4,4'-methylenedianiline

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1976

Report date:

1976

Materials and methods

Principles of method if other than guideline:

Noakes, D.N. and Sanderson, D.M.: A Method for Determining the Dermal Toxicity of Pesticides. Brit. J. Industr. Med. 26,59 (1969).

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

4,4'-methylenedianiline

EC Number:

202-974-4

EC Name:

4,4'-methylenedianiline

Cas Number:

101-77-9

Molecular formula:

C13H14N2

IUPAC Name:

4,4'-methylenedianiline

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Purity: >98 %

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: SPF-breed, Wiga, Sulzfeld, Germany
- Weight at study initiation: 155 g
- Diet: Altromin-R, Lage, Germany, ad libitum
- Water: ad libitum

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

other: water or DMSO

Details on dermal exposure:

TEST SITE
shaved skin of back- and side flank, under semiocclusive cover, permeable to air.
- Area of exposure: 50 cm²

REMOVAL OF TEST SUBSTANCE
- Washing: no data

TEST MATERIAL
- Concentration: 50%

Duration of exposure:

24 h

Doses:

Aqueous solution: 1000 mg/kg and 2500 mg/kg bw
DMSO solution: 500, 1000, 1250, 2000, 2500 mg/kg bw

No. of animals per sex per dose:

10

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes

Statistics:

Litchfield and Wilcoxon

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 080 mg/kg bw

95% CL:

ca. 1 631 - ca. 2 652

Remarks on result:

other: 50% DMSO solution

Effect levels 2

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 500 mg/kg bw

Remarks on result:

other: 50% aqueous solution, no mortalities

Mortality:

50% DMSO solution: at 1000 mg/kg bw and higher, animals started to die during the first week (see table 1).
50% aqueous solution: no mortalities

Clinical signs:

other: 50% DMSO solution: Animals at all doses displayed marked apathy, hyperchromodacryorrhea, and intensely stained yellow urine. At the dose levels of 500-2000 mg/kg bw, poisoning symptoms were no longer observed 6-9 days after the beginning of the test. A

Gross pathology:

50% DMSO solution: animals which died, and some of those sacrificed after 14 days, exhibited a bright, clay-coloured to yellowish colour change of the liver parenchyma. In the case of the 2500 mg/kg bw dose group, some of the 10 animals which died displayed an extreme, general jaundice, and some displayed a slimy to bloody enteritis, as well as bleeding stomach ulcers.
50% aqueous solution: no effects

Any other information on results incl. tables

Table 1: Mortalities after application of 50% MDA in DMSO

	500 mg/kg bw		1000 mg/kg bw		1250 mg/kg bw		2000 mg/kg bw		2500 mg/kg bw
	male	female	male	female	male	female	male	female	male	female
1 h	0/10	0/10	0/10	0/10	0/10	0/10	0/10	0/10	0/10	0/10
1 d	0/10	0/10	0/10	0/10	0/10	0/10	0/10	0/10	0/10	0/10
2 d	0/10	0/10	0/10	0/10	0/10	0/10	0/10	0/10	0/10	0/10
7 d	0/10	0/10	0/10	5/10	0/10	0/10	2/10	9/10	3/10	7/10
14 d	0/10	0/10	0/10	5/10	0/10	0/10	2/10	9/10	3/10	7/10

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met