2-(4-methylcyclohex-3-en-1-yl)propan-2-ol

Short-term toxicity to aquatic invertebrates

Link to relevant study record(s)

Reference

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

calculation (if not (Q)SAR)

Remarks:

Migrated phrase: estimated by calculation

Adequacy of study:

key study

Study period:

2016-03-07 to 2016-03-08

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Calculation method is used ; calculation method applicable for the endpoint

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 202 (Daphnia sp. Acute Immobilisation Test)

Deviations:

yes

Remarks:

calculation method

Principles of method if other than guideline:

The acute toxicity to daphnia was determined using a validated QSAR for the Mode of Action in question. The first step of the iSafeRat mixture toxicity calculation employs phase equilibrium thermodynamics in order to determine the concentrations of each constituent within the WAF. This fraction equates to the analyzable fraction of a WAF study.
Within the WAF, the constituents also partition between themselves further reducing the bioavailable fraction and thus the toxicity of the mixture compared to the individual constituents. In the calculation the second step is to remove this non-bioavailable fraction.
The final step is to determine the truly bioavailable fraction of the WAF per constituent. The EC50s of each constituent are already known from literature or calculated using the iSafeRat QSAR model. Each value and calculation has been included as a supporting study in the IUCLID. An additivity approach (based on Chemical Activity of each constituent) is used in order to calculate the Effective Loading rate of the WAF.
The method has been validated using data derived from 48-hour EC50 tests on aquatic invertebrates, for which the concentrations of the test item had been determined by chemical analyses over the test period. Further to this the effective loading rate of the WAF is determined by using a series of calculation steps using phase equilibrium thermodynamics and excluding the non-bioavailable fraction.

GLP compliance:

no

Analytical monitoring:

no

Details on sampling:

not applicable

Vehicle:

no

Details on test solutions:

not applicable

Test organisms (species):

Daphnia sp.

Details on test organisms:

not applicable

Test type:

other: calculation method

Water media type:

freshwater

Limit test:

no

Total exposure duration:

48 h

Remarks on exposure duration:

48h-EL50 (effective loading rate of WAF)

Post exposure observation period:

not applicable

Hardness:

Hardness is not a necessary component of the WAF calculation

Test temperature:

The Temperature is not a necessary component of the WAF calculation but extremely low or high temperatures could influence the solubility of certain constituents. Therefore, the calculation method is considered acceptable to determine EL50s for daphnia between 12 and 28°C.

pH:

The pH is not a necessary component of the WAF calculation

Dissolved oxygen:

The oxygen concentration is not a necessary component of the WAF calculation

Salinity:

Salinity is not a necessary component of the WAF calculation. However as the fish QSAR for the constituents calculation was based on data from freshwater studies, the resulting calculation is considered valid for freshwater organisms

Nominal and measured concentrations:

The calculation determines measured concentrations

Details on test conditions:

calculation method

Reference substance (positive control):

not required

Key result

Duration:

48 h

Dose descriptor:

EL50

Effect conc.:

12 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

mobility

Details on results:

not applicable

Results with reference substance (positive control):

not applicable

Reported statistics and error estimates:

not applicable

Table 6.1.3/1: Short-tetm toxicity to Daphnids values for components used in the calculation.

constituents	48h-EC50 (mg/L)
α-terpineol	61
γ-terpineol	61
β-terpineol	51
terpinolene	0.73
3-terpinen-1-ol	61
borneol	23
fenchol	23
terpinen-1-ol 4	61
limonene	0.62

Table 6.1.3/2: Expected concentrations at this 48h-EL50.

constituents	concentration in the WAF (mg/L)
α-terpineol	7.4
γ-terpineol	1.2
β-terpineol	0.61
terpinolene	1.2
3-terpinen-1-ol	0.42
borneol	0.48
fenchol	0.29
terpinen-1-ol 4	0.19
limonene	0.07

Validity criteria fulfilled:

yes

Conclusions:

The 48h-EL50 for Terpineol multiconstituent is estimated at 12 mg test item/L.

Executive summary:

The registered substance is a multiconstituent substance with a well-defined composition for which the relative percentage and the reported variation of each constituent is known. Its acute toxicity to aquatic invertebrates property has been investigated using an in-house calculation method that replaces an OECD 202 study and guideline for Testing of Chemicals No. 23 (i.e. WAF conditions). The worst case composition was investigated.

The first step of the iSafeRat mixture toxicity calculation employs phase equilibrium thermodynamics in order to determine the concentrations of each constituent within the WAF. This fraction equates to the analysable fraction of a WAF study.

Within the WAF, the constituents also partition between themselves further reducing the bioavailable fraction and thus the toxicity of the mixture compared to the individual constituents. In the calculation the second step is to remove this non-bioavailable fraction.

The final step is to determine the truly bioavailable fraction of the WAF per constituent. The EC50s of each constituent are already known from literature or calculated using the iSafeRat QSAR model. Each value and calculation has been included as a supporting study in IUCLID. An additivity approach (based on Chemical Activity of each constituent) is used in order to calculate the Effective Loading rate of the WAF.

The 48-h EL50 was 12 mg test material/L for the registered substance. EL50 was based on immobility. 

This toxicity study is acceptable and can be used for that endpoint.

Description of key information

The substance exhibits an EL50 for freshwater invertebrates of 12 mg/L.

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Effect concentration:

12 mg/L

Additional information

The registered substance is a multiconstituent substance with a well-defined composition for which the relative percentage of each constituent is known. The ecotoxicological properties of the registered substance may be derived from the aquatic toxicity values of the individual components using an additivity calculation approach.

It has been observed that CLP additivity calculations for mode of action 1 compounds are unreasonably conservative when compared to classic experimental studies using Water Accommodated Fractions (WAF), and this has been proved in a number of cases with substances of natural origin. Indeed, substance of natural origin may be composed of hydrophilic alcohol molecules and hydrophobic hydrocarbon terpene molecules. Therefore, when a WAF is performed most of substances fully dissolved in the aqueous phase are the hydrophilic fraction while the hydrophobic fraction (the more toxic elements for MOA 1 substances) may be below their water solubility value. The first step of the iSafeRat mixture toxicity calculation employs phase equilibrium thermodynamics in order to determine the concentrations of each constituent within the WAF. This fraction equates to the analysable fraction of a WAF study. On the other hand, the CLP additivity approach is calculated on the basis that all the substances are at their maximum solubility. Within the WAF, the constituents also partition between themselves further reducing the bioavailable fraction and thus the toxicity of the mixture compared to the individual constituents. In the calculation the second step is to remove this non-bioavailable fraction. These two reasons explain why ecotoxicity values from WAF studies are always higher for non-polar narcotic mixtures than the calculated values from CLP additivity calculation. The final step is to determine the truly bioavailable fraction of the WAF per constituent. The EC₅₀s of each constituent are already known from literature or calculated using the iSafeRat QSAR model. Each value and calculation has been included as a supporting study in the IUCLID. An additivity approach (based on Chemical Activity of each constituent) is used in order to calculate the Effective Loading of the WAF.

A predicted acute toxicity value to Daphnid is available. The estimated EL₅₀ for Daphnid is 12 mg/L. This prediction is obtained with QSAR for the Mode of Action 1, based on validated data derived from standard toxicity test, for which the concentrations of the test item had been determined by chemical analyses over the test period. The prediction is sufficiently robust, and is appropriate for the purposes of chemical safety assessment required for REACH.

Besides, one reliable experimental study is available for the registered substance. The toxicity to Daphnia magna was studied according to OECD TG No. 202 and GLP. Daphnids were exposed to substance at nominal test concentrations of 0 (test medium control), 40, 48, 58, 69, 83 and 100 mg/L over a test period of 48 hours (static test). Concentrations were verified by TOC determinations at relevant concentrations (69 and 100 mg/L). The endpoint was based on the nominal concentrations. The 48-h EC₅₀ was approximately 73 mg/L. Sublethal effects were observed at the concentration equal or higher than 69 mg of terpineol multiconstituent /L: abnormal swimming behaviour.