4,4'-methylenedianiline

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:

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1961

Report date:

1961

Materials and methods

Principles of method if other than guideline:

BASF-Test: Test substance was applied by gavage in a 1.25 - 2.5% aqueous traganth suspension. Mortality, clinical signs, and pathology of animals was investigated. Additionally, methemoglobin and Heinz bodies were investigated.

GLP compliance:

no

Test type:

standard acute method

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

Test animals

Species:

cat

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: see table 1

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: aqueous traganth suspension

Details on oral exposure:

1.25 - 2.5% aqueous traganth suspension were used.

Doses:

10, 25, 50, 100, 200, and 400 mg/kg bw

No. of animals per sex per dose:

10: 1 male; 2 female
25: 0 male; 3 female
50: 1 male; 2 female
100: 6 male; 5 female
200: 2 male; 5 female
400: 1 male; 1 female

Control animals:

no

Details on study design:

One application of 1.25 - 2.5% aqueous tragacanth suspension were used.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 50 mg/kg bw

Based on:

test mat.

Mortality:

10: 0/3
25: 1/3; 1 female after 6 days
50: 0/3
100: 7/11; 3 male; 4 female
200: 6/7; 1 male; 5 female
400: 2/2; 1 male; 1 female

Clinical signs:

other: After treatment animals were atonic, staggering and mostly vomitting. Animals had mydriasis, showed no pupil reaction to light and had a reduced corneal sensibility. The animals were amblyopic or suffered from blindness. These chacteristics could be obse

Gross pathology:

Hepatotoxicity:
One day after treatment damage of the liver was observed with a disturbed excretion of bromosulphthaleine. Also the activity of serume glutamate-pyruvate-transaminase was disturbed. High bilirubin levels in urin and icterus were observed. Damage of liver functions seemed to be reversible, but occured beginning with 10 mg/kg bw.
Kidney:
High urea levels were observed in blood, accompanied with high protein, leukocytes, erythrocytes levels in urine. Additionally kidney epithelial cells and granulated cylinders were verified in urine. These characteristics also occured from the dose level 10 mg/kg bw.

Other findings:

Ophthamologigal reevaluation revealed strong mydriasis with no or weak reactivity toward light pulses. Blindeness was diagnosed by unsecure motion of the animals. Animals partly exhibited a spastic constriction of arteries (diameter decreased to approx. half) 43 and 22 days following application of the test substance.

Any other information on results incl. tables

Table 1: Body weights of cats (at study initiation and determination), Met-Hb levels (in %), Heinz bodies (% erythrocytes) and mortalities (day after application).

Dose (mg/kg)	Bodyweight (kg)	Bodyweight (kg)	Methaemoglobine (%)	Dead after days	Killed after day	Heinz bodies (%)	characteristic intoxication
	study init.	end det.
10	3.3	3.2	-	-	-	15	-
	2.7	2.6	-	-	-	8	-
	2.8	2.6	-	-	-	9	-
25	2.5	2.5	-	-	29	28	mydriasis up to blindness, nephrosis
	2.3	2.0	-	-	31	30	mydriasis up to blindness, mild liver and kidney damage
	2.6	2.2	-	6		24	mydriasis up to blindness, mild ikterus
50	2.6	2.4	-	-	54	47	mydriasis up to blindness, mild hepatitis and nephrosis
	2.2	2.0	9	-	54	41	mydriasis up to blindness, hepatitis
	2.2	2.1	11	-	43	76	mydriasis up to blindness
100	2.5	2.2	-	-	-	-	mydriasis up to blindness, ikterus
	3.3	3.1	12	5		14 -73	mydriasis up to blindness, ikterus, liver and kidney damage
	2.3	2.2	-	4		-	mydriasis up to blindness (?), ikterus, mild kidney damage
	2.5	2.3	-	2		-	mydriasis up to blindness, kidney damage
	3.9	3.9	13	2		27 -67	mydriasis up to blindness, mild ikterus, mild liver and kidney damage
	3.6	3.0	11	-	71	26 -45	mydriasis up to blindness, nephrosis
	3.1	2.3	-	-	71	10 -94	mydriasis up to blindness, nephritis and nephrosis
	3.3	2.9	-	-	98	35 -46	mydriasis up to blindness, nephritis
	2.5	2.3	17	2		35 -46	mydriasis up to blindness, kidney damage
	2.9	2.7	-	1		-	mydriasis up to blindness, mild ikterus,
	2.6	2.4	11	3		18 -41	mydriasis up to blindness, mild ikterus, liver and kidney damage
200	2.9	2.6	-	1		-	mydriasis up to blindness, ikterus, kidney damage
	1.7	1.6	15	3		71	mydriasis up to blindness, severe ikterus, liver and kidney damage
	2.9	2.4	-	2		-	mydriasis up to blindness, mild ikterus, kidney damage
	3.6	3.1	-	-	-	12 -83	mydriasis up to blindness
	2.8	2.8	-	1		-	mydriasis,
	3.3	3.0	-	2		-	mydriasis up to blindness,
	2.8	2.6	-	4		-	mydriasis up to blindness, ikterus, liver/kidney damage
400	3.5	3.2	-	2		-	mydriasis,
	2.7	2.7	-	3		6 -24	mydriasis, ikterus, liver/kidney damage

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria