Maleic anhydride

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Data source

Reference

Reference 1

Reference Type:

review article or handbook

Title:

Maleic Anhydride and Maleic Acid

Author:

OECD

Year:

2004

Bibliographic source:

SIDS Initial Assessment Report for SIAM 18 Paris, France, 20-23 April 2004

Reference 2

Reference Type:

other: secondary source

Title:

Unnamed

Year:

1984

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Maleic anhydride

EC Number:

203-571-6

EC Name:

Maleic anhydride

Cas Number:

108-31-6

Molecular formula:

C4H2O3

IUPAC Name:

2,5-dihydrofuran-2,5-dione

Details on test material:

- Analytical purity: 99.7%

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: mean body weights in females 113 g and in males 134 g

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 (+/- 1)
- Humidity (%): 60 (+/- 5)

Administration / exposure

Route of administration:

oral: unspecified

Vehicle:

water

Details on oral exposure:

The test substance was formulated with distilled water warmed to approximately 50 °C.

Doses:

1.0, 1.125, 1.25 and 1.99 g/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 090 mg/kg bw

Based on:

test mat.

Mortality:

Number of deaths:
1.0 g/kg bw = 1 male and 1 female
1.125 g/kg bw = 2 males and 4 females
1.25 g/kg bw = 4 males and 5 females
1.99 g/kg bw = 5 males and 5 females

Clinical signs:

other: Two animals in the 1.0 mg/kg dose group, six animals in the 1.125 g/kg dose group, nine animals in the 1.25 g/kg bw dose group and all animals in the 1990 mg/kg bw dose group showed signs of toxicity. Signs of toxicity began 15 minutes post-application an

Gross pathology:

Postmortem examinations showed hyperemia of the stomach an duodenum mucous membranes, liver congestion, and spotted and pale kidneys.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Based on the results, the LD50 value was determined to be 1090 mg/kg bw. Thus, the substance meets the criteria of the CLP regulation 1272/2008 for being classified as Acute Tox. 4, H302.

Executive summary:

In an acute oral toxicity study (OECD 401), four groups of male and female Wistar rats (5 rats/sex/dose) were given a single oral dose of 1.0, 1.125, 1.25, or 1.99 g/kg bw of maleic anhydride (99.7 % purity). After treatment the animals were observed for 14 days. All animals treated with 1.99 g/kg bw died, four males and five females treated with 1.25 g/kg bw died, two males and four females treated with 1.125 g/kg bw died and one male and one female treated with 1.0 g/kg bw died. Furthermore, two animals in the 1.0 g/kg bw dose group, six animals in the 1.125 g/kg bw dose group, nine animals in the 1.25 g/kg bw dose group and all animals in the 1.99 g/kg bw dose group showed signs of toxicity. The signs of toxicity began 15 minutes post-application and included sedation and ataxia, ruffled fur, squatting posture, staggering gait, breathing difficulty, tremors, convulsions and glassy eyes. At necropsy, hyperaemia of the stomach and duodenum mucous membranes, liver congestion, and spotted and pale kidneys were observed.

Based on the results and in accordance with OECD guideline 401 the LD50 value was determined to be 1090 mg/kg bw. Thus, the substance meets the criteria of the CLP regulation 1272/2008 for being classified as Acute Tox. 4, H302.