Maleic anhydride

Short-term toxicity to fish

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

short-term toxicity to fish

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1982

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

significant methodological deficiencies

Remarks:

Purity and origin of the test substance are missing. Furthermore the actual concentrations were not measured.

Qualifier:

according to guideline

Guideline:

other: EPA-660/3-75-009, EPA Methods for Acute Toxicity Tests with fish, macroinvertebrates and amphibians

Principles of method if other than guideline:

EPA Methods for Acute Toxicity Tests with fish, macroinvertebrates and amphibians

GLP compliance:

no

Remarks:

GLP-like but predates GLP regulations

Analytical monitoring:

no

Vehicle:

no

Test organisms (species):

Lepomis macrochirus

Details on test organisms:

TEST ORGANISM
- Common name: Bluegill Sunfish
- Source: Fattig Fish Hatchery, Brady, Nebraska (USA)
- Length at study initiation (length definition, mean, range and SD): 17 mm mean
- Weight at study initiation (mean and range, SD): 0.11 g mean
- Feeding during test: Fish were fed standard commercial fish food daily until 48 hours prior to testing, at which time feeding was discontinued.

Test type:

static

Water media type:

freshwater

Limit test:

no

Total exposure duration:

96 h

Hardness:

40 to 45 mg/l as CaCO3

Test temperature:

22 ± 1 °C

pH:

The initial pH was 3.3 (highest concentration) to 7.6.

Dissolved oxygen:

8.8 to 9.4 mg/l

Nominal and measured concentrations:

Nominal test concentrations (mg/l): 0, 10, 18, 32, 56, 100

Details on test conditions:

TEST SYSTEM
- Test vessel: 5-gallon glass vessels
- Fill volume: 15 liters
- No. of organisms per vessel: 10
- No. of vessels per concentration (replicates): 1
- No. of vessels per control (replicates): 1

TEST MEDIUM / WATER PARAMETERS
- Source/preparation of dilution water: Soft reconstituted water
- Alkalinity: 30 to 35 mg/liter as CaCO3,

EFFECT PARAMETERS MEASURED (with observation intervals if applicable) :
Mortality after 24, 48, 72 and 96 hours

Reference substance (positive control):

yes

Remarks:

Antimycin A

Duration:

96 h

Dose descriptor:

LC50

Effect conc.:

75 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Remarks on result:

other: 95 % CI = 56–100

Results with reference substance (positive control):

Antimycin A was used as a reference compound on a separate group of fish with 96-hour LC50 of 0.000084 mg/L which was reported to be within the 95% confidence intervals reported in the literature.

Reported statistics and error estimates:

Stephen et al. calculation of LC50 and 95% confidence limits using the binomial, moving average and probit tests.

Sublethal observations / clinical signs:

Endpoint values: Time Endpoint (mg/L) Statistical Range (mg/L)
24 hr LC50 = 75 (95% conf. interval = 56 to 100)
48 hr LC50 = 75 (95% conf. interval = 56 to 100)
      96 hr        LC50 =  75       (95% conf. interval = 56 to 100)

Cumulative response: Number of affected individuals of _10_ per treatment
Control Dose 1 Dose 2 Dose 3 Dose 4 Dose 5
24 hours 0 0 0 0 0 10
48 hours 0 0 0 0 0
72 hours
96 hours 0 0 0 0 0
Water quality: The final (96-hour) DO, NH3 concentration and pH values were 5.8 to 7.2 mg/liter, 0.34 to 0.40 mg/liter, and 5.2 to 6.8, respectively. (No measurements in the 100 mg/liter vessels were made after initial readings). The pH values decreased with increasing test compound concentrations.
Observations/protocol deviations: Antimycin A was used as a reference compound on a separate group of fish with 96-hour LC50 of 0.000084 mg/L which was reported to be within the 95% confidence intervals reported in the literature.

Validity criteria fulfilled:

yes

Conclusions:

Bluegill sunfish, a representative fresh water fish, was tested for acute toxicity with maleic anhydride.
Maleic anhydride hydrolyzes under test conditions. As a result, maleic acid and its salts are believed to be the test materials investigated in this study.
The final (96-hour) DO, NH3concentration and pH values were 5.8 to 7.2 mg/liter, 0.34 to 0.40 mg/liter, and 5.2 to 6.8, respectively.
(No measurements in the 100 mg/liter vessels were made after initial readings).
The pH values decreased with increasing test compound concentrations.

Executive summary:

In a 96-h acute toxicity study, Lepomis macrochirus (Bluegill Sunfish) were exposed to maleic anhydride at nominal concentrations of 0, 10, 18, 32, 56, 100 mg./L under static conditions.  The 96 -h LC50 was 75 mg/L (nominal concentration).

This toxicity study is classified as supplementary.

Results Synopsis

Test organism: Mean length – 17 mm, mean weight– 0.11 g

Test Type: Static

LC50:  75 mg/L                         95% C.I.: 56 to 100 mg/L

Endpoint(s) Effected: Mortality

Reference 2

Endpoint:

short-term toxicity to fish

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1982

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

significant methodological deficiencies

Remarks:

Purity and origin of the test substance are missing. Furthermore the actual concentrations were not measured.

Qualifier:

according to guideline

Guideline:

other: EPA-660/3-75-009

Principles of method if other than guideline:

EPA Methods for Acute Toxicity Tests with fish, macroinvertebrates and amphibians

GLP compliance:

no

Remarks:

GLP-like but predates GLP regulations

Analytical monitoring:

no

Vehicle:

no

Test organisms (species):

Oncorhynchus mykiss (previous name: Salmo gairdneri)

Details on test organisms:

TEST ORGANISM
- Common name: Rainbow trout
- Source: Trout Lodge, Washington (USA)
- Length at study initiation (length definition, mean, range and SD): 41 mm
- Weight at study initiation (mean and range, SD): 1.1 g mean
- Feeding during test: Fish were fed standard commercial fish food daily until 48 hours prior to testing, at which time feeding was discontinued.

Test type:

static

Water media type:

freshwater

Limit test:

no

Total exposure duration:

96 h

Hardness:

40 to 45 mg/l as CaCO3

Test temperature:

12 ± 1 °C

pH:

The initial pH was 3.3 (highest concentration) to 7.6.

Dissolved oxygen:

8.8 to 9.4 mg/l

Nominal and measured concentrations:

Nominal test concentrations (mg/l):
0, 10, 18, 32, 56, 100

Details on test conditions:

TEST SYSTEM
- Test vessel: 5-gallon glass vessels
- Fill volume: 15 liters
- No. of organisms per vessel: 10
- No. of vessels per concentration (replicates): 1
- No. of vessels per control (replicates): 1


TEST MEDIUM / WATER PARAMETERS
- Source/preparation of dilution water:Soft reconstituted water
- Alkalinity: 30 to 35 mg/liter as CaCO3,
EFFECT PARAMETERS MEASURED (with observation intervals if applicable) :
Mortality after 24, 48, and 96 hours

Reference substance (positive control):

yes

Remarks:

Antimycin A

Duration:

96 h

Dose descriptor:

LC50

Effect conc.:

75 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Remarks on result:

other: 95% conf. interval = 56 to 100

Details on results:

- Mortality of control: 0 individuals
The final (96-hour) DO, NH3 concentration and pH values were 5.8 to 7.2 mg/liter, 0.34 to 0.40 mg/liter, and 5.2 to 6.8, respectively.
(No measurements in the 100 mg/liter vessels were made after initial readings).
The pH values decreased with increasing test compound concentrations.

Results with reference substance (positive control):

Antimycin A was used as a reference compound on a separate group of fish with 96-hour LC50 of 0.000084 mg/L which was reported to be within the 95% confidence intervals reported in the literature.

Reported statistics and error estimates:

Stephen et al. calculation of LC50 and 95% confidence limits using the binomial, moving average and probit tests.

Sublethal observations / clinical signs:

Endpoint values: Time Endpoint (mg/L) Statistical Range (mg/L)
24 hr LC50 = 75 (95% conf. interval = 56 to 100)
48 hr LC50 = 75 (95% conf. interval = 56 to 100)
96 hr        LC50 =  75       (95% conf. interval = 56 to 100)

Cumulative response: Number of affected individuals of _10_ per treatment
Control Dose 1 Dose 2 Dose 3 Dose 4 Dose 5
24 hours 0 0 0 0 0 10
48 hours 0 0 0 0 0
72 hours
96 hours 0 0 0 0 0

Validity criteria fulfilled:

yes

Conclusions:

Rainbow trout, a representative fresh water fish, was tested for acute toxicity with maleic anhydride.
Maleic anhydride hydrolyzes under test conditions. As a result, maleic acid and its salts are believed to be the test materials investigated in this study.
The final (96-hour) dissolved oxygen, NH3 concentration and pH values were 5.8 to 7.2 mg/liter, 0.34 to 0.40 mg/liter, and 5.2 to 6.8, respectively. (No measurements in the 100 mg/liter vessels were made after initial readings).
The pH values decreased with increasing test compound concentrations.

Result: LC50 (fish, 96 h) = 75 mg/L (95% 56-100 mg/L)

Executive summary:

In a 96-h acute toxicity study, Salmo gairdneri (rainbow trout) were exposed to maleic anhydride at nominal concentrations of 0, 10, 18, 32, 56, 100 mg/l under static conditions.  The 96-h LC50 was 75 mg/L (nominal conce,tration). 

This toxicity study is classified as supplementary.

Results synopsis

Test organism size/age: Mean length – 41 mm, mean weight– 1.1 g

Test type: Static

LC50:  75 mg/L (95 % C.I.:  56 to 100 mg/L)

Endpoint(s) effected: Mortality

Description of key information

Two studies with representative freshwater fish species (rainbow trout and bluegill sunfish) showed similar results. In both tests, fish were exposed to nominal concentrations of 0, 10, 18, 32, 56, 100 mg maleic anhydride/L under static conditions for 96 hours. The pH values decreased with increasing test compound concentration (pH 3.3 at 100 mg/L). While no mortality was observed at test concentrations ranging between 10 and 56 mg/L after up to 96 hours, all fish died already after 24 hours in the highest test concentration, resulting in a LC50 (fish, 96 h) = 75 mg/L (non-neutralized test solution). The observed toxicity was presumably determined by pH effects.

For both studies, information on the purity and origin of the test substance is missing. Furthermore, the actual concentrations were not measured during the test. Therefore, both studies are considered as not reliable. However, the information can be used in a weight-of-evidence approach to fill the REACH endpoint requirements for short-term toxicity to fish.

Key value for chemical safety assessment

Fresh water fish

Fresh water fish

Effect concentration:

75 mg/L

Additional information

Two studies testing the toxicity of maleic anhydride to fish are available which are used in a weight-of-evidence approach in the assessment of the short-term toxicity of maleic anhydride to fish (ABC Laboratories, 1982 a & b).

As maleic anhydride hydrolyses in contact with water by forming maleic acid, the substance tested in the toxicity studies is considered to be maleic acid.

In the study on rainbow trout using not neutralised maleic anhydride, a LC50 of 75 mg/L was determined after 96 hours of exposure. The pH values measured ranged from 3.3 in the highest test concentration to 7.6 in the controls. It can not be excluded that observed effects are related to the change in pH induced by the test substance. In an additional study using the same test setup but Lepomis macrochirus as test organism the same LC50 was determined.

Seven studies support the limited toxicity to fish of maleic anhydride; although these studies are disregraded due to insufficient exposure duration (Trenel & Kühn, 1982 a & b; Turnbull et. al, 1954; Knie et al., 1983; Lysak & Marcinek, 1972; Hüls AG, 2004) or treatment of fish with terramycin during exposure (Wallen et al., 1957). The studies report an LC100 at 260 mg/L, LC50 values in the range between 115 mg/L and 275 mg/L, and LOEC values in the range of 138-230 mg/L.

Overall it can be stated, that maleic acid and its anhydride reveal a low to moderate hazard potential for fish. Effects of the substance might occur due to pH shift in test the solutions.