m-tolylidene diisocyanate

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

significant methodological deficiencies

Remarks:

After oral administration, the test substance is degraded very rapidly to a variety of breakdown and polymerization products including 2,4-TDA and 2,6-TDA salts under the acidic conditions in the stomach; this study used a route of exposure inappropriate for assessing occupational risk in humans.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1978

Report date:

1978

Materials and methods

Test guideline

Qualifier:

no guideline followed

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

m-tolylidene diisocyanate

EC Number:

247-722-4

EC Name:

m-tolylidene diisocyanate

Cas Number:

26471-62-5

Molecular formula:

C9H6N2O2

IUPAC Name:

2,4-diisocyanato-1-methylbenzene, 2,6-diisocyanato-1-methylbenzene

Details on test material:

- Name of test material (as cited in study report): TDI unspecified.

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 11 weeks
- Housing: 5♂/5♀ per cage

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Amount of vehicle: 2.5 mL

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

90 days

Frequency of treatment:

daily, 5 days per week, 13 weeks

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

15 mg/kg bw/day (actual dose received)

Doses / concentrations 2

Dose / conc.:

30 mg/kg bw/day (actual dose received)

Doses / concentrations 3

Dose / conc.:

60 mg/kg bw/day (actual dose received)

Doses / concentrations 4

Dose / conc.:

120 mg/kg bw/day (actual dose received)

Doses / concentrations 5

Dose / conc.:

240 mg/kg bw/day (actual dose received)

No. of animals per sex per dose:

10

Control animals:

yes, concurrent vehicle

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily

BODY WEIGHT: Yes
- Time schedule for examinations: weekly

Sacrifice and pathology:

GROSS PATHOLOGY: Yes, all animals

HISTOPATHOLOGY: Yes
All control and high dose animals on 28 tissues as well as on intercurrent deaths. Low and mid dose animals were subjected to similar histopathologic examination if high dose animals displayed effects.

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

See table 1.

Mortality:

mortality observed, treatment-related

Description (incidence):

See table 1.

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

A depression in body weight gain in males treated at 60 mg/kg and above and in females treated at 120 mg/kg and above was observed.

Food consumption and compound intake (if feeding study):

no effects observed

Gross pathological findings:

not specified

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

See table 3.

Effect levels

1

Key result

Dose descriptor:

NOAEL

Effect level:

30 mg/kg bw/day (actual dose received)

Sex:

male

Basis for effect level:

clinical signs

2

Key result

Dose descriptor:

NOAEL

Effect level:

60 mg/kg bw/day (actual dose received)

Sex:

female

Basis for effect level:

clinical signs

Any other information on results incl. tables

Table 1: Clinical signs and mortality

Dose (mg/kg bw)	60	120	240
Mortality (intercurrent deaths)	1/10 males	2/10 males	1/10 females
Respiratory noises	1/10 males	1/10 males	3/10 males

Table 2: Body weight

Dose (mg/kg bw)	Body weight (% controls at week 12)
	♂	♀
60	97.7	100
120	90.7	96.4
240	89.7	94.8

Table 3: Histopathology

Dose (mg/kg bw)	60	120	240
Mucoid bronchopneumonia (accumulation of mucoid material in the bronchioles) - mild to moderate - moderate to severe - less severe	1/10 males	3/10 males 1/10 females	8/10 males 2/10 females