4,4'-methylenediphenyldiisocyanate and 2,4'-diisocyanatodiphenylmethane and their oligomerisation reaction products with 2,2'-oxydiethanol, propane-1,2-diol and butane-1,3-diol

Acute Toxicity: other routes

Administrative data

Endpoint:

acute toxicity: other routes

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable well documented study report which meets basic scientific principles.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1963

Report date:

1963

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

BASF-Test: The substance was injected into the peritoneal cavity. Young adult laboratory mice were purchased from breeder. Usually the source and strain of animals were not documented. Several groups of 5 mice per sex and dose were treated simultaneously with preparations of the test substance in suitable vehicle. The concentrations of these preparations were used to achieve comparable volumes per kg body weight. Group-wise documentation of clinical signs was performed over the 7 day study period. Body weight was determined before the start of the study only, as it was needed for determination of dose.

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Methylenediphenyl diisocyanate

EC Number:

247-714-0

EC Name:

Methylenediphenyl diisocyanate

Cas Number:

26447-40-5

IUPAC Name:

1,1'-methylenebis(2-isocyanatobenzene)

Details on test material:

- Name of test material (as cited in study report): Diphenylmethandiisocyanat (MDI), roh
- Physical state: liquid
- Analytical purity: test substance comprises of 4 isomers of MDI in concentration of 5, 15, 25 and 55%

Test animals

Species:

mouse

Strain:

not specified

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Mean body weight at study initiation:
119 mg/kg bw: 33.1 g (30-38 g)
238 mg/kg bw: 35.8 g (31-40 g)
476 mg/kg bw: 34.7 g (30-39 g)
1904 mg/kg bw: 34.5 g (31-37 g)

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

other: aqueous emulsion with Traganth

Details on exposure:

DOSAGE PREPARATION:
- Stock solutions prepared:
2% for the 119, 238 and 476 mg/kg bw dose group;
16% for the 1904 mg/kg bw dose group,

- Dose volume applied:
5 ml/kg bw of the 2% stock solution for the 119 mg/kg bw dose group,
10 ml/kg bw of the 2% stock solution for the 238 mg/kg bw dose group,
20 ml/kg bw of the 2% stock solution for the 476 mg/kg bw dose group,
8 ml/kg bw of the 16% stock solution for the 1904 mg/kg bw dose group.

Doses:

100, 200, 400 and 1600 ml/kg bw (corresponding to 119, 238, 476 and 1904 mg/kg bw) Calculation in mg/kg bw based on density of the test substance (1.19 g/L).

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: mortality and clinical signs of toxicity were observed several times on the application day and thereafter once each working day, body weights were only recorded at the beginning of the study
- Necropsy of survivors performed: yes

Results and discussion

Effect levels

Sex:

male

Dose descriptor:

LD50

Effect level:

ca. 298 mg/kg bw

Mortality:

No mortalities in the lowest dose group, 4/10 died in the 238 mg/kg bw dose group, 7/10 died in the 476 mg/kg bw dose group, and 8/9 died in the 1904 mg/kg bw dose group. One animal died due to injection injury in the 1904 mg/kg bw dose group.

Clinical signs:

Immediately after application, uneasiness, agitation, hollow-back like appearance, accelerated respiration and later silent behaviour with jerky respiration were observed. In next days, animals were in poor general condition and were not without sysmptoms till 7 days post application.

Body weight:

not reported

Gross pathology:

In the deceased animals, substance rests and sticky organs were observed in the abdominal cavity. The medulla renalis of kidney was hyperemic in 5 animals. In the sacrificed animals, substance rests and sticky organs were observed in the abdominal cavity with barely appreciable fibrinous exudate.

Any other information on results incl. tables

Mortalities of rats after ip application of MDI

Dose (mg/kg bw)	Died within
	1 hr	24 hr	48 hr	7 days
119	0/9*	5/9	8/9	8/9
238	0/10	2/10	7/10	7/10
476	0/10	0/10	2/10	4/10
1904	0/10	0/10	0/10	0/10

*: one animal died due to injection injury

LD50: original value reported was 250 ml/kg bw (corresponding to 298 mg/kg bw).