Reactionmass of octan-2-yl prop-2-enoate and octan-3-yl prop-2-enoate and octan-4-yl prop-2-enoate

Short-term toxicity to aquatic invertebrates

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

experimental study

Adequacy of study:

disregarded due to major methodological deficiencies

Study period:

26th-28th November, 2019

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

significant methodological deficiencies

Qualifier:

according to guideline

Guideline:

OECD Guideline 202 (Daphnia sp. Acute Immobilisation Test)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 3M FMRD, S352546
- Expiration date: 2020.05.01
- Purity: 99.7%
- Physical state: Clear and colorless liquid

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Stored at room temperature (15-25°C).
- Stability under test conditions: Due to analytical issus, stability during the test is unknown.

Analytical monitoring:

yes

Details on sampling:

- Concentrations: 14.6 mg/L and a blank control.
- Sampling method: A sample of ~20 mL was taken from each test solution and control solution. The sample was taken from excess test solution and control solution for fresh samples. For old solution sampling, 5 mL solution was sampled from each replicate of test group and control solutions and pooled. 5 mL of the sample was pre-treated before analysis. The extracts were analyzed immediately after pretreatment. The residue sample was stored in refrigerator (2-8 °C) for possible re-analysis.

Vehicle:

no

Details on test solutions:

PREPARATION AND APPLICATION OF TEST SOLUTION (especially for difficult test substances)
- Method: 0.1612 and 0.1608 g of test item (actual weights for the stock solutions at 0 and 24 hours) was weighed and added into a glass bottle with 11L of test water. A magnetic stirrer was added, the bottle was capped, and the solution mixed for 24 hours (210 rpm). The solution was allowed to stand for 30 minutes and test solutions were drawn from a tap at 7cm from the bottom of the bottle.
- Controls: Test medium without test substance or other additives.
- Chemical name of vehicle: No vehicle

Test organisms (species):

Daphnia magna

Details on test organisms:

TEST ORGANISM
- Common name: Water flea
- Strain/clone: Daphnia magna (Straus)
- Source: Applied Chemistry Department Pesticide Environmental Evaluation Lab of the China Agricultural University
- Age at study initiation: <24 hours
- Feeding during test: No
- Culture conditions: Adult daphnids were cultured in tap water treated with Aquapro Pure Water Systems. During the period preceding the test, water temperatures were 18 - 22°C, photoperiod of 16h light, 8 h dark. Daphnids in the cultures were fed daily a suspension of concentrated alga. Neonates were not the first brood.
- Health: The test Daphnia magna was derived from a healthy stock (i.e. showing no signs of stress such as high mortality, presence of males and ephippia, delay in the production of the first brood, discolored animals, etc.)

Test type:

semi-static

Water media type:

freshwater

Limit test:

yes

Total exposure duration:

48 h

Hardness:

190 mg/L CaCO3

Test temperature:

19.5-20.1°C

pH:

8.29-8.46

Dissolved oxygen:

8.35-9.18

Nominal and measured concentrations:

Nominal: 14.6 mg/L and blank control
Measured: Fresh media 1.27 mg/L (arithmetic mean), Old media 0.095 mg/L (arithmetic mean), Time weighted average: 0.44 mg/l

Details on test conditions:

TEST SYSTEM
- Test vessel: 250 mL, glass beakers.
- Test solution volume: 50 mg/L
- Aeration: No
-Renewal rate: 24 hours
- No. of organisms per vessel: five
- No. of vessels per concentration (replicates): four
- No. of vessels per control: four
TEST MEDIUM / WATER PARAMETERS
- Source/preparation of dilution water: Tap water treated with Aquapro Pure Water System
- Total organic carbon:<2 mg/L
- Particulate matter: <5 mg/L suspended solids
- Metals:All less than detection limits, except fluoride (0.31 mg/L)
- Pesticides: All less than detection limits
- Culture medium different from test medium: No
- Pesticides: All less than detection limits

OTHER TEST CONDITIONS
- Adjustment of pH: No
- Photoperiod: 16h light, 8h dark

EFFECT PARAMETERS MEASURED : Immobilization (including mortality) at 24 and 48 hours.

RANGE-FINDING STUDY
- Test concentrations: 0 mg/L (control), 0.146, 1.46, 14.6 mg/L (nominal)
- Results used to determine the conditions for the definitive study: yes

Reference substance (positive control):

yes

Remarks:

potassium dichromate

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

> 14.6 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mobility

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

> 0.44 mg/L

Nominal / measured:

meas. (TWA)

Conc. based on:

test mat.

Basis for effect:

mobility

Details on results:

- Behaviorall abnormalities: None
- Mortality of control: No mortality in control Daphnids
- Effect concentrations exceeding solubility of substance in test medium: yes

Results with reference substance (positive control):

24 hour EC50 = 1.95 mg/L for Daphnia magna (95% CI: 1.50-2.55)

Validity criteria fulfilled:

yes

Remarks:

<10% mortality in controls (0%), Dissolved oxygen concentration was ≥ 3 mg/L during test period (DO=8.35-9.18).

Conclusions:

48 hour EC50>14.6 mg/L (nominal) in Daphnia magna (OECD 202).
48 hour EC50>0.44 mg/L (measured) in Daphnia magna (OECD 202).

Executive summary:

The 48 hour EC50 to Daphnia magna was determined in a limit test under semi-static conditions according to OECD 202 guidelines. Nominal concentrations of 100 mg/L and a blank control were run using 5 animals per vessel in four replicates and no dispersant. No immobilization nor mortalities were observed throughout the test. An EC50 >14.6 mg/L (nominal concentration) and EC50 >0.44 mg/L (time weighted average) was determined.

This study was conducted under international guidelines and was compliant with GLP criteria. However, the analytical data for the test indicates that the EC50 value reported in this study is not reliable. From available data in the study report, the analytical data does not confirm test substance concentration and shows the test substance was not maintained throughout the test. The measured test concentrations were 1/10th of the nominal in fresh solution and could not be reliably detected in old solutions. The mechanisms of the chemicals disappearance is not understood and was unexpected given results of an analogous compound. Further, no toxicity to aquatic invertebrates was found for test solutions, which is contradictory to the analogous substance for which aquatic invertebrates were the most sensitive phyla. For these reasons, this study has been deemed unreliable. Thus these results are not considered suitable for use in Risk Assessment, Classification & Labeling, and PBT analysis.

.

Reference 2

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

experimental study

Adequacy of study:

key study

Study period:

21 Jan 1992 to 23 Jan 1992

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Test substance concentrations were not consistently maintained. Sharp reduction in measured test substance concentrations over the exposure period and low recovery (77%) from the test medium.

Qualifier:

according to guideline

Guideline:

OECD Guideline 202 (Daphnia sp. Acute Immobilisation Test)

Deviations:

no

GLP compliance:

yes

Analytical monitoring:

yes

Details on sampling:

- Sampling method: Samples were taken at hours 0, 24, and 48. Composite samples were taken of each concentration at hour 0. At hour 24, test chambers in which all organisms were immobile were sampled individually, whereas composite samples were taken of test chambers with surviving organisms. At hour 48, all remaining test chambers were sampled individually. The composite samples were prepared by combining 15 mL from the appropriate test chamber into 60-mL brown glass bottles. Each subsample was collected using a 15-ml volumetric pipet. The pipets were preconditioned using the corresponding test substance solutions from the corresponding monitoring chambers.
- Sample storage conditions before analysis: Samples analyzed daily

Details on test solutions:

PREPARATION AND APPLICATION OF TEST SOLUTION (especially for difficult test substances)
- Method: Stock solution prepared by adding 600 uL of test substance to 6 liter of dilution water in a reaction flask. Test substance was stirred gently for 48 hrs at 21.2 °C. After stirring, the mixture was allowed to settle until any visible emulsion was absent. The first 100 ml of aqueous solution was discarded, and 1.4 L of aqueous solution was collected. This was considered a saturated solution. The pH of the test substance at the nominal high test concentration (8.0 mg/L) was 8.2 and was not adjusted.

- Chemical name of vehicle (organic solvent, emulsifier or dispersant): None used

- Evidence of undissolved material (e.g. precipitate, surface film, etc): None

Test organisms (species):

Daphnia magna

Details on test organisms:

TEST ORGANISM
- Common name: Water flea
- Strain: Not reported
- Source: Stock culture maintained at testing lab
- Age at study initiation: < 24 hours
- Feeding during test: Not fed

ACCLIMATION
- Acclimation period: Gravid daphnids were isolated in food-free dilution water 24 h before test initiation. Neonates were obtained at the end of this period
- Health during acclimation (any mortality observed): Test organisms appeared to be free from any disease or stress.

Test type:

static

Water media type:

freshwater

Limit test:

no

Total exposure duration:

48 h

Remarks on exposure duration:

Test chambers were sampled (15 mL) at 0 and 24 hours. Test solution from a separate monitoring chamber was added back to the test chambers to restore volume removed for analysis.

Hardness:

193 - 197 mg/L as CaCO3

Test temperature:

21.0 - 21.3 °C

pH:

8.1 - 8.5

Dissolved oxygen:

8.7 - 8.9 mg/L

Nominal and measured concentrations:

Nominal concentrations: 0, 0.5, 1.0, 2.0, 4.0, and 8.0 mg/L
Mean measured concentrations (corrected for recovery): <0.04, 0.24, 0.53, 1.21, 2.78, 7.40 mg/L

Details on test conditions:

TEST SYSTEM
- Test vessel: 250 mL Erlenmeyer flasks with ground glass stoppers. A separate monitoring chamber was assembled for each concentration to allow measurement of test conditions and to replace volume lost to sampling. During the test, the exposure chambers were kept sealed, except when experimental observations were made or when samples of test solution were collected for analytical monitoring. Following sample collection, 250-ml test volume in each test and control exposure was restored from the monitoring chamber.
- Type : closed
- Material, size, headspace, fill volume: 250 mL of test solution, headspace not reported
- Aeration: Not during test
- No. of organisms per vessel: 5
- No. of vessels per concentration (replicates): 4
- No. of vessels per control (replicates): 4

TEST MEDIUM / WATER PARAMETERS
- Source/preparation of dilution water: Well water from the Two Harbors, (Minnesota) area.
- Total organic carbon: Not reported, but COD was 9 mg/L
- Particulate matter: < 4 mg/L
- Metals (reported if above detection limit):
Calcium, 46.5 mg/L
Copper, 13 µg/L
Iron, 3 µg/L
Magnesium, 16.3 mg/L
Sodium, 6.5 mg/L
Zinc, 30 µg/L

- Pesticides: none above detection limit.
- Chlorine: Not reported
- Alkalinity: 181 mg/L to 183 mg/L (as CaCO3)
- Ca/mg ratio: 2.85
- Conductivity: between 354 µmhos/cm and 381 µmhos/cm

- Intervals of water quality measurement: Annually (most recent was August-September 1991)

OTHER TEST CONDITIONS
- Adjustment of pH: None
- Photoperiod: 16h:8h light:dark
- Light intensity: Cool white light, intensity not reported

EFFECT PARAMETERS MEASURED (with observation intervals if applicable) :
Immobilization: exposure chambers were gently agitated and then observed to count the number of test organisms that did not swim within 15 seconds. After each observation, all affected test organisms were removed from the exposure chambers.


TEST CONCENTRATIONS
- Spacing factor for test concentrations: 2
- Range finding study: yes
- Results used to determine the conditions for the definitive study: 24-hour EC50 between 1.4 mg/L and 14 mg/L.

Reference substance (positive control):

no

Key result

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

0.4 mg/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat.

Basis for effect:

mobility

Remarks on result:

other: 95 % CI, 0.29-0.53 mg/L. LOEC, 0.24 mg/L

Details on results:

48-hour EC50, 0.40 mg/L; 95 % CI, 0.29-0.53 mg/L. No NOEC could be determined. The LOEC is 0.24 mg/L. Endpoints based on mean measured concentration.

- Mortality of control: None
- Abnormal responses: None
- Any observations (e.g. precipitation) that might cause a difference between measured and nominal values:
Considerable reduction (ca. 50%) of test substance concentration occurred between time 0 and time 48 hr (See Table 2). At time of test, the Sponsor suspected that the test substance may have glass surface activity. Since aseptic techniques were not used in this study, it is expected that the substance may have undergone extensive primary biodegradation during the exposure period.
- Effect concentrations exceeding solubility of substance in test medium: No

Reported statistics and error estimates:

For EC50 calculations, the test substance effect data (Table 3) were analyzed using the trimmed Spearman-Karber method (Hamilton et. al. 1977), and for NOEC calculation, the data were analyzed using TOXSTAT (University of Wyoming 1989) statistical software.

The sample means used for statistical analysis give improper weight to individual samples at time 48 Hours relative to the composite samples taken earlier in the study. However, the effect of this calculation is to reduce the calculated mean concentration at the endpoint and provide a more conservative estimate of test substance toxicity.

Table 1, Matrix spike recoveries for the test substance
Matrix	Time of analysis (h)	Test substance conc'n (mg/L)		Percent recovery
		nominal	measured
Matrix ─ Deionized water
Method blank
	0	0.0	<0.04	─
	24	0.0	<0.04	─
	48	0.0	<0.04	─
Spike solution
	0	0.123	0.097	79
	24	0.103	0.071	69
	48	0.123	0.085	69
Mean spike recovery 72 ± 5.8%
Matrix ─ Well water
Method blank
	0	0.0	<0.04	─
	24	0.0	<0.04	─
	48	0.0	<0.04	─
Spike solution
	0	0.123	0.087	71
	24	0.103	0.085	83
	48	0.123	0.089, 0.101^a	77
Mean spike recovery 77 ± 6.0%
a, duplicate analyses, percent recovery is mean value

Table 2, Nominal and mean measured concentrations of substance during test
Test substance nominal conc'n (mg/L)	Replicate	Test substance measured conc'n (mg/L)
		0 hrs	24 hrs	48 hrs	Overall mean
0.0 (control)	A	─	─	<0.04
	B	─	─	<0.04
	C	─	─	<0.04
	D	─	─	<0.04
	Composite	<0.04	<0.04	─	─
0.5	A	─	─	0.14
	B	─	─	0.18
	C	─	─	0.12
	D	─	─	0.13
	Composite	0.56	0.33	─	0.24 ± 0.174
1.0	A	─	─	0.43
	B	─	─	0.45
	C	─	─	0.47
	D	─	─	0.38
	Composite	0.92	0.52	─	0.53 ± 0.197
2.0	A	─	─	1.20
	B	─	─	0.88
	C	─	─	1.17
	D	─	─	0.90
	Composite	1.67	1.45	─	1.21 ± 0.310
4.0	A	─	─	1.82
	B	─	─	2.11
	C	─	3.14	─
	D	─	─	2.30
	Composite	3.83	3.46	─	2.78 ± 0.812
8.0	A	─	7.64	─
	B	─	5.67	─
	C	─	6.49	─
	D	─	7.12	─
	Composite	10.05	─	─	7.40 ± 1.657

Table 3, Immobilization ofD. magna
Test substance conc'n (mg/L)			Cumulative number of immobilized organisms (% effect)^b
nominal	measured^a
	initial	reported mean	24 h	48 h
0.0 (control)	<0.04	<0.04	0 (0)	0 (0)
0.5	0.56	0.24	0 (0)	5 (25)
1.0	0.92	0.53	2 (10)	13 (65)
2.0	1.67	1.21	5 (25)	20 (100)
4.0	3.83	2.78	15 (75)	20 (100)
8.0	10.05	7.40	20 (100)	20 (100)
a, Measured concentrations were corrected for daily well water spike recovery.
b, For each concentration, four replicate exposure were made with a total of 20 test organisms, and percentage effect is given in parenthesis.

Validity criteria fulfilled:

yes

Conclusions:

The 48-hour EC50 of the test substance to Daphnia magna is 0.40 mg/L. No NOEC could be determined. The LOEC is 0.24 mg/L.

Executive summary:

The 48-hour acute toxicity of the test substance to Daphnia magna was studied under static, closed conditions. Daphnids were exposed to nominal concentrations of 0, 0.5, 1.0, 2.0, 4.0 and 8.0 mg/L, corresponding to mean measured concentrations of < 0.04, 0.24, 0.53, 1.21, 2.78, and 7.40 mg/L for 48-hours. Mortality/immobilization were determined daily until test termination. The 48-hour EC50 was 0.40 mg/L based on mean measured concentrations. No NOEC could be determined. The LOEC is 0.24 mg/L based on mean measured concentrations.

This study is classified as acceptable and satisfies the guideline requirements for an OECD Guideline 202, acute toxicity study with freshwater invertebrates. It has been given a reliability score of 2 (reliable with restrictions) because of sharp reduction in measured test substance concentrations over the exposure period and low recovery (77%) from the test medium.

Reference 3

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

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

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The target chemical (MTDID 44428 (CAM-8) CASRN 87015-11-0) and the source chemical (isooctyl acrylate (IOA) CAS 29590-42-9) are isomers that contain the same functional acrylate moiety attached to primarily C8 alkyl hydrocarbon chains (C7-C9, C8 rich for the source chemical) with variable branching. The source chemical differs from the target chemical in both the degree and position of branching of the alkyl ester group with the source chemical being branched at the terminal end of the alkyl chain while the target chemical is branched near the acrylate functional group. The acrylate group is expected to be metabolized in the same manner in both substances and the remaining alkyl chain will be metabolized and excreted via the same pathway. The source chemical and target chemical have the same molecular weight and very similar log Kow values (Target: 4.7-4.8, Source: 4.5-4.7). Similar ADME profiles are expected between the two substances as the metabolic pathway of acrylate esters has been well characterized. Acrylate and methacrylate functionalities are electrophilic and both may participate in Michael addition reactions. Metabolism is expected to occur through the same pathways, hydrolysis by carboxylesterases into two metabolites, an alcohol and
an acrylic acid moiety with minor conjugation to gluthathione. Hydrolysis is similar across the acrylate family and enhances the elimination of the chemical upon exposure (McCarthy & Witz, 1997). Studies with n-butyl acrylate and 2-ethylhexyl acrylate confirm that the acrylic acid metabolite enters aerobic oxidation and in completely metabolized to CO2 with only a minor proportion be conjugated to glutathione and excreted in the urine as a N-acetyl cysteine conjugate (Sanders, JM et. al, 19188; Gut, I, et al. 1988). The previously mentioned studies have also demonstrated that enzymatic hydrolysis kinetic constants for methacrylate and acrylate esters are similar.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Target Chemical
The target molecule, MTDID 44428 (CASRN 87015-11-0), is a multi-constituent substance defined as the reaction mass of octan-2-yl acrylate, octan-3-yl acrylate and octan-4-yl acrylate as represented by the following structures (see attached read-across justification document). Molecular weight of the target chemical is 184.3
Source Chemical:
The source chemical, isooctyl acrylate (IOA) CAS 29590-42-9, is defined as a UVCB and is represented by the following structure (see attached read-across justification document). The average molecular weight of the source substance is ca. 184.0. The source chemical differs from the target chemical in the degree and position of branching of the alkyl ester group with the source chemical having variable methyl branching along the alkyl chain while the target chemical is branched immediately adjacent to the acrylate functional group.
Purity and Impurities :
MTDID 44428 is a multi-constituent substance and the three acrylate constituents contribute >99% of the content. There are very low levels of residual reactants and reaction side products. Isooctyl acrylate is a UVCB substance, based on the mixed-isomer nature of the material. As a UVCB substance, all components are considered part of the substance and the concept of impurities has little meaning. Acrylate ester content of IOA is >99 %, with very low levels of residual reactants and reaction side products. These non-acrylate components are substantially similar and do not impact the read-across of test results from IOA.

3. ANALOGUE APPROACH JUSTIFICATION
The target chemical and source chemical are closely related alkyl acrylate compounds. They differ slightly in the structure of the alkyl ester portion of the molecule. MTDID 44428 contains a methyl, ethyl or propyl branch at the 1-carbon of the alkyl chain portion of the molecule, which is always C8 in total. IOA may have methyl or ethyl branches at one or more positions along the alkyl ester group. The carbon chain is predominantly C8 in total with lesser contributions of C7 and C9 (C8 on average). The environmental toxicity of low molecular weight acrylate esters (aquatic mortality and immobilization) is by protein adduct formation via a Michael-type addition mechanism. In the environment, toxicity increases on a molar concentration basis with molecular weight (and concomitantly, hydrophobicity) due to increased ability of the molecule to reach its active site. The excess toxicity is mitigated in high molecular weight acrylate esters with log P > 5. The mammalian toxicity of IOA and MTDID 44428 is also based on protein adduct formation via a Michael-type addition with the acrylate groups. Both the target and source chemical are weak dermal sensitizers (section 5 in attached read-across justification and data matrix table) indicating that an equivalent mechanism of toxicity is at work for both substances based on identical functional groups and molecular weights and very similar log Kow values and water solubilities. The number of hydrophobic carbons of IOA relative to MTDID 44428 is predicted to be similar resulting in very similar octanol water partition coefficient values. This was confirmed experimentally and the log Kow for IOA is 4.5-4.7 while the log Kow for MTDID 44428 is 4.7-4.8. Additionally, IOA and MTDID 44428 have very similar water solubility at 12.44 and 14.6 mg/L, respectively. IOA is expected to be metabolized via the same hydrolytic and enzymatic pathways as MTDID 44428, forming acrylic acid and isooctanol. Similar mammalian metabolic pathways are expected for IOA and MTDID 44428 based on Sanders, et. al and Gut, et al. The source chemical and target chemical have the same molecular weight and very similar log Kow values. Similar ADME profiles are expected between the two substances as the metabolic pathway of acrylate esters has been well characterized. Acrylate and methacrylate functionalities are electrophilic and both may participate in Michael addition reactions. Metabolism is expected to occur through the same pathways, hydrolysis by carboxylesterases into two metabolites, 2an alcohol and an acrylic acid moiety with minor conjugation to gluthathione. Hydrolysis is similar across the acrylate family and enhances the elimination of the chemical upon exposure (McCarthy & Witz, 1997). Studies with n-butyl acrylate and 2-ethylhexyl acrylate confirm that the acrylic acid metabolite enters aerobic oxidation and in completely metabolized to CO2 with only a minor proportion be conjugated to glutathione and excreted in the urine as a N-acetyl cysteine conjugate (Sanders, JM et. al, 1988; Gut, I, et al. 1988). The previously mentioned studies have also demonstrated that enzymatic hydrolysis kinetic constants for methacrylate and acrylate esters are similar. As can be seen in section 5 in attached read-across justification and data matrix table, the source and target substances have very similar environmental and mammalian hazard profiles for endpoints where each substance has experimental data. This further supports the hypothesis that the target and source substances are expected to behave similarly in mammalian and environmental systems with the same mechanism of action and that read-across of the data for higher-tier endpoints is appropriate in an effort to reduce unnecessary animal testing.


4. DATA MATRIX
See 'Other Information Including Tables' or attached justification.
Supporting References
Gut, I, Vodička, Cikrt, M, Sapota, A, and Kavan, I (1988) Distribution and elimination of (14C)-2-ehtylheyxyl acrylate radioactivity in rats. Archives of Toxicology 62:346-350.
McCarty, TJ and Witz, G (1997) Structure-activity relationships in the hydrolysis of acrylate and methacrylate esters by carboxylesterase in vitro. Toxicology 116: 153-158.
Sanders, JM, Burka, LT, and Matthews, HB (1988) Metabolism and disposition of n-butyl acrylate in male Fischer rats. Drug Metabolism and Disposition 16(3): 429-434

Reason / purpose for cross-reference:

read-across source

Key result

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

0.4 mg/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat.

Basis for effect:

mobility

Remarks on result:

other: 95 % CI, 0.29-0.53 mg/L.

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

1.4 mg/L

Nominal / measured:

meas. (initial)

Conc. based on:

test mat.

Basis for effect:

mobility

Remarks on result:

other: Read across from supporting study

Read-Across Data Matrix

	Target substance	Source substance
CHEMICAL NAME	Reaction mass of octan-2-yl acrylate, octan-3-yl acrylate and octan-4-yl acrylate	Isooctyl acrylate
CAS#	44914-03-6	29590-42-9
Molecular formula	C11H20O2	C11H20O2 (on average)
Molecular Weight	184.3	184.3 (on average)
Melting Point	Experimental: <-35 °C	Experimental: < -90 °C at 1004 hPa
Boiling Point	Experimental: 217.6 °C (normalized)	Experimental: 196.8 °C at 1016 hPa
Density	Experimental: 0.8665 at 23 °C	Experimental: 0.885 g/cm3 at 20.0 °C
Vapour Pressure	Experimental: .06 hPa at 18 °C	Experimental: 1 hPa at 20 °C
Partition Coefficient (log KOW)	Experimental: 4.7-4.8	Experimental: 4.5 - 4.7
Water Solubility	Experimental: Individual isomers had solubilites of 4-5 mg/L, total was 14.6 mg/L	Experimental: 12.44 mg/L at 23.1 °C
Stability in Water	Experimental: t1/2at 25 °C, pH 9, 37.7-116 days t1/2at 25 °C, pH 7, 137 days - not determinable t1/2at 25 °C, pH 4, 154 days - not determinable. Hydrolysis product could be detected at pH 9 but not pH 7 and 4. Half-life increased from 2-octyl < 3-octyl < 4-octyl isomers.	Adaptation, readily biodegradable
Aerobic Biodegradation	Experimental: 54.7% after 28 days, biodegradation essentially stopped at day 11 (OECD 301F)   67% after 28 days. No residual material could be detected in test chambers on day 28. In abiotic control, residual test material was 4.8% of initial result (OECD 302C)	Experimental: 93-95% after 28 days (OECD 301D)
Bioconcentration		Not bioaccumulative (Extensive metabolism)
Transport and Distribution	Experimental: Koc 630 (OECD121)	Experimental: Koc 650-3900 (OECD121)
Henry's Law constant	NDA	Experimental: 1780 Pa*m3/mol at 23.1 °C
Acute Toxicity to Fish  (P. promelasunless noted)	NDA	Experimental: 96-hour LC50 0.67 mg/L (OECD 202)
Chronic Toxicity to Fish	NDA	Waived
Acute Toxicity to Aquatic Invertebrates (D. magna)	NDA	Experimental: 48-hour EC50 0.4 mg/L (OECD 202)
Long-Term Toxicity to Aquatic Invertebrates (D. magna)	NDA	Experimental: 28-day NOEC 0.065 mg/L (OECD 202 rev 1984)
Toxicity to Algae and Aquatic Plants (P. subcapitata)	NDA	QSAR result. Not read across
Toxicity to Microorganisms (activated sludge respiration)	Experimental: 3-hour EC50 >1000 mg/L (OECD 209)	Experimental: 3-hour EC50 >1000 mg/L (OECD 209)
Acute Oral Toxicity	Experimental: Rat oral LD50 > 2,000 mg/kg	Experimental: Rat oral LD50 > 5,000 mg/kg
Acute Dermal Toxicity	Read-across from source: Rabbit dermal LD50 > 2,000 mg/kg	Experimental: Rabbit dermal LD50 > 2,000 mg/kg
Acute Inhalation Toxicity	Read-across from source: NDA	Experimental: NDA
Skin Irritation	Experimental: Irritating (GHS Cat. 2)	Experimental: Not irritating
Eye Irritation	Experimental: Not Irritating	Experimental: Not irritating
Skin Sensitization	Experimental: Weak sensitizer (GHS Category 1B)	Experimental: Weak sensitizer (GHS Category 1B)
Ames Assay	Experimental: Non-mutagenic	Experimental: Non-mutagenic
in vitroChromosome Aberration	Read-across from source: Clastogenic at cytotoxic concentrations	Experimental: Clastogenic at cytotoxic concentrations
in vitroMouse Lymphoma Assay	Read-across from source: Non-mutagenic	Experimental: Non-mutagenic
28 Day Oral Toxicity	Read-across from source: NOAEL = 1,000 mg/kg/day	Experimental: NOAEL = 1,000 mg/kg/day
90 Day Oral Toxicity	Read-across from source: NOAEL = 600 mg/kg/day	Experimental: NOAEL = 600 mg/kg/day
Reproductive/Developmental Screening Study (Dermal)	Read-across from source: NOAEL = 20% Dermal Exposure	Experimental: NOAEL = 20% Dermal Exposure
Prenatal Developmental Study (Oral)	Read-across from source: NOAEL = 1,000 mg/kg/day	Experimental: NOAEL = 1,000 mg/kg/day
Carcinogenicity (Dermal)	Read-Across from source: Not Carcinogenic	Experimental: Not Carcinogenic (5% Dermal Exposure)

Conclusions:

MTDID 44428 is estimated to have a 48hr EC50=0.40 mg/L to Daphnia magna by read across from isooctyl acrylate.

Executive summary:

The similarities between the structural, physical & chemical, toxicity, and predicted metabolic properties of the source and target substances presented above support the read-across hypothesis for short term toxicity to aquatic invertebrates. The data are adequate and reliable scientific information to support the hypothesis. Therefore, based upon the data and considerations presented in the above sections, it can be concluded that the results of the short term toxicity to aquatic invertebrates study with source substance will accurately predict the results for the target substance and are considered as adequate to fulfill the information requirement of Annex VIII, of the REACH Regulation for the target substance.

Description of key information

48 hour EC50=0.40 mg/L (arith. mean) in Daphnia magna (OECD 202)

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Dose descriptor:

EC50

Effect concentration:

0.4 mg/L

Additional information

A study performed using MTDID 44428 with Daphnia magna under OECD 202 was considered unreliable due to methodological deficiences. The data gap for invertebrate acute toxicity was filled by using read across from isooctyl acrylate. The key value for acute invertebrate toxicity was a 48 hour EC50=0.40 mg/L of isooctyl acrylate to Daphnia magna, determined in a definitive test according to OECD 202 guidelines. The key value was supported by a secondary read across data point for isooctyl acrylate for inital test material concentrations (48hr EC50=1.40 mg/L) using OECD 202 guidelines with static conditions. While the study reports are available, written reports on the test material analysis were not. The key read across source data has been given a reliability score of 2 (reliable with restrictions) because of sharp reduction in measured test substance concentrations over the exposure period and low recovery (77%) from the test medium. However, available test substance retention and analytical results were of much higher quality than the values reported for MTDID 44428.