Reaction mass of 4,4'-isopropylidenediphenol and phenol

Toxicity to aquatic algae and cyanobacteria

Link to relevant study record(s)

Reference

Endpoint:

toxicity to aquatic algae and cyanobacteria

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
This read-across is based on the hypothesis that the properties of the target substance Reaction mass of phenol and 4,4’-isopropylidenediphenol can be predicted by studies conducted with the source substances phenol, 4,4’-isopropylidenediphenol (BPA), and 2-acetone, polymer with phenol, because the target substance Reaction mass of phenol and 4,4’-isopropylidenediphenol contains phenol (40-45%, typical concentration ca. 40%) and 4,4’-isopropylidenediphenol (BPA) (20-40%, typical concentration ca. 33%) as main constituents. Both constituents are data rich substances with distinct hazard properties, so that mainly data on the constituents have been applied to characterize the Reaction mass of phenol and 4,4’-isopropylidenediphenol. Since this is a common approach in mixture hazard assessment, is reasonable to apply it also to multi-constituent substances.
Additionally, some data from a structurally related substance (2-acetone, polymer with phenol) containing the same constituents/impurities at different concentrations are available, which are applied to characterize the environmental fate and ecotoxicity of the impurities present in the Reaction mass of phenol and 4,4’-isopropylidenediphenol.

This read-across hypothesis corresponds to scenario 2 - different compounds have qualitatively and quantitatively the same type of effects - of the read-across assessment framework i.e. properties of the target substance Reaction mass of phenol and 4,4’-isopropylidenediphenol are predicted to be similar to those of the source substances phenol, 4,4’-isopropylidenediphenol (BPA), and 2-acetone, polymer with phenol.

Therefore, read-across from the available studies with the source substances is considered as an appropriate adaptation to the standard information requirements of the REACH Regulation for the target substance Reaction mass of phenol and 4,4’-isopropylidenediphenol, in accordance with the provisions of Annex XI, 1.5 of the REACH Regulation.


2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
please refer to justification for read-across attached to Iuclid section 13

3. ANALOGUE APPROACH JUSTIFICATION
please refer to justification for read-across attached to Iuclid section 13

4. DATA MATRIX
please refer to justification for read-across attached to Iuclid section 13

Reason / purpose for cross-reference:

read-across: supporting information

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Duration:

96 h

Dose descriptor:

EC50

Effect conc.:

61.1 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

cell number

Remarks on result:

other: Phenol

Duration:

96 h

Dose descriptor:

EC50

Effect conc.:

2.73 mg/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat.

Basis for effect:

cell number

Remarks on result:

other: BPA, freshwater

Duration:

96 h

Dose descriptor:

EC10

Effect conc.:

1.36 mg/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat.

Basis for effect:

cell number

Remarks on result:

other: BPA, freshwater

Duration:

96 h

Dose descriptor:

EC50

Effect conc.:

1.1 mg/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat.

Basis for effect:

cell number

Remarks on result:

other: BPA, marine

Duration:

96 h

Dose descriptor:

EC10

Effect conc.:

0.4 mg/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat.

Basis for effect:

cell number

Remarks on result:

other: BPA, marine

Duration:

72 h

Dose descriptor:

EC50

Effect conc.:

> 100 mg/L

Nominal / measured:

meas. (geom. mean)

Conc. based on:

test mat.

Basis for effect:

growth rate

Remarks on result:

other: 2-acetone, polymer with phenol

Duration:

72 h

Dose descriptor:

EC10

Effect conc.:

10.3 mg/L

Nominal / measured:

meas. (geom. mean)

Conc. based on:

test mat.

Basis for effect:

growth rate

Remarks on result:

other: 2-acetone, polymer with phenol

Conclusions:

Of all the tested source substances, Bisphenol A was most toxic to algae. In a 96 hour test with the saltwater algae, Skeletonema costatum, the EyC10 and EyC50 (based on cell number) for Bisphenol A was determined to be 0.4 mg/L and 1.1 mg/L, respectively. Furthermore, in a 96 hour test with the freshwater algae, Pseudokirchnerella subcapitata, the EyC10 and the EyC50 (based on cell number) for Bisphenol A was determined to be 1.36 mg/L and 2.73 mg/L, respectively.
The 96 h EC50 for phenol was 61.1 mg/L (95 % confidence limits: 37.1 - 84.5 mg/L)
Due to the physicochemical properties of phenol, this major constituent of the reaction mass is capable of targeting aquatic and terrestrial wildlife through a different exposure route than 4,4’-isopropylidenediphenol. Therefore, to adequately characterize the hazard of the reaction mass toward ecotoxicology endpoints, the toxicity and fate of both major constituents of the reaction mass of phenol and 4,4’-isopropylidenediphenol were considered and two sets of PNECs (one for phenol one for 4,4’-isopropylidenediphenol) were derived and an assessment entity approach was applied.

Description of key information

Of all the tested components of the reaction mass of phenol and 4,4’-isopropylidenediphenol , Bisphenol A was most toxic to algae.  In a 96 hour test with the saltwater algae, Skeletonema costatum, the EyC10 and EyC50 (based on cell number) for Bisphenol A was determined to be 0.4 mg/L and 1.1  mg/L, respectively.  Furthermore, in a 96 hour test with the freshwater algae, Pseudokirchnerella subcapitata, the EyC10 and the EyC50 (based on cell number) for Bisphenol A was determined to be 1.36 mg/L and 2.73 mg/L, respectively.

Key value for chemical safety assessment

EC50 for freshwater algae:

2.73 mg/L

EC50 for marine water algae:

1.1 mg/L

EC10 or NOEC for freshwater algae:

1.36 mg/L

EC10 or NOEC for marine water algae:

0.4 mg/L

Additional information

No experimental data are available for the target substance reaction mass of phenol and 4,4’-isopropylidenediphenol. The toxicity to fish was assessed by examination of the properties of the constituents and impurities of the multi-constituent substance. A justification for read-across is attached to Iuclid section 13.

 

Studies with Bisphenol A

In a valid toxicity study (Klimish score = 2) with the freshwater algae, Pseudokirchnerella subcapitata,the 96-hour EyC50 (cell number) for phenol was determined to be 61.1 mg/L. In a valid toxicity study (Klimish score = 2) with the saltwater algae, Skeletonema costatum, the 96-hour EyC10 and EyC50 values for Bisphenol A (based on yield, or cell number) were determined, based on probit analysis, to be 0.4 mg/L and 1.1 mg/L, respectively. In a valid toxicity study (Klimish = 1) with the freshwater algae, Pseudokirchnerella subcapitata, the 96-hour EyC10 and EyC50 values for Bisphenol A (based on yield, or cell number) were determined to be 1.36 mg/L and 2.73 mg/L, respectively.  

 

Studies with Phenol

A 96 hour alga growth inhibition test was performed with the green alga Pseudokirchneriella subcapitata (reported as Selenastrum capricornutum) exposed to ten concentrations of phenol. Details of the test (cell numbers, growth curve) were not reported and the validity of the test according to current OECD or EEC guidelines can not be assessed. The test result is considered plausible due to comparable results from other 96 hour studies and is the most sensitive out of the 96 hour tests:  96 h EC50 (cell number increase): 61.1 mg phenol/L (95 % confidence limits: 37.1 - 84.5 mg/L)

 

Studies with 2-Acetone, polymer with phenol

 One 72-hour algal study with Desmodesmus subspicatus was available for 2-acetone, polymer with phenol (a mixture of some of the major and minor components of the reaction mass of phenol and 4,4’-isopropylidenediphenol). This study was deemed reliable for use in risk assessments (Klimish score = 1). The 72-hour ErC10 and ErC50 values (based on growth rate) for 2-acetone, polymer with phenol are 10.3 mg/L and >100 mg/L, respectively. From the same study, the 72-hour EyC10 and EyC50 values (based on cell number) for 2-acetone, polymer with phenol were determined to be 2.7 mg/L and 15.6 mg/L, respectively. Algal toxicity tests with the two major components of the reaction mass, phenol and 4,4’-isopropylidenediphenol (a.k.a Bisphenol A), were also available. 

 

Conclusion

Bisphenol A was the most toxic component of the reaction mass of phenol and 4,4’-isopropylidenediphenol based on EyC50 values. The growth rate endpoint is preferred over the cell number (yield) endpoint according to ECHA guidance (Chapter R.7B). However, only one available study reported a growth rate endpoint, and the raw data for the other studies was not readily available in order to calculate the ErC50 based on growth rate. Since the EyC50, based on yield, is generally a lower, more conservative value than the growth rate, the studies reporting the lowest EyC50 values of 1.1 mg/L and 2.7 mg/L Bisphenol A determined using the saltwater algae, Skeletonema costatum, and the freshwater algae, Pseudokirchnerella subcapitata, respectively, are reported as the key studies for this endpoint.

 

Due to the physicochemical properties of phenol, this major constituent of the reaction mass is capable of targeting aquatic and terrestrial wildlife through a different exposure route than 4,4’-isopropylidenediphenol. Therefore, to adequately characterize the hazard of the reaction mass toward ecotoxicology endpoints, the toxicity and fate of both major constituents of the reaction mass of phenol and 4,4’-isopropylidenediphenol were considered and two sets of PNECs (one for phenol one for 4,4’-isopropylidenediphenol) were derived and an assessment entity approach was applied.