(3S-cis)-3,6-dimethyl-1,4-dioxane-2,5-dione

Short-term toxicity to fish

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

short-term toxicity to fish

Type of information:

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

Adequacy of study:

weight of evidence

Justification for type of information:

For details and justification of read-across please refer to the read-across report attached to IUCLID section 13.

Reason / purpose for cross-reference:

read-across source

Water media type:

freshwater

Key result

Duration:

96 h

Dose descriptor:

LC50

Effect conc.:

> 320 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Remarks on result:

other: 95 % CL = 320-468

Duration:

96 h

Dose descriptor:

NOEC

Effect conc.:

ca. 320 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Details on results:

- Behavioural abnormalities: No data
- Observations on body length and weight: No data
- Other biological observations: No data
- Mortality of control: No data
- Other adverse effects control: No data
- Abnormal responses: No data
- Any observations (e.g. precipitation) that might cause a difference between measured and nominal values: No data
- Effect concentrations exceeding solubility of substance in test medium: No

Reported statistics and error estimates:

LC50, 95 % confidence interval (CI)

Sublethal observations / clinical signs:

The apparent toxicity of lactic acid to D. rerio can be explained by the low pH values of the test substance solutions (pH 4.1 and 3.5 at concentrations of 320 and 560 mg/L, respectively).

Validity criteria fulfilled:

not specified

Remarks:

Poor documentation, validity cannot be assessed

Conclusions:

The short-term toxicity testing of lactic acid on freshwater fish (Danio rerio) resulted in an LC50 (96 h) of 320 mg/L (nominal), which can be attributed to a pH effect.

Executive summary:

In a 96-h acute toxicity study, zebra fish (Danio rerio) were exposed to L-(+)-lactic acid at nominal concentrations of 0 (control), 320 and 560 mg/L (further information on the number of concentration levels not available) under semi-static conditions. The 96-h LC50 was > 320 mg/L. The observed effects can be attributed to a pH effect. The NOEC value, based on mortality effects, was 320 mg/L, respectively. Sublethal effects were not reported. Based on the results of this study, L-(+)-lactic acid would not be classified as hazardous to the aquatic environment according to the CLP Regulation (EC) No 1272/2008. This toxicity study is classified as supplementary information and does not satisfy the guideline requirement for a fish short-term toxicity study but can nevertheless be used as supportive data or in a weight-of-evidence approach.

Results synopsis

Test organism: Zebra fish (Danio rerio)

Test type: Semi-static

LC50: > 320 mg/L

NOEC: 320 mg/L

Endpoint(s) effected: Survival/mortality

This information is used in a read-across approach in the assessment of the target substance. For details and justification of read-across please refer to the read-across report attached to IUCLID section 13.

Reference 2

Endpoint:

short-term toxicity to fish

Type of information:

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

Adequacy of study:

weight of evidence

Justification for type of information:

For details and justification of read-across please refer to the read-across report attached to IUCLID section 13.

Reason / purpose for cross-reference:

read-across source

Key result

Duration:

96 h

Dose descriptor:

LC50

Effect conc.:

130 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Remarks on result:

other: 95 % CL = 100-180

Details on results:

The 24, 48 and 96 hour LC50 values for SY-83 in the 96 hour static toxicity test with rainbow trout (Salmo gairdneri) were 150, 130 and 130 mg/L, respectively. All results were based on the nominal concentrations of 32, 56, 100, 180 and 320 mg/L. The no-effect concentration based on absence of mortality and abnormal effects after 96 hours of exposure was 56 mg/L.
The effects observed for the positive control Antimycin A were within the 95 % confidence intervals reported in the literature. An examination of the fish culture and acclimation records for this test indicated that the fish were in good condition for testing.
The dissolved oxygen concentrations ranged from 6.1 to 9.2 mg/L during the test. These values represented 56 and 85 % saturation at 12 °C, respectively, and were considered adequate for testing. The pH values ranged from 3.5 to 7.3. The pH values decreased with higher test substance concentrations.
The study was conducted following the intent of the Good Laboratory Practice Regulations and the final report was reviewed by Analytical Bio-Chemistry Laboratories' Quality Assurance Unit. All original raw data was provided to Union Oil Company, with a copy retained at Analytical Bio-Chemistry Laboratories.

Results with reference substance (positive control):

Antimycin A
96-hour LC50 = 4.8e-5 mg/L

Validity criteria fulfilled:

yes

Remarks:

Water quality parameters of temperature, dissolved oxygen and pH were measured throughout the test and were within acceptable limits.

Conclusions:

The test for toxicity of lactic acid to rainbow trout resulted in an LC50 (96 h) of 130 mg/L (nominal).

Executive summary:

The acute toxicity of lactic acid to rainbow trout (Salmo gairdneri) was assessed using the methods outlined by the Committee on Methods for Toxicity Tests with Aquatic Organisms. Water quality parameters of temperature, dissolved oxygen and pH were measured throughout the test and were within acceptable limits. As a method precision check, the rainbow trout were challenged with a reference compound, Antimycin A. The estimated 96 hour LC₅₀ and 95 % confidence limits (C.L.) were within the 95 % confidence limits reported in the literature. Culture and acclimation records indicated that the fish were in good condition for testing. The study was conducted at the following nominal concentrations of lactic acid: 32, 56, 100, 180 and 320 mg/L. Ten fish, with a mean weight of 1.09 (± 0.28) g and a mean standard length of 42 (± 3.4) mm, were exposed to each test concentration and a blank control. The results of the four day static fish toxicity studies on lactic acid and Antimycin A are summarised below. The 24 and 48 hour LC₅₀ values were also determined.

Lactic acid:

LC₅₀ (96 h) = 130 mg/L (95 % CI = 100–180 mg/L)

Antimycin A

LC50 (96 h) = 4.8 × 10^–5 mg/1 (95 % CI = 2.4–7.5 × 10^–5 mg/1)

Furthermore, the results indicate a 96-hour no-observed effect concentration for lactic acid of 56 mg/1, which is based on the absence of mortality and abnormal effects.

This information is used in a read-across approach in the assessment of the target substance. For details and justification of read-across please refer to the read-across report attached to IUCLID section 13.

Reference 3

Endpoint:

short-term toxicity to fish

Type of information:

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

Adequacy of study:

weight of evidence

Justification for type of information:

For details and justification of read-across please refer to the read-across report attached to IUCLID section 13.

Reason / purpose for cross-reference:

read-across source

Key result

Duration:

96 h

Dose descriptor:

LC50

Effect conc.:

ca. 130 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Remarks on result:

other: 95 % CL = 100-180

Details on results:

The 24, 48 and 96 hour LC50 values for SY-83 were 140, 130 and 130 mg/L, respectively. All results were based on the nominal concentrations of 56, 100, 180, 320 and 560 mg/L. The no-effect concentration based on absence of mortality and abnormal effects after 96 hours of exposure was 56 mg/L.
An examination of the fish culture and acclimation records for this test indicated that the fish were in good condition for testing. The dissolved oxygen concentrations ranged from 5.6 to 9.0 mg/L during the test. These values represented 64 and 102 % saturation at 22 °C, respectively, and were considered adequate for testing. The pH values ranged from 3.1 to 7.2, with decreasing levels as test concentrations increased.

Results with reference substance (positive control):

The bluegill sunfish were challenged with a reference compound, Antimycin A, to verify method precision. The 96 hour LC50 for bluegill sunfish exposed to Antimycin A was 1.0 × 10-4 mg/L and was within the 95 % confidence intervals reported in the literature.

Validity criteria fulfilled:

yes

Remarks:

Water quality parameters of temperature, dissolved oxygen and pH were measured throughout the test and were within acceptable limits.

Conclusions:

A test of the short-term toxicity of lactic acid (SY-83) to bluegill sunfish resulted in an LC50 of 130 mg/L (nominal).

Executive summary:

The acute toxicity of lactic acid (SY-83) to bluegill sunfish (Lepomis macrochirus) was assessed using the methods outlined by the Committee on Methods for Toxicity Tests with Aquatic Organisms. Water quality parameters of temperature, dissolved oxygen and pH were measured throughout the test and were within acceptable limits. As a method precision check, the bluegill sunfish were challenged with a reference compound, Antimycin A. The estimated 96 hour LC₅₀ and 95 % confidence limits (C.L.) were within the 95 % confidence limits reported in the literature. Culture and acclimation records indicated that the fish were in good condition for testing. The study was conducted at the following nominal concentrations of SY-83: 56, 100, 180, 320 and 560 mg/1. Ten fish, with a mean weight of 0.37 (± 0.15) g and a mean standard length of 24 (± 2.3) mm, were exposed to each test concentration and a blank control. The results of the four day static fish toxicity studies using lactic acid and Antimycin A are summarized below. The 24 and 48 hour LC50 values were also determined.

Lactic acid:

LC₅₀ (96 h) = 130 mg/L (95 % CI: 100–180 mg/L)

Antimycin A:

LC50 (96 h) = 1.0 × 10^–4 mg/L (95 % CI: 0.75–1.4 × 10^–4 mg/L)

Furthermore, the results indicate a 96-hour no-observed effect concentration of 56 mg/1, which was based on absence of mortality and abnormal effects.

This information is used in a read-across approach in the assessment of the target substance. For details and justification of read-across please refer to the read-across report attached to IUCLID section 13.

Reference 4

Endpoint:

short-term toxicity to fish

Type of information:

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

Adequacy of study:

weight of evidence

Justification for type of information:

For details and justification of read-across please refer to the read-across report attached to IUCLID section 13.

Reason / purpose for cross-reference:

read-across source

Duration:

96 h

Dose descriptor:

NOEC

Effect conc.:

180 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Duration:

96 h

Dose descriptor:

LC50

Effect conc.:

320 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Key result

Duration:

96 h

Dose descriptor:

LC50

Effect conc.:

195 mg/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat. (dissolved fraction)

Basis for effect:

mortality (fish)

Details on results:

Test solutions were not neutralised. It is therefore concluded that the low pH value affected the survival of the fish.

Validity criteria fulfilled:

yes

Conclusions:

The LC50 of lactic acid to Danio rerio was determined to be 195 mg/L (mean measured concentration).

Executive summary:

The acute toxicity of the test substance, a solution of about 80 % L-(+)-lactic acid, to the freshwater fish species Brachydanio rerio was determined according to OECD guideline no. 203 and under GLP. The study was carried out as a semi-static test with daily replacement of the test solutions and with 10 fish for each concentration. The exposure duration was 96 hours. The nominal concentrations tested were 100, 180, 320, 560 and 1000 mg/L. The test substance appeared to be completely dissolved at all concentrations tested (visually assessed). The actual concentrations of L-(+)-lactic acid were determined enzymatically with a Boehringer test kit. They were between 70 and 77 % of nominal just after dosing (average 74 %). To test the stability the concentrations of L-(+)-lactic acid were also analysed just before renewal and were between 56 and 82 % of nominal (average 70 %).

The results of the test were (as nominal concentrations):

96-h LC₅₀ = 320 mg/L

96-h LC₁₀₀ = 560 mg/L

96-h NOEC (mortality) = 180 mg/L

96-h LC₅₀ = 195 mg/L (mean measured concentration)

The nominal concentrations quoted in this report relate to the test material (a solution of about 80 % L-(+)-lactic acid) as supplied by the sponsor. Toxic effects are probably caused by acidification, since test solutions were not buffered or neutralised.

This information is used in a read-across approach in the assessment of the target substance. For details and justification of read-across please refer to the read-across report attached to IUCLID section 13.

Description of key information

In short-term toxicity tests of lactic acid in three different fish species mortality was observed resulting in estimated LC50 values ranging between 130 and > 320 mg/L (nominal) which can be attributed to a pH effect. Lactate as such is considered not exert any systemic effects on fish in the tested concentration range of up to 560 mg/L. Since LL-lactide undergoes immediate hydrolysis in contact with water, forming lactic acid, this is the moiety of interest by read-across.

Additional information

Since LL-lactide undergoes immediate hydrolysis in contact with water, forming lactic acid, this is the moiety of interest by read-across. For details and justification of read-across please refer to the read-across report attached to IUCLID section 13.

In four studies on short-term toxicity of the read across substance L(+) lactic acid to fish (three different species:Danio rerio,Lepomis macrochirus,Oncorhynchus mykiss) mortality was observed resulting in estimated LC₅₀values ranging between 130 and > 320 mg/L (nominal). All studies are relatively poorly documented and therefore reliable only with restrictions. However, they can be used in a weight-of-evidence approach. In one of the studies (Bowmer et al., 1998) the observed mortality was explicitly attributed to pH effects: pH at the test concentrations of 320 and 560 mg/L was measured to be 4.1 and 3.5.

The theoretical pH shift caused by lactic acid at the lowest identified LC₅₀of 130 mg/L (= 1.443 mmol/L), considering a pKa of 3.9, would result in a final pH of 3.43. This compares quite well to the measured pH values of 4.1 and 3.5 at test concentrations of 320 and 560 mg/L in a slightly buffered system (Bowmer et al., 1998).

Therefore, the mortality observed in the available short-term toxicity tests on fish can undoubtfully be attributed to a pH shift instead of being a toxic effect of the lactate ion/molecule. Accordingly, since any toxic effects of the lactate are of interest instead of acidification it can be concluded that within the tested concentration range (up to 560 mg/L) lactic acid does not cause lethal effects on fish, except pH related mortality. A key value (LC₅₀) for chemical safety assessment hence cannot be identified.