Registration Dossier

Administrative data

Description of key information

A read-across to data of the metabolic precursor substance 2-phenoxyethanol was performed, followed by correction of the starting point.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
376 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
Reliability 2.
System:
urinary
Organ:
bladder
kidney

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records
Reference
Endpoint:
sub-chronic toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Justification for type of information:
JUSTIFICATION FOR DATA WAIVING
According to column 2 of Annex IX "Testing by the inhalation route is appropriate if:
— exposure of humans via inhalation is likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size."
Toxic effects in humans by inhalation of the substance are unlikely because the substance has a very low vapour pressure and the exposure of humans will be low.
Investigations are available that report a rather complete absorption of the test item after oral administration to mammals, see the records WHO 2003 in Section 7.1.1. It is generally accepted that absorption after inhalation exposure is at least that after oral exposure.
Investigations are available that report no relevant metabolisation of the test item after oral absorption. It is therefore concluded that rather the same amount of the test item will be present and will be distributed in the body when the oral or the inhalation route is chosen. Therefore no difference in the systemic toxicity is expected if the oral or the inhalation route is chosen.
The test item is not classified as irritant to eyes. In the acute inhalation toxicity test, only dyspnoea during and shortly after the exposure period (which is likely a sign of discomfort of the rats sitting in the inhalation tubes), and no macroscopic lesions were observed with aerosols of the test item. Therefore no relevant indications were obtained that the test item might cause local lesions to the mucosa of the respiratory tract.
The NOEC for the inhalation route can therefore be derived from the NOELoral, as described in the Guidance Document on Information Requirements Chapter R.8.4.2.
It is considered that this approach is sufficient for a risk assessment.
An inhalation animal experiment is therefore considered not to be justified.
In the ECHA Guidance on Info Requirements Part 7.a of August 2014, p. 294 it is stated "Concerning repeated dose toxicity testing the oral route is the preferred one. However, dependent on the physico-chemical properties of a substance as well as on the most relevant route of human exposure, the dermal or the inhalation route could also be appropriate as specified in REACH Annex VIII and IX."

Dose descriptors for the oral route were derived by a read-across procedure described in Section 7.5.1. These dose descriptors can be used to correct the starting point to obtain dose descriptors for the inhalation route. A read-across approach for the oral route and afterwards to adjust the starting point seems to be more advisable than to read-across directly to an inhalation toxicity study with the source molecule. See Section 3.4 in the document "Analogue approach for sodium phenoxyacetate", attached to the record "Read-across target. 90 day toxicity" in Section 7.5.1.

Reason / purpose:
data waiving: supporting information
Reason / purpose:
data waiving: supporting information
Endpoint conclusion
System:
urinary

Repeated dose toxicity: dermal - systemic effects

Link to relevant study records
Reference
Endpoint:
sub-chronic toxicity: dermal
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Justification for type of information:
JUSTIFICATION FOR DATA WAIVING
According to column 2 of Annex IX "Testing by the dermal route is appropriate if: (1) skin contact in production and/or use is likely; and ...". The dermal contact to the substance in production is not likely.
A dermal repeated dose toxicity study is furthermore is not required because
1. the absorption after oral dosing is complete and the dermal absorption is therefore either lower or equal to the oral absorption. Only lower or equal internal doses can occur after dermal exposure compared to the same external dose applied orally.
2. The test item is largely not metabolised in the body and is excreted largely unchanged. No different behaviour will occur after dermal exposure.
3. Local effects are not expected for the substance as no skin irritation was observed.
No new information are therefore expected from a dermal experiment compared to the otherwise similar oral study.
A risk assessment do not need the results from the dermal toxicity study but can be performed with results of the study with oral dosing as a worst case.
In the ECHA Guidance on Info Requirements Part 7.a of August 2014, p. 294 it is stated "Concerning repeated dose toxicity testing the oral route is the preferred one. However, dependent on the physico-chemical properties of a substance as well as on the most relevant route of human exposure, the dermal or the inhalation route could also be appropriate as specified in REACH Annex VIII and IX."

Dose descriptors for the oral route were derived by a read-across procedure described in Section 7.5.1. A read-across approach for the oral route and afterwards to adjust the starting point seems to be more advisable than to read-across directly to a dermal toxicity study with the source molecule. See Section 3.3 in the document "Analogue approach for sodium phenoxyacetate", attached to the record "Read-across target. 90 day toxicity" in Section 7.5.1.
Reason / purpose:
data waiving: supporting information
Reason / purpose:
data waiving: supporting information

Additional information

Justification for classification or non-classification

Results are conclusive but not sufficient for classification.