Dimethyl maleate

Endpoint summary

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:

other information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline with restrictions (method shortly described; LD50 expressed in mL/kg instead of mg/kg; animals not fasted before exposure).

Reason / purpose for cross-reference:

reference to same study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

method shortly described; LD50 expressed in mL/kg instead of mg/kg; animals not fasted before exposure.

GLP compliance:

no

Remarks:

GLP was not mandatory at the time of the study

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Winkelmann, Germany.
- Weight at study initiation: 160-180 g.
- Housing: animal were housed in groups of 5 animals per cage.

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

Observation period: 14 days.

Doses:

Doses: 1.0, 1.5, 1.8, 2.0, and 3.1 mL/kg (1150, 1750, 2070, 2300, 3565 mg/kg bw).

No. of animals per sex per dose:

10

Control animals:

other: not necessary

Statistics:

The calculation of the LD50 was performed according to Fink and Hund, Arzneim.-Forsh 15, 1965, 624.

Sex:

male

Dose descriptor:

LD50

Effect level:

1 909 mg/kg bw

95% CL:

1 644 - 2 116

Remarks on result:

other: rat

Mortality:

Mortality occurred at doses of 1750 mg/kg bw and higher concentrations.

Clinical signs:

other: Toxic symptoms: reduction of general conditions.

LD 50= 1.66 mL/kg. The density of dimethyl maleate is 1.15 g/cm³ at 20 °C. Therefore LD50 expressed in mg/kg is calculated to be 1909 mg/kg.

Table 1. Acute oral toxicity results

Dosis mg/kg b.w	Time of death	Toxicological Results Dead animals/ Aanimals with symptoms/Animals used
1150	-	0/0/10
1750	2 -5^d	3/10/10
2070	2 -7^d	7/10/10
2300	2 -4^d	8/10/10
3565	4^h -2^d	10/10/10

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Based on the study results and according to EU classification criteria, the test substance is classified as Acute Tox. 4, according to the CLP regulation.

Executive summary:

Bayer (1977)

 

In an acute oral toxicity 10 non-fasted male rats were administered with 1150, 1750, 2070, 2300, 3565 mg/kg bw dimethyl maleate with a method similar to OECD guideline 401 with acceptable deviations (method shortly described; LD50 expressed in mL/kg instead of mg/kg; animals not fasted before exposure).

The animals were observed for 14 days after administration.

Mortality occurred at doses of 1750 mg/kg bw and higher concentrations. Reduction of general conditions was observed. The acute oral LD50 was calculated to be 1909 mg/kg bw.

Based on the study results and according to EU classification criteria, the test substance is classified as Acute Tox. 4, according to the EU-CLP regulation.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 909 mg/kg bw

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP-Guideline study with restrictions (analytical purity not reported; occlusive dressing instead of porous dressing).

Reason / purpose for cross-reference:

reference to same study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

analytical purity not reported, occlusive dressing instead of porous dressing.

Principles of method if other than guideline:

This study was conducted using the method of Noaks and Sanderson (1969). British Journal of Industrial Medicine 26:59-64.

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:

- Age at study initiation: 9-12 weeks old.
- Weight at study initiation: 235-288 g (males); 179-230 g (female).

Type of coverage:

occlusive

Vehicle:

not specified

Details on dermal exposure:

5/rats/sex/group received a single application of 500 or 2000 mg MAD/kg body weight on their shaved backs (area approx. 20 cm²), and this was covered with an occlusive dressing for 24 hours. The rats were observed for 14 days after application, and systemic and local effects were recorded.

Duration of exposure:

24 hours

Doses:

500 or 2000 mg of dimethyl maleate/kg body weight.

No. of animals per sex per dose:

5/sex/ group

Control animals:

no

Details on study design:

Details on study design
- Duration of observation period following administration: 14 days.
- Examinations performed: systemic and local effects were recorded.

Statistics:

no data

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Remarks on result:

other: rat

Mortality:

No deaths occurred after application of 500 or 2000 mg dimethyl maleate/kg body weight.

Clinical signs:

other: No systemic effects occurred after application of 500 or 2000 mg dimethyl maleate/kg body weight. Local erythema followed by necrosis could be observed in the treated skin in both groups.

Interpretation of results:

GHS criteria not met

Executive summary:

Heimann (1991)

Acute dermal toxicity study was conducted according to OECD guideline 402 with acceptable restrictions (analytical purity not reported, occlusive dressing instead of porous dressing).

5 rats/sex/group received a single application of 500 or 2000 mg dimethyl maleate/kg body weight on their shaved backs (area approx. 20 cm²), and this was covered with an occlusive dressing for 24 hours. The rats were observed for 14 days after application, and systemic and local effects were recorded.

No deaths and no systemic effects occurred after application of 500 or 2000 mg dimethyl maleate/kg body weight. Therefore, the LD50 was concluded to be greater than 2000 mg/dimethyl maleate body weight. Local erythema and followed by necrosis could be observed on the treated skin in both groups.

Based on the study results and according to EU and EU-CLP classification criteria, the test substance is not to be classified.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Justification for classification or non-classification

Acute oral toxicity:

The acute oral LD50 was calculated to be 1909 mg/kg bw. Based on the study results,  the test substance is classified as Acute Tox. 4, according to the EU-CLP regulation.

 

Acute dermal toxicity: 

The LD50 was concluded to be greater than 2000 mg/kg bw. Based on the study results and according to  EU-CLP classification criteria, the test substance is not to be classified.