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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
The study was conducted between 7 December 1994 and 27 December 1994
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
The present information is used for read across to Muguesia.
Cross-reference
Reason / purpose:
read-across: supporting information
Reference
Muguesia, acute oral toxicity > 2000 mg/kg bw based on read across from Vetikon (OECD TG 401). 
Study name / type:
Composition 1
Composition 2
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The acute oral toxicity result is of sufficient quality and adequate for this dossier.

First the summary of the acute oral toxicity study of Vetikon is presented and thereafter the justification of the read across to Muguesia.

Vetikon LD50 study

In this study, 10 rats (5 males and 5 females) were administered Vetikon at a single dose level of 2000 mg/kg bw by oral gavage. The study was performed according to OECD guideline 401. A preliminary study was conducted with 2 female rats for range finding; in this study there were no deaths recorded. During the main study there were also no mortalities recorded.Clinical signs were observed up to 24 hours after administration. These effects included abnormal gait, squatting position, reduced activity, piloerection and decreased respiratory rate. No body weight or gross pathology abnormalities were detected.The acute oral LD50 for Vetikon in male and female rats was determined to be >2000 mg/kg bw.

The acute oral toxicity of Muguesia using read across from Vetikon

 

Executive summary:

Muguesia has similar acute oral toxicity compared to Vetikon, resulting in a similar LD50 > 2000 mg/kg bw. This is because the substances are sufficiently similar including their degradation products. Structural similarities and differences:The target and the source chemicals have a phenyl-butyl backbone. The differences between the two are: 1) that Muguesia contains a secondary alcohol and Vetikon has a ketone group in the butyl chain; 2) Muguesia has one carbon at the next carbon from the phenyl –ring while Vetikon has two carbons on the same spot.

Toxico-kinetic: Oral absorption:Muguesia and Vetikon have similar absorption characteristics based on the similarity in chemical structure and physico-chemical properties: MW, appearance, VP, WS and log Know. The metabolism processes are similar. Muguesia can be reduced to a ketone and Vetikon can be oxidised to a secondary alcohol during Phase 1 metabolism after which they can be become conjugated and excreted via the urine.

Toxico-dynamics:the substances are expected to be similarly non-reactive based on their functional groups. In view of the alcohol being interchangeable with the ketone group no difference in reactivity is expected.

Similarities in results for toxicological endpoints between the target and the source chemical(s):The non-reactivity is supported with absence of skin irritation and skin sensitization potential of both substances. They are also both negative in the Ames test.Uncertainty of the prediction:The read across is certain based on the reasoning above considering all aspects of acute oral toxicity.

 

The acute oral toxicity of Muguesia using read across from Vetikon

Introduction

Muguesia consists of an aromatic ring to which a butyl chain is attached, with a methyl group on the second spot and a (secondary) alcohol on the third spot. 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 Muguesia the analogue approach is selected because for one closely related analogue reproductive toxicity information is available which can be used for read across.

Hypothesis: Muguesia has similar acute oral toxicity compared to Vetikon, resulting in a similar LD50 of > 2000 mg/kg bw, This is because the substances are sufficiently similar including their degradation products.  

Available information: The source chemical Vetikon has been tested in a well conducted acute oral toxicity test (method similar to OECD TG 401 under GLP) up to 2000 mg/kg bw and the test result receives a reliability of 1.

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, 2017) a clear documentation is needed on the selection of potential source substances. Vetikon being a ketone was considered a better analogue compared to primary alcohols because the secondary alcohol of Muguesia can be converted to a ketone, while a primary alcohol can be converted to an acid which is not possible for a secondary alcohol.

Structural similarities and differences:The target and the source chemicals have a phenyl-butyl backbone. The differences between the two are: 1) that Muguesia contains a secondary alcohol and Vetikon has a ketone group in the butyl chain; 2) Muguesia has one carbon at the next carbon from the phenyl –ring while Vetikon has two carbons on the same spot.

Toxico-kinetic: Oral absorption:Muguesia and Vetikon have similar absorption characteristics based on the similarity in chemical structure and physico-chemical properties: MW, appearance, VP, WS and log Know. The metabolism processes are similar. Muguesia can be reduced to a ketone and Vetikon can be oxidised to a secondary alcohol during Phase 1 metabolism after which they can be become conjugated and excreted via the urine

Toxico-dynamics:the substances are expected to be similarly non-reactive based on their functional groups. In view of the alcohol being interchangeable with the ketone group no difference in reactivity is expected.

Similarities in results for toxicological endpoints between the target and the source chemical(s):The non-reactivity is supported with absence of skin irritation and skin sensitization potential of both substances. They are also both negative in the Ames test.

Uncertainty of the prediction:The read across is certain based on the reasoning above considering all aspects of acute oral toxicity. In accordance with ECHA guidance (2017, RAAF) the quality score assigned can be 5(acceptable with high confidence).

Data matrix

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

Conclusions per endpoint for hazard and 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 Vetikon a well conducted acute oral toxicity test is available (Reliability 1) with a LD50 of > 2000 mg/kg bw which leads to absence of classification for this endpoint, Therefore also Muguesia has an LD50 of > 2000 mg/kg bw.

Final conclusion on hazard and C&L: Muguesia has a LD50 of > 2000 mg/kg bw and therefore does not need to be classified for acute oral toxicity in accordance with the CLP Regulation (1272/2008/EC and its amendment).

Data matrix with information on Muguesia and Vetikon important for the assessment of acute oral toxicity properties.

Common names

Muguesia

Vetikon

CAS number

56836-93-2

7403-42-1

Chemical structures

Empirical formula

C11H16O

C12H18O

Molecular weight

164.25

176

Physico-chemical properties

 

 

Physical state

Liquid

Liquid

Vapour pressure (Pa)

1.1 (IFF, 2015)

3.7 (EpiWIN)

Water solubility (mg/l)

3300 (IFF, 2015)

179-217 (EpiWIN)

Log Kow

2.89 (EPIWIN) ; 3.1 (IFF, 2015)

2.84 (EPIWIN)

Human health

 

 

Acute oral tox in mg/kg bw

Read across to Vetikon

LD50 > 2000 mg/kg

Skin irritation

Not irritating

Not Irritating

(OECD TG 404, RIFM database)

Eye irritation

Irritating

No information available

Skin sensitisation

Not sensitising

Not sensitising

(OECD TG 406; RIFM database)

 

Based on the LD50 of > 2000 mg/kg bw Muguesia does not need to be classified for acute oral toxicity with the criteria outlined in EU-CLP Regulation (1272/2008/EC and its amendments).

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1994
Report Date:
1995

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
February 24, 1987
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Version / remarks:
July 31, 1992
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
other: Hsd/Win: WU
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Fa. Harlan Winkelmann GmbH
- Age at study initiation: no information available
- Weight at study initiation: males: 201-237 g, females: 177-203 g
- Fasting period before study: ~16 h
- Housing: collective housing up to a maximum of 5 animals per cage (Makrolon type III)
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ±3
- Humidity (%): 30-70
- Air changes (per hr): no information available
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 2.02 mL/kg (for 2000 mg/kg bw dose)
Doses:
2000 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: The animals were observed 10 minutes, 1, 2 and 6 hours after application and thereafter daily
- Necropsy of survivors performed: yes, at the end of the observation period the animals were killed by CO2 asphyxiation, necropsied and subjected to examination for gross pathological changes.
- Body weights: Individual body weights were recorded immediately before treatment (day 1) and then on the 7th and 14th day of the observation period.

Results and discussion

Preliminary study:
None of the animals died in the preliminary study.
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No animals died during the course of the main study.
Clinical signs:
In some animals abnormal clinical signs were observed up to 24 hours after administration of the test substance. These signs included abnormal gait, squatting position, reduced activity, piloerection and decreased respiratory rate.
Body weight:
No treatment related changes were recorded in the body weights of the animals during the study period.
Gross pathology:
No abnormalities observed.

Applicant's summary and conclusion

Interpretation of results:
other: not classified for actute oral toxicity
Remarks:
Based on CLP criteria (EC 1272/2008 and its amendments)
Conclusions:
The acute oral LD50 for Vetikon in male and female rats was determined to be >2000 mg/kg bw. Based on this result, the test material does not need to be classified for acute oral toxicity.
Executive summary:

In this study, 10 rats (5 males and 5 females) were administered Vetikon at a single dose level of 2000 mg/kg bw by oral gavage. The study was performed according to OECD guideline 401. A preliminary study was conducted with 2 female rats for range finding; in this study there were no deaths recorded. During the main study there were also no mortalities recorded. Clinical signs were observed up to 24 hours after administration. These effects included abnormal gait, squatting position, reduced activity, piloerection and decreased respiratory rate. No body weight or gross pathology abnormalities were detected. The acute oral LD50 for Vetikon in male and female rats was determined to be >2000 mg/kg bw. Based on this result, Vetikon does not need to be classified for acute oral toxicity.