Registration Dossier

Administrative data

Description of key information

Acute oral toxicity (read across from Etaphen, which is tested in an OECD TG 401): LD50 = 1609.3 mg/kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The information is derived from read across
Justification for type of information:
Executive Summary: The acute oral toxicity of Peomosa is assessed by using read across from Etaphen resulting in an LD50 for Peomosa of 1603.9 mg/kg bw. Full details are provided in the attached file in the study record. Structural similarities and differences: The target and the source chemicals, have a similar backbone and functional group consisting of phenylethanol, and differ in an additional methyl group at the ortho position of the phenyl ring present in the target. These differences between the target and source chemicals are not expected to influence their acute oral toxicity. Toxico-kinetic: The source chemicals and the target chemicals indicate similar toxico-kinetic characteristics based on the similarity in chemical structure and physico-chemical properties: Mw, appearance, VP, WS and log Kow. The metabolism processes are similar. Etaphen will be metabolised into a carboxylic acid (phenylacetic acid or benzoic acid) that will be subsequently excreted to the urine after phase 2 conjugation. Peomosa will be metabolised analogously to Etaphen (yielding the corresponding ortho-methyl analogues), and there are no significant differences in rates to be expected. Toxico-dynamic: Peomosa and Etaphen have similar reactivity because both have the alcohol as their functional group. Uncertainty of the prediction: There are no remaining uncertainties, because of the reasons presented above.
Reason / purpose:
read-across source
Related information:
Composition 1
Test material information:
Composition 1
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 609.3 mg/kg bw
Based on:
test mat.
95% CL:
>= 1 399.6 - <= 1 850.4
Sex:
male
Dose descriptor:
LD50
Effect level:
1 692.6 mg/kg bw
Based on:
test mat.
95% CL:
>= 1 433.3 - <= 1 998.9
Clinical signs:
S
Interpretation of results:
other: Category 4
Remarks:
According to EU CLP 1272/2008 and its amendments.
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2 December 1982 - 21 December 1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Remarks:
Reliability 2 is assigned because the study was used for read-across.
Reference:
Composition 1
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Test material information:
Composition 1
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Blue Spruce Farms, Altamont, New York
- Age at study initiation: No data
- Weight at study initiation: 180-280 grams (after fasting)
- Fasting period before study: 18 hours
- Housing: Individually in stainless steel wire mesh cages
- Diet (e.g. ad libitum): Ad libitum (Wayne Lab Blox)
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30-70
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
methylcellulose
Remarks:
0.25% concentration
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 0.2, 0.32, 0.4, 0.5 and 0.64 g/ml

MAXIMUM DOSE VOLUME APPLIED: 5 ml/kg
Doses:
1000, 1600, 2000, 2500, 3200 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days.
- Frequency of observations: 1 hour, 4 and 24 hours and twice daily.
- Necropsy of survivors performed: Yes.
- Other examinations performed: clinical signs (pharmacotoxic, CNS effects and mortality), body weights (after fasting and on the 14th day of the observation period).
Statistics:
LD50 was determined with the method of Litchfield and Wilcoxon.
Preliminary study:
None of the rats died at 500 mg/kg bw, one rat died at 1600 mg/kg bw and all rats died at 5000 mg/kg bw. Clinical signs observed were body drop, ptosis, diarrhea, decreased activity, decreased body tone, poor grooming, abnormal stance, hypersensitivity, piloerection, chromodacryorrhea and prostration.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 609.3 mg/kg bw
Based on:
test mat.
95% CL:
>= 1 399.6 - <= 1 850.4
Mortality:
- 1000 mg/kg bw: no mortality
- 1600 mg/kg bw: 5/10 animals died
- 2000 mg/kg bw: 9/10 animals died
- 2500 and 3200 mg/kg bw: 10/10 animals died
Clinical signs:
Semi-prostration, abnormal gait, body drop, exophthalmus, decreased activity, dyspnea, tremors, ataxia, ptosis, diarrhea, decreased body tone, hypersensitivity, hyperactivity and chromodacryorrhea.
Body weight:
No treatment related changes were recorded during the study period.
Gross pathology:
Distended stomachs with hemorrhages present on the mucosa, distended bladders, red foci on the thymus and discolored adrenals. In the surviving animals no visible lessions were observed via terminal necropsy.

An acute oral LD50 for females was not calculated as the data generated were not suitable to be analysed with the statistical method chosen.

Interpretation of results:
other: Category 4
Remarks:
According to EU CLP 1272/2008 and its amendments.
Conclusions:
Under the conditons of this study, the acute oral LD50 in male and female rats was determined to be 1609.3 mg/kg bw for Etaphen. Based on these results, the substance needs to be classified as Acute Tox. Category 4 in accordance with the criteria outlined in Annex I of CLP (1272/2008/EC) and its amendments.
Executive summary:

In this study, 5 groups of 10 rats (5 males and 5 females) were administered Etaphen at dose levels of 1000, 1600, 2000, 2500 and 3200 mg/kg bw. Animals were observed for 14 days. None of the 10 test animals died at 1000 mg/kg, 5 out of 10 died at 1600 mg/kg, 9 out of 10 died at 2000 mg/kg, and all rats died at the 2500 and 3200 mg/kg levels. Observed clinical signs included body drop, prostration, exophthalmus, decreased activity, semi-prostration, abnormal gait, dyspnea, tremors, ataxia, ptosis, diarrhea, decreased body tone, hypersensitivity, hyperactivity and chromodacryorrhea. The acute oral LD50 for the substance in male and female rats was determined to be 1609.3 mg/kg bw with a 95% CI of 1399.6 to 1850.4 mg/kg bw and is considered harmful.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
1 609.3 mg/kg bw
Quality of whole database:
The selected study is the key study for this endpoint.

Additional information

The acute oral toxicity is based on read across to Etaphen. First the study with the analogue is described and thereafter the read across justification is presented.

Acute oral toxicity with Etaphen:

In the key study, 5 groups of 10 rats (5 males and 5 females) were administered Etaphen at dose levels of 1000, 1600, 2000, 2500 and 3200 mg/kg bw. The results are used for read-across to Peomosa. Animals were observed for 14 days. None of the 10 test animals died at 1000 mg/kg, 5 out of 10 died at 1600 mg/kg, 9 out of 10 died at 2000 mg/kg, and all rats died at the 2500 and 3200 mg/kg levels. Observed clinical signs included body drop, prostration, exophthalmus, decreased activity, semi-prostration, abnormal gait, dyspnea, tremors, ataxia, ptosis, diarrhea, decreased body tone, hypersensitivity, hyperactivity and chromodacryorrhea. The acute oral LD50 for the substance in male and female rats was determined to be 1609.3 mg/kg bw with a 95% CI of 1399.6 to 1850.4 mg/kg bw and is considered harmful.

Read-across justification -The acute oral toxicity of Peomosa using read across from Etaphen

Introduction and hypothesis for the analogue approach

Peomosa is a primary alcohol, specifically a phenylethanol. For this substance no acute oral toxicity data are available.

In accordance with Article 13 of REACH, lacking information should be generated whenever possible by means other than vertebrate animal tests, i. e. applying alternative methods such as in vitro tests, QSARs, grouping and read-across. For assessing the acute oral toxicity of Peomosa the analogue approach is selected because for one closely related analogue the acute oral toxicity information is available which can be used for read across.

Hypothesis:Peomosa has similar acute oral toxicity compared to Etaphen resulting in a similar LD50 of 1609 mg/kg bw because the methyl group present in the ortho position of the phenyl ring in Peomosa does not affect the organ toxicity and the LD50.

Available information:The source substance Etaphen has been tested in a well conducted acute oral toxicity test (method similar to OECD TG 401 under GLP) with an LD50 of 1609 mg/kg bw and the test result receives a reliability of 2.

Target chemical and source chemical(s)

Chemical structures of the target and the source chemicals are shown in Appendix 1, including physico-chemical properties and toxicological information, thought relevant for acute oral toxicity, of all substances.

Purity / Impurities

The purity and impurities of the target chemical do not indicate acute oral toxicity potential other than indicated by the parent substance. The impurities are all below < 10%.

Analogue approach justification

According to Annex XI 1.5 read across can be used to replace testing when the similarity can be based on a common backbone and a common functional group. When using read across the result derived should be applicable for C&L and/or risk assessment and it should be presented with adequate and reliable documentation.

Analogue selection:According to ECHA guidance (RAAF, 2015) a clear documentation is needed on the selection of potential source substances. In accordance with ECHA Guidance (2015, RAAF), Etaphen was selected being the closest analogue for which acute oral toxicity information was available. Etaphenwas selected based on structural similarity and the presence of useful data for read-across, out of all analogues identified in the OECD QSAR toolbox and analogues identified in the RIFM database.

Structural similarities and differences:The target and the source chemicals, have a similar backbone and functional group consisting of phenylethanol, and differ in an additional methyl group at the ortho position of the phenyl ring present in the target. These differences between the target and source chemicals are not expected to influence their acute oral toxicity.

Toxico-kinetic:The source chemicals and the target chemicals indicate similar toxico-kinetic characteristics based on the similarity in chemical structure and physico-chemical properties: Mw, appearance, VP, WS and log Kow. The metabolism processes are similar. Etaphen will be metabolised into a carboxylic acid (phenylacetic acid or benzoic acid) that will be subsequently excreted to the urine after phase 2 conjugation. Peomosa will be metabolised analogously to Etaphen (yielding the corresponding ortho-methyl analogues), and there are no significant differences in rates to be expected.

Toxico-dynamic:Peomosa and Etaphen have similar reactivity because both have the alcohol as their functional group.

Uncertainty of the prediction:There are no remaining uncertainties, because of the reasons presented above. Therefore, in the ECHA guidance (RAAF, 2015) terminology it receives a score of 5 (acceptable with high confidence), because the rationale for the selection of the analogues is clearly documented and there is supporting evidence provided).

Data matrix

The relevant information on physico-chemical properties and toxicological characteristics are presented in the Data Matrix below.

 Conclusions per endpoint for C&L

When using read across the result derived should be applicable for C&L and/or risk assessment, cover an exposure period duration comparable or longer than the corresponding method and be presented with adequate and reliable documentation. For Etaphen a well conducted acute oral toxicity test is available (Reliability 2) with an LD50 of 1609 mg/kg bw which leads to classification for this endpoint as Acute Tox. 4. Based on these data for Peomosa also an LD50 of 1609 mg/kg bw can be derived for the acute oral toxicity endpoint.

Final conclusion on hazard and C&L: Peomosa has an LD50 of 1609 mg/kg bw. Classification and labeling for this endpoint is assigned as Acute Tox. 4 according to CLP Regulation (EC) No. 1272/2008 and its updates.

 

Data matrix with information on Peomosa and analogues important for assessment of acute oral toxicity properties.

Common names

Peomosa

Etaphen

CAS number

19819-98-8

60-12-8

Chemical structure

Empirical formula

C9H12O

C8H10O

Molecular weight

136.94

122.17

Physicochemical properties

 

 

Physical state

Liquid

Liquid

Vapour pressure (Pa)

1.9(measured)

3.24(EpiSuite)

Water solubility (mg/l)

12339(measured)

21990(EpiSuite)

Log Kow

2.1(measured)

1.6(EpiSuite)

Human health

 

 

Acute oral tox

Read across to Etaphen

LD50 = 1609 mg/kg bw

 

Justification for classification or non-classification

Based on the LD50 of 1609.3 mg/kg bw as determined in the key study, the substance should be classified as Acute Tox. Category 4 in accordance with the criteria outlined in Annex I of the CLP Regulation (1272/2008/EC) and its amendments.