Sodium 1-(3,4-dihydro-6-methyl-2,4-dioxo-2H-pyran-3-ylidene)ethanolate

Endpoint summary

Description of key information

Oral:

The LD50 in the mouse was 1175 mg/kg bw.

The LD50 in the rat was > 1000 and <=2500 mg/kg bw.

The LD50 in the rabbit was >500 and <= 1000 mg/kg bw.

Dermal:

The LD50 in the rabbit was considered to be greater than 3000 mg/kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1973

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

(only basic information given)

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

mouse

Strain:

other: Tylers Original

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 20 ± 2
- Fasting period before study: overnight
- Housing: in solid floor polycarbonate boxes

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22
- Photoperiod: natural lighting conditions

Route of administration:

oral: gavage

Vehicle:

not specified

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 100 mg/mL solution

Doses:

500, 1000, 1500, 2000 and 2500 mg/kg bw (and also 5000 mg/kg bw in the preliminary study).

No. of animals per sex per dose:

2 in preliminary study
10 in main study

Control animals:

no

Details on study design:

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

Preliminary study:

A rangefinding trial was performed with 2 animals per dose (500, 1000, 2500 and 5000 mg/kg bw)
500 and 1000 mg/kg bw: no deaths occured
2500 mg/kg bw and more: all animals died on Day 1

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 175 mg/kg bw

Based on:

test mat.

95% CL:

>= 987 - <= 1 410

Mortality:

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

Clinical signs:

other: 500 mg/kg bw and more: convulsions and stretching within 90 min of dosing, symptoms less severe in survivors after 48 h, asymptomatic after 72 h

Table 1 Acute oral toxicity: main study data for Day 14 only

Dose	Mortality on Day 14
[mg/kg bw]
	N*
Males/Females
500	0/10
1000	6/10
1500	8/10
2000	9/10
2500	10/10

Table 2 Acute oral toxicity in the mouse: combined preliminary and main study data

Dose mg/kg bw	Mortality on Day 4 (No.)
500	0/12
1000	6/12
1500	6/12
2000	8/10
2500	11/12

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

LD50 = 1175 mg/kg bw.

Executive summary:

The LD50 in the mouse was 1175 mg/kg bw.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

(only basic information given)

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

test performed using 2 animals only

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

New Zealand White

Sex:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 2000 ± 200 g
- Fasting period before study: overnight
- Housing: individually caged

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22
- Photoperiod: natural lighting conditions

Route of administration:

oral: gavage

Vehicle:

not specified

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL solution

Doses:

500, 1000, 2500 and 5000 mg/kg bw

No. of animals per sex per dose:

2

Control animals:

no

Details on study design:

- Duration of observation period following administration: 7 days
- Frequency of observations: daily

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 500 - <= 1 000 mg/kg bw

Based on:

test mat.

Mortality:

500 mg/kg bw: 0/2
1000 mg/kg bw and more: 1/2 (24 h post-dose), 2/2 (at 48 h post-dose)
2500 mg/kg bw and more: 2/2

Clinical signs:

other: 500 mg/kg bw and more: disorientation and stretching within 120 min of dosing, survivors asymptomatic after 48 h

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

LD50 >500 and <= 1000 mg/kg bw.

Executive summary:

The LD50 in the rabbit was >500 and <= 1000 mg/kg bw.

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1973

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

(only basic information given)

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

test performed using 2 animals only

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 200 ± 20 g
- Fasting period before study: overnight
- Housing: in grid-floor cages

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22
- Photoperiod: natural lighting conditions

Route of administration:

oral: gavage

Vehicle:

not specified

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL solution

Doses:

500, 1000, 2500 and 5000 mg/kg bw

No. of animals per sex per dose:

2

Control animals:

no

Details on study design:

- Duration of observation period following administration: 7 days
- Frequency of observations: daily

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

> 1 000 - < 2 500 mg/kg bw

Based on:

test mat.

Mortality:

500 and 1000 mg/kg bw: 0/2
2500 mg/kg bw and more: 2/2 (24 h post-dose)

Clinical signs:

other: 500 mg/kg bw and more: trembling and convulsions within 120 min of dosing, survivors asymptomatic after 48 h

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

LD50 > 1000 and <=2500 mg/kg bw.

Executive summary:

The LD50 in the rat was > 1000 and <=2500 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 000 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 inductrial 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

Reference 1

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:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Qualifier:

no guideline followed

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

Specific details on test material used for the study:

Dehydroacetic acid.

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:

GHS criteria not met

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.

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

refer to analogue justification provided in IUCLID section 13

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 3 000 - < 5 000 mg/kg bw

Based on:

test mat.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

3 000 mg/kg bw

Justification for classification or non-classification

Oral:

The LD50 in the mouse was 1175 mg/kg bw. : GHS Cat. 4

The LD50 in the rat was > 1000 and <=2500 mg/kg bw. : GHS Cat. 4

The LD50 in the rabbit was > 500 and <= 1000 mg/kg bw. : GHS Cat. 4

Dermal:

The LD50 in the rabbit was > 3000 mg/kg bw : GHS not classified