2H-Pyran-2-one, tetrahydro-5-pentyl-

Endpoint summary

Description of key information

Oral LD50 > 2000 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 09 and 24 November 2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP study conducted in compliance with OECD Guideline No. 423 with deviations not affecting the reliability of the study: details on age, fasting period, housing, environmental conditions not reported

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

17 December 2001

Deviations:

yes

Remarks:

details on age, fasting period, housing and environmental conditions not reported.

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:

yes

Remarks:

details on age, fasting period, housing and environmental conditions not reported.

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

Inspected on 2004-07-01 / Signed on 2004-09-13.

Test type:

acute toxic class method

Limit test:

yes

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: no data
- Weight at study initiation: 187 - 220 g.
- Fasting period before study: no data
- Housing: no data
- Diet: foodstuff (A04)
- Water: no data.
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-23 °C
- Humidity: 27-56 %. A relative humidity of 27% was registered instead of 30% (minimal limit) as planned in the experimental protocol. This deviation did not, in any case, influence the development and the results of the study.
- Air changes: no data
- Photoperiod: no data

IN-LIFE DATES: from 09 to 24 November 2005 (for treated group). From 09 to 23 November 2005 (for control group).

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

TEST SUBSTANCE ADMINISTRATION
- Test substance was administered by gavage under a volume of 2.06 mL/kg bw using a suitable syringe graduated fitted with an oesophageal metal canula.

MAXIMUM DOSE VOLUME APPLIED: 2.06 mL/kg bw

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6 females/dose

Control animals:

yes

Remarks:

Control animals received distilled water at 2 mL/kg bw.

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; On Day 14, the animals were anaesthetised with sodium pentobarbital and administration continued to fatal levels, then animals were subjected to macroscopic observations.

Statistics:

None

Preliminary study:

None

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: One mortality was noted.

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, 24 hours after the test item administration.

Clinical signs:

other: A decrease of the spontaneous activity (6/6) associated with a decrease of the muscle tone (3/6), a piloerection (3/6) associated with a dyspnea and a decrease of the righting reflex in one animal was registered during the 1st day of the test. The animals

Gross pathology:

The macroscopical examination of the animal, which died during the test, revealed a thickening and a red coloration of the fundus stomacal mucous.
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 Regulation (EC) No. 1272/2008 (CLP) and classified in category 5 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 substance at 2000 mg/kg bw. Control animals (6 females) received distilled water at 2 mL/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, 24 hours after the test item administration. A decrease of the spontaneous activity (6/6), a decrease of the muscle tone (3/6), a piloerection (3/6) associated with a dyspnea and a decrease of the righting reflex in one animal was registered during the 1st day of the test. The animals recovered a normal activity the 2nd 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 thickening and a red coloration of the fundus stomacal mucous. 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 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:

2 500 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, 2005, rel. 2). 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.

Control animals (6 females) received distilled water at 2 mL/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, 24 hours after the test item administration. Adecrease of the spontaneous activity (6/6), a decrease of the muscle tone (3/6), a piloerection (3/6) associated with a dyspnea and a decrease of the righting reflex in one animal was registered during the 1st day of the test.The animals recovered a normal activity the 2nd 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 thickening and a red coloration of the fundus stomacal mucous.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 LD50 cut-off (OECD 423)  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 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.