3-hydroxy-2-methyl-4-pyrone

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

11 April 2019 - 18 September 2019

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2019

Report date:

2019

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

2017

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

3-hydroxy-2-methyl-4-pyrone

EC Number:

204-271-8

EC Name:

3-hydroxy-2-methyl-4-pyrone

Cas Number:

118-71-8

Molecular formula:

C6H6O3

IUPAC Name:

3-hydroxy-2-methyl-4H-pyran-4-one

Test material form:

solid

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: ANHUI JINHE INDUSTRIAL CO., LTD., 201902271
- Expiration date of the lot/batch: 26 February 2021
- Purity: 99.96%

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Controlled room temperature (15-25oC), protected from light and humidity (beside silica)

OTHER SPECIFICS:
- measurement of pH: If the pH is 2 or less or 11.5 or greater, a study cannot be conducted, unless there is evidence that the test item is not severely irritating or corrosive to the skin. The pH of the test item in this study was determined prior to the initiation of the experiment and it was found to be 5.0, therefore the experiment could be started.

Test animals

Species:

rat

Strain:

other: Crl:WIWistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, D-97633 Sulzfeld, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: ~8 weeks old
- Weight at study initiation: Between 205 g and 223 g
- Housing: Individual and group caging (Type II. polypropylene/polycarbonate). Rodents were housed with deep wood sawdust bedding (SAFE 3/4 S certified wooden chips) to allow digging and other normal rodent activities.
- Diet: Animals received ssniff SM R/M "Autoclavable complete diet for rats and mice – breeding and maintenance" produced by ssniff Spezialdiäten GmbH, D-59494, Soest, Germany, ad libitum
- Water: tap water from the municipal supply ad libitum
- Acclimation period: 6 or 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.1–24.9°C
- Humidity (%): 29–78%
- Air changes (per hr): 15-20 air exchanges/hour
- Photoperiod (hrs dark / hrs light): 12 hours daily, from 6.00 a.m. to 6.00 p.m.

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: The back of each animal
- % coverage: approximately 10% area of the total body surface
- Type of wrap if used: Sterile gauze pads were placed on the skin of rats to cover the test item. These gauze pads were kept in contact with the skin using a patch with adhesive hypoallergenic plaster. The entire trunk of the animal was then wrapped with semi occlusive plastic wrap for 24 hours.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): At the end of the exposure period, the treated area of skin with the test item was washed with water at body temperature.
- Time after start of exposure: 24 hrs

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.45 g (DRF); 0.43g and 0.41g (main study)
- For solids, paste formed: Sufficient amount of water was used to moisten the test item to ensure good contact with the skin.

Duration of exposure:

24 hrs

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

1 female (DRF)
2 females (main study)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: Clinical observations were performed on the day of treatment at 30 minutes, 1, 2 and 5 hours after application of the test item and once each day for 14 days thereafter. Observations included the skin and fur, eyes and mucous membranes, the respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma. Animals were inspected for signs of morbidity and mortality twice daily (at the beginning and end of each working day). The body weights were recorded on Day 0 (before the test item administration) and on Days 7 and 14 (before necropsy).

- Necropsy of survivors performed: Yes; Macroscopic examination was performed on all animals. All animals were anaesthetised with sodium pentobarbital and exsanguinated. Following confirmation of death, after examination of the external appearance, the cranial, thoracic and abdominal cavities were opened and the appearance of the tissues and organs was observed. All macroscopic changes were recorded.

- Other examinations performed: Adverse skin reactions at the site of application were recorded daily following the removal of the dressing.

Statistics:

The method used was not intended to allow the calculation of a precise LD50 value so statistical analysis was not performed.

Results and discussion

Preliminary study:

Initially one animal was dosed at the selected limit dose (2000 mg/kg bw). As the animal survived, the second and third animals received the same dose (Tables 1, 2, 3).

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

The test item did not cause mortality at a dose level of 2000 mg/kg bw.

Clinical signs:

other: There were no systemic clinical signs noted in any animal throughout the study (Table 1).

Gross pathology:

There was no evidence of any gross macroscopic changes at a dose level of 2000 mg/kg bw (Table 3, Appendix 1)

Other findings:

- Other observations: No adverse local dermal signs were observed after treatment with the test item or during the 14-day observation period.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

In an acute dermal toxicity study in Crl:WI Wistar rats, the LD50 (female) of Maltol was >2000 mg/kg bw.

Executive summary:

In an acute dermal toxicity study (19/080-002P), 3 Wistar Crl: WI female rats were dermally exposed (10% total body area; semi-occlusive) to the test item Maltol (99.96%) in sterile water for 24 hours at doses of 2000 mg/kg bw. At the end of the exposure period the residual test item was removed using sterile water.

The LD50 (female) was >2000 mg/kg bw.

Initially one animal was dosed at the selected limit dose (2000 mg/kg bw). As the animal survived, the second and third animals received the same dose. The test item did not cause mortality at a dose level of 2000 mg/kg bw in the main study. There were no systemic clinical signs noted in any animal throughout the study. There were no test item related effects on body weight or body weight gain during the observation period. There was no evidence of any gross macroscopic changes at a dose level of 2000 mg/kg bw. No adverse local dermal signs were observed after treatment with the test item or during the 14-day observation period.