Undecanal

Short-term toxicity to fish

Link to relevant study record(s)

Reference

Endpoint:

short-term toxicity to fish

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

March 2018

Reliability:

1 (reliable without restriction)

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:

ECHA advocates using OECD QSAR Toolbox v.4 “to fulfil REACH information requirements and assess the (eco)toxicity of substances without needing to do new tests.” This applies especially with regard to the automated or standardized workflows available with Toolbox v.4.0 and higher, making consistent predictions easier. (1)
The prediction from trend analysis for acute fish toxicity was performed using QSAR Toolbox v.4.2 and applying the corresponding standardized workflow.
The reliable result from trend analysis is supported by experimental data for an analogue compound (the structural isomer 2-methyldecanal), further corroborating the predicted value.
The semi-automatically generated report from OECD QSAR Toolbox containing also a robust summary and discussion of results from the supporting analogue compound is attached to this robust study summary. Further, the data matrix underlying the Toolbox prediction is available under section "Attached background material".

(1) ECHA, European Chemicals Agency (2017); Newsletter No. 1 (February 2017)

Qualifier:

no guideline required

Principles of method if other than guideline:

QSAR Toolbox v.4.2: QSAR Toolbox prediction for single chemical
Data gap filling method: Trend analysis, executed via Standard (standardized workflow) "Ecotoxicological Endpoint" for Fish Acute Toxicity.
Predicted endpoint: LC50; Mortality; Actinopterygii; 96h; No guideline specified

Specific details on test material used for the study:

Under the non-editable fields of the prediction report generated from OECD QSAR Toolbox V.4.2 the following information is given under target information / chemical names:

dicyclopentylsilanediol
Undecanal
undecylic_aldehyde

The first given substance name "dicyclopentylsilanediol" is unrelated to the target substance and must have been erroneously linked to the target substance n-undecanal.
The two further names are correct, as are SMILES code, structural representation as well as the CAS number given under section “target information”.

Further, an invalid EC-number is given under section target information / Numerical identifiers in the report (not editable): 4075387. A corresponding search with 4075387 and 407-538-7 at ECHA-Chem yielded no results.

Prediction results are nonetheless valid because of correct assignment of the structure.

Analytical monitoring:

not required

Details on sampling:

Not applicable, QSAR

Details on test solutions:

Not applicable, QSAR

Test organisms (species):

other: Actinopterygii

Details on test organisms:

Not applicable, QSAR

Total exposure duration:

96 h

Details on test conditions:

In silico method: QSAR Toolbox v.4.2 standardized workflow (SW) for single chemical;
Data gap filling method: Trend analysis, for fish acute toxicity.
Predicted endpoint: LC50; Mortality; Actinopterygii; 96h;

Key result

Duration:

96 h

Dose descriptor:

LC50

Effect conc.:

1.97 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Remarks on result:

other: QSAR Toolbox v.4.2 standardized workflow (SW), Fish acute toxicity (Actinopterygii)

Details on results:

Uncertainty of the prediction (OECD principle 4 - Uncertainty of the prediction):
The prediction is based on 19 values within range 0.35 - 51.2 mg/L
Prediction confidence range (0.95%): ± 0.858 log(1/mol/L), i.e. 95% CI: 0.274 mg/L to 14.2 mg/L)

For further details, please see IUCLID section "Any other information on results incl. tables".

Sublethal observations / clinical signs:

QSAR Toolbox v.4.2 prediction:

The prediction from trend analysis for acute fish toxicity was performed using QSAR Toolbox v.4.2 and applying the corresponding standardized workflow.

Underlying mechanistic interpretation:

Unspecific reactivity caused by the aldehyde group is assumed to cause toxicity: According to McFarland (1), the toxicity to aquatic organisms depends on penetration (log Kow) of the chemical, followed by interaction with cellular biomolecules. Therefore, it is justified to derive a value for the acute fish toxicity of the target compound (n-undecanal) from known fish toxicities (ordinate) of sufficiently similar aldehydes as a function of log Kow (abscissa, Kow expressing the potential for penetrating biological membranes). The basic mechanism of action is believed to be the same, namely unspecific reactivity of the aldehyde moiety with biomolecules.

(1) McFarland, J.W. (1970)

On the parabolic relationship between drug potency and hydrophobicity.

Journal of Medicinal Chemistry, 13, 1192-1196

Categorization and results:

Categorization was started based on chemical class “Aldehydes (Mono)” according to “Aquatic toxicity classification by ECOSAR”. This was decided to be most appropriate, as toxicity is assumed to be caused by the functional group aldehyde, and thus oligomers of this functional group within one molecule would be expected to cause higher toxicity or even to act as a crosslinking agent.

Otherwise, suggestions as given according to the standardized workflow for subgrouping were followed, and the resulting value for LC50 met the acceptance criteria for trend analysis (R^2≥ 0.7 and NA≥ 10):

R^2 = 0.713;

Number of analogues (NA) = 19.

Further, the sample standard deviation of residuals is low (0.361), such that the 95% confidence range is narrow:

LC50 (trend analysis; 96 h; Actinopterygii) = 1.97 mg/L (95% CI: 0.274 mg/L to 14.2 mg/L).

The elements of the category are all saturated aliphatic monovalent aldehydes, without any other functional groups (elements C, H, and O). Therefore, the analogues are of high functional similarity.

Further, the analogues comprise compounds with calculated log Kow values below as well as above the one of the target compound. Therefore, no extrapolation of toxicity beyond the log Kow range defined by the analogues was performed. All this adds to the reliability and adequacy of the prediction for hazard and risk assessment as well as classification and labelling.

Support from experimental results for structural isomer:

Further support comes from a reliable study (with restrictions, RL2) performed with a close structural isomer, namely 2-methyldecanal (CAS No.: 19009-56-4 / EC No. 242-745-6) – due to the same

molecular weight and same elemental composition, physico-chemical properties (incl. log Kow) are highly similar and therefore, ecotoxicity is assumed to be representative for the target compound.

This test was performed compliant with GLP between 08th Feb 1988 to 18th Mar 1988 (Hoechst AG, 1988; report No. 88.0402; company study number T01228; date: 1988-04-14).

The study was performed as a static test with Danio rerio. The test was performed according to OECD 203. No vehicle was used (homogenized by means of an Ultra-Turrax and ultrasound bath; stirring of

test solutions in aquaria for 2 h prior to test start), and the highest applied test item concentration of 10 mg/L was below the water solubility limit (16 mg/L; ECHA, disseminated registration dossier for 2-

methyldecanal). Test basins were not aerated during test, which reduces volatilization of the test item. However, information is lacking if basins were covered.

10 fish per vessel and replicate were exposed for 96 h. The following concentrations were tested:

Test item concentrations, control and treatment groups: 0 (control), 1, 1.8, 2.5, 3.5, 5, 7.1, 10 mg/L.

The concentrations were not analytically verified. In one vessel (5 mg/L), slight turbidity was observed during the second half of the test period. At all other test concentrations (higher and lower), no evidence of undissolved test material was observed.

The fish showed symptoms from 1 to 10 mg/L, while mortality occurred from 5 to 10 mg/L. All validity criteria of OECD 203 were met.

Results:

<= 3.5 mg/L: no mortality (LC0);

5 mg/L: 2, 3, 4, 4 dead fish after 24, 48, 72, and 96 hours, respectively (40%);

7.1 mg/L: 10 dead fish after 24 hours (100%, LC100);

10 mg/L: 10 dead fish after 2-4 hours (100%).

The LC50 is conservatively derived from the geometric mean of LC0 and LC100: LC50 = 5.0 mg/L

No mortality occurred in the control, dissolved oxygen concentration was above saturation value and constant conditions were maintained with regard to temperature and pH for all groups during the test.

A draw-back of the study is that analytical monitoring of test item concentrations was not performed, while the test item must be regarded as moderately volatile (Henry’s law constant target compound n-undecanal: 64.3 Pa*m^3/mol (20°C)).

However, during the test basins were not aerated, reducing potential loss by volatilisation. Further, a ready biodegradability study performed with the target substance n-undecanal (OECD 301B; LAUS,

2010; report no. 10041903G605) resulted in 65% mineralisation within 28 days based on CO2 at an initial concentration of ca. 26.5 mg/L test item. For this test, a continuous flow of CO2-free air is passed through the flasks, increasing the potential for volatilisation. It may be concluded from this test, that after 28 days, at least 65% of the test item must have been available for biodegradation, i.e. cannot

have been volatilized. At day 4, biodegradation extent was 24%, only, as such, 65% - 24% = 41% of the initial test item amount must have still been available in solution after 4 days (96 hours). Taking into

account the competing losses from biodegradation and volatilisation, a loss of 50% within 4 days is a conservative estimate: in the acute fish test with 2-methyldecanal, there was no aeration and further,

test item concentration was less than half, further reducing volatilisation extent.

Assuming a loss by volatilisation of 50% till the end of the test (96 h), the corrected LC50 is calculated:

LC50 (Danio rerio; 96 h; corrected for volatilization) = 5.0 mg/L * 50% = 2.5 mg/L

This is very close to the predicted value of 1.97 mg/L (95% CI: 0.274 mg/L to 14.2 mg/L) from trend analysis following the Standardized Workflow for acute fish toxicity (QSAR toolbox 4.2).

Overall conclusion:

The key value for acute fish toxicity derived from trend analysis met the acceptance criteria, and a narrow 95% confidence interval confirms reliability of this value. The result is corroborated by experimental data on fish toxicity (Danio rerio, 96 hours) for a close structural isomer (2-methyldecanal): the volatility corrected LC50 is very close to

the key value (higher by a factor of 1.27) and increases confidence in the calculated value.

Validity criteria fulfilled:

yes

Remarks:

the acceptance criteria for trend analysis (R2≥ 0.7 and NA≥ 10) were met: R2 = 0.713; number of analogues (NA) = 19

Conclusions:

Acute fish toxicity was estimated using OECD QSAR Toolbox V.4.2 and following the standardized workflow (SW):

LC50 (trend analysis; 96 h; Actinopterygii) = 1.97 mg/L (95% CI: 0.274 mg/L to 14.2 mg/L).

Executive summary:

QSAR Toolbox V.4 -2 Estimation

A reliable (without restrictions) QSAR study supported by experimental data for a structural isomer was performed to determine acute fish toxicity of n-undecanal.

The prediction was performed using trend analysis for acute fish toxicity implemented in QSAR Toolbox v.4.2 and applying the corresponding standardized workflow.

The underlying mechanistic interpretation is an unspecific reactivity caused by the aldehyde group causing observed toxicity. According to McFarland (1970), the toxicity to aquatic organisms depends on penetration (log Kow) of the chemical, followed by interaction with cellular biomolecules. Therefore, it is justified to derive a value for the acute fish toxicity of the target compound (n-undecanal) from known fish toxicities (ordinate) of sufficiently similar aldehydes as a function of log Kow (abscissa, Kow expressing the potential for penetrating biological membranes).

Therefore, categorisation started based on chemical class “Aldehydes (Mono)”, as oligomers of this functional group within one molecule would be expected to cause higher toxicity or even to act as a crosslinking agent. Otherwise, suggestions as given according to the standardized workflow for subgrouping were followed, and the resulting value for LC50 met the acceptance criteria for trend analysis (R^2≥ 0.7 and NA≥ 10):

R^2 = 0.713;

Number of analogues (NA) = 19.

Further, the sample standard deviation of residuals is low (0.361), such that the 95% confidence range of the final result is narrow:

LC50 (trend analysis; 96 h; Actinopterygii) = 1.97 mg/L (95% CI: 0.274 mg/L to 14.2 mg/L).

Supporting experimental data

This reliable and adequate (for hazard and risk assessment as well as classification and labelling) result from trend analysis using QSAR Toolbox V.4.2 standardized workflow is corroborated by experimental results for a structural isomer:

2-methyldecanal (CAS No.: 19009-56-4 / EC No. 242-745-6) was tested according to OECD 203 in a reliable study (with restrictions, RL2) for acute fish toxicity using Danio rerio. The static test design took volatility of the test item (HLC: 64.3 Pa*m^3/mole at 20°C) insofar into account, as there was no aeration during the test. However, information is lacking if basins were covered, and analytical confirmation of test item concentration was not performed.

From the exposure of 7 treatment groups and a control (10 fish, each), the LC50 was estimated to 5 mg/L, corresponding to 40% actual lethality in the 5 mg/L treatment group after 96 hours.

To correct for potential volatilization losses, from a valid biodegradation study performed according to OECD 301B - a test design prone to volatilisation losses - a worst case loss within 96 hours of 50% was estimated.

Volatility-corrected result from this study on Danio rerio:

LC50 (Danio rerio; 96 h; corrected for volatilization) = 5.0 mg/L * 50% = 2.5 mg/L

Overall conclusion:

The volatility corrected result from a study on Danio rerio using a structural isomer of n-undecanal (2-methyldecanal) corroborates the valid result of the prediction according to QSAR: The LC50 (Danio rerio; 96 h; corrected for volatilization) of 2.5 mg/L is very close to the predicted value of 1.97 mg/L (95% CI: 0.274 mg/L to 14.2 mg/L) from trend analysis following the Standardized Workflow for acute fish toxicity (QSAR toolbox 4.2).

Therefore, because the key value for acute fish toxicity derived from trend analysis using QSAR toolbox 4.2 met the acceptance criteria, is characterized by a narrow 95% confidence interval  and is further corroborated from experimental results for a close analogue, reliability and applicability of the QSAR estimated for environmental hazard and risk assessment as well as classification and labelling is confirmed.

Final result used for chemical safety assessment:

LC50 (trend analysis; 96 h; Actinopterygii) = 1.97 mg/L (95% CI: 0.274 mg/L to 14.2 mg/L).

Description of key information

Acute fish toxicity was estimated using OECD QSAR Toolbox V.4.2 and following the standardized workflow (SW):

LC50 (trend analysis; 96 h; Actinopterygii) = 1.97 mg/L (95% CI: 0.274 mg/L to 14.2 mg/L).

Key value for chemical safety assessment

Fresh water fish

Fresh water fish

Effect concentration:

1.97 mg/L

Additional information

QSAR Toolbox V.4 -2 Estimation

A reliable (without restrictions) QSAR study supported by experimental data for a structural isomer was performed to determine acute fish toxicity of n-undecanal.

The prediction was performed using trend analysis for acute fish toxicity implemented in QSAR Toolbox v.4.2 and applying the corresponding standardized workflow.

The underlying mechanistic interpretation is an unspecific reactivity caused by the aldehyde group causing observed toxicity. According to McFarland (1970), the toxicity to aquatic organisms depends on penetration (log Kow) of the chemical, followed by interaction with cellular biomolecules. Therefore, it is justified to derive a value for the acute fish toxicity of the target compound (n-undecanal) from known fish toxicities (ordinate) of sufficiently similar aldehydes as a function of log Kow (abscissa, Kow expressing the potential for penetrating biological membranes).

Therefore, categorisation started based on chemical class “Aldehydes (Mono)”, as oligomers of this functional group within one molecule would be expected to cause higher toxicity or even to act as a crosslinking agent. Otherwise, suggestions as given according to the standardized workflow for subgrouping were followed, and the resulting value for LC50 met the acceptance criteria for trend analysis (R^2≥ 0.7 and NA≥ 10):

R^2 = 0.713;

Number of analogues (NA) = 19.

Further, the sample standard deviation of residuals is low (0.361), such that the 95% confidence range of the final result is narrow:

LC50 (trend analysis; 96 h; Actinopterygii) = 1.97 mg/L (95% CI: 0.274 mg/L to 14.2 mg/L).

Supporting experimental data

This reliable and adequate (for hazard and risk assessment as well as classification and labelling) result from trend analysis using QSAR Toolbox V.4.2 standardized workflow is corroborated by experimental results for a structural isomer:

2-methyldecanal (CAS No.: 19009-56-4 / EC No. 242-745-6) was tested according to OECD 203 in a reliable study (with restrictions, RL2) for acute fish toxicity using Danio rerio. The static test design took volatility of the test item (HLC: 64.3 Pa*m^3/mole at 20°C) insofar into account, as there was no aeration during the test. However, information is lacking if basins were covered, and analytical confirmation of test item concentration was not performed.

From the exposure of 7 treatment groups and a control (10 fish, each), the LC50 was estimated to 5 mg/L, corresponding to 40% actual lethality in the 5 mg/L treatment group after 96 hours.

To correct for potential volatilization losses, from a valid biodegradation study performed according to OECD 301B - a test design prone to volatilisation losses - a worst case loss within 96 hours of 50% was estimated.

Volatility-corrected result from this study on Danio rerio:

LC50 (Danio rerio; 96 h; corrected for volatilization) = 5.0 mg/L * 50% = 2.5 mg/L

Overall conclusion:

The volatility corrected result from a study on Danio rerio using a close structural isomer of n-undecanal (2-methyldecanal) corroborates the valid result of the prediction according to QSAR: The LC50 (Danio rerio; 96 h; corrected for volatilization) of 2.5 mg/L is very close to the predicted value of 1.97 mg/L (95% CI: 0.274 mg/L to 14.2 mg/L) from trend analysis following the Standardized Workflow for acute fish toxicity (QSAR toolbox 4.2).

Therefore, because the key value for acute fish toxicity derived from trend analysis using QSAR toolbox 4.2 met the acceptance criteria, is characterized by a narrow 95% confidence interval  and is further corroborated from experimental results for a close analogue, reliability and applicability of the QSAR estimated for environmental hazard and risk assessment as well as classification and labelling is confirmed.

Final result used for chemical safety assessment:

LC50 (trend analysis; 96 h; Actinopterygii) = 1.97 mg/L (95% CI: 0.274 mg/L to 14.2 mg/L).