N-butyl 4-oxopentanoate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

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)

Cross-reference

Reason / purpose for cross-reference:

data waiving: supporting information

Reference

Endpoint:

acute toxicity: oral

Type of information:

other: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

September 26th to October 11th, 2018

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

Reliability of original study is 1

Justification for type of information:

Justification for Read Across is given in Section 13 of IUCLID.

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

adopted December 17th, 2001

Deviations:

no

Principles of method if other than guideline:

Guidance Document on Acute Oral Toxicity Testing, OECD Series on Testing and Assessment No 24, 2001
Guidance Document on the Recognition, Assessment and Use of Clinical Signs as Humane Endpoints for Experimental Animals Used in Safety Evaluation. Environmental Health and Safety Publications Series on Testing and Assessment No 19, 2000

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Slovak Academy of Sciences Dobrá Voda, Slovak Republic
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8-9 weeks
- Weight at study initiation: 211-222 g
- Fasting period before study: 10-12 h prior to dosing. After test item administration, food was withheld for further 3-4 hours.
- Housing: housed in plastic cages suspended on stainless steel racks, 3 animals per cage in a room equipped with central air-conditioning. Bedding Lignocel S3/4, Lufa - ITL GmbH, Germany
- Diet: laboratory food ssniff (ssniff Spezialdiäten GmbH, Germany), ad libitum
- Water: tap water for human consumption. Supply of drinking water was unlimited.
- Acclimation period: the animals were acclimated under the conditions identical to the conditions during the experiment 5 days prior to the start of treatment.

ENVIRONMENTAL CONDITIONS
- Temperature: 22.38 ± 0.17 °C.
- Humidity: 53.58 ± 4.94 %.
- Air changes: 13 per hr
- Photoperiod: 12-hour light /12-hour dark cycle

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

VEHICLE
- Justification for choice of vehicle: olive oil is a common vehicle in toxicity studies like OECD TG 423
- Lot/batch no: L71143

DOSAGE PREPARATION: the required amount of the test item was mixed with the addition of vehicle (olive oil) followed by stirring with the calculated volume of vehicle shortly before administration. Calculations were based on the dosage level (2000 mg/kg) and dosage volumes (5 ml/kg).

CLASS METHOD
- Rationale for the selection of the starting dose: the starting dose could be selected from the fixed dose levels of 5, 50, 300, and 2000 mg/kg body weight. A limit dose of 2000 mg/kg body weight was used as a starting dose. One group of 3 females was dosed. Test item-related mortality was not observed during 24 hours and therefore, in a second step, another 3 females were treated at the same dose.

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: animals were observed individually immediately after administration of the test item and 0.5, 1, 2, and 4 hours later. Each animal was inspected daily for the next 14 days. Individual weights of animals were measured immediately prior to administration of the test item and weekly thereafter. Weight differences after first and second weeks after administration were calculated and recorded.
- Necropsy of survivors performed: yes. Surviving animas were sacrificed on Day 15 by anesthetic overdose (Isoflurane). All test animals were subjected to gross necropsy and the results were recorded for each animal.
- Observations included: changes in skin, fur, eyes, mucous membranes, respiratory, circulatory, autonomic and central nervous systems (CNS), somatomotor activity, and behavioural pattern. Particular attention was given to potential neurologic endpoints such as tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

All (6/6 females) animals survived the limit dose of 2000 mg/kg body weight.
No mortality was observed during the study.

Clinical signs:

other: During the follow up period, no animals displayed signs of intoxication, change of health, nor any other adverse reaction.

Gross pathology:

All animals were necropsied. During necropsy, no macroscopic findings were observed.

Interpretation of results:

other: not classified as harmful or toxic according to the CLP Regulation (EC) No. 1272/2008

Conclusions:

LD50 (rat, female) > 2000 mg/kg bw

Executive summary:

The potential toxic effect of the test item when administered as a single oral dose to Wistar rats was evaluated according to the OECD Guideline 423. One group of 3 females was dosed. Test item-related mortality was not observed during 24 hours and therefore, in a second step, another 3 females were treated at the same dose. Animals were observed individually immediately after administration of the test item and 0.5, 1, 2, and 4 hours later. Each animal was inspected daily for the next 14 days after which, all animals were killed and subjected to necropsy examination. Individual weights of animals were measured immediately prior to administration of the test item and weekly thereafter.

The test item administered to 6 females at a limit dose did not cause death. No signs of toxicity were observed during the first 4 hours in females or the 14-day observation period thereafter. The body weights of all animals increased during the study. No body weight losses were observed between the first and second week after administration. During necropsy, no macroscopic findings were observed.

The LD50 of the test item is greater than 2000 mg/kg bw after single oral administration to Wistar rats.