3-acetyl-6-methyl-2H-pyran-2,4(3H)-dione

Endpoint summary

Description of key information

Oral LD50 in rats 1480/1620 mg/kg (females/males); range of doses 1000 to 6400 mg/kg bw; significant toxicity at 2000 mg/kg.

Dermal LD50 in rabbits >3000 mg/kg; low dose 1000 mg/kg, top dose 5000 mg/kg; one animal died at 5000 mg/kg

.

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:

Study reported in 1975

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

(only basic data given)

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

adopted Feb 1987

Deviations:

yes

Remarks:

(only basic data given)

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

Dehydroacetic acid

Species:

rat

Strain:

other: albino

Remarks:

200-300 grams body weight

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Fasting period before study: 24 h
- Housing: 5 animals of the same sex per common cage
- Diet: ad libitum
- Water: ad libitum

Route of administration:

oral: gavage

Vehicle:

propylene glycol

Doses:

1000, 1600, 2000, 2500, 3200, 4000, 5000 and 6400 g/kg (males)
1000, 1250, 1600, 2000, 2500, 3200, 4000, 5000 and 6400 g/kg (females)

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: daily

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

1 480 mg/kg bw

Based on:

test mat.

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

1 620 mg/kg bw

Based on:

test mat.

Mortality:

For details refer to Table 1 under "any other information on results"

Clinical signs:

other: All dose goups: lethargy 2000 mg/kg bw or more: gradual loss of motor control on the second day, magnified loss of motor control in further study progress, weight loss and debilitated survivors 5000 mg/kg or more: lack of motor control, hyperactive respo

Table 1: Acute oral toxicity

Dose	Mortality	Clinical signs
[mg/kg bw]
	N*	N*
Males
1000	0/5	5/5
1600	2/5	5/5
2000	4/5	5/5
2500	5/5	5/5
3200	5/5	5/5
4000	5/5	5/5
5000	5/5	5/5
6400	5/5	5/5
Females
1000	0/5	5/5
1250	1/5	5/5
1600	3/5	5/5
2000	5/5	5/5
2500	5/5	5/5
3200	5/5	5/5
4000	5/5	5/5
5000	5/5	5/5
6400	5/5	5/5

*N = Number of animals

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The LD50 values determined were 1620 mg/kg bw for the males and 1480 mg/kg bw for the females.

Executive summary:

An acute oral toxicity study was conducted in male and female rats. Dosages in the range 1000 to 6400 mg/kg bw were tested. The LD50 values determined were 1620 mg/kg bw for the males and 1480 mg/kg bw for the females. Clinical signs noted included: lethargy, lack of motor control, hyperactive responses, convulsions and hemorrhaging from the nose and mouth.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 480 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

other justification

Justification for data waiving:

the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
Acute toxicity data are available for the oral and dermal routes. Examination of the life cycle of the substance indicates that human exposure is controlled by risk management measures in the industrial and professional settings. It is therefore expected that inhalation exposure from the identified uses will be low. In addition, the most likely route of exposure for workers and consumers is the dermal route, where lack of systemic toxicity has been experimentally demonstrated. Consumers will only be exposed to low concentrations of the substance in solutions, where inhalation exposure is unlikely.

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Reported in 1950

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Principles of method if other than guideline:

Method was described as essentially like that of Draize et al., (1944) J. Pharmacol. Exp. Therap. 82; 377. Cited in Principles and Methods of Toxicology, 5th Edition; ed. A. Wallace-Hayes, 2008.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

not specified

Sex:

not specified

Type of coverage:

occlusive

Vehicle:

other: Greaseless base - "Neobase".

Details on dermal exposure:

After application of the dosage, the site was occluded by bandages for 24 hours after which time they were removed and the site washed with soap and water.

Duration of exposure:

24 hours

Doses:

1000, 3000 or 5000 mg/kg bw

No. of animals per sex per dose:

2

Control animals:

no

Sex:

not specified

Dose descriptor:

approximate LD50

Effect level:

> 3 000 - < 5 000 mg/kg bw

Based on:

test mat.

Mortality:

One of the two rabbits treated at 5000 mg/kg bw died

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation(EC) No. 1272/2008

Conclusions:

No rabbits died at 1000 or 3000 mg/kg bw. The LD50 was considered to be greater than 3000 mg/kg bw

Executive summary:

Rabbits were treated dermally for 24 hours with dihydroacetic acid at dosages between 1000 and 5000 mg/kg bw. There were no deaths at 1000 or 3000 mg/kg bw. The LD50 was considered to be greater than 3000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

3 000 mg/kg bw

Additional information

Inhalation study waived because the study need not be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size.

Justification for classification or non-classification

Oral: Category 4 based on CLP criteria

Dermal: Not classified according to CLP criteria, based on LD50 > 2000 mg/kg bw.