Tetrahydromethylphthalic anhydride

Long-term toxicity to fish

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

adult fish: sub(lethal) effects

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1997.5.23-1997.6.30

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: This study was according to OECD guidelines and was performed under GLP.

Qualifier:

according to guideline

Guideline:

OECD Guideline 204 (Fish, Prolonged Toxicity Test: 14-day Study)

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

Details on properties of test surrogate or analogue material (migrated information):
PHYSICO-CHEMICAL PROPERTIES
- Vapour pressure: 0.44 Pa at 23 degree C (Antonie equation)
- Water solubility (under test conditions): below 0.1g/100g (hydrolysed)

Analytical monitoring:

yes

Details on sampling:

- Sample storage conditions before analysis: room temperature

Vehicle:

no

Details on test solutions:

Tetrahydromethyl-1,3-isobenzofuranedione was added in dechlorinated tap water (1000 mg/l) and stirred more than 60 min by magnetic stirrer. The test solution was supplied continuously by mixing the working solution and the dilution water with the help of a mechanically operated quantitative water-pump.

Test organisms (species):

Oryzias latipes

Details on test organisms:

TEST ORGANISM
- Common name: Medaka
- Strain: Oryzias latips
- Source: Nango Suisan center Shiga-prif.
- Length at study initiation (length definition, mean, range and SD): 2.0-2.2cm
- Weight at study initiation (mean and range, SD): 0.15-0.17g
- Feeding during test
- Food type: Comercial food (tetramine stable)
- Amount: 2% of body weight
- Frequency: once a day

ACCLIMATION
- Acclimation period: more than 12 days.
- Acclimation conditions (same as test or not): same as test
- Type and amount of food: Commercial food (tetramine stable)
- Health during acclimation (any mortality observed): mortality before test is less than 5%.

Test type:

flow-through

Water media type:

freshwater

Limit test:

yes

Total exposure duration:

14 d

Post exposure observation period:

no details given

Hardness:

62mg/L(CaCO3)

Test temperature:

Nominal: 22-26°C. Measured: 23.7-24.1°C

pH:

fresh water : 7.9

Dissolved oxygen:

7.6-7.9 mg/L
Oxygen saturation level: >=60%

Salinity:

no details given

Nominal and measured concentrations:

- Nominal concentrations: 0 and 100 mg/L
- Measured concentrations: 0 and 86 mg/L

Details on test conditions:

TEST SYSTEM
- Type of flow-through (e.g. peristaltic or proportional diluter): flow-through
- Renewal rate of test solution (frequency/flow rate): 10 times/day
- No. of vessels per concentration (replicates): 1 vessel/dose
- No. of vessels per control (replicates): 1 vessel

TEST MEDIUM / WATER PARAMETERS
- Pesticides: total chlorinated pesticides <0.005mg/L, total organophoshorus pesticides <0.005mg/L
- Chlorine: free chlorine <0.01mg/L
- Ca/mg ratio: 12/4
- Conductivity: 392 micro s/cm

OTHER TEST CONDITIONS
- Photoperiod:16h/8h light/dark

Reference substance (positive control):

yes

Remarks:

LC50 96h = 3,6mg/L CuSO4 5H2O

Duration:

14 d

Dose descriptor:

LC50

Effect conc.:

>= 100 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality

Duration:

7 d

Dose descriptor:

LC50

Effect conc.:

>= 100 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality

Duration:

14 d

Dose descriptor:

NOEC

Effect conc.:

100 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality

Duration:

14 d

Dose descriptor:

LOEC

Effect conc.:

>= 100 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality

Duration:

14 d

Dose descriptor:

other: LCL0

Effect conc.:

>= 100 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality

Details on results:

Toxic symptoms : Toxic symptoms were not observed

Results with reference substance (positive control):

96h LC50 = 3.6 mg(CuSO4 5H2O)/L

Reported statistics and error estimates:

Not used, because this test was limited test.

Nominal concentration (mg/l)	Measured concentration(mg/l) (percentage of nominal)
	0-day	7-day	14-day	Mean*
Control	<5	<5	<5	-
100	83 (83)	83 (83)	92 (92)	86

Measured concentration (mg/l)	pH
	0-day	2-day	4-day	7-day	9-day	11-day	14-day
Control	7.9	7.9	7.7	7.8	8.0	7.8	8.0
100	6.4	6.4	6.3	6.5	6.6	6.5	6.3

Measured concentration (mg/l)	Cumulative number of dead fish (percentage mortality)
	0-day	2-day	4-day	7-day	9-day	11-day	14-day
Control	0(0)	0(0)	0(0)	0(0)	0(0)	0(0)	0(0)
100	0(0)	0(0)	0(0)	0(0)	0(0)	0(0)	0(0)

Validity criteria fulfilled:

yes

Conclusions:

In a 14 d long-term toxicity test to fish no toxic symptoms were observed (LC50>100mg/L).

Executive summary:

The 14-day-chronic toxicity of tetrahydromethylphthalic anhydride (MTHPA) to Oryzias latipswas studied under flow through conditions. Fish were exposed to control and test chemical at nominal/measured concentrations of 0 and 100 mg/L. The 14 day LC50/EC50 based on mortality was > 100 mg/L. The 14-day NOEC was 100 mg/L. No toxic symptoms were observed. This study is classified as acceptable and satisfies the guideline requirements for a chronic toxicity study with freshwater fish.

Reference 2

Endpoint:

long-term toxicity to fish, other

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

2021

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

Please refer to attached QMRF and QPRF Documents.

Qualifier:

according to guideline

Guideline:

other: REACH guidance on QSAR R.6

Principles of method if other than guideline:

Calculation of Long-Term toxicity in fish. Software used: ECOSAR 2.0 for chemical class "Neutral Organic SAR (Baseline Toxicity)"

Specific details on test material used for the study:

MTHPA Structure 1: SMILES: O=C(OC(=O)C1C(C=CC2)C)C12
MTHPA Structure 2: SMILES: O=C1OC(=O)C2CCC(=CC12)C
MTHPA Structure 3: SMILES: O=C(OC(=O)C1CC=C(C2)C)C12
MTHPAc Structure 1: SMILES: O=C(O)C1CC=CC(C)C1(C(=O)O)
MTHPAc Structure 2: SMILES: O=C(O)C1C=C(C)CCC1(C(=O)O)
MTHPAc Structure 3: SMILES: O=C(O)C1CC(=CCC1(C(=O)O))C

Analytical monitoring:

not required

Test organisms (species):

other: fish

Water media type:

freshwater

Total exposure duration:

30 d

Remarks on exposure duration:

chronic exposure

Duration:

30 d

Effect conc.:

6.39 mg/L

Remarks on result:

ChV (chronic value, QSAR)

Remarks:

The substance is within the applicability domain of the model. ECOSAR class "Neutral Organic SAR (Baseline Toxicity)". MTHPA Structure 1

Key result

Duration:

30 d

Effect conc.:

4.96 mg/L

Remarks on result:

ChV (chronic value, QSAR)

Remarks:

The substance is within the applicability domain of the model. ECOSAR class "Neutral Organic SAR (Baseline Toxicity)". MTHPA Structure 2+3

Duration:

30 d

Effect conc.:

776.87 mg/L

Remarks on result:

ChV (chronic value, QSAR)

Remarks:

The substance is within the applicability domain of the model. ECOSAR class "Neutral Organic SAR (Baseline Toxicity)". MTHPAc Structure 1

Duration:

30 d

Effect conc.:

602.56 mg/L

Remarks on result:

ChV (chronic value, QSAR)

Remarks:

The substance is within the applicability domain of the model. ECOSAR class "Neutral Organic SAR (Baseline Toxicity)". MTHPAc Structure 2+3

Validity criteria fulfilled:

yes

Conclusions:

Using ECOSAR v2.0 the long-term toxicity ChV value for fish was calculated for the main consitutents of the multi-constituent substance to be between 4.96 - 6.39 mg/L. The substance is within the applicability domain of the model. Because the test item hydrolyses fast to the acid form, the long-term toxicity ChV value for fish was also calculated for the acid forms to be between 10463.18 and 13502.9 mg/L.

Executive summary:

The long-term toxicity in fish was calculated using ECOSAR v2.0 from US Environmental Protection Agency.

 

The adequacy of a prediction depends on the following conditions:

a) the (Q)SAR model is scientifically valid: the scientific validity is established according to the OECD principles for (Q)SAR validation;

b) the (Q)SAR model is applicable to the query chemical: a (Q)SAR is applicable if the query chemical falls within the defined applicability domain of the model;

c) the (Q)SAR result is reliable: a valid (Q)SAR that is applied to a chemical falling within its applicability domain provides a reliable result;

d) the (Q)SAR model is relevant for the regulatory purpose.

 

For assessment and justification of these 4 requirements the QMRF and QPRF files were developed and attached to this study record.

 

Description of the prediction Model

The prediction model was descriped using the harmonised template for summarising and reporting key information on (Q)SAR models. For more details please refer to the attached QSAR Model Reporting Format (QMRF) file. 

 

Assessment of estimation domain

The assessment of the estimation domain was documented in the QSAR Prediction Reporting Format file (QPRF). Please refer to the attached document for the details of the prediction and the assessment of the estimation domain.

Description of key information

The lowest value for the long-term toxicity ChV value for fish was calculated to be between 4.96 mg/L.

Additional information

Key study:

Using ECOSAR v2.0 the long-term toxicity ChV value for fish was calculated for the main consitutents of the multi-constituent substance to be between 4.96 - 6.39 mg/L. The substance is within the applicability domain of the model. Because the test item hydrolyses fast to the acid form, the long-term toxicity ChV value for fish was also calculated for the acid forms to be between 10463.18 and 13502.9 mg/L.

Supporting study:

The 14-day-chronic toxicity of tetrahydromethylphthalic anhydride (MTHPA) to Oryzias latipswas studied under flow through conditions. Fish were exposed to control and test chemical at nominal/measured concentrations of 0 and 100 mg/L. The 14 day LC50/EC50 based on mortality was > 100 mg/L. The 14-day NOEC was 100 mg/L. No toxic symptoms were observed.This study is classified as acceptable and satisfies the guideline requirements for a chronic toxicity study with freshwater fish.