3-ETHYL-5,5-DIMETHYL-GAMMA BUTYROLACTONE

Endpoint summary

Description of key information

Oral LD50 > 2000 mg/kg bw and the LD50 cut-off  is 2500 mg/kg bw (OECD 423, K, Rel.1, class method in rats)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Between 10 and 25 June 2008.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP study conducted in compliance with OECD Guideline No. 423 without any deviation.

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

17 December 2001

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

Directive N° 2004/73/EC

Deviations:

no

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

Inspected on 2007-01-11 / Signed on 2007-02-21

Test type:

acute toxic class method

Limit test:

yes

Specific details on test material used for the study:

- Date received: 02 June 2008
- The test item was considered as 100% of the study

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage JANVIER (53940 Le Genest St Isle, France)
- Age at study initiation: 8 - 9 weeks.
- Weight at study initiation: 184 - 221 g
- Housing: housed by group of three in solid-bottomed clear polycarbonate cages with a stainless steel mesh lid.
- Diet: foodstuff, ad libitum but food was removed at D-1 and then redistributed 4 hours after the test item administration.
- Water: tap-water from public distribution, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-23 °C
- Humidity: 41-70%
- Air changes: at least ten changes per hour
- Photoperiod: 12 h dark / 12 h light

IN-LIFE DATES: from 10 To 25 June, 2008.

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 2.13 mL/kg bw

ADMINISTRATION OF TEST ITEM:
Animals received an effective dose of 2000 mg/kg bw of the test item, administered by gavage under a volume of 2.13 mL/kg bw using a suitable syringe graduated fitted with an oesophageal metal canula.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed 30 min, 1, 3 and 4 hours after test item administration and thereafter once daily for 14 days. Animals were weighed pretest (Day 0) and on Day 2, 7 and 14.
- Necropsy of survivors performed: Yes; Animals were killed on Day 14 and subjected to macroscopic examination.

Statistics:

None

Preliminary study:

Not applicable

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: It was noted the death of 1 treated rat, 6 hours after the test item administration.

Key result

Sex:

female

Dose descriptor:

LD50 cut-off

Effect level:

2 500 mg/kg bw

Based on:

test mat.

Mortality:

It was noted the death of 1 treated rat, 6 hours after the test item administration.

Clinical signs:

other: A decrease of the spontaneous activity (6/6) associated with a myosis (3/6), a decrease of Preyer's reflex (6/6), muscle tone (3/6) and righting reflex (6/6) was registered in the treated animals, during the 1st day of the test. The animals recovered a no

Gross pathology:

The macroscopical examination of the animal which died during the study revealed a thinning of the forestomach.
The macroscopical examination of the animals at the end of the study did not reveal treatment-related changes.

Other findings:

None

None

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

Under the test conditions, the oral LD50 for test substance is higher than 2000 mg/kg bw and the LD50 cut-off is 2500 mg/kg bw in female rats. Therefore the test substance is not classified according to the criteria of the Annex I of the Regulation (EC) No. 1272/2008 (CLP) and classified in category 5 (H303) according to the GHS.

Executive summary:

In an acute oral toxicity study (limit test) performed according to OECD Guideline 423 and in compliance with GLP, 6 female Sprague Dawley rats were given a single oral (gavage) dose of test item at 2000 mg/kg bw. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and were all sacrificed for macroscopic examination.

 

It was noted the death of 1 treated rat, 6 hours after the test item administration.A decrease of the spontaneous activity (6/6) associated with myosis (3/6), a decreased of Preyer’s reflex (6/6), muscle tone (3/6) and righting reflex (6/6) was registered in the treated animals, during the first day of the test. The animals recovered a normal activity the 2 nd day of the test.The body weight evolution of the animals remained normal throughout the study.The macroscopical examination of the animal which died during the study revealed a thinning of the corpus and the forestomach.The macroscopical examination of the animals at the end of the study did not reveal treatment-related changes

Under the test conditions, the oral LD50 for test substance is higher than 2000 mg/kg bw and the LD50 cut-off is 2500 mg/kg bw in female rats. Therefore the test substance is not classified according to the criteria of the Annex I of the Regulation (EC) No. 1272/2008 (CLP) and classified in category 5 (H303) according to the GHS.

This study is considered as acceptable and satisfies the requirement for acute oral toxicity endpoint.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The key study is GLP compliant and of high quality (Klimisch score 1)

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

 

Acute toxicity: oral:

A key study was identified (Phycher, 2008, rel. 1). In this acute oral toxic class method study performed according to the OECD guideline No. 423 and in compliance with GLP, six fasted female Sprague Dawley rats received a single oral (gavage) dose of the test substance at a dose level of 2000 mg/kg bw.

Animals were then observed for mortality, clinical signs and bodyweights for 14 days and were all sacrificed for macroscopic examination.

 

It was noted the death of 1 treated rat, 6 hours after the test item administration. A decrease of the spontaneous activity (6/6) associated with myosis (3/6), a decreased of Preyer’s reflex (6/6), muscle tone (3/6) and righting reflex (6/6) was registered in the treated animals, during the first day of the test. The animals recovered a normal activity the 2 nd day of the test.The body weight evolution of the animals remained normal throughout the study.The macroscopical examination of the animal which died during the study revealed a thinning of the corpus and the forestomach.The macroscopical examination of the animals at the end of the study did not reveal treatment-related changes

 

Oral LD50 > 2000 mg/kg bw and the LD50 cut-off  is 2500 mg/kg bw

Justification for classification or non-classification

 

Harmonized classification:

The substance has no harmonized classification according to the Regulation (EC) No. 1272/2008 (CLP).

 

Self classification:

Acute toxicity (Oral):

Based on the available information, the substance is:

- not classified according to the CLP as the oral LD50 is higher than 2000 mg/kg bw

- classified according to the GHS into Category 5 as the LD50 cut-off  is 2500 mg/kg bw.

 

Acute toxicity (Dermal):

No information was available. Not required for substances at the REACH Annex VII tonnage level.

 

Acute toxicity (Inhalation):

No information was available. Not required for substances at the REACH Annex VII tonnage level.

 

Specific target organ toxicity: single exposure (Oral):

The classification criteria according to the CLP and to the GHS as specific target organ toxicant (STOT) – single exposure, oral are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value (oral) for a Category 1 classification (C≤ 300 mg/kg bw) and at the guidance value (oral) for a Category 2 classification (2000 mg/kg bw≥C > 300 mg/kg bw). No classification is required.

The criteria for Transient Organ effects (STOT-SE Category 3) according to the CLP and the GHS are met since narcotic effects were observed following dosing at 2000 mg/kg bw.

 

Specific target organ toxicity: single exposure (Dermal):

No information was available. Not required for substances at the REACH Annex VII tonnage level.

 

Specific target organ toxicity: single exposure (Inhalation):

No information was available. Not required for substances at the REACH Annex VII tonnage level.

 

Aspiration hazard:

The substance is not a hydrocarbon and no effects were observed on lungs in oral studies, therefore the criteria for aspiration toxicity according to the CLP and to the GHS are not met.