Reaction mass of 4,4'-isopropylidenediphenol and phenol

Endpoint summary

Description of key information

The reaction mass of phenol and 4,4'-isopropylidenediphenol (BPA) contains phenol and BPA. The acute mammalian toxicity of this product is expected to be affected most by the presence of phenol.
PHENOL:
Phenol causes severe chemical burns. The local effects are concentration dependent; occasionally skin necrosis was seen in humans with solutions as dilute as 1%. The threshold concentration for local effects in experimental animals is not clearly stated. Irreversible corneal opacity was found in rabbits caused by 5% aqueous phenolic solution. Classification: Causes burns (R 34)
BPA:
The 2003 EU RAR on BPA concluded: 
"However, a recent well conducted animal study clearly shows that BPA is not a skin irritant. A recent well conducted animal study shows that BPA is an eye irritant; effects persisted until the end of the study (day 28 postinstillation) in 1 of 3 rabbits. Overall, taking into account the animal and human evidence, BPA has the potential to cause serious damage to the eyes. Slight and transient nasal tract epithelial damage was observed in rats exposed to BPA dust at 170 mg/m3 for 6 hours. Slight local inflammatory effects in the upper respiratory tract were observed in rats exposed to 50 mg/m3 and 150 mg/m3 of BPA in 2 and 13 week repeat inhalation studies, but were not observed at 10 mg/m3 in the same studies. Taken together with anecdotal human evidence, these data suggest BPA has a limited respiratory irritation potential." 
There is no significant new information on irritation/corrosion of BPA in the updated 2008 EU RAR or elsewhere.
Overall, data on phenol and BPA indicate that the reaction mass should be regarded to be corrosive to skin,  to cause serious damage to the eye and to have respiratory irritation potential .

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

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

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

positive indication of irritation

Remarks:

corrosive

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

positive indication of irritation

Remarks:

corrosive

Interpretation of results:

Category 1 (corrosive) based on GHS criteria

Conclusions:

No experimental data are available for the target substance Reaction mass of phenol and 4,4’-isopropylidenediphenol. However, based on the general principles of mixture toxicology, data on the main constituents of this multi-constituent substance are used as surrogate. Due to the corrosive properties of Phenol, the the target substance Reaction mass of phenol and 4,4’-isopropylidenediphenol is also considered to be corrosive.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

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

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

positive indication of irritation

Remarks:

irreversible effects

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

positive indication of irritation

Remarks:

irreversible effects

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

positive indication of irritation

Remarks:

irreversible effects

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

positive indication of irritation

Remarks:

irreversible effects

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

No experimental data are available for the target substance Reaction mass of phenol and 4,4’-isopropylidenediphenol. However, based on the general principles of mixture toxicology, data on the main constituents of this multi-constituent substance are used as surrogate. Phenol and BPA caused both irreversible effects to the eye. Therefore, also the target substance Reaction mass of phenol and 4,4’-isopropylidenediphenol is classified as Cat 1 (irreversible effects on the eye).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Additional information

No experimental data are available for the target substance Reaction mass of phenol and 4,4’-isopropylidenediphenol. However, based on the general principles of mixture toxicology, data on the main constituents of this multi-constituent substance are used as surrogate. A justification for read-across is attached to Iuclid section 13.

The mammalian toxicity of this product is mostly determined by the presence of phenol.

Data on PHENOL:

Data on irritation/corrosivity of phenol in experimental animals and humans are presented in EU-RAR (2006), Section 4.1.2.3-4 (page 86ff). The authors concluded that phenol causes severe chemical burns. 

SKIN IRRITATION/CORROSION

Mild to severe chemical burns were observed even after a 1-minute uncovered application of undiluted (molten) phenol in five male and five female rats (Brown et al., 1975). The contact of 0.5 g of phenol moistened with physiological saline with the intact and abraded areas of the skin of the bellies of rabbits for a maximum period of 24 hours produced necrosis of the intact skin (limited documentation; Flickinger, 1976). 

 

EYE IRRITATION

According to OECD Guideline 405 no testing is required for corrosive substances. However, the available data in non-contemporary studies confirmed the corrosive properties of phenol (Flickinger, 1976). Rabbits received instillations of 100 mg phenol into the conjuntival sac. Examination of the exposed eyes 24 hours following exposure showed severe conjunctivitis, iritis, corneal opacities occluding most of the iris, and corneal ulcerations extending over the entire corneal surface. There was almost no perceptible improvement in the condition of the eyes during the observation period, and by the 14th day all of the exposed eyes exhibited keratoconus and pannus formation. 

 

HUMAN DATA

Initial skin contact with phenol produces a white wrinkled discoloration with no experience of pain due to the local anaesthetic properties of phenol, with the affected area turning brown and subsequently becoming gangrenous. Ten percent solutions regularly produce corrosion, and occasionally skin necrosis is seen with solutions as dilute as 1% (Kania, 1981; IUCLID Section 7.10.3). Concentrated solutions are severely irritating to the eyes and cause conjunctival swelling with the cornea becoming white and hyperaesthetic; loss of vision has occurred in some cases. Concentration is more critical than volume with respect to local response (Kania, 1981; IUCLID Section 7.10.3).

 

Data on BPA:

The 2003 EU RAR concluded: "Limited human anecdotal information of uncertain reliability is available from written industry correspondence suggesting that workers handling BPA have in the past experienced skin, eye and respiratory tract irritation. It cannot be determined whether the reported skin reactions were related to skin sensitisation or irritation. However, a recent well conducted animal study clearly shows that BPA is not a skin irritant. A recent well conducted animal study shows that BPA is an eye irritant; effects persisted until the end of the study (day 28 postinstillation) in 1 of 3 rabbits. Overall, taking into account the animal and human evidence, BPA has the potential to cause serious damage to the eyes. Slight and transient nasal tract epithelial damage was observed in rats exposed to BPA dust at 170 mg/m³for 6 hours. Slight local inflammatory effects in the upper respiratory tract were observed in rats exposed to 50 mg/m³and 150 mg/m³of BPA in 2 and 13 week repeat inhalation studies, but were not observed at 10 mg/m³in the same studies. Taken together with anecdotal human evidence, these data suggest BPA has a limited respiratory irritation potential."

There is no significant new information on irritation/corrosion of Bisphenol A in the updated 2008 EU RAR or elsewhere.

Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: corrosive

Effects on respiratory irritation: irritating

Justification for classification or non-classification

The constituent phenol is corrosive to skin and causes severe damage to the eye. The constituent BPA causes severe damage to the eye and respiratory irritation. Therefore, the reaction mass will be classified with: Skin Corr. 1A, Eye Damage 1 and STOT SE 3 (H335 : May cause respiratory irritation) according to CLP.