2,2'-p-phenylenedioxydiethanol

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

HQEE was considered to be non-mutagenic to bacteria and to mouse lymphoma cells in vitro.

Link to relevant study records

Reference

Reference 1

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Species / strain / cell type:

E. coli WP2 uvr A

Metabolic activation:

with and without

Metabolic activation system:

S9 from the livers of male Fischer rats induced with Arochlor 1254

Test concentrations with justification for top dose:

17, 50, 167, 500, 1667 and 5000 ug/plate

Vehicle / solvent:

DMSO

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

9-aminoacridine

2-nitrofluorene

sodium azide

N-ethyl-N-nitro-N-nitrosoguanidine

other: 2-aminoanthracene

Details on test system and experimental conditions:

The study used both plate incorporation and pre-incubation protocols.

Species / strain:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Positive controls validity:

valid

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Conclusions:

Interpretation of results (migrated information): negative

HQEE was considered to be non-mutagenic to bacteria in vitro.

Reference 2

Endpoint:

in vitro gene mutation study in mammalian cells

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

Type of assay:

mammalian cell gene mutation assay

Species / strain / cell type:

mouse lymphoma L5178Y cells

Metabolic activation:

with and without

Metabolic activation system:

Liver S9 from Aroclor 1254 induced rats

Test concentrations with justification for top dose:

0, 1000, 1250, 1500, 1750, 1984 µg/mL.

Vehicle / solvent:

Sterile distilled water

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

7,12-dimethylbenzanthracene

methylmethanesulfonate

Evaluation criteria:

A result was considered positive if a concentration-related increase in induced mutant frequency was observed in the treated cultures and one or more treatment conditions with 10% or greater total growth exhibited induced mutant frequencies of >= 90 mutants per million clonable cells (based on the average mutant frequency of duplicate cultures). If the average solvent control mutant frequency was >90 mutants per million clonable cells, a doubling of mutant frequency over the background will also be required.
A result was considered negative if the treated cultures exhibited induced mutant frequencies of less than 90 mutants per million clonable cells (based on the average mutant frequency of duplicate cultures) and there was no concentration-related increase in mutant frequency.

Species / strain:

mouse lymphoma L5178Y cells

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Conclusions:

Interpretation of results (migrated information):
negative

HQEE was considered to be non-mutagenic to mouse lymphoma cells in vitro.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

HQEE was considered to be non-mutagenic in an vivo micronucleus assay.

Link to relevant study records

Reference

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

GLP compliance:

yes

Type of assay:

micronucleus assay

Species:

mouse

Strain:

CD-1

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

0.5% CMC

Duration of treatment / exposure:

Oral gavage dose

Frequency of treatment:

Twice, at 0 and 24 hours

Post exposure period:

24 hours after second dose

Remarks:

Doses / Concentrations:
2000 mg/kg
Basis:
actual ingested

No. of animals per sex per dose:

10 males and 10 females

Control animals:

yes, concurrent vehicle

Positive control(s):

50 mg/kg Cyclophosphamide

Tissues and cell types examined:

Bone marrow from one femur

Sex:

male/female

Genotoxicity:

negative

Toxicity:

no effects

Vehicle controls validity:

valid

Positive controls validity:

valid

No deaths or adverse reactions were observed following dosing.

Conclusions:

Interpretation of results: negative
HQEE was considered to be non-mutagenic in an vivo micronucleus assay.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Mode of Action Analysis / Human Relevance Framework

Not applicable

Additional information

The substance gave a negative results in an in vitro bacterial mutation assay and an in vitro gene mutation assay. It also gave negative results in an in vivo micronucleus assay. The requirement for an in vitro cytogenetics assay was waived on the basis that the results of an in vivo study were already available.

Short description of key information: the substance was negative in two in vitro genotoxicity assays and an in vivo genotoxicity assay.

Endpoint conclusion: No adverse effects obersved (negative).

Justification for classification or non-classification

The substance gave negative results in two in vitro gentoxicity assays and and in vivo assay. Therefore there is no requirement for classification.