4-methyl-m-phenylene diisocyanate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

data not available

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Similar to guideline study. No GLP. TDI isomer ratio is specified but the purity is not stated.

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Toxicology and Carcinogenesis studies of commercial grade 2,4(80%)- and 2,6(20%)- toluene diisocyanate (CAS No. 26471-62-5) in F344/N rats and B6C3F1 mice (gavage studies)

Author:

National Toxicology Program

Year:

1986

Bibliographic source:

NTP TR 251, NIH Publication No. 86-2507, US Dept. of Health and Human Services, NC, USA

Reference 2

Reference Type:

publication

Title:

Toxicology, industrial hygiene and medical control of TDI, MDI and PMPPI

Author:

Woolrich PF

Year:

1982

Bibliographic source:

Am. Ind. Hyg. Assoc. J. 43 (2): 89-97

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

no

Test type:

standard acute method

Limit test:

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:

C9 H6 N2 O2

IUPAC Name:

m-tolylidene diisocyanate

Details on test material:

- Name of test material (as cited in study report title): commercial grade 2,4(80%)- and 2,6(20%)- toluene diisocyanate (CAS No. 26471-62-5)

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Frederick Cancer Research Center (Frederick MD)
- Age at study initiation: approximately 10 weeks old
- Weight at study initiation: 144-163 g for female; 222-272 g for male
- Fasting period before study: no data
- Housing: two or three per cage
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: approximately 6 weeks


ENVIRONMENTAL CONDITIONS: no data



IN-LIFE DATES: no data

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 500 mg/ml
- Amount of vehicle (if gavage): data not available
- Justification for choice of vehicle: data not available.



MAXIMUM DOSE VOLUME APPLIED: data not available

Doses:

2150, 3160, 4640, 6810, 10000, 14700 mg/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
- Frequency of observations (1) and weighing (2):
(1) Observations for mortality: they were made every 30 minutes for the first 8 hours and then daily for the rest of the study,
(2) Weighing: on test day 1 (prior to administration) and on day 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs.

Statistics:

no statistical analysis was used

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

5 110 mg/kg bw

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

4 130 mg/kg bw

Mortality:

Yes. Mortality was proportional to the dose of substance administered. For more details see Table 1 in the text field "remarks on results including tables and figures".

Clinical signs:

other: At 10,000 or 14,700 mg/kg death was preceded by laboured breathing,  inactivity and diarrhea.

Gross pathology:

No macroscopic findings were reported.

Other findings:

White crystals in  stomach and dark red lungs were found at necropsy, findings were dose related.

Any other information on results incl. tables

Table 1: Number of animals dead and time range within which mortality occured

Dose (mg/kg bw)	Mortality (# dead/total)			Time range of deaths (days)
	Male	Female	Combined
2150	2/5	0/5	2/10	(5-9)
3160	3/5	2/5	5/10	(1-14)
4640	2/5	2/5	4/10	(2-10)
6810	2/5	5/5	7/10	(2-5)
10000	5/5	4/5	9/10	(1-3)
14700	5/5	5/5	10/10	(1-2)

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: other: EU-GHS

Conclusions:

The commercial grade 2,4 (80 %)-and 2,6 (20 %)-TDI was not considered to be toxic by this route. This test substance is not classified according to EU criteria and the EU-GHS.

Executive summary:

In an acute oral toxicity study (NTP, 1986), groups of 10 weeks old F344/N rats (5/sex) were given a single oral dose of commercial grade toluene diisocyanate (80% 2,4- and 20% 2,6 -) in corn oil by gavage at doses of 2150, 3160, 4640, 6810, 10000, 14700 mg/kg bw and observed for 14 days. Mortality was proportional to the dose of substance administered. Loss in mean body weight was greater than 10 g in all groups of dosed males. In rats receiving 10,000 or 14,700 mg/kg death was preceded by labored breathing, inactivity, and diarrhea. White, crystalline material was found in the stomach and dark red lungs were observed at necropsy: these findings were dose related. Under the conditions of this test, the acute oral LD50 is > 2,000 mg/kg.