Octyloxirane

Endpoint summary

Description of key information

The oral LD50 was determined to be >5000 mg/kg bw.
The dermal LD50 was determined to be >2000 mg/kg bw.

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Animal experimental study, predates implementation of GLP and/or development of study guidelines, limitations in design and/or reporting but otherwise adequate for assessment

Principles of method if other than guideline:

Ten male Wistar rats were exposed to test substance dissolved in olive oil via oral gavage. Animals received 5000 mg/kg bw. Animals were observed for 7 days and the LD50 was determined.

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Winkelmann, Borchen
- Weight at study initiation: mean 160 g
- Fasting period before study: 16 hours
- Housing: five animals per cage, in Makrolon 3 cages with Weichholzgranlat bedding (ARWI-Center Essen)
- Diet: ad libitum, Altromin-Haltungsdiät 1324, Fa. Altromin GmbH, 4937 Lage, Germany
- Water: ad libitum, tap water
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 25
- Humidity (%): 45 - 60
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 25 % (g/v)
- Amount of vehicle (if gavage): 20 mL/kg

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

- Duration of observation period following administration: 7 days
- Frequency of observations: Clinical signs and mortality: multiple days on the day of administration and twice daily on the following days
- Necropsy of survivors performed: no

Sex:

male

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed.

Clinical signs:

other: Diarrhea was observed in all animals. Effect was reversible.

Gross pathology:

Gross pathology was not performed.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

5 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP compliant, guideline study, available as unpublished report, no restrictions, fully adequate for assessment

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Qualifier:

according to guideline

Guideline:

other: Japan MAFF 12 Nosan No. 8147

GLP compliance:

yes (incl. QA statement)

Remarks:

Bioassay, Labor für biologische Analytik GmbH, Im Neuenheimer Feld 515/519, 69120 Heidelberg

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Germany
- Age at study initiation: males approx. 8 weeks, females approx. 12 weeks
- Weight at study initiation: mean males 231.2 g, mean females 203.0 g
- Housing: single housing, in Makrolon type III cages; H15005-29 bedding, Ssniff, Spezialitäten GmbH (Experimental Animal Diets Inc., 59494 Soest, Germany); NGM E-022 enrichment, ABEDD® LAB & VET Service GmbH, Hasnerstraße 84/6; 1160 Wien – Austria
- Diet: VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany
- Water: tap water, ad libitum
- Acclimation period: at least 5 days before the experimental phase
- Females were nulliparous and non-pregnant

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 – 70
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 40 cm2
- % coverage: 10
- Type of wrap if used: semi-occlusive dressing (4 layers of absorbent gauze (Ph. Eur. Supplied by Lohmann GmbH & Co., KG) and stretch bandage (Fixomull® Stretch (adhesive fleece) supplied by Beiersdorf AG)

REMOVAL OF TEST SUBSTANCE
- Washing: after removal of the semi-occlusive dressing, the application site was rinsed with warm water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.4 mL/kg bw was applied to the clipped epidermis (dorsal and dorsolateral parts of the trunk)

Duration of exposure:

24 hours

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 and weighing: Clinical signs for each animal were recorded several times on the day of administration and at least once during each workday thereafter. Individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation.
- Necropsy of survivors performed: yes
- Scoring of the skin finding: Individual readings 30 – 60 minutes after removal of the semi-occlusive dressing (day 1), several times until the last day of observation.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occured.

Clinical signs:

other: No systemic clinical signs were observed during clinical examination.

Gross pathology:

No macroscopic pathologic abnormalities were noted in the animals (5 males and 5 females) examined on the last day of observation.

Other findings:

LOCAL EFFECTS:
- Males: Four out of five male animals revealed moderate erythema (grade 3) on day 1 and well-defined erythema (grade 2) from day 2 until day 3. The fifth animal showed moderate erythema from day 1 until day 2 and well-defined erythema on day 3. In all male animals moderate edema (grade 3) occurred on day 1, which decreased to very slight edema (grade 1) from day 2 until day 3. Incrustations were noted in four animals on day 6 and in one animal from day 3 until day 6. Scaling was observed in four animals from day 3 until day 10, 13 or 14, respectively. One animal revealed scaling from day 6 until day 10.
- Females: Four out of five female animals revealed well-defined erythema (grade 2) from day 1 until day 3. The fifth animal showed moderate erythema (grade 3) from day 1 until day 2 and well-defined erythema on day 3.In all female animals moderate edema (grade 3) was observed on day 1 and very slight edema (grade 1) from day 2 until day 3. In all female animals incrustations were noted on study day 6. Scaling was noticed in these animals from day 6 until day 10 or 14, respectively.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Additional information

Acute toxicity: oral

Ten male Wistar rats were exposed to the homolog 2 -Decyloxirane dissolved in olive oil via oral gavage. Animals received 5000 mg/kg bw and were observed for 7 days. Diarrhea (reversible) was observed in all animals and the LD50 was determined to be >5000 mg/kg bw.

 

Acute toxicity: dermal

In a GLP complaint OECD 402 guideline study, five Wistar rats per sex were exposed to the limit dose of 2000 mg/kg bw. The homolog 2 -decyloxirane was administered as 2.4 mL/kg bw to the clipped epidermis and wrapped with a semi-occlusive dressing. After an exposure period of 24 hours the dressing was removed and the application site rinsed with warm water. After an observation period of 14 days animals were necropsied. No mortality occurred and no systemic clinical signs were observed. The mean body weight increased within the normal range throughout the study. Well-defined to moderate erythema, very slight or moderate edema, incrustations and scaling were observed. No macroscopic pathologic abnormalities were noted in all animals examined at the end of the study. The LD50 was determined to be >2000 mg/kg bw.

Justification for selection of acute toxicity – oral endpoint
There is only one study available.

Justification for selection of acute toxicity – dermal endpoint
There is only one study available.

Justification for classification or non-classification

Based on an oral LD50 of > 5000 mg/kg bw and a dermal LD50 of >2000 mg/kg bw, classification for acute oral toxicity and acute dermal toxicity are not warranted in accordance with EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation No. 1272/2008.