Estr-4-ene-3,11,17-trione, cyclic 17-(2,2-dimethyl-1,3-propanediyl acetal) cyclic 3-(1,2-ethanediyl dithioacetal)

Endpoint summary

Description of key information

Oral: LD50 = > 2000 and <= 5000 mg/kg bw, female rat; OECD 423, Lütkenhaus 2012

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:

2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: According to guideline; under GLP conditions.

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: EPA OPPTS 870.1000 (Acute Toxicity testing background)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

other: Wistar Crl:WI(Han)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Recognised animal supplier
- Age at study initiation: 8-11 weeks
- Weight at study initiation: 154 - 179g
- Fasting period before study: Prior to test material administration, food was withheld from test animals for 16-19 hours.
- Housing: Housed in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding (lot no. 110811).
- Diet (e.g. ad libitum): Altromin 1324 maintenance diet for rats and mice (lot no. 0815) ad libitum.
- Water (e.g. ad libitum): Tap water (sulphur acidified to a pH value of approximately 2.8) ad libitum.
- Acclimation period: At least 5 days under laboratory conditions.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 55 +/- 10
- Air changes (per hr): 10
- Photoperiod: 12 hours light (artificial light)/12 hours dark

Route of administration:

oral: gavage

Vehicle:

cotton seed oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 300 mg/ml and 2000 mg/ml
- Amount of vehicle (if gavage): 10 ml/kg
- Justification for choice of vehicle: chosen due to its non-toxic characteristics.
- Lot/batch no. (if required): MKBJ0602V

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/ml

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: limited information on test material, for animal welfare reasons the OECD 423 guideline recommends using a starting dose of 300 mg/kg body weight.

Doses:

300 mg/kg, 2000 mg/kg

No. of animals per sex per dose:

3 animals per step

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Test animals were observed several times on the day of dosing with special attention during the first 4 hours. Thereafter test animals were observed for clinical signs once daily until the end of the observation period. Body weights were recorded on day 1 (prior to test material administration) and on days 8 and 15.
- Necropsy of survivors performed: yes

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 - <= 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortalities were observed in any dose group.

Clinical signs:

other: 300 mg/kg dose group: no signs of toxicity. 2000 mg/kg dose group: slightly reduced spontaneous activity, bradykinesia, half eyelid-closure, slight piloerection.

Gross pathology:

Necropsy of the test animals showed no treatment-related macroscopic findings.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study, the acute oral median lethal dose (LD50) of the test material in the female Wistar strain rat was estimated to be between 2000 and 5000 mg/kg bodyweight.

Executive summary:

The study was performed to assess the acute oral toxicity of the test material in the Wistar strain of rat. The study was performed to GLP and the method was designed to meet the requirements of OECD 423 guideline, EU method B.1 tris, OPPTS 870.1000 and 870.1100 guidelines. A stepwise approach was used to evaluate the toxicity of the test material. Absence or presence of compound-related mortality of the animals dosed at one step determined the next step. Groups of 3 animals were used for each dose. The test material was administered orally, after overnight fasting, once only by gavage, as a suspension in cotton seed oil. The test material concentrations in the vehicle were 300 mg/mL and 2000 mg/mL and the administered volume of suspension was 10 mL/kg body weight.Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy after an observation period of 14 days. No clinical signs of toxicity were observed in the 300 mg/kg dose group. Clinical observations in the 2000 mg/kg bw group included: slightly reduced spontaneous activity, bradykinesia, half eyelid-closure, slight piloerection. Animals of the 300 mg/kg bw survived to the end of the study; animals in the 2000 mg/kg recovered within one day and also survived to the end of the study. All surviving animals showed expected gains in bodyweight during the study. No abnormalities were noted at necropsy. The acute oral median lethal dose (LD50) of the test material in the female Wistar strain rat was estimated to be between 2000 and 5000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

The study is GLP compliant and has a 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 oral:

The acute oral toxicity of the substance was evaluated in the Wistar rat in a GLP study designed to meet the requirements of OECD 423. A stepwise approach was used to evaluate the toxicity of the test material. Absence or presence of compound-related mortality of the animals dosed at one step determined the next step. Groups of 3 animals were used for each dose. The test material was administered orally, after overnight fasting, once only by gavage, as a suspension in cotton seed oil. The test material concentrations in the vehicle were 300 mg/mL and 2000 mg/mL and the administered volume of suspension was 10 mL/kg body weight.Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy after an observation period of 14 days. No clinical signs of toxicity were observed in the 300 mg/kg dose group. Clinical observations in the 2000 mg/kg bw group included: slightly reduced spontaneous activity, bradykinesia, half eyelid-closure, slight piloerection. Animals of the 300 mg/kg bw survived to the end of the study; animals in the 2000 mg/kg recovered within one day and also survived to the end of the study. All surviving animals showed expected gains in bodyweight during the study. No abnormalities were noted at necropsy. The acute oral median lethal dose (LD50) of the test material in the female Wistar strain rat was estimated to be between 2000 and 5000 mg/kg bw.

Justification for selection of acute toxicity – oral endpoint
Only one study available; study estimates the LD50 range and therefore provides information on a discriminating dose level (the highest concentration administered that has not caused significant effects to the test organisms).

Justification for classification or non-classification

The test substance does not meet classification criteria under EU Directive 67/548/EEC for acute toxicity.

The test substance does not meet classification criteria under Regulation (EC) No 1272/2008 for acute toxicity.