4-(α,α-dimethylbenzyl)phenol

Long-term toxicity to aquatic invertebrates

Link to relevant study record(s)

Reference

Endpoint:

long-term toxicity to aquatic invertebrates

Type of information:

(Q)SAR

Adequacy of study:

key study

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:

A reliable QSAR model (Ecological Structure-Activity Relationship (ECOSAR) version 1.11) was used to predict the chronic aquatic toxicity of p-Cumylphenol to daphnids. The daphnid 21 day ChV’s were 0.201 mg/L and 0.438 mg/L for the phenols class and neutral organic class, respectively. Comparing the measured 48 hour Daphnia magna EC50 (0.9 mg/L) to the ECOSAR predicted value of 1.060 mg/L for the phenolic class, the model appears to be very accurate.

The ECOSAR predicted chronic aquatic toxicity values for p-Cumylphenol are considered valid and fit for purpose. A calculated value from a QSAR model is considered valid and fit for purpose if the following conditions are met: 1) Results are derived from a (Q)SAR model whose scientific validity has been established; 2) The substance falls within the applicability domain of the (Q)SAR model; 3) Results are adequate for the purpose of classification and labelling and/or risk assessment and 4) Adequate and reliable documentation of the applied method is provided.

1) Results are derived from a (Q)SAR model whose scientific validity has been established

ECOSAR had been utilized by the scientific community for prediction of aquatic toxicity since the 1990’s. While developed by the US EPA, the program underwent an independent peer review as a part of the development of the Organization for Economic Cooperation and Development (OECD) principles established for quantitative structure-activity relationship ((Q)SAR) validation. As of 2011, ECOSAR was the subject of 20 peer reviewed publications regarding its validation and performance.

Also ECOSAR has been incorporated into the OECD Toolbox and was considered a top performer for use in profiling chemicals. Inclusion in the OECD toolbox requires specific documentation, validation and acceptability criteria and subjects ECOSAR to international use, review, providing a means for receiving additional and on-going input for improvements.

ECOSAR is listed as one of the QSARs tools for use in predicting aquatic toxicity values in the Guidance on information requirements and chemical safety assessment Chapter R.10: Characterisation of dose [concentration]-response for the environment and Chapter R.6: QSARs and grouping of chemicals.

In summary, ECOSAR has had its scientific validity established repeatedly.

2) The substance falls within the applicability domain of the (Q)SAR model

ECOSAR’s training set generally includes chemicals that had log Kow’s between -3 and 8 with molecular weights less than 1000. While the applicability domain of ECOSAR is considered to be larger than just the training set, p-Cumylphenol’s log Kow (3.8) and molecular weight (212.29) fall within the range of the training set values and is thus considered within the applicability domain. The log Kow (3.8) is also lower than the maximum log Kow (8.0) for the phenol and neutral organics equations. In addition, p-Cumylphenol is considered a member of the phenol class for which special calculations have been developed within ECOSAR.

3) Results are adequate for the purpose of classification and labelling and/or risk assessment

ECOSAR’s Neutral Organic’s (Baseline Toxicity) model uses the following equation for calculation of chronic aquatic toxicity to daphnids:

Organism Endpoint Equation
Daphnid 21 d ChV Log ChV (mmol/L) = - 0.7464 log Kow + 0.1507

The equation has the following statistics:
Number of substances = 26
Correlation coef (r2) = 0.872

ECOSAR’s Phenol model uses the following equation for the calculation of chronic aquatic toxicity to daphnids:

Organism Endpoint Equation
Daphnid 21 d ChV Log ChV (mmol/L) = -0.5674 (log Kow) - 0.8674

The equation has the following statistics:
Number of substances = 14
Correlation coef (r2) = 0.702

These correlation coefficients indicate the ECOSAR models calculate results that are equivalent to those generated experimentally and are, hence, adequate for the purpose of classification and labelling and/or risk assessment.

4) Adequate and reliable documentation of the applied method is provided

Documentation and validity of the ECOSAR QSAR models are provided in the following references:

Clements, RG, Nabholz, JV and Zeeman, R. 1996. Estimating Toxicity of Industrial Chemicals to Aquatic Organisms Using Structure-activity Relationships.

ECHA (2008) “Guidance on information requirements and chemical safety assessment Chapter R.6: QSARs and grouping of chemicals”.

ECHA (2008) “Guidance on information requirements and chemical safety assessment Chapter R.10: Characterisation of dose [concentration]-response for the environment”.

Mayo-Bean, K, Nabholz, JV, Clements, R, Zeeman, M, Henry, T, Rodier, D, Moran, K, Meylan, WM and Ranslow, P. 2011a. Methodology Document for the Ecological Structure-Activity Relationship Model (ECOSAR) Class Program.

Mayo-Bean, K, Nabholz, JV, Meylan, WM, Howard, PH and Moran-Bruce, K. 2011b. Operation Manual for the Ecological Structure-Activity Relationship Model (ECOSAR) Class Program.

Qualifier:

no guideline required

Principles of method if other than guideline:

The QSAR model, Ecological Structure Activity Relationships (ECOSAR) Class Program was used to estimate long-term toxicity to daphnids. A SMILES notation of Oc(ccc(c1)C(c(cccc2)c2)(C)C)c1 was used. Also the measured log Kow value of 3.8 was used.

Specific details on test material used for the study:

SMILES : Oc(ccc(c1)C(c(cccc2)c2)(C)C)c1

Analytical monitoring:

not required

Test organisms (species):

Daphnia sp.

Water media type:

freshwater

Key result

Duration:

21 d

Dose descriptor:

other: chronic value (geometric mean of NOEC and LOEC)

Effect conc.:

0.201 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

not specified

Details on results:

As per REACH Guidance Ch 10, a NOEC can be calculated from the chronic value. Therefore, the calculated NOEC = 0.142 mg/L and will be used in the assessment.

SMILES : Oc(ccc(c1)C(c(cccc2)c2)(C)C)c1

CHEM   : Phenol, 4-(1-methyl-1-phenylethyl)-

CAS Num: 000599-64-4

ChemID1:

MOL FOR: C15 H16 O1

MOL WT : 212.29

Log Kow: 4.123      (EPISuite Kowwin v1.68 Estimate)

Log Kow: 3.800      (User Entered)

Log Kow:            (PhysProp DB exp value - for comparison only)

Melt Pt:            (User Entered for Wat Sol estimate)

Melt Pt: 74.00      (deg C, PhysProp DB exp value for Wat Sol est, 74-76)

Wat Sol: 164.3      (mg/L, EPISuite WSKowwin v1.43 Estimate)

Wat Sol:            (User Entered)

Wat Sol:            (PhysProp DB exp value)

--------------------------------------

Values used to Generate ECOSAR Profile

--------------------------------------

Log Kow: 3.800      (User Entered)

Wat Sol: 164.3      (mg/L, EPISuite WSKowwin v1.43 Estimate)

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Available Measured Data from ECOSAR Training Set

------------------------------------------------

  No Data Available

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ECOSAR v1.1 Class-specific Estimations

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Phenols

                                                                   Predicted

ECOSAR Class                 Organism            Duration  End Pt   mg/L (ppm)

===========================  ==================  ========  ======   ==========

Phenols                    : Fish                96-hr     LC50        1.580

Phenols                    : Daphnid             48-hr     LC50        1.060

Phenols                    : Green Algae         96-hr     EC50        4.094

Phenols                    : Fish                          ChV         0.208

Phenols                    : Daphnid                       ChV         0.201

Phenols                    : Green Algae                   ChV         1.880

Phenols                    : Fish (SW)           96-hr     LC50        0.511

Phenols                    : Earthworm           14-day    LC50       36.217

Phenols                    : Lemna gibba         7-day     EC50        0.722

===========================  ==================  ========  ======   ==========

Neutral Organic SAR        : Fish                96-hr     LC50        4.217

(Baseline Toxicity)        : Daphnid             48-hr     LC50        2.827

                          : Green Algae         96-hr     EC50        4.187

                          : Fish                          ChV         0.501

                          : Daphnid                       ChV         0.438

                          : Green Algae                   ChV         1.588

Note:  * = asterisk designates: Chemical may not be soluble enough to

       measure this predicted effect. If the effect level exceeds the

       water solubility by 10X, typically no effects at saturation (NES)

       are reported.

------------------------------

Class Specific LogKow Cut-Offs

------------------------------

If the log Kow of the chemical is greater than the endpoint specific cut-offs

presented below, then no effects at saturation are expected for those endpoints.

Phenols:

-------

Maximum LogKow: 7.0 (Fish 96-hr LC50, Daphnid LC50)

Maximum LogKow: 6.4 (Earthworm, Lemna)

Maximum LogKow: 7.0 (Green Algae EC50

Maximum LogKow: 8.0 (ChV)

Maximum LogKow: 5.0 (Fish (SW) 96-hr LC50, Mysid)

Baseline Toxicity SAR Limitations:

---------------------------------

Maximum LogKow: 5.0 (Fish 96-hr LC50; Daphnid LC50)

Maximum LogKow: 6.4 (Green Algae EC50)

Maximum LogKow: 8.0 (ChV)

Validity criteria fulfilled:

yes

Conclusions:

The calculated ChV for p-Cumylphenol was 0.201 mg/L which can be converted to a NOEC of 0.142 mg/L.

Executive summary:

Using a reliable QSAR model, Ecological Structure Activity Relationships (ECOSAR) Class Program was used to estimate long-term toxicity to aquatic invertebrates. The measured Kow of 3.8 was used in the model. Model results indicate a 21 day chronic value (the geometric mean of the NOEC and LOEC) to be 0.201 mg/L for p-Cumylphenol using the phenolic class equation. The baseline 21 day chronic value was 0.438 mg/L. Since p-Cumylphenol is in the class of phenols, the result for the phenol class will be used as key for long-term toxicity to aquatic invertebrates. As per REACH Guidance Ch 10, a NOEC can be calculated from the chronic value. Therefore, the calculated NOEC = 0.142 mg/L and will be used in the assessment.

Description of key information

Using a reliable QSAR model, Ecological Structure Activity Relationships (ECOSAR) Class Program was used to estimate long-term toxicity to aquatic invertebrates. The measured Kow of 3.8 was used in the model. Model results indicate a 21 day chronic value (the geometric mean of the NOEC and LOEC) to be 0.201 mg/L for p-Cumylphenol using the phenolic class equation. The baseline 21 day chronic value was 0.438 mg/L. Since p-Cumylphenol is in the class of phenols, the result for the phenol class will be used as key for long-term toxicity to aquatic invertebrates. As per REACH Guidance Ch 10, a NOEC can be calculated from the chronic value. Therefore, the calculated NOEC = 0.142 mg/L and will be used in the assessment.

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Effect concentration:

0.142 mg/L