Hexan-4-olide

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Dihydro-5-octylfuran-2(3H)-one

EC Number:

218-971-6

EC Name:

Dihydro-5-octylfuran-2(3H)-one

Cas Number:

2305-05-7

Molecular formula:

C12H22O2

IUPAC Name:

Dihydro-5-octylfuran-2(3H)-one

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Species Wistar rats
Source Dobrá Voda, Slovak Republic
Number and Sex of Animals 3 females
Age at First Dose 9-10 weeks; female animals were non-pregnant and nulliparous
Animal Health The health condition of animals was examined by a veterinarian before initiation of the study.
Acclimation The animals were acclimated to the condition identical to the conditions during the experiment 5 days prior to the start of treatment. The acclimation was according to the standard operation procedure.
Housing Condition The animals were housed in plastic cages suspended on stainless steel racks, 1-3 animals per cage, in a room equipped with central air-conditioning. The average room temperature was maintained within the range of 22.10 ± 0.21 °C, relative humidity within 54.30 ± 2.33 %. The light regimen was set to a 12-hour light /12-hour dark cycle. The sanitation was performed according to the standard operation procedures.
Diet A laboratory food ssniff (ssniff Spezialdiäten GmbH) was offered in recommended doses each day approximately at the same time. The certificate of analysis is included in the raw data.
Water The animals received tap water for human consumption. Supply of drinking water was unlimited. The quality of drinking water is periodical analysed (including microbiological control) and recorded; certificate of analysis is included in raw data.
Bedding Lignocel S3/4, Lufa - ITL GmbH, Germany
Animals Identification Each animal was marked with an ID number. Each cage was affixed with a cage card containing pertinent animal and study information. The animals in cages were marked by a line (I-III) on the tail with an ink marker.
Justification for the Choice of Species Normally females are used in the test according to OECD TG 402 because mostly females are the more sensitive gender.

Administration / exposure

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

Approximately 24 hours before the test, fur was removed from the dorsal area of the trunk of the test animals by clipping and shaving. A precise amount of the test item was aspirated into an adjustable pipette and applied directly on the shaved skin of the back in a single dose uniformly over an area approximately 10 % of the total body surface area. Test item was held in contact with the skin by using semi-occlusive dressing with non-irritating tape throughout the 24-hours exposure period. At the end of the exposure period, any residuals of the test item were removed by using lukewarm water without altering the existing response or integrity of the epidermis.

Duration of exposure:

Animals were observed individually immediately after the application of the test item and then 0.5, 1, 2, 4 and 6 hours later. Each animal was inspected daily for the next 14 days.
Observations included changes in skin and fur, eyes and mucous membranes, and also respiratory, circulatory, autonomic and central nervous systems, and somatomotor activity and behaviour pattern. Attention was directed to observations of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma. In addition, the treatment site was observed at 24, 48 and 72 hours after removal of test chemical using the Draize criteria in Table 1.

Table 1 Assessment of the skin reaction according to the Draize et al. scale
Erythema and Eschar Formation Grade
no erythema 0
very slight erythema (barely perceptible) 1
well - defined erythema 2
moderate erythema 3
severe erythema (beet red) to slight eschar formation 4
Total possible erythema score = 4

Oedema Formation Grade
no oedema 0
very slight oedema (barely perceptible) 1
well - defined oedema (edges are well-defined by definite raising) 2
moderate oedema (raised approximately 1 mm) 3
severe oedema (raised more than 1 mm and extending beyond area exposure) 4
Total possible oedema score = 4

Doses:

A limit dose of 2000 mg/kg body weight was used as a starting dose. One female was dosed. Test item-related mortality was not observed during 48-hours exposure period. The sighting study was finished; the main test was started with dose of 2000 mg/kg body weight.

No. of animals per sex per dose:

3

Control animals:

no

Results and discussion

Preliminary study:

A limit dose of 2000 mg/kg body weight was used as a starting dose. One female was dosed. Test item-related mortality was not observed during 48-hours exposure period.

Effect levels

Key result

Sex:

female

Dose descriptor:

other: Clinical Observations

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

The test item gamma-Dodecalactone applied to 3 females at a limit dose of 2000 mg/kg body weight did not cause death.

Clinical signs:

other: No signs of toxicity were observed at the dosage of 2000 mg/kg body weight during the first 4 hours or 14-day observation period. No dermal changes were observed. During necropsy no macroscopic findings were noticed.

Gross pathology:

No signs of toxicity were observed at the dosage of 2000 mg/kg body weight during the first 4 hours or 14-day observation period. No dermal changes were observed. During necropsy no macroscopic findings were noticed.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on OECD Guideline 402 it can be concluded, that for the test item gamma-Dodecalactone according to the Globally Harmonised System and Category Labelling of Chemicals can be classified in Category 5/Unclassified after single dermal application to Wistar rats.