Maleic anhydride

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:

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

Adequacy of study:

key study

Justification for type of information:

Upon contact with water, maleic anhydride hydrolyses rapidly (DT50 = 0.3 min), forming maleic acid (Bunton et al., 1963). This constitutes almost instantaneous abiotic degradation, particularly in comparison to the residence/transport times in the wastewater stream. Therefore, both sewage treatment plants and subsequently surface waters will be exposed to maleic acid (if at all) instead of maleic anhydride. Accordingly, read-across of environmental effects from maleic acid to maleic anhydride is justified.

Reason / purpose for cross-reference:

read-across source

Key result

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

42.81 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mobility

Remarks on result:

other: Non-neutralized test solution.

Duration:

48 h

Dose descriptor:

NOEC

Effect conc.:

17.5 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mobility

Duration:

48 h

Dose descriptor:

LOEC

Effect conc.:

30.63 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mobility

Key result

Duration:

48 h

Dose descriptor:

other: "EC55"

Remarks:

55% immobilisation were observed at test concentration (neutralised solution)

Effect conc.:

93.8 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mobility

Remarks on result:

other: pH adjusted to 7.61-7.66

Details on results:

The substance caused a decrease of the pH in the test medium. This caused an immobilisation by 100 % at the highest test concentrations. In the repeat test with pH adjustment 55 % of the test animals were immobile at 93.80 mg test substance/L.

Reported statistics and error estimates:

EC50 was determined by Probit analysis (Finney 1971)

Validity criteria fulfilled:

yes

Conclusions:

In an acute toxicity test conducted according to the OECD guideline 202 Daphnia magna were exposed to test item loading rates of 93.8, 53.60, 30.63, 17.5, 10 mg/L (nominal) maleic acid. The EC50 (Daphnia magna, 48 h) for maleic acid was 93.80 mg/L, pH adjusted to 6 to 9. The EC50 (Daphnia magna, 48 h) for non-neutralised maleic acid test solution was 42.81 mg/L. This corresponds to an EC50 (48 h) of 37.9 mg maleic anhydride/L.

Executive summary:

The 48-h toxicity of maleic acid to Daphnia magna was studied under static conditions. Daphnia magna were exposed to control and test chemical at nominal concentrations of 93.8, 53.60, 30.63, 17.5, and 10 mg/L (nominal concentration). The 48 h EC₅₀ based on immobilisation was 42.81 mg/L (non-neutralised solution). The 48 h NOEC based on immobilisation was 17.5 mg/L (non-neutralised solution). 

As the pH ranged between 4.13 to 4.17 at 93.8 mg/L (nominal concentration), the pH was adjusted to 7.61–7.66 at 93.80 mg/L (nominal concentration) in the repeat test. During the repeat test, 55 % immobilisation wa observed at 93.8 mg/L in neutralised test solution.

This study is classified as acceptable and satisfies the guideline requirements for a acute toxicity study with freshwater invertebrates.

Results synopsis

Test organism age: 1st instar < 24 h

Test type: Static

Non-neutralised solution:

EC50: 42.81 mg/L  

NOEC:  17.5 mg/L

LOEC: 30.63 mg/L

Endpoint(s) effected: Immobilisation

Neutralised solution:

93.8 mg/L: 55 % immobilisation

The information on maleic acid is used in a read-across approach in the assessment of the target substance maleic anhydride.

Upon contact with water, maleic anhydride hydrolyses rapidly (DT50 = 0.3 min), forming maleic acid. Therefore, read-across from maleic acid to maleic anhydride is justified.

Reference 2

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

experimental study

Adequacy of study:

key study

Study period:

03 May 2010–15 October 2010

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

Confounding with pH effects due to partial lack of neutralisation; over-conservative endpoint conclusion.

Qualifier:

according to guideline

Guideline:

OECD Guideline 202 (Daphnia sp. Acute Immobilisation Test)

Deviations:

yes

Remarks:

The substance caused a decrease in pH of the test solution at the highest test concentration. The test was repeated with the highest test concentration (pH adjusted).

GLP compliance:

yes (incl. QA statement)

Analytical monitoring:

yes

Details on sampling:

- Concentrations: control, 10 mg/L and 93.8 mg/L
- Sampling method: Test solution of 10 and 93.8 mg/L and the negative control were analyzed for the active ingredients at the beginning and at the end of the test.

Vehicle:

no

Details on test solutions:

PREPARATION AND APPLICATION OF TEST SOLUTION (especially for difficult test substances)
- Method: a stock solution was prepared by dissolving 250 mg test substance in 25 ml test water. The test concentrations were prepared by separately by diluting the required amount of stock solution.
- Eluate: N/A
- Differential loading: N/A
- Controls: The negative control was the untreated test medium
- Chemical name of vehicle (organic solvent, emulsifier or dispersant): N/A
- Concentration of vehicle in test medium (stock solution and final test solution(s) or suspension(s) including control(s)): N/A

Test organisms (species):

Daphnia magna

Details on test organisms:

TEST ORGANISM
- Common name: Daphnia magna
- Justification for species other than prescribed by test guideline: N/A
- Age at study initiation (mean and range, SD): < 24h
- Source: The test animals were bred at the testing facility
- Feeding during test: No
- Food type: N/A
- Amount: N/A
- Frequency: N/A

Test type:

static

Water media type:

freshwater

Limit test:

no

Total exposure duration:

48 h

Test temperature:

20.3 and 20.4 ºC

pH:

- Control up to a test substance concentration of 53.6 mg/l: 6.13–7.89
- At a test substance concentration of 93.8 mg/l: 4.13–4.17
- Repeated test with a test substance concentration of 93.8 mg/l: 7.61–7.66

Dissolved oxygen:

6.0–7.2 mg/l

Nominal and measured concentrations:

Nominal test concentrations:
Control, 10, 17.5, 30.63, 53.60, 93.80 mg/l
The test was repeated with the hightest test concentration of 93.80 mg/l. The pH of the test medium was adusted to pH 6-9.

Measured test concentrations:
- Dose level 10 mg/L: start: 9.1942 mg/L, end: 10.3137 mg/L
- Dose level 93.8 mg/L: start: 98.5667 mg/L, end: 104.8511 mg/L

Details on test conditions:

TEST SYSTEM
- Test vessel: glass beaker (250 ml)
- Fill volume: 150 ml
- No. of organisms per vessel: 5
- No. of vessels per concentration (replicates): 4
- No. of vessels per control (replicates): 4
- Biomass loading rate: at least 2 ml/animal

TEST MEDIUM / WATER PARAMETERS
- Source/preparation of dilution water: reconstituted water according to OECD guideline 202

OTHER TEST CONDITIONS
- Adjustment of pH: yes at 93.80 mg/l
- Photoperiod: continous darkness

EFFECT PARAMETERS MEASURED (with observation intervals if applicable) :
Mobility at 0, 24 and 48 hours

TEST CONCENTRATIONS
- Spacing factor for test concentrations: 1.75
- Test concentrations: (control), 10, 30.63, 53.60, and 93.80 mg/L
- Results used to determine the conditions for the definitive study: no immobility at 0.1, 1 and 10 mg/l; 100 % immobility at 100 mg/L at 24 hours and 48 hours.

Reference substance (positive control):

yes

Remarks:

Potassium dichromate

Key result

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

42.81 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mobility

Remarks on result:

other: Non-neutralized test solution.

Duration:

48 h

Dose descriptor:

NOEC

Effect conc.:

17.5 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mobility

Duration:

48 h

Dose descriptor:

LOEC

Effect conc.:

30.63 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mobility

Key result

Duration:

48 h

Dose descriptor:

other: "EC55"

Remarks:

55% immobilisation were observed at test concentration (neutralised solution)

Effect conc.:

93.8 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mobility

Remarks on result:

other: pH adjusted to 7.61 to 7.66

Details on results:

The substance caused a decrease of the pH in the test medium. This caused an immobilisation by 100 % at the highest test concentrations. In the repeat test with pH adjustment 55 % of the test animals were immobile at 93.8 mg test substance/L.

Reported statistics and error estimates:

EC50 was determined by Probit analysis (Finney 1971)

Validity criteria fulfilled:

yes

Conclusions:

In an acute toxicity test conducted according to the OECD guideline 202 Daphnia magna were exposed to test item loading rates (maleic acid) of 93.8, 53.60, 30.63, 17.5, 10 mg/L (nominal). The EC50 (Daphnia magna, 48 h) for maleic acid was 93.80 mg/L, pH adjusted to 6 to 9. The EC50 (Daphnia magna, 48 h) for non-neutralised maleic acid test solution was 42.81 mg/L.

Executive summary:

The 48-h toxicity of maleic acid to Daphnia magna was studied under static conditions. Daphnia magna were exposed to control and test chemical at nominal concentrations of 93.8, 53.60, 30.63, 17.5, and 10 mg/L (nominal concentration). The 48 h EC₅₀ based on immobilisation was 42.81 mg/L (non-neutralised solution). The 48 h NOEC based on immobilisation was 17.5 mg/L (non-neutralised solution). 

As the pH ranged between 4.13 and 4.17 at 93.8 mg/L (nominal concentration), the pH was adjusted to 7.61–7.66 at 93.80 mg/L (nominal concentration) in the repeat test, where 55 % immobilisation was observed at 93.8 mg/L in neutralised test solution.

This study is classified as acceptable and satisfies the guideline requirements for a acute toxicity study with freshwater invertebrates. Nevertheless, the non-neutralised EC₅₀ of 42.81 mg/L constitutes an over-conservative endpoint conclusion due to confouding with pH effects.

Results synopsis

Test organism age: 1st instar < 24 h

Test type: Static

Non-neutralised solution:

EC₅₀: 42.81 mg/L  

NOEC:  17.5 mg/L

LOEC: 30.63 mg/L

Endpoint(s) effected: Immobilisation

Neutralised solution:

93.8 mg/L: 55 % immobilisation

Reference 3

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

no data

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Remarks:

Guideline study with restrictions from reliable source, neutralized samples tested, however only limited information on test performance available but without sufficient data for scientific evaluation.

Qualifier:

according to guideline

Guideline:

other: German Industrial Standard DIN 38412 part 11

Principles of method if other than guideline:

Mobility testing
Testing was performed with neutralized and non-neutralized test solution.

GLP compliance:

no

Analytical monitoring:

not specified

Vehicle:

not specified

Test organisms (species):

Daphnia magna

Test type:

static

Water media type:

freshwater

Limit test:

no

Total exposure duration:

24 h

Nominal and measured concentrations:

Nominal test concentration (%): 93

Duration:

24 h

Dose descriptor:

EC50

Effect conc.:

5 600 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Remarks:

neutralised

Basis for effect:

mobility

Duration:

24 h

Dose descriptor:

EC50

Effect conc.:

88 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Remarks:

not neutralised

Basis for effect:

mobility

Validity criteria fulfilled:

not specified

Conclusions:

The result support a hypothesis that acidity is a primary factor in the observed aquatic toxicity.

Executive summary:

The 24-h acute toxicity of maleic anhydride to Daphnia magna was studied under static conditions. The 24 h EC₅₀ based on sublethal effects was 5600 mg/L (neutralised solution), and 82 mg/L (non-neutralised solution).

The sublethal effects included were mobilisation.

This study is classified as supplementary and performed according to German Industrial Standard DIN 38412 part 11.

Reference 4

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

No data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

study comparable to guideline study (adopted from OECD SIDS) but without detailed documentation

Qualifier:

according to guideline

Guideline:

other: EPA Methods for Acute Toxicity with Fish, Macroinvertebrates and Amphibians (EPA 660/3-75-009)

Principles of method if other than guideline:

Organism age/pre-treatment: Less than 24 hr-old first instar; adults fed suspension of trout chow and alfalfa supplemented with algae every three days.
Dilution water source/chemistry: Well water. The initial DO was 7.6 mg/liter and the initial pH was 8.3 in the control. Hardness was 255 ppm (CaCO3) and alkalinity was 368 ppm (CaCO3)

Preparation of test solutions
- Carrier/solvents used: None
- Container size/seals/headspace: 250 ml glass beakers with 200 ml media
- Replicates per treatment/individuals per replicate: 2 replicates, 10 per replicate
- Lighting quality/intensity/schedule: The lighting was maintained at 50 to 70 foot-candles on a 16-hour daylight photoperiod.
- Temperature range: 20 ± 2 °C
- Statistical methods: The statistical methods used was a computerized program developed by Stephen et al. which calculates the LC50 and 95 % confidence limits using the binomial, moving average and probit tests.

GLP compliance:

no

Remarks:

GLP-like but predates GLP regulations

Analytical monitoring:

no

Vehicle:

no

Details on test solutions:

Well water

Test organisms (species):

Daphnia magna

Details on test organisms:

TEST ORGANISM
- Common name: Daphnia magna
- Justification for species other than prescribed by test guideline: N/A
- Age at study initiation (mean and range, SD): Less than 24 hr-old first instar

Test type:

static

Water media type:

freshwater

Limit test:

no

Total exposure duration:

48 h

Hardness:

Hardness was 255 ppm (CaCO3) and alkalinity was 368 ppm (CaCO3)

Test temperature:

20 ± 2 °C

pH:

pH was 2.4 (highest concentration) to 8.3 (controls).

Dissolved oxygen:

7.0 to 9.1 mg/liter

Nominal and measured concentrations:

Nominal concentrations (mg/L): 0, 100, 180, 320, 560, 1000
Measured concentrations (mg/L): (Not measured)

Details on test conditions:

TEST SYSTEM
- Test vessel: 250 ml glass beakers
- Volume of solution: 200 ml media
- Type of flow-through (e.g. peristaltic or proportional diluter): N/A
- Renewal rate of test solution (frequency/flow rate): N/A
- No. of organisms per vessel: 10
- No. of vessels per concentration (replicates): 2
- No. of vessels per vehicle control (replicates): N/A

TEST MEDIUM / WATER PARAMETERS
- Source/preparation of dilution water: Well water
- Photoperiod: 16-hour daylight
- Light intensity: The lighting was maintained at 50 to 70 foot-candles

Reference substance (positive control):

not specified

Key result

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

330 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mobility

Details on results:

Water quality: The final (48-hour) dissolved oxygen concentration was 7.0 to 9.1 mg/L and the pH was 2.4 (highest concentration) to 8.3 (controls).

Reported statistics and error estimates:

The statistical methods used was a computerized program developed by Stephen et al. which calculates the LC50 and 95 % confidence limits using the binomial, moving average and probit tests.

Endpoint values:     24 hr   EC₅₀= 340 mg/L (95% conf. interval = 180 to 560)

 48 hr   EC₅₀= 330  mg/L   (95% conf. interval = 180 to 560)

Remarks:

Cumulative response: Number of individuals of 20 per treatment

	Control	Dose 1	Dose 2	Dose 3	Dose 4	Dose 5
24 hours	0	0	0	8	20	20
48 hours	0	0	0	9	-	-

Water quality:The final (48-hour) DO concentration was 7.0 to 9.1 mg/liter and the pH was 2.4 (highest concentration) to 8.3 (controls).

Observations/protocol deviations: Control response was satisfactory.

Validity criteria fulfilled:

yes

Conclusions:

In an acute toxicity test conducted according to the guideline "EPA Methods for Acute Toxicity with Fish, Macroinvertebrates and Amphibians (EPA 660/3-75-009)" Daphnia magna were exposed to test item loading rates of 100, 180, 320, 560, 1000 mg/L (nominal) maleic anhydride. The EC50 (48 h) was determined to be 330 mg/L (nominal).

Executive summary:

The 48-hour acute toxicity of maleic anhydride to Daphnia magna was studied under static conditions. Daphnia magna were exposed to control and test chemical at nominal concentration of 100, 180, 320, 560, 1000 mg/L.

The 48 h EC₅₀ was 330 mg/L. 

This study is classified as supplementary and satisfies the guideline requirements for an acute toxicity study with freshwater invertebrates.

Results synopsis

Test organism age 1st instar: < 24 h

Test type: Static

The 48 h EC₅₀ was 330 mg/L.

Reference 5

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1980

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Qualifier:

according to guideline

Guideline:

other: Methods for Acute Toxicity Tests with Fish, Macroinvertebrates and Amphibians (EPA-660/3-75-009, 1975)

GLP compliance:

no

Analytical monitoring:

not specified

Test organisms (species):

Daphnia magna

Details on test organisms:

Daphnia magna (obtained from EPA Laboratory, Duluth, Minnesota)
Organism age/pretreatment: first instar Daphnia (12 ± 12 hours old)

Test type:

static

Water media type:

freshwater

Limit test:

no

Total exposure duration:

48 h

Hardness:

Hardness measured as CaCO3 averaged 154.5 mg/liter over the study period.

Test temperature:

22 °C

pH:

7.7

Details on test conditions:

Local spring-fed pond water

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

316 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mobility

Remarks on result:

other: 95 % CI = 250–400 mg/L

Validity criteria fulfilled:

not specified

Conclusions:

In an acute toxicity test conducted according to the methods for acute toxicity tests with fish, macroinvertebrates and amphibians (EPA-660/3-75-009, 1975), Daphnia magna were exposed to the test item maleic acid. The EC50 (48 h) was determined to be 316.2 mg/L (nominal).

Executive summary:

The 48 h toxicity of maleic acid to Daphnia magna was studied under static conditions. The 48 h EC₅₀ was 316.2 mg/L. 

This study was performed according to the guideline EPA 660/3-75-009 (1975) and is classified as supplementary.

Results synopsis

Test organism age: 1st instar < 24 h

Test type: Static

EC₅₀ (48 h) = 316.2 mg/L

Reference 6

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

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

Adequacy of study:

supporting study

Justification for type of information:

Upon contact with water, maleic anhydride hydrolyses rapidly (DT50 = 0.3 min), forming maleic acid (Bunton et al., 1963). This constitutes almost instantaneous abiotic degradation, particularly in comparison to the residence/transport times in the wastewater stream. Therefore, both sewage treatment plants and subsequently surface waters will be exposed to maleic acid (if at all) instead of maleic anhydride. Accordingly, read-across of environmental effects from maleic acid to maleic anhydride is justified.

Reason / purpose for cross-reference:

read-across source

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

316.2 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mobility

Remarks on result:

other: 95% conf. interval = 250 to 400 mg/L

Validity criteria fulfilled:

not specified

Conclusions:

In an acute toxicity test conducted according to the methods for acute toxicity tests with fish, macroinvertebrates and amphibians (EPA-660/3-75-009, 1975), Daphnia magna were exposed to the test item maleic acid. The EC50 (48 h) was determined to be 316.2 mg/L (nominal). This EC50 (48 h) corresponds to 279.8 mg maleic anhydride/L.

Executive summary:

The 48 h toxicity of maleic acid to Daphnia magna was studied under static conditions. The 48 h EC₅₀ was 316.2 mg/L. 

This study was performed according to the guideline EPA 660/3-75-009 (1975) and is classified as supplementary.

Results synopsis

Test organism age: 1st instar < 24 h

Test type: Static

EC₅₀ (48 h) = 316.2 mg/L

This information on maleic acid is used in a read-across approach in the assessment of the target substance maleic anhydride.

Upon contact with water, maleic anhydride hydrolyses rapidly (DT₅₀ = 0.3 min), forming maleic acid. Therefore, read-across from maleic acid to maleic anhydride is justified.

Description of key information

In the key study on the acute toxicity of the hydrolysis product maleic acid to Daphnia magna an EC₅₀ of 42.81 mg/l (corresponding to 37.9 mg maleic anhydride/L) was reported with non-neutralized test solution (Indrani 2010); pH adjusted test solution resulted in mitigation of effects.

The study design resulted in confounding of pH effects with potential maleate-related effects, which do not allow differentiation.

Therefore, in a worst-case approach the EC₅₀ estimated from non-neutralized samples was taken for further assessment, at the cost of accepting acidity as a major confounder.

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Effect concentration:

37.9 mg/L

Additional information

In the supporting study (Bringmann & Kuehn, 1982)Daphnia magnawere exposed to neutralized and non-neutralized maleic anhydride solutions. The mobility of the test animals was determined after 24 hours of exposure. For the non-neutralized test substance an EC₅₀of 88 mg/L was determined, whereas the mobility of 50 % of the test animals was affected at a concentration of 5,600 mg/L maleic anhydride in the neutralized trials. The test was performed a second time with maleic acid as test substance. After 24 hours an EC₅₀of 83 mg/L was determined for non-neutralized test material and an EC₅₀of 6250 mg/l for pH adjusted test solutions. The low toxicity to aquatic invertebrates is also supported by the study of ABC Laboratories (1982), reporting a result for non-neutralized test solution (EC₅₀(Daphnia magna, 48h) = 330 mg/L), and by Randall and Knopp (1980) with a reported EC₅₀(Daphnia magna, 48 h) of 316 mg maleic acid/L (corresponding to 279.8 mg maleic anhydride/L).