Cyclooctane

Endpoint summary

Description of key information

The test item showed low toxicity and the LD50 value was determined to be higher than 2000 mg/kg body weight after single oral administration in female rats (reference 7.2.1-1).

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:

2021-10-19 to 2021-11-23

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2008

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2001-12-17

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Remarks:

Crl:WI (Han)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River GmbH , Sulzfeld, Germany
- Females nulliparous and non-pregnant: not specified
- Age at study initiation: 9 weeks at treatment start
- Weight at study initiation: 175 g (168 – 182 g)
- Fasting period before study: Yes. Diet was withheld from about 17 to 20 hours before start of treatment until 4 hours after administration.
- Housing: During the acclimation phase, the three rats per treatment group were group-housed in type IV Makrolon cages with a shelter on softwood bedding material (ABEDD LTE E-001, ABEDD LAB&VET Service GmbH, Austria). Play tunnels (Ref. 14153, Plexx BV, Netherlands) were placed in the cages as additional enrichment. After treatment, the rats were single housed in type III Makrolon cages with a shelter and a play tunnel on softwood bedding material overnight. One day after treatment the rats were group-housed again in type IV Makrolon cages until the end of the observation period. The bedding was changed once a week.
- Diet: ad libitum, maintenance diet (V1534, ssniff Spezialdiäten GmbH, Germany)
- Water: ad libitum, community water in Makrolon bottles (BIOSCAPE GmbH, Castrop-Rauxel, Germany). Drinking water was changed at least three times per week.
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.2 – 22.9
- Humidity (%): 42.7 – 57.4
- Air changes (per hr): not specified; fully air-conditioned room
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

VEHICLE
Not applicable

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

CLASS METHOD
- Rationale for the selection of the starting dose: Due to the chemical properties of the test item, mortality was not expected at the highest starting dose of 2000 mg/kg bw. Therefore, the treatment was started with 2000 mg/kg bw in three female rats and continued with further three females at 2000 mg/kg bw.

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: On the day of treatment, each animal was observed for mortality and for symptoms of intoxication at scheduled intervals according to the record sheets. On the following days, the rats were examined once daily. Symptoms were recorded individually for each animal. All animals were weighed before treatment (day 1) and on day 2, 4, 6, 8, 11, 13 and 15.
- Necropsy of survivors performed: yes

Statistics:

The study data, mortality , symptoms and body weights were manually recorded on study specific forms. The mean initial body weight was calculated with a packet calculator.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was seen.

Clinical signs:

salivation

Body weight:

other body weight observations

Remarks:

The body weight gain was lower one day after treatment than usual. One rat showed even a decrease in body on day 2. On the following days there were no effects on the body weight development. For details please refer to "Any other information on results".

Gross pathology:

No organ alterations were identified during the gross pathological examination.

Animal No.	Sex	Dose [mg/kg bw]	Body weight in g on day								Body weight gain in g
			1	2	4	6	8	11	13	15	Day 1 to 15
1	Female	2000	178	179	194	191	203	196	205	208	+30
2	Female	2000	175	179	183	188	194	199	200	205	+30
3	Female	2000	168	169	183	183	185	182	189	190	+22
4	Female	2000	175	176	180	188	196	196	197	203	+28
5	Female	2000	172	172	193	195	197	199	200	204	+32
6	Female	2000	182	181	192	191	200	204	206	212	+30

Interpretation of results:

GHS criteria not met

Conclusions:

The test item showed low toxicity and the LD50 value was determined to be higher than 2000 mg/kg body weight after single oral administration in female rats.

Executive summary:

The objective of the present study was to identify potential toxic effects of the test item after single oral administration to rats in a stepwise procedure. The study was conducted according to OECD TG 423.

The treatment was started with 2000 mg/kg body weight in 3 female rats and continued with further 3 females treated with 2000 mg/kg bw.

Mortality and clinical signs were monitored for at least 6 hours after administration and then daily. All animals were weighed before treatment (day 1) and on days 2, 4, 6, 8, 11, 13, and 15. At the end of the observation period, all surviving rats were sacrificed and subjected to a detailed necropsy.

No mortality occurred during the course of this study. All rats treated with 2000 mg /kg bw showed salivation immediately after treatment. Two hours after treatment, salivation was no longer observed. The body weight gain was lower one day after treatment than usual. One rat showed even a decrease in body on day 2. On the following days there were no effects on the body weight development. The gross pathological examination revealed no organ alterations.

The test item showed low toxicity under the conditions of the present study, and the LD50 value is higher than 2000 mg/kg body weight after single oral administration in female rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Quality of whole database:

The guideline study is of sufficient quality to address the endpoint.

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

The objective of the present study was to identify potential toxic effects of the test item after single oral administration to rats in a stepwise procedure. The study was conducted according to OECD TG 423.

The treatment was started with 2000 mg/kg body weight in 3 female rats and continued with further 3 females treated with 2000 mg/kg bw.

Mortality and clinical signs were monitored for at least 6 hours after administration and then daily. All animals were weighed before treatment (day 1) and on days 2, 4, 6, 8, 11, 13, and 15. At the end of the observation period, all surviving rats were sacrificed and subjected to a detailed necropsy.

No mortality occurred during the course of this study. All rats treated with 2000 mg /kg bw showed salivation immediately after treatment. Two hours after treatment, salivation was no longer observed. The body weight gain was lower one day after treatment than usual. One rat showed even a decrease in body on day 2. On the following days there were no effects on the body weight development. The gross pathological examination revealed no organ alterations.

The test item showed low toxicity under the conditions of the present study, and the LD50 value is higher than 2000 mg/kg body weight after single oral administration in female rats.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on available data on acute toxicity, the test item does not require classification for acute toxicity via the oral route according to Regulation (EC) No 1272/2008 (CLP).