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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
data not available
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

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
Remarks:
/ TDI isomer ratio is specified but the purity is not stated.
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:
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 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: ~10 weeks
- Weight at study initiation: ♀: 144 - 163 g ; ♂: 222 - 272 g
- Housing: two or three per cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: ~6 weeks

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 500 mg/mL
- Preparation: within 2 h of dosing



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: every 30 minutes for the first 8 hours, 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
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
5 110 mg/kg bw
Based on:
test mat.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
4 130 mg/kg bw
Based on:
test mat.
Mortality:
Yes. Mortality increased proportionally 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 10000 or 14700 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. The findings were regarded as 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:
GHS criteria not met