Reaction mass of 4,4'-isopropylidenediphenol and phenol

PBT assessment

PBT assessment: overall result

Reference

Name:

Reaction mass of phenol and 4,4'-isopropylidenediphenol

Type of composition:

legal entity composition of the substance

State / form:

other: semi solid to liquid

Reference substance:

Reaction mass of phenol and 4,4'-isopropylidenediphenol

Reference substance:

Reaction mass of phenol and 4,4'-isopropylidenediphenol

PBT status:

the substance is not PBT / vPvB

Justification:

The available information shows that the properties of the substance, reaction mass of phenol and 4,4’-isopropylidenediphenol, do not meet all of the specific criteria detailed in Annex XIII.

The available information indicates that some of the constituents of the substance meet criteria for persistence (P) and toxicity (T), but do not meet the criteria for bioaccumulation (B).

It is concluded that the reaction mass of phenol and 4,4’-isopropylidenediphenol cannot be considered a PBT/vPvB substance.

 

The reaction mass of phenol and 4,4’-isopropylidenediphenol is a multi constituent substance which consists of two main constituents (phenol and bisphenol A), and several impurities with decreasing prevalence.

Persistence, bioaccumulation and toxicity characteristics of the substance were assessed by examination of the properties of the constituents and impurities of the mixture.

 

Relevant constituents in reaction mass of phenol with 4,4'-isopropylidenediphenol (EC: 904-653-0).

Constituent / Impurity	CAS#	Typical wt%
Phenol	108-95-2	40-45%
4,4'-Isopropylidenediphenol (Bisphenol A)	80-05-7	20-40%
2,4'-Isopropylidenediphenol (o,p-Bisphenol A)	837-08-1	2-10%
3-(4-hydroxyphenyl)-1,1,3-trimethylindan-5-ol (Dihydroxyindane)	10527-11-4	5-12%
2,4-bis[1-(4-hydroxyphenyl)isopropyl]phenol (Trisphenol)	2300-15-4	2-5%
p-(3,4-dihydro-2,2,4-trimethyl-2H-1-benzopyran-4-yl)phenol (Dianin)	472-41-3	1-5%
Acetone, polymer with phenol	35238-34-7	2-6%

 

Persistence assessment

Biodegradation would be expected to be the dominant process affecting fate and lifetime of the substance and its constituents in water, soil, and sediment. The constituents, phenol and 4,4’-

isopropylidenediphenol (representing 60-85% of the composition) have been shown to meet criteria for classification as readily biodegradable. Phenol showed 62% biodegradation within 100 hours in the OECD 301C screening test. Extensive biodegradation (86-96%) was also noted for phenol in biochemical oxygen demand tests conducted with both freshwater and saltwater inocula. 4,4’-

Isopropylidenediphenol has also been shown to be extensively degraded in OECD 301F manometric respirometry tests. The extent of degradation ranged from 77 to 92.3% and 76 to 81% based on oxygen consumption and CO2 formation, respectively.

Biodegradation of the impurities of the substance was assessed using both QSAR estimation and experimental methods. Screening tests were conducted according to OECD 301F with a test material identified as acetone, condensation product with phenol. The test material, which is a suitable surrogate for impurities present in the reaction mass of phenol and 4,4’-isopropylidenediphenol,

showed 16% biodegradation after 28 days. Biodegradation may have been limited by availability of the impurities to the microorganisms.

QSAR model predictions of biodegradation potential were determined using the BIOWIN modules in the EPIWIN Suite (U.S. Environmental Protection Agency), a widely used computer estimation

program. A variety of phenolic compounds are included in the training set used to develop the biodegradation models. QSAR model predictions indicate the various minor constituents of the reaction mass are expected to biodegrade at varying rates, ranging from weeks to months, as summarized below:

 

Summary of measured and predicted biodegradability of the relevant constituents

Constituent	Ready test	BIOWIN 2 Probability	BIOWIN 3 Probability (Timeframe)	BIOWIN Prediction of Ready Biodegradability	Conclusion
Phenol	Yes	0.9876	3.0696 (weeks)	Yes	Not P
4,4'-Isopropylidenediphenol (Bisphenol A)	Yes	0.4653	2.5953 (weeks-months)	No	Not P
2,4'-Isopropylidenediphenol (o,p-Bisphenol A)	16% in 28 days Note that this result is far from showing ready biodegradation	0.4653	2.5953 (weeks-months)	No	Likely not P – analogy with BPA
3-(4-hydroxyphenyl)-1,1,3- trimethylindan-5-ol (Dihydroxyindane)		0.0808	2.2947 (weeks-months)	No	Potential P
2,4-bis[1-(4- hydroxyphenyl)isopropyl]phenol (Trisphenol)		0.0542	2.1431 (months)	No	Likely not P – analogy with BPA
p-(3,4-dihydro-2,2,4-trimethyl- 2H-1-benzopyran-4-yl)phenol (Dianin)		0.2513	2.1802 (months)	No	Potential P
Acetone, polymer with phenol					Not assessed, polymer

 

Comparison of the QSAR predictions for the various constituents versus the screening criteria outlined in REACH Guidance Document R.11 (ECHA, 2008) suggests some substances potentially meet the P criteria, while others do not. However, the reliability of the QSAR predictions needs to be taken into consideration, as QSAR predictions for bisphenol A do not indicate the substance will pass a ready test, while experimental data indicate otherwise. In view of the structural similarities between bisphenol A, o,p-bisphenol A, and trisphenol, all of these substances would be expected to be readily degradable.

QSAR predictions for the remaining impurities, i.e., dihydroxy-indane and dianin, show lower probability for biodegradation in BIOWIN 2 model (non-linear model), although rates predicted by

BIOWIN 3 are close to the criterion (2.2) for ultimate biodegradation. While these compounds exceed the screening criterion, in view of the structural similarity to bisphenol A, they are likely to be

ultimately biodegradable in the environment.

In view of the available information and the criteria summarized in Annex XIII, it is concluded that some of the impurities of the reaction mass of phenol and 4,4’-isopropylidenediphenol potentially meet

the criteria for persistence (P).

 

Bioaccumulation assessment

Measured bioconcentration factors (BCF) have been reported for the constituents of the reaction mass of phenol and 4,4’-isopropylidenediphenol. BCF values reported for fish for phenol and bisphenol A range from 1.2 to 67 indicating a low bioaccumulation potential. Thus, the major constituents do not meet the B criterion.

The bioconcentration potential for the impurities of the substance was assessed using both QSAR estimation and experimental methods. The log Kow was determined for a test material identified as

acetone, condensation product with phenol, in accordance with OECD guideline 107. The test material, which is a suitable surrogate for the impurities present in the reaction mass, showed a measured log Kow of > 3.24. According to screening criteria outlined in REACH Guidance Document R.11 (ECHA, 2008), substances are considered insufficient to meet the B criterion when the log Kow <4.5.

QSAR model predictions of bioconcentration potential were determined using the KOWWIN, BCFWIN and BCFBAF modules in the EPIWIN Suite (U.S. Environmental Protection Agency), a

widely used computer estimation program. A variety of phenolic compounds are included in the training set used to develop the bioconcentration models. Bioconcentration potentials for the various

constituents are summarized below:

 

Constituent	Measured Log Kow	Estimated Log Kow	BCF Measured	Estimated BCF BCFWIN Regression Method	Estimated BCF BCFBAF Arnot-Gobas Model	Conclusion
Phenol	1.46	1.51	1.2 – 2.3	4.269	2.419	Not B
4,4'-Isopropylidenediphenol (Bisphenol A)	3.32	3.64	5.1 – 67	72.03	172.7	Not B
2,4'-Isopropylidenediphenol (o,p-Bisphenol A)	3.24   Log Kow determined for surrogate test material (BPA Harz) according to OECD 107	3.64	NA	70.58	107.3	Likely not B – analogy with BPA
3-(4-hydroxyphenyl)-1,1,3- trimethylindan-5-ol (Dihydroxyindane)		4.95	NA	855.8	178.4	Likely not B
2,4-bis[1-(4- hydroxyphenyl)isopropyl]phenol (Trisphenol)		5.77	NA	1795	311.6	Likely not B – analogy with BPA
p-(3,4-dihydro-2,2,4-trimethyl- 2H-1-benzopyran-4-yl)phenol (Dianin)		4.96	NA	873.9	1838	Likely not B
Acetone, polymer with phenol						Not assessed, polymer

 

Although the predicted log Kow for some impurities exceeds the screening criterion (log Kow < 4.5), all of the impurities are structural analogs of phenol. Phenolic substances are known to be readily

metabolized in fish, resulting in formation of conjugates, which are rapidly excreted from the organism.

The fact that the conjugates are rapidly eliminated results in a lower bioconcentration potential than might be predicted based on log Kow.

QSAR estimates of bioconcentration potentials were determined using two different models developed by USEPA for predicting bioconcentration potential, namely the BCFWIN regression method, and the recently developed BCFBAF model of Arnot and Gobas, which incorporates consideration of metabolism in the organism. Estimated BCF values for the minor constituents ranged from 107 to

1838, indicating low to moderate bioconcentration potential. In view of the available information and the criteria summarized in Annex XIII, it is concluded that the reaction mass of phenol and 4,4’-isopropylidenediphenol does not meet the criteria for bioconcentration (B and vB).

 

Toxicity assessment:

Aquatic toxicity, in the form of both acute and chronic experimental results, have been reported for the constituents of the reaction mass of phenol and 4,4’-isopropylidenediphenol. In regard to

phenol, the lowest reported acute toxicity values for fish, invertebrates and algae are 8.9 mg/L, 3.1 mg/L, and 61.1 mg/L, respectively. The lowest reported NOEC for phenol among aquatic organisms

was 0.05 mg/L in a 21-day reproduction test withDaphnia magna. In regard to Bisphenol A, the lowest reported acute toxicity values for fish, invertebrates and algae were 4.6 mg/L, 1.1 mg/L, and 1.0

mg/L, respectively. The lowest reported NOEC for Bisphenol A among aquatic organisms was 0.016 mg/L in a multigenerational study with the fathead minnow (Pimephales promelas). For all three

trophic levels, the acute effect concentrations for both phenol and Bisphenol A are higher than the screening criterion of 0.1 mg/L. In addition, the chronic effect concentrations for fish, invertebrates

and algae are higher than the defined criterion of 0.01 mg/L.

The acute aquatic toxicity for the impurities of the substance was also assessed using experimental methods. The acute toxicity was determined for a test material identified as acetone, condensation

product with phenol, which is a suitable surrogate for minor constituents present in the reaction mass.

In regard to acetone, condensation product with phenol, the reported acute toxicity values for fish, invertebrates and algae are 4.95 mg/L, 8.27 mg/L, and >100 mg/L, respectively. The ErC10 for

acetone, condensation product with phenol was 10.3 mg/L in a 72-hour algal growth inhibition study withDesmodesmus subspicatus.For all three trophic levels, the acute effect concentrations for acetone, condensation product with phenol are higher than the screening criterion of 0.1 mg/L. In addition, the chronic effect concentration for algae is higher than the defined criterion of 0.01 mg/L.

Therefore, based on aquatic toxicity data alone, the constituents and impurities of the reaction mass of phenol with 4,4'-isopropylidenediphenol do not meet the criteria for toxicity (T).

Toxicity data from the mammalian data set indicate that the constituent phenol is classified as STOT RE2 (H373). Phenol is regarded as a somatic cell mutagen based on weak positive results in micronucleus tests that were found at dose levels inducing severe signs of intoxication (Cat 2 Mutagen).

Additionally, the constituent Bisphenol A is classified as Repr. 1B according to Annex VI of Regulation (EC) No 1272/2008. The effects of BPA on fertility and reproductive performance have been investigated in two-generation and multi-generation studies in the rat and a continuous breeding study in mice. Effects were seen in both species at approximately the same dose level and it is considered that the NOAEL of 50 mg/kg/day identified in the rat multi-generation study is also likely to produce no adverse effects in mice.

No mammalian toxicological data are available to evaluate the hazard profile of the impurities of the reaction mass of phenol with 4,4'-isopropylidenediphenol (i.e. o,p-Bisphenol A, Dihydroxyindane,

Trisphenol, Dianin, and Acetone, polymer with phenol). Due to the relatively high hazard posed by phenol, which drives strict exposure control measures, and the lower concentration of the impurities, it

is highly unlikely that the impurities would have a relevant impact on the human health hazard profile.

Based on the repeated dose toxicity of phenol and the reproductive toxicant classification for Bisphenol A, the reaction mass of phenol with 4,4’-isopropylidenediphenol meets the criteria for toxicity (T).

 

Summary of toxicity information for the constituents and impurities

 

Constituent	Acute Aquatic toxicity	Chronic Aquatic Toxicity	Carcinogenic	Mutagenic	Reproductive Toxicant	Evidence of Chronic Toxicity	Conclusion
Phenol	96-hr LC50fish = 8.9 mg/L 48-hr EC50invert = 3.1 mg/L 72-hr EyC50algae = 61.1 mg/L	Lowest NOEC value = 0.05 mg/L resulting from a 21-day daphnia reproduction test	Not carcinogenic	Mutagen category 2	Not a reproductive toxicant	STOT RE2 (H373)	T based on evidence of chronic toxicity
4,4'-Isopropylidenediphenol (Bisphenol A)	96-hr LC50fish = 4.6 mg/L 48-hr EC50invert = 1.1 mg/L 72-hr EyC50algae = 1 mg/L	Lowest NOEC value of 0.016 mg/L resulting from a 444-day study with the fathead minnow	Not carcinogenic	Not mutagenic	Reproductive toxicant Category 1B	No	T based on reproductive toxicant category
2,4'-Isopropylidenediphenol (o,p-Bisphenol A)	96-hr LC50fish = 4.95 mg/L 48-hr EC50invert = 8.27 mg/L 72-hr ErC50algae >100 mg/L determined for surrogate test material (BPA Harz)	ErC10 algae = 10.3 mg/L	No data	No data	No data	No data	Not T based on screening level criteria
3-(4-hydroxyphenyl)-1,1,3- trimethylindan-5-ol (Dihydroxyindane)
2,4-bis[1-(4- hydroxyphenyl)isopropyl]phenol (Trisphenol)
p-(3,4-dihydro-2,2,4-trimethyl- 2H-1-benzopyran-4-yl)phenol (Dianin)
Acetone, polymer with phenol