Reaction mass of 4,4'-isopropylidenediphenol and phenol

Short-term toxicity to fish

Link to relevant study record(s)

Reference

Endpoint:

short-term toxicity to fish

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

Reason / purpose for cross-reference:

read-across source

Key result

Duration:

96 h

Dose descriptor:

LC50

Effect conc.:

4.6 mg/L

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Remarks on result:

other: BPA

Key result

Duration:

96 h

Dose descriptor:

LC50

Effect conc.:

8.9 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Remarks on result:

other: phenol

Conclusions:

The 96-hour LC50 of 4.6 mg/L Bisphenol A with fathead minnow was the lowest, and thus most conservative, fish acute toxicity value reported for the major constituents or impurities of the target substance.
The most sensitive endpoint for Phenol was the LC50 of 8.9 mg/L, based on measured concentrations, obtained in a 96-h acute toxicity study under flow-through conditions with rainbow trout.
However, 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

When a freshwater species, the fathead minnow (Pimephales promelas), was exposed to Bisphenol A, the 96-hour LC50 value was 4.6 mg/L. When a saltwater species, the Atlantic silverside (Menidia menidia), was exposed to Bisphenol A (a.k.a. 4,4’-isopropylidenediphenol), the 96-hour LC50 value was 9.4 mg/L.  These results were selected as key studies, since they were from valid toxicity tests that reported the lowest LC50 values for these parameters.

Key value for chemical safety assessment

Fresh water fish

Fresh water fish

Dose descriptor:

LC50

Remarks:

BPA

Effect concentration:

4.6 mg/L

Fresh water fish

Dose descriptor:

LC50

Remarks:

phenol

Effect concentration:

8.9 mg/L

Marine water fish

Marine water fish

Dose descriptor:

LC50

Remarks:

BPA

Effect concentration:

9.4 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 mulli-constituent substance. A justification for read-across is attached to Iuclid section 13.

 

Studies with Bisphenol A

The acute freshwater toxicity of Bisphenol A to the fathead minnow, Pimephales promelas, was determined in both static and flow-through exposures according to ASTM E-35.21 guidance. This is similar to the OECD 203 guideline. The results from the static and the flow-through exposures were very similar and demonstrated that Bisphenol A was stable in the test system during the course of the study. The 96-hr static acute LC50 value (and 95% confidence interval) was determined to be 4.7 (4.0 -5.5) mg/L. The 96-hr flow-through acute LC50 value (and 95% confidence interval) was determined to be 4.6 (3.6 -5.4) mg/L. No effects were observed at or below the analysed Bisphenol A concentrations of 2.26 and 2.28 mg/L in static and flow-through tests, respectively.

 

A 96 -h flow-through acute study exposed the saltwater Atlantic silverside, Menidia menidia, to Bisphenol A at measured concentrations ranging from 4.8 to 26 mg/L. The 96-hr LC50 value was calculated using probit analysis as 9.4 mg/L. Over the same period of time, a concentration of less than 5.9 mg/L was determined to have "no discernible effect" on the fish. A single mortality (5%) occurred at 72-hrs at 4.8 mg/L, however, the lack of mortality at the next highest dose suggests that 5.9 mg/L could be considered the NOEC.

 

The toxicity of Bisphenol A was determined in a 96-hour flow-through acute toxicity test using a representative saltwater fish species, the sheepshead minnow (Cyprinodon variegatus). The methods employed in the study meet the testing requirements of the Ecological Effects Test Guidelines draft OPPTS 850.1075 Fish Acute Toxicity Test, Freshwater and Marine, OPPTS 850.1000 Special Considerations for Conducting Aquatic Laboratory Studies, and OECD Guideline for Testing of Chemicals #203, Fish Acute Toxicity Test. The toxicity test was conducted using an exposure system consisting of an intermittent-flow proportional diluter and a set of 12 exposure vessels with 10 fish per tank, 20 per concentration. Based on preliminary testing, nominal Bisphenol A test concentrations of 3.1, 6.3, 13, 25 and 50 mg/L were selected for definitive testing. Mean measured concentrations ranged from 81 to 130% of nominal and defined the treatment levels as 2.5, 8.3, 12, 26 and 53 mg/L. Following 96 hours of exposure, 70, 100 and 100% mortality was observed among fish exposed to the 12, 26 and 53 mg/L treatment levels, respectively. The 96-hour LC50 value was estimated by binomial probability to be 11 mg/L, with 95% confidence intervals of 8.3 to 26 mg/L. The No-Observed-Effect Concentration (NOEC) was determined to be 8.3 mg/L.

 

A 14-day, fish prolonged toxicity test under semi-static conditions exposing zebrafish, Danio rerio, to Bisphenol A was performed according to OECD guideline 204. Nominal concentrations in the study were 0.1, 0.32, 1.0, 3.16, and 10.0 mg/L. The endpoints in the study were mortality and visible effects on appearance or behavior. Analysis of all test concentrations plus the control was performed at the start of the study and after 48 hours of exposure.  The 14-day LOEC and NOEC were determined to be 10.15 mg/L and 3.2 mg/L, respectively.

 

Studies with Phenol

A 96 -hour acute toxicity test with rainbow trout (O. mykiss) was conducted according to the US EPA Guideline (Methods for acute toxicity tests with fish, macroinvertebrates, and amphibians, 1974).

The rainbow trout were exposed to phenol at measured concentrations up to 100 mg/L (seven concentrations, graded by a factor of 2, details of measured concentrations not reported) under flow through conditions at 14°C. The most sensitive endpoint was the 96-h LC₅₀ of 8.9 mg/L (measured, 95% C.I.:not calculated). Sublethal effects of hyperactivity, gasping at the surface, rapid operculation were observed in O. mykiss exposed to 6.3 mg/L.

 

The toxicity of phenol to Poecilia reticulata was investigated in a study conducted according to OECD Guideline 204 (Fish, Prolonged Toxicity Test: 14-day Study) under semi-static conditions (renewal of test solutions on monday, wednesday, and friday). 10 Fish were exposed to phenol at nominal concentrations of 0 (control), 1, 2, 4, 8, 16 mg/L for 14 d. The stability of the test solutions was investigated over a period of 5 days via TOC analysis. After 5 d 92.1% of the initial test substance concentration was found. Therefore the effect values refer to nominal concentrions. The 14 d NOEC, LC50, and LC100 were determined to be 4, 21.93, and >16 mg/L nominal, respectively.

 

In a 96-h acute toxicity studies Pimephales promelas was exposed to phenol at measured concentrations up to 100 mg/L (seven concentrations, graded by factor 2, detailed measured concentrations not reported) under flow through conditions at 14°C or 25 °C. The study was conducted acc. US EPA Methods for acute toxicity tests with fish, macroinvertebrates, and amphibians (1974).

Sublethal effects of loss of equilibrium, gasping at the surface and twitching were observed at 0.5 mg/L in P. promelas (14 °C) and hyperactivity and rapid operculation at 17.6 mg/L in P. promelas (25 °C). The 96 h LC50 values were estimated to be 67.4 mg phenol/L for 14 °C exposure and 24.9 mg/L for 25 °C exposure.

 

Studies with 2-Acetone, polymer with phenol

A study was performed to assess the acute toxicity of 2-Acetone, polymer with phenol to Danio rerio under static conditions. The study was conducted in accordance with Council Regulation (EC) No 440/2008, Method C.1 'Acute toxicity for Fish' (2008) which is in most parts equivalent to the OECD Guideline for Testing of Chemicals No. 203 'Fish, Acute Toxicity Test' (1992).

Groups of seven fish of the recommended size were exposed to a range of concentrations, nominally 6.25, 12.5, 25, 50 and 100 mg/L of 2-Acetone, polymer with phenol dissolved in water. Observations were made on the numbers of dead fish and the incidence of sub-lethal effects after 2, 24, 48, 72 and 96 hours of exposure. The 96 h LC50 was 4.95 mg/L.

All results are expressed in terms of initial concentrations. Effective concentrations ranged from 27.8 – 28.1 % of nominal values at 0 hours and from 25.9 – 26.4 % of nominal values at 96 hours, respectively. Based on initial concentrations the measured concentration 12.5 mg/L corresponds to 93.1 % of the initial value after 96 hours of exposure.

 

Conclusion 

The 96-hour LC50 of 4.6 mg/L Bisphenol A with fathead minnow was the lowest, and thus most conservative, fish acute toxicity value reported for the major constituents or impurities of the target substance.

The most sensitive endpoint for Phenol was the LC50 of 8.9 mg/L, based on measured concentrations, obtained in a 96-h acute toxicity study under flow-through conditions with rainbow trout.

However, 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.