Methacrylic anhydride

Long-term toxicity to aquatic invertebrates

Link to relevant study record(s)

Reference

Endpoint:

long-term toxicity to aquatic invertebrates

Type of information:

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

Adequacy of study:

key study

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

According to OECD-guideline no. 202, part II five concentrations (14, 30, 53, 110 and 230 mg/l; measured) were tested. Due to the steep dose/response curve in both acute and chronic daphnia toxicity study, the missing result of the 30 mg/l concentration group is without relevance because this concentration was less than the established NOEC (53 mg/l).

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
Methacrylic acid is the hydrolysis product of Methacrylic anhydride. One molecule of methacrylic anhydride willl hydrolyse into two molelules methacrylic acid.


2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Source substance: Methacrylic acid, purity >= 98 %
Target substance: Methacrylic anhydride: purity: >=94 %, other components: Methacrylic acid and adducts of methacrylic aanhydride and adducts of methacrylic acid and methacrylic anhydride.

3. ANALOGUE APPROACH JUSTIFICATION
Like other acid anhydrides, methacrylic anhydride was found to be hydrolytically unstable in water at pH 4, 7 and 9. The half lives (DT50) were found to be 56.4 min at pH 4 (25 °C), 25.5 min at pH 7 (25 °C) respectively 10.3 min at 37 °C and 2.29 min at pH 9. The initial hydrolysis product is methacrylic acid (Noack 2012).

4. Data Matrix
Target: Methacrylic anhydride CAS 760-93-0
Source: Methacrylic acid CAS 79-41-4

Reason / purpose for cross-reference:

read-across source

GLP compliance:

yes

Analytical monitoring:

yes

Details on sampling:

Both replicates of each treatment level and control were analyzed for MAA concentration twice prior to the start of the definitive exposure. Each
replicate solution was sampled and analyzed for MAA concentration on day 0 and weekly thereafter (day 7, 14 and 21)

Vehicle:

no

Details on test solutions:

Nominal concentrations were maintained by introducing approximately 6.0 aquarium volumes per day of newly prepared test solution via an intermittent proportional flow through dilution apparatus.

Test organisms (species):

Daphnia magna

Details on test organisms:

Organisms were obtained from laboratory cultures maintained at Springborn. Culture water was prepared by fortifying well water and filtering. Two weeks prior to study intiation the water had total hardness and total alkalinity ranges of as CaCO3 of 160-180 and 110-120 mg/L, respectively, a pH range of 7.4 to 8.5, a specific conductance range of 500-600 umhos/cm and a dissolved oxygen concentration >60%. Light intensity ranged from 70-90 footcandles. The culture solution temperature was maintained at 20 +/-2C. Daphnia were fed once daily.

Test type:

flow-through

Water media type:

freshwater

Limit test:

no

Total exposure duration:

21 d

Hardness:

160-180 mg CaCO3/L.

Test temperature:

20 - 21°C

pH:

5.6 - 8.1 (at 14 - 110 mg/l)
4.2 - 5.7 (at 230 mg/l)

Dissolved oxygen:

8.6 - 9.2 mg/l

Nominal and measured concentrations:

Nominal 13, 25, 50, 100 and 200 mg a.i./L.
Based on results of weekly analysis, mean measured concentrations of MAA averaged 110% of nominal concentrations and defined the exposure
concentrations as 14, 30, 53, 110 and 230 mg a.i./L.

Details on test conditions:

TEST SYSTEM
- Test vessel: Set of 12 exposure vessels. The test system was designed to provide five concentrations of the test material and a dilution water control

- Material, size, headspace, fill volume: glass test vessel (1.6-L battery jar) maintained a constant solution volume of 1.4 L and a solution depth of approximately 15 cm

- Aeration: no aeration
- Type of flow-through: intermittend flow through diluter apparatus
- Renewal rate of test solution (frequency/flow rate): daily renewal
- No. of organisms per vessel: 20 daphnids per replicate vessel
- No. of vessels per concentration (replicates): 2
- No. of vessels per control (replicates): 2
- No. of vessels per vehicle control (replicates): not applicable
- Biomass loading rate: Biomass will not exceed 0.1 grams for each 11ter per day of test solution flow

TEST MEDIUM / WATER PARAMETERS
- pH: 7.9 to 8.3

- Source/preparation of dilution water:
- Alkalinity: Total alkalinity as CaC03: 110 to 120 mg/L
- Ca/mg ratio: Total hardness as CaC03: 160 to 180 mg/L

- Conductivity: 500 to 600 μmhos/cm

Culture and test dilution water were prepared in 1900-liter batches by fortifying well water according to the formula for hard water (U.S. EPA, 1975) and filtering it through an Amberlite
XAD-7 resin column to removed any potential organism contaminants. Generally, several batches of water were prepared each week. The frequency at which the dilution water was
prepared depended on the requirements of the laboratory. Fortified water was discarded if not used within 14 days of preparation.
Representative samples of the dilution water source were analyzed periodically for the presence of pesticides, PCBs and toxic metals (Appendix IV). None of these compounds have been
detected at concentrations that are considered toxic in any of the water samples analyzed, in agreement with ASTM (1989) standard practice.
OTHER TEST CONDITIONS

- Photoperiod: 16 hours of light and 8 hours of darkness
- Light intensity: 70 to 90 footcandles

Reference substance (positive control):

no

Duration:

21 d

Dose descriptor:

NOEC

Effect conc.:

53 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

mortality

Duration:

21 d

Dose descriptor:

EC50

Effect conc.:

70 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

immobilisation

Remarks on result:

other: 95% CI of 53-110 mg/L

Duration:

21 d

Dose descriptor:

other: EC100

Effect conc.:

110 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Key result

Duration:

21 d

Dose descriptor:

NOEC

Effect conc.:

53 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

reproduction

Details on results:

Exposure solutions were clear, colorless and contained no visible signs of undissolved material throughout the test. Total alkinlinity and pH of the solutions decreased with increasing concentration of MAA.
Following 21 days of exposure survival of control Daphnids was 95%. No organism survived the 21 day exposure to the two highest dose levels (110 and 230 mg a.i./L). Survival of 85 and 90% was observed among the organisms exposed to 14 and 53 mg a.i./L, respectively, and was not significantly different from controls.

At test termination ( day 21 ), reproduction among organisms exposed to the 14 and 53 mg A.I.IL treatment levels was 70 and 50 offspring per female, respectively, and was not
significantly different as compared to the performance of control organisms (56 offspring per female). Since organism survival was significantly affected by exposure to 110 and 230 mg
A.I.IL methacrylic acid, reproduction data for these two exposure concentrations were not statistically analyzed to establish treatment effects on reproduction. Time to first brood release
by organisms exposed to 14 and 53 mg A.I.IL methacrylic acid was day 7, which was similar to the time to first brood release by the control population.

Cumulative number of offspring produced per female

daphnid(Daphnia magna)during the 21-day chronic

exposure to methacrylic acid.

		Mean Cumulative Number of Offspring/Female
Mean Measured Concentration (mg A.I.IL)	Day:	7	8	9	11	14	16	18	21
Control		0	3	4	12	23	30	39	56
14		1	4	6	21	36	40	51	70
30 (a)		0	0	0	0	0	0	0	5
53		0	2	4	13	21	31	39	50
110		0	0	0	0	0	0	0	0 (b)
230		0	0	0	0	0	0	0	0 (b)

 

(a)       Due to the diluter system malfunction which resulted in the direct addition of test material to this test concentration, the biological-response data for this treatment level was not used in the statistical analysis to evaluate the toxicity of methacrylic acid to D. magna.

 

(b)      Significantly different (p ~ 0.005) from the control organisms.

At test termination ( day 21 ), reproduction among organisms exposed to the 14 and 53 mg A.I.IL treatment levels was 70 and 50 offspring per female, respectively, and was not

significantly different as compared to the performance of control organisms (56 offspring per female). Since organism survival was significantly affected by exposure to 110 and 230 mg

A.I.IL methacrylic acid, reproduction data for these two exposure concentrations were not statistically analyzed to establish treatment effects on reproduction. Time to first brood release

by organisms exposed to 14 and 53 mg A.I.IL methacrylic acid was day 7, which was similar to the time to first brood release by the control population

Validity criteria fulfilled:

yes

Conclusions:

Methacrylic anhydride rapidly hydrolysis to methacrylic acid in aqueous media. Therefore assessment of aquatic toxicity to Methacrylic anhydride based on studies with methacrylic acid is recommended.
In a valid guideline study the LOEC was 110 mg a.i./L; the NOEC was 53 mg a.i./L

Executive summary:

Methacrylic anhydride rapidly hydrolysis to methacrylic acid in aqueous media. Therefore assessment of aquatic toxicity to Methacrylic anhydride based on studies with methacrylic acid is recommended.

Methacrylic acid was tested in a Daphnia magna reproduction toxicity test for 21 days under flow through conditions at mean measured test concentrations of 14, 30, 53, 110 and 230 mg a.i./L. At test termination ( day 21 ), reproduction among organisms exposed to the 14 and 53 mg A.I.IL treatment levels was 70 and 50 offspring per female, respectively, and was not significantly different as compared to the performance of control organisms (56 offspring per

female). Since organism survival was significantly affected by exposure to 110 and 230 mg A.I.IL methacrylic acid, reproduction data for these two exposure concentrations were not

statistically analyzed to establish treatment effects on reproduction. Time to first brood release by organisms exposed to 14 and 53 mg A.I.IL methacrylic acid was day 7, which was similar to the time to first brood release by the control population.

Result: NOEC Daphnia magna reproduction (21 d): 53 mg/l

Description of key information

NOEC (21d) daphnia magna OECD 211. Read across from methacrylic anhydride.

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Effect concentration:

58 mg/L

Additional information

Methacrylic anhydride is hydrolytically unstable in water. The initial hydrolysis product is methacrylic acid.

In an OECD 211 fresh water Daphnia magna reproduction test with methacrylic acid the NOEC (21d)

was >= 53 mg/l.