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Toxicological information

Acute Toxicity: oral

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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

Referenceopen allclose all

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 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

Constituent 1
Chemical structure
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 levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
5 110 mg/kg bw
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:
At 10,000 or 14,700 mg/kg death was preceded by laboured breathing,  inactivity and diarrhea.
Body weight:
Weight loss in all male survivors.
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.