Dimethyl maleate

Endpoint summary

Description of key information

Oral:
Smyth 1962. Acute oral toxicity, rat, OECD401: LD50=1410 mg/kg body weight.
Inhalation:
Smyth 1962. Acute inhalation toxicity, rat: The saturated vapour of 2800 mg/m³ did not cause deaths when exposing rats for 4 h. The saturation vapour concentration of 2842 mg/m³ is derived from the vapour pressure of 48 Pa at 25 °C by applying the ideal gas laws. 
Dermal:
Ullmann 1985. Acute dermal toxicity rat: LD50>2000 mg/kg body weight.

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:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Documentation insufficient for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

not specified

GLP compliance:

no

Test type:

standard acute method

Species:

rat

Strain:

other: Carworth-Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

age: 4-5 weeks
body weights: 90-120 g

Route of administration:

oral: gavage

Vehicle:

not specified

Details on oral exposure:

no data

Doses:

no data

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

animals non-fasted
dosages arranged in a logarithmic series differing by a factor of 2
observation period: 14 days p.a.

Statistics:

method of Thompson-Weil for the calculation of the LD50 value

Sex:

male

Dose descriptor:

LD50

Effect level:

1 410 mg/kg bw

Based on:

test mat.

Mortality:

no data

Clinical signs:

other: no datano data

Gross pathology:

no data

Other findings:

no data

no data

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD50,oral,rat was 1.41 g per kg body weight when administered by gavage.

Executive summary:

The test substance was administered to groups of 5 male rats each. Mortality was recorded during an observation period of 14 days p.a. The LD50, calcluated by the method of Thompson and Weil, was 1.41 g per kg body weight.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 410 mg/kg bw

Quality of whole database:

A review article without much details.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: A review article. Documentation insufficient for assessment.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

not specified

Principles of method if other than guideline:

Exposing groups of rats to a saturated vapour of the test substance for different times, from 1/4 up to 8 h. The result is presented as the highest exposure time causing no deaths within an observation time for 14 days.
The results are found on page 101 of the report.

GLP compliance:

no

Test type:

standard acute method

Species:

rat

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

no data

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

clean air

Details on inhalation exposure:

- Concentrated vapor inhalation consists of subjecting groups of six male or female albino rats to a flowing stream of vapor-ladened air.
- flowing stream of vapour-loaded air
- generation of vapour-air-mixture by passing 2.5 L/min of dried air at room temperature through a fritted glass disc immersed to a depth of at least one inch in approx. 50 mL of the test chemical contained in a glass-washing bottle
- inhalations continued for time periods in a logarithmic series with a ratio of two extending from one-fourth to 8 hours, until the inhalation period killing about half the number of rats within 14 days is defined

Analytical verification of test atmosphere concentrations:

no

Duration of exposure:

ca. 8 h

Remarks on duration:

Different exposure times from 1/4 h to 8 h were used. The results in the publication indicate the longest inhalation period which permitted all rats to survive the two-week obsevation period.

Concentrations:

no data

No. of animals per sex per dose:

6

Details on study design:

see above

Sex:

not specified

Dose descriptor:

LC0

Effect level:

other: 4 h exposure to the saturated vapour of the test substance.

Based on:

test mat.

Remarks on result:

other: An LC0 was obtained after 4 h of exposure to the saturated vapour of the test substance.

Sex:

not specified

Dose descriptor:

LC0

Effect level:

2 842 mg/m³ air

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: The saturation vapour concentration of 2842 mg/m³ is derived from the vapour pressure of 48 Pa at 25 °C by applying the ideal gas laws.

Mortality:

no data

Clinical signs:

other: no data

Body weight:

no data

Gross pathology:

no data

Other findings:

no data

Interpretation of results:

other: no interpretation possible

Remarks:

Criteria used for interpretation of results: not specified

Conclusions:

Each of 6 rats, exposed for 4 hours to a saturated vapours of dimethyl maleate, survived 14 d.

Executive summary:

Rats (6 per group) were exposed to saturated vapours of dimethyl maleate for time periods up to 8 hours. The observation time after exposure was 14 days. The rats, exposed for 4 h, survived 14 d.

The saturation vapour concentration of 2842 mg/m³ is derived from the vapour pressure of 48 Pa at 25 °C by applying the ideal gas law.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

discriminating conc.

Value:

2 800 mg/m³ air

Quality of whole database:

A review article without much details.
The saturated vapour of 2842 mg/m³ did not cause deaths when exposing rats for 4 h.

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1985

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, publication/study report which meets basic scientific principles, but details missing

Qualifier:

according to guideline

Guideline:

other: method of Noaks and Sanderson, 1969

Deviations:

not specified

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 9-12 weeks
- Weight at study initiation: 235-288 (males) and 179-230 (females)

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: ca. 20 cm2. This is less than 10 % of the body surface as required with regards to more actual guidelines.
- Type of wrap if used: occlusive

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 24 hrs

TEST MATERIAL
- Amount(s) applied: 500 or 2000 mg per kg bw

Duration of exposure:

24 hrs

Doses:

500 and 2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days

Sex:

male/female

Dose descriptor:

LD0

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

none

Clinical signs:

other: local erythema followed by necrosis (treated skin, both doses)

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD50 (dermal, rat) was >2000 mg/kg bw.

Executive summary:

The test substance was administered to 2 groups of 5 male and 5 female rats each. Doses were 500 and 2000 mg/kg bw. Duration of administration was 24 hours. Occlusive dressings were used. The animals were observed until 14 days p.a. The surface area treated was 20 cm2 which is less than 10 % of the body surface, as required by more actual guidelines.

No deaths occurred in any group. Local erythema followed by necrosis were noted on the treated skin in both groups.

It was concluded that the LD50 (dermal, rat) was >2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

A guideline study with GLP.
The LD50 is >2000 mg/kg.

Additional information

Justification for selection of acute toxicity – oral endpoint
Three available studies report about the same result, an LD50oral in the range of 1340 to 1909 mg/kg bw. The Smyth study was selected, because it is a study with the usual species rat and not with mice, and with the lower LD50 of both rat studies.

Justification for selection of acute toxicity – inhalation endpoint
The only available study with rats.

Justification for selection of acute toxicity – dermal endpoint
A guideline study with GLP, and the usual species rat.

Justification for classification or non-classification

Acute oral toxicity:

1410 mg/kg body weight is taken as the basis for classification Xn R22, respectively Acute Tox. 4, H302

 

Acute toxicity, inhalation:

An LC0vapour,4h,rat of 2800 mg/m³ is not considered to be sufficient for classification.

Acute dermal toxicity:

The LD50,dermal,rat of >2000 mg/kg is considered as the most appropriate result and no classification is derived for acute dermal toxicity.