Reaction mass of 4,4'-Isopropylidenediphenol, oligomeric reaction products with 1-chloro-2,3-epoxypropane and Orthophosphoric acid, oligomeric reaction products with 4,4'-isopropylidenediphenol -1-chloro-2,3-epoxypropane co-oligomer

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Link to relevant study records

Reference

Reference 1

Endpoint:

in vitro gene mutation study in bacteria

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
[Please provide information for all of the points below. Indicate if further information is included as attachment to the same record, or elsewhere in the dataset (insert links in 'Cross-reference' table)]

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
[Describe why the read-across can be performed (e.g. common functional group(s), common precursor(s)/breakdown product(s) or common mechanism(s) of action]

The read-across target substance EP-49-10P2 is composed of a mixture of phosphate esters with bisphenol A diglycidylether (BADGE, CAS 1675-54-3, EC 216-823-5) that is dissolved in BADGE. The amount of esters in the target substance EP-49-10P2 ranges between 10% and 20%; the large rest is BADGE. Therefore, BADGE can be used as read-across source substance.

Based on the high content of BADGE (80-90%) and on the fact that the phosphate esters have higher molecular weights (MW > 1200 Da – approx. 3500 Da) and accordingly lower bioavailability it is concluded that the toxic and eco-toxic potential of EP-49-10P2 will be the same as that of BADGE. With the phosphate esters no hazardous functional groups are introduced.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
[Provide here, if relevant, additional information to that included in the Test material section of the source and target records]

3. ANALOGUE APPROACH JUSTIFICATION
[Summarise here based on available experimental data how these results verify that the read-across is justified]

No experimental data from toxicological or eco-toxicological studies with the target substance EP-49-10P2 are available for comparison of effects. However, based on the composition of EP-49-10P2 it is considered justified to make read-across from study results obtained with the read-across source substance BADGE in order to fulfil the information requirements for REACH registration of EP-49-10P2.

Reason / purpose for cross-reference:

read-across source

Key result

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Key result

Species / strain:

E. coli WP2 uvr A pKM 101

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Reference 2

Endpoint:

in vitro gene mutation study in mammalian cells

Type of information:

other:

Adequacy of study:

supporting study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
[Please provide information for all of the points below. Indicate if further information is included as attachment to the same record, or elsewhere in the dataset (insert links in 'Cross-reference' table)]

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
[Describe why the read-across can be performed (e.g. common functional group(s), common precursor(s)/breakdown product(s) or common mechanism(s) of action]

The read-across target substance EP-49-10P2 is composed of a mixture of phosphate esters with bisphenol A diglycidylether (BADGE, CAS 1675-54-3, EC 216-823-5) that is dissolved in BADGE. The amount of esters in the target substance EP-49-10P2 ranges between 10% and 20%; the large rest is BADGE. Therefore, BADGE can be used as read-across source substance.

Based on the high content of BADGE (80-90%) and on the fact that the phosphate esters have higher molecular weights (MW > 1200 Da – approx. 3500 Da) and accordingly lower bioavailability it is concluded that the toxic and eco-toxic potential of EP-49-10P2 will be the same as that of BADGE. With the phosphate esters no hazardous functional groups are introduced.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
[Provide here, if relevant, additional information to that included in the Test material section of the source and target records]

3. ANALOGUE APPROACH JUSTIFICATION
[Summarise here based on available experimental data how these results verify that the read-across is justified]

No experimental data from toxicological or eco-toxicological studies with the target substance EP-49-10P2 are available for comparison of effects. However, based on the composition of EP-49-10P2 it is considered justified to make read-across from study results obtained with the read-across source substance BADGE in order to fulfil the information requirements for REACH registration of EP-49-10P2.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)

Key result

Species / strain:

mouse lymphoma L5178Y cells

Metabolic activation:

with

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Key result

Species / strain:

mouse lymphoma L5178Y cells

Metabolic activation:

without

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Conclusions:

Based on the positive result of this in vitro gene mutation test in mammalian cells it will be necessary to perform an in vivo test. This test currently is being performed upon a decision from ECHA (see information in 7.6.2 "Genetic toxicity in vivo").

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (positive)

Genetic toxicity in vivo

Endpoint conclusion

Endpoint conclusion:

no study available (further information necessary)

Justification for classification or non-classification

In the in vitro test for gene mutation in mammalian cells genetic toxicity was observed in the absence of S-9 mix. Performance of an in vivo study is ongoing upon a decision of ECHA. Therefore, currently no classification is made.