0.1538, 14.2 young per day, 193 young per adult and 231 young per adult, respectively. Since there were no statistically significant differences between the negative and solvent control groups for any of these parameters (p > 0.05), the control data were pooled for comparisons among the treatment groups .

The production rate of first brood for the pooled control and the 10, 22, 37, 79, and 140 µg a.i./L treatment groups was 0.1512, 0.1538, 0.1487, 0.1436, 0.1289, and 0.1384, respectively. According to the Jonckheere Terpstra step-down trend test, a statistically significant decreasing trend was evident in the production rate of first brood data for the 79and 140 µg a.i./L treatment groups, in comparison to the pooled control (p ≤ 0.05).

Validity criteria fulfilled:

yes

Conclusions:

The most sensitive overall effect parameter observed was on daphnid Survival :

21-day EC10 = 0.05 mg/L (95% CI :0.043 - 0.059 mg/L)

The EC10 and NOEC for live neonate production were, respectively, 0.099 and 0.079 mg/L.

Reference 2

Endpoint:

long-term toxicity to aquatic invertebrates

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

March, 2020

Rationale for reliability incl. deficiencies:

accepted calculation method

Justification for type of information:

To address long-term toxicity testing to the long-term Daphnia endpoint as part of the REACH reg-istration of AMYL SALICYLATE (target substance) it is proposed to read-across to HEXYL SALICYLATE (source substance). This is an analogue approach for which the read-across hypothe-sis is based on different compounds which have the same type of effect(s). It is covered by scenar-io 2 in the ECHA Read-Across Assessment Framework [RAAF, ECHA 2017].

This document provides scientific justification for the proposed read-across and shows that the source and target substance have similar ecotoxicological properties as a result of structural simi-larity, the same expected mode of action for aquatic toxicity and similar physicochemical proper-ties.

Read-across works within the spirit of REACH and the stated aim of the legislation to reduce ani-mal testing where possible. Additionally, ECHA has put much effort and emphasis in to develop-ing, validating and refining the process and procedures to be adopted for establishing successful read-across.

This read-across is based on the hypothesis that the source and target substance have similar eco-toxicological properties as a result of structural similarity (both the target- and source-substances are Carboxylic Acid-Esters), the same expected mode of action for aquatic toxicity and similar physicochemical properties relevant for the read-across ecotoxicological endpoint.

The justification of the proposed read-across is elaborated in the attached read-across document.

Reason / purpose for cross-reference:

read-across source

Principles of method if other than guideline:

To address long-term toxicity testing to the long-term Daphnia endpoint as part of the REACH reg-istration of AMYL SALICYLATE (target substance) it is proposed to read-across to HEXYL SALICYLATE (source substance). This is an analogue approach for which the read-across hypothe-sis is based on different compounds which have the same type of effect(s). It is covered by scenar-io 2 in the ECHA Read-Across Assessment Framework [RAAF, ECHA 2017].

This document provides scientific justification for the proposed read-across and shows that the source and target substance have similar ecotoxicological properties as a result of structural simi-larity, the same expected mode of action for aquatic toxicity and similar physicochemical proper-ties.

Read-across works within the spirit of REACH and the stated aim of the legislation to reduce ani-mal testing where possible. Additionally, ECHA has put much effort and emphasis in to develop-ing, validating and refining the process and procedures to be adopted for establishing successful read-across.

This read-across is based on the hypothesis that the source and target substance have similar eco-toxicological properties as a result of structural similarity (both the target- and source-substances are Carboxylic Acid-Esters), the same expected mode of action for aquatic toxicity and similar physicochemical properties relevant for the read-across ecotoxicological Endpoint.

Hydrophobicity (as modelled by log Kow) is also known to be a determinant of the toxicity in aquatic organisms when the effect is mediated by mechanisms of narcosis. It is also an important aspect when comparing the aquatic toxicity of classes of chemicals that have specific modes of action since a trend of increasing aquatic toxicity with increasing log Kow is usually observed up to a log Kow cut-off value of approximately 5.0 – 6.4 [EPA, 2017]. The most favourable scenario is to have similar log Kow values between the source and target substance to support a direct read-across for aquatic toxicity. The measured log Kow value for the target-substance, AMYL SALICYLATE, is 4.47 (OECD 117 – weighted value from two isomers). The log Kow for the source-substance, HEXYL SALICYLATE, is 5.5 (OECD 117). In correlation with the determined water solubility values, the log Kow values indicate that the source substance is more hydrophobic than the target substance. This has been accounted for in the subsequent assessment, and, the aquatic toxicity has been correspondingly cor-rected for this influence via application of the Acute-to-Chronic ratio observed for the source sub-stance to the short-term Daphnia EC50 of the target substance.

The data presented (key physical chemical parameters, ecotoxicological data available for both substances) indicates that the aquatic ecotoxicity mechanism of AMYL SALICYLATE (target sub-stance) and HEXYL SALICYLATE (source substance) are similar.

Furthermore the output from the OECD QSAR Toolbox shows that the structural and mechanistic pro-files of AMYL SALICYLATE (target substance) and HEXYL SALICYLATE (source substance) are sufficiently similar such that available aquatic ecotoxicity data from HEXYL SALICYLATE can be used to address aquatic ecotoxicity endpoints in the REACH registration dossier for AMYL SALICYLATE.

In order to derive the 21-day EC10 for AMYL SALICYLATE from the source substance and to compen-sate for the higher hydrophobicity of HEXYL SALICYLATE, the ratio of the Acute-to-Chronic ratio (ACR) for the Daphnia toxicity for the source substance (ACR = 7.2) is derived, which is then applied to the 48 hour EC50 value of the target substance in order to derive the AMYL SALICYLATE 21-day EC10:

AMYL SALICYLATE 48hr EC50 (0.88 mg/L) ÷ ACR HEXYL SALICYLATE (7.2) = 0.122 mg/L

Subsequently, the HEXYL SALICYLATE 21-day EC10 of 0.05 mg/L (time-weighted mean measured expo-sure concentrations) yields a predicted 21-day EC10 for AMYL SALICYLATE via read-across of 0.122 mg/L.

Test organisms (species):

Daphnia magna

Duration:

21 d

Dose descriptor:

EC10

Effect conc.:

0.05 mg/L

Nominal / measured:

meas. (TWA)

Conc. based on:

test mat.

Basis for effect:

mortality

Remarks on result:

other: Most sensitive effect end-point observed in Daphnia Reproduction study with source substance, HEXYL SALICYLATE.

Key result

Duration:

21 d

Dose descriptor:

EC10

Effect conc.:

0.122 mg/L

Nominal / measured:

meas. (TWA)

Conc. based on:

test mat.

Basis for effect:

mortality

Remarks on result:

other: The most sensitive end-point observed in the source substance study was Survival.

Details on results:

Read-across from HEXYL SALICYLATE, and applying an Acute-to-Chronic ratio of 7.2 to the 48 hour EC50 of Daphnia for AMYL is considered to give a reliable estimate of the 21 day EC10 for Daphnia for AMYL SALICYLATE, which is a value of 0.122 mg/L.

Conclusions:

The long-term EC10 for the most sensitive effect end-point for Daphnia for AMYL SALICYLATE derived through a robust and conservative Read-Across approach is established to be :

EC10 = 0.122 mg/L

In summary, important considerations for the use of the read-across are:

• There are close structural similarities between the two chemicals.
• Both substances are expected to act via the same mode of action for aquatic toxicity.
• There are no impurities that are expected to affect nor bear significance on the ecotoxicologi-cal properties of the source and target substance.
• Both substances have similar physico-chemical and biodegradability properties relevant for behaviour of the substance under aquatic toxicity test conditions (e.g. water solubility and log Kow) which follow a coherent pattern with increasing number of carbons.
• The measured log Kow values for the main constituents of the target-substance AMYL SALICYLATE is 4.47 (OECD 117). The log Kow for the source-substance HEXYL SALICYLATE is 5.5 (OECD 117) To derive the 21-day EC10 for AMYL SALICYLATE from the source substance and to compensate for the higher hydrophobicity of HEXYL SALICYLATE, the ratio of the Acute-to-Chronic ratio (ACR) for the Daphnia toxicity for the source substance (ACR = 7.2) is derived, which is then applied to the 48 hour EC50 value of the target substance in order to derive the AMYL SALICYLATE 21-day EC10.
• Based on the above, the read-across is considered adequate for the purpose of classification and labelling and/or risk assessment.

Description of key information

To address long-term toxicity testing to the long-term Daphnia endpoint as part of the REACH registration of AMYL SALICYLATE (target substance) it is proposed to read-across to HEXYL SALICYLATE (source substance). This is an analogue approach for which the read-across hypothesis is based on different compounds which have the same type of effect(s). It is covered by scenario 2 in the ECHA Read-Across Assessment Framework [RAAF, ECHA 2017].

 

This document provides scientific justification for the proposed read-across and shows that the source and target substance have similar ecotoxicological properties as a result of structural similarity, the same expected mode of action for aquatic toxicity and similar physicochemical properties.

 

Read-across works within the spirit of REACH and the stated aim of the legislation to reduce animal testing where possible. Additionally, ECHA has put much effort and emphasis in to developing, validating and refining the process and procedures to be adopted for establishing successful read-across.

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Effect concentration:

0.122 mg/L

Additional information

In order to derive the 21-day EC₁₀ for AMYL SALICYLATE from the source substance and to compensate for the higher hydrophobicity of HEXYL SALICYLATE, the ratio of the Acute-to-Chronic ratio (ACR) for the Daphnia toxicity for the source substance (ACR = 7.2) is derived, which is then applied to the 48 hour EC₅₀ value of the target substance in order to derive the AMYL SALICYLATE 21-day EC₁₀:

 

AMYL SALICYLATE 48hr EC₅₀ (0.88 mg/L) ÷ ACR HEXYL SALICYLATE (7.2) = 0.122 mg/L

 

Subsequently, the HEXYL SALICYLATE 21-day EC₁₀ of 0.05 mg/L (time-weighted mean measured exposure concentrations) yields a predicted 21-day EC₁₀ for AMYL SALICYLATE via read-across of 0.122 mg/L.