2,2'-[(1-methylethylidene)bis(cyclohexane-4,1-diyloxymethylene)]bisoxirane

Endpoint summary

Description of key information

Oral (Gamer, 2005)

Under the conditions of the study, the median lethal dose of the test material after oral administration was found to be greater than 2,000 mg/kg bw in rats.

Inhalation (Waiver)

The study does not need to be conducted because exposure of human via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size – (exposure considerations).

Dermal (Waiver)

The study does not need to be conducted because the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and no systemic effects have been observed in in vivo studies with dermal exposure (e.g. skin irritation, skin sensitisation) – study scientifically not necessary / other information available).

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:

14 June 2004 to 07 October 2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2001

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2004

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

2002

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Remarks:

HanBrI:WIST(SPF)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Females nulliparous and non-pregnant: yes
- Age at study initiation: approx. 8 -12 weeks
- Weight at study initiation: 177-179 g
- Fasting period before study: Feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum .
- Housing: individually housed in stainless steel wire mesh cages, type DK-III
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 - 24°C
- Humidity: 30 - 70%
- Photoperiod: 12h/12h (6.00 a.m. - 6.00 p.m. / 6.00 p.m. - 6 .00 a.m.)

Route of administration:

oral: gavage

Vehicle:

other: Olive oil Ph .Eur./DAB

Details on oral exposure:

VEHICLE
- Olive oil Ph .Eur./DAB
- Justification for choice of vehicle: Inhomogeneous in aqueous preparations. Olive oil Ph .Eur./DAB had to be used to ensure homogeneity of the preparation.

MAXIMUM DOSE VOLUME APPLIED: 5 mL/kg

DOSAGE PREPARATION: The test material preparation was produced for each administration group shortly before administration by stirring with a magnetic stirrer. This formed a solution.

CLASS METHOD
- 2000 mg/kg

Doses:

2000 mg/kg

No. of animals per sex per dose:

6 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Recording of signs and symptoms several times on the day of administration and at least daily thereafter for 14 days.
- Individual body weights were determined shortly before administration (day 0), weekly thereafter and at the end of the study.
- A check for any dead or moribund animal was made twice each workday and once on Saturdays, Sundays and on public holidays.
- Necropsy with gross-pathology examination was performed on the last day of the observation period after killing with CO2.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: Clinical observation in the 2,000 mg/kg administration groups revealed impaired general state, dyspnoea, staggering and piloerection and were observed from hour 1 until including hour 4 after administration.

Gross pathology:

No macroscopic pathologic abnormalities were noted in the animals examined at termination of the study.

Interpretation of results:

other: Not classified in accordance with EU Criteria

Conclusions:

Under the conditions of this study, the median lethal dose of the test material after oral administration was found to be greater than 2,000 mg/kg bw in rats.

Executive summary:

The acute oral toxicity of the test material was investigated in accordance with the standardised guidelines OECD 423, EU Method B.1 tris and EPA OPPTS 870.1100, under GLP conditions.

During the study, single doses of 2,000 mg/kg body weight of test material preparations in olive oil Ph .Eur./DAB were given to two administration groups of three fasted female animals each, by gavage in a sequential manner.

No mortality occurred. Clinical observation revealed impaired general state, dyspnoea, staggering and piloerection. Findings were observed 1 to 4 hours after administration. The mean body weights of the administration groups increased throughout the study period and no macroscopic pathologic abnormalities were noted in the animals examined at the end of the observation period.

Under the conditions of this study, the median lethal dose of the test material after oral administration was found to be greater than 2,000 mg/kg bw in rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

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

Oral (Gamer, 2005)

The acute oral toxicity of the test material was investigated in accordance with the standardised guidelines OECD 423, EU Method B.1 tris and EPA OPPTS 870.1100, under GLP conditions. The study was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997).

During the study, single doses of 2,000 mg/kg body weight of test material preparations in olive oil Ph .Eur./DAB were given to two administration groups of three fasted female animals each, by gavage in a sequential manner.

No mortality occurred. Clinical observation revealed impaired general state, dyspnoea, staggering and piloerection. Findings were observed 1 to 4 hours after administration. The mean body weights of the administration groups increased throughout the study period and no macroscopic pathologic abnormalities were noted in the animals examined at the end of the observation period.

Under the conditions of this study, the median lethal dose of the test material after oral administration was found to be greater than 2,000 mg/kg bw in rats.

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No 1272/2008, the material does not require classification with respect to acute toxicity.