Benzenepropanal, 2-methyl-4-(2-methylpropyl)-

Long-term toxicity to aquatic invertebrates

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

long-term toxicity to aquatic invertebrates

Type of information:

experimental study

Adequacy of study:

key study

Study period:

09 July, 2001 - 21 May, 2002 Dates of Experimental Phase : 01 August - 20 November, 2001

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

OECD Guideline 211 (Daphnia magna Reproduction Test)

Version / remarks:

1998

GLP compliance:

yes

Specific details on test material used for the study:

Batch No. 9000421832;
Purity 98.5%;
Expiry Date : 17 April, 2002

Analytical monitoring:

yes

Details on sampling:

Semi-static set-up used. The main period of renewal was every 48 hours, with 2 chnages being made after 72 hours (Renewals on Day 2, 5, 7, 9, 12, 14, 16 and 19).

One sample was taken from the freshly prepared stock solution and duplicate samples were taken from the freshly prepared test media of all test concentrations and the Control at the first treatment period (Day 0), at a treatment period in the second week (Day 12) and at a treatment period in the last week (Day 16).

Vehicle:

no

Details on test solutions:

The following Nominal exposure concentrations were prepared :

Control
0.038 mg/L
0.12 mg/L
0.38 mg/L
1.2 mg/L
3.8 mg/L

Prior to the start of the test and prior to each test medium renewal a stock solution of Nominal 10 mg/L was freshly prepared by dissolving 20 mg of test substance completely in 2 L test water by intensive stirring for 20 minutes at room temperature.

Adeuqate volumes of the stock solution were diluted in test water to obtain the desired Nomi-nal test concentration.

Test organisms (species):

Daphnia magna

Details on test organisms:

Daphnia magna Strauss.

Daphnia were acclimated in the same water as that used for the study. At the start of the test the young daphnids used were less than 24 hours old and were not first brood progeny.

Test type:

semi-static

Water media type:

freshwater

Remarks:

Elendt M7

Limit test:

no

Total exposure duration:

21 d

Hardness:

250 mg/L as CaCO3

Test temperature:

20 - 22 °C

pH:

pH 7.5 - 7.9

Dissolved oxygen:

> = 8.0 mg O2/L

Nominal and measured concentrations:

The Nominal and mean measured concentrations were, as follows : Nominal (mg/L) Mean Msd. (mg/L) Control < LOD (0.174 mg/L) 1.2 mg/L 0.709 mg/L 3.8 mg/L 2.55 mg/L.

These two concentration levels englobe the effects range observed in the study.

Details on test conditions:

No. of Daphnids : 10 per test concentration, each test animal in a separate beaker
Exposure Vessels : 100 mL glass beaker containing 80 mL of media, covered with glass plates.
Water Temperature : 20 - 22°C
Light Conditions : 16 hours light / 8 hours dark, with 30 minute transition period (370 - 380 lux);
Test Duration : 21 days
Test Water : Elendt M7 with initial pH 7.9
Feeding : On each working day, 50% algae / 50% fish food suspension, administered at be-tween 0.10 and 0.25 mg TOC/daphnia/day

Reference substance (positive control):

no

Key result

Duration:

21 d

Dose descriptor:

NOEC

Effect conc.:

0.71 mg/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat.

Basis for effect:

reproduction

Duration:

21 d

Dose descriptor:

EC50

Effect conc.:

1.7 mg/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat.

Basis for effect:

reproduction

Details on results:

In all test concentrations the survival rate of the test animals at the end of the test was at least 90% or higher. Thus, the survival rate after 21 days was not signifcantly (< 10%) reduced up to the highest test concentration of 2.6 mg/L (3.8 mg/L Nominal).

The first young offspring released from their parent animals were recorded in the Control and at all test concentrations up to and including 0.71 mg/L (1.2 mg/L Nominal) at the observation on Day 9. At the highest test concentration a delay of the first brood was determined (Day 12).

The mean reproduction rate of the daphnids in the Control was 67.1 +/- 7.5 alive offspring per adult. According to the results of a Williams-Test, no significant toxic effect of the test item on the mean reproduction rate was determined up to and including the test concentration of 0.71 mg/L (1.2 mg/L Nominal).

Validity criteria fulfilled:

not specified

Conclusions:

The results of the 21-day OECD 211 Daphnia reproduction study performed with Florhydral are :
21 day NOEC = 0.71 mg/L.

Reference 2

Endpoint:

long-term toxicity to aquatic invertebrates

Type of information:

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

Adequacy of study:

key study

Study period:

06 February 2020

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Read-Across from a structural analogue

Justification for type of information:

To address long-term toxicity testing to the long-term Daphnia endpoint as part of the REACH reg-istration of NYMPHEAL (target substance) it is proposed to read-across to FLORHYDRAL (source substance). This is an analogue approach for which the read-across hypothesis is based on differ-ent compounds which have the same type of effect(s). It is covered .

This read-across is based on the hypothesis that the source and target substance have similar eco-toxicological properties as a result of structural similarity (both the target- and source-substances are primary aldehydes), the same expected mode of action for aquatic toxicity and similar physico-chemical properties relevant for the read-across ecotoxicological Endpoint.

A full justification for the source- and target-substance is provided on the attached document by scenario 2 in the ECHA Read-Across Assessment Framework [RAAF, ECHA 2017] and covers, in detail, the elements required for the Read-Across approach, as described for scenario 2 in the ECHA Read-Across Assessment Framework [RAAF, ECHA 2017] and covering :
- The hypothesis for the Read-Across approach;
- Details on structure and composition of Source- and Target-Substances;
- Justification for structural analogue approach - structure, predicted mechanism of toxicity, physico-chemical properties, comparison of existing lower-tier aquatic toxicity data between Source- and Target-Substance, comparison of output via ECOSAR modelling;
- Data matrix for other structurally similar analogues and justification of choice of Source-Substance.

Reason / purpose for cross-reference:

read-across source

Specific details on test material used for the study:

The source substance is a mono-constituent substance (EC 412-050-4, CAS 125109-85-5, 3-(3-isopropylphenyl)butanal, common name / trade-name FLORHYDRAL). The typical concentration is 97 – 100%. The chemical structure of the substance is shown in Table 1 of the attached Read-Across document. The Source Substance is a primary aldehyde.

The Source-Substance is structurally very similar to the Target-Substance.

The target substance is a mono-constituent substance (EC 811-285-3, CAS 1637294-12-2, 3-(4-isobutyl-2-methylphenyl)propanal, common name / trade-name NYMPHEAL, synonymous with GR-88-0778), which comprises 80 – 100% of the technical end-product. The main impurity (specifications 0 – 20% relative) is an Isomer of the target substance (CAS 1924655-28-6, 3-(2-isobutyl-4-methylphenyl)propanal) and is expected to have the same mode of toxicity as the main component. The chemical structures of the main constituent and its isomer are shown in Table 1 of the attached Read-Across document. The Target Sub-stance is a primary aldehyde.

Key result

Duration:

21 d

Dose descriptor:

NOEC

Effect conc.:

0.32 mg/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat.

Basis for effect:

reproduction

Remarks on result:

other: NOEC value corrected for difference in log Kow between the Source- and Target-Substance.

Duration:

21 d

Dose descriptor:

NOEC

Effect conc.:

0.71 mg/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat.

Basis for effect:

reproduction

Remarks on result:

other: NOEC value by direct read-across

Details on results:

Hydrophobicity (as modelled by log Kow) is also known to be a determinant of the toxicity in aquatic organisms when the effect is mediated by mechanisms of narcosis. It is also an important aspect when comparing the aquatic toxicity of classes of chemicals that have specific modes of action since a trend of increasing aquatic toxicity with increasing log Kow is usually observed up to a log Kow cut-off value of approximately 5.0 – 6.4 [EPA, 2017]. The most favourable scenario is to have similar log Kow values between the source and target substance to support a direct read-across for aquatic toxicity. The measured log Kow value for the the target-substance, NYMPHEAL, is 3.7 (OECD 117). The log Kow for the source-substance, FLORHYDRAL, is 3.1 (OECD 117) (Table 2 of Read-Across document). In correlation with the determined water solubility values, the log Kow values indicate that the target substance is more hydrophobic than the source substance. This has been accounted for in the subsequent assessment, and, the aquatic toxicity has been correspondingly corrected for this influence via application of a calculated safety assessment factor.

In order to derive the 21-day NOEC for NYMPHEAL from the source substance and to compensate for the lower hydrophobicity of FLORHYDRAL, the ratio of the acute Daphnia toxicity value for the source substance divided by that of the target substance 48 hour EC50 has been used to calculate a safety assessment factor to derive the NYMPHEAL 21-day NOEC.

FLORHYDRAL 48hr EC50 (2.26 mg/L) ÷ NYMPHEAL 48hr EC50 (1.01 mg/L) = 2.238

Subsequently, the FLORHYDRAL 21-day NOEC of 0.71 mg/L (mean measured value) yields a predicted 21-day NOEC for NYMPHEAL via read-across of 0.32 mg/L.

ECOSAR (v2.0) predicts very similar short-term toxicity to daphnids for the source and target sub-stance compared with the values actually determined in the laboratory studies (Table 2 of Read-Across document).

For the long-term Daphnia end-point, ECOSAR (v2.0) predicts the target substance to be two-times more toxic than the source substance (Table 2 of Read-Across document) when the difference in hydrophobicity (log Kow) is taken in to account. ECOSAR (v2.0) recognises that both the source and the target substance are members of the category of aldehydes (mono).

Conclusions:

In an OECD 211 Daphnia reproduction study performed Under GLP on a closely-ralted substance, FLORHYDRAL, the NOEC was determined to be 0.71 mg/L.

The detailed information provided in the read-across justification document indicates that the aquatic ecotoxicity of Nympheal (the Target Substance) and Florhydral (the Source Substance) are expected to be similar as a result of structural similarity, similar mechanistic profiles and similar physico-chemical properties.

Hydrophobicity (as modelled by log Kow) is also known to be a determinant of the toxicity in aquatic organisms when the effect is mediated by mechanisms of narcosis. It is also an important aspect when comparing the aquatic toxicity of classes of chemicals that have specific modes of action since a trend of increasing aquatic toxicity with increasing log Kow is usually observed up to a log Kow cut-off value of approximately 5.0 – 6.4 [EPA, 2017]. The most favourable scenario is to have similar log Kow values between the source and target substance to support a direct read-across for aquatic toxicity. The measured log Kow value for the the target-substance, NYMPHEAL, is 3.7 (OECD 117). The log Kow for the source-substance, FLORHYDRAL, is 3.1 (OECD 117) (Table 2 of Read-Across document). In correlation with the determined water solubility values, the log Kow values indicate that the target substance is more hydrophobic than the source substance. This has been accounted for in the subsequent assessment, and, the aquatic toxicity has been correspondingly corrected for this influence via application of a calculated safety assessment factor.

In order to derive the 21-day NOEC for NYMPHEAL from the source substance and to compensate for the lower hydrophobicity of FLORHYDRAL, the ratio of the acute Daphnia toxicity value for the source substance divided by that of the target substance 48 hour EC50 has been used to calculate a safety assessment factor to derive the NYMPHEAL 21-day NOEC.

FLORHYDRAL 48hr EC50 (2.26 mg/L) ÷ NYMPHEAL 48hr EC50 (1.01 mg/L) = 2.238

Subsequently, the FLORHYDRAL 21-day NOEC of 0.71 mg/L (mean measured value) yields a predicted 21-day NOEC for NYMPHEAL via read-across of 0.32 mg/L.

ECOSAR (v2.0) predicts very similar short-term toxicity to daphnids for the source and target sub-stance compared with the values actually determined in the laboratory studies (Table 2 of Read-Across document).

For the long-term Daphnia end-point, ECOSAR (v2.0) predicts the target substance to be two-times more toxic than the source substance (Table 2 of Read-Across document) when the difference in hydrophobicity (log Kow) is taken in to account. ECOSAR (v2.0) recognises that both the source and the target substance are members of the category of aldehydes (mono).


In summary, read-across from Florhydral is considered to give a reliable estimate of the Daphnia 21-day NOEC for Nympheal, which is calculated to be 0.32 mg/L.

The read-across is justified and considered adequate for the purpose of classification and la-belling, and PNEC derivation.

Description of key information

To address long-term toxicity testing to the long-term Daphnia endpoint as part of the REACH registration of NYMPHEAL (target substance) it is proposed to read-across to FLORHYDRAL (source substance). This is an analogue approach for which the read-across hypothesis is based on different compounds which have the same type of effect(s). It is covered by scenario 2 in the ECHA Read-Across Assessment Framework [RAAF, ECHA 2017].

This read-across is based on the hypothesis that the source and target substance have similar ecotoxicological properties as a result of structural similarity (both the target- and source-substances are primary aldehydes), the same expected mode of action for aquatic toxicity and similar physicochemical properties relevant for the read-across ecotoxicological Endpoint.

The results of the 21-day OECD 211 Daphnia reproduction study performed with Florhydral are :

21 day NOEC = 0.71 mg/L

In order to derive the 21-day NOEC for NYMPHEAL from the source substance and to compensate for the lower hydrophobicity of FLORHYDRAL, the ratio of the acute Daphnia toxicity value for the source substance divided by that of the target substance 48 hour EC50 has been used to calculate a safety assessment factor to derive the NYMPHEAL 21-day NOEC.

 FLORHYDRAL 48hr EC50 (2.26 mg/L)  ÷  NYMPHEAL 48hr EC50 (1.01 mg/L)  =  2.238

Subsequently, the FLORHYDRAL 21-day NOEC of 0.71 mg/L (mean measured value) yields a predicted 21-day NOEC for NYMPHEAL via read-across of 0.32 mg/L.

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Effect concentration:

0.32 mg/L