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EC number: 218-485-4
CAS number: 2162-73-4
EFFECTS OF INHALATION
The mortality data in the study by Duncan et
al. (1962) were obtained through exposure of four animal species (mice,
rats, guinea pigs and rabbits) to one of the following concentrations:
0.1, 1.0, 2.0, 5, 10, 20 and 34 ppm of TDI for one 4 -hour period. They
were observed for 28 days following the exposure. The inhalation 14 -day
LC50 for each of the four species was as follows:
LC50 (rat): 14 ppm/4h
LC50 (mouse): 10 ppm/4h
LC50 (rabbit): 11 ppm/4h
LC50 (gpg): 13 ppm/4h
EFFECTS OF INGESTION
Data developed by Litton Bionetics (1976)
(cross-reference not available) in connection with the National Cancer
institute's Chemical Carcinogenesis Bioassay Program (cross-reference
not available) points out that oral administration of TDI to rats is
associated with the accumulation of an abnormal amount of mucinous
material in the pulmonary bronchioles. These data present:
Oral LD50 (male rats): 5110 mg/kg
Oral LD50 (female rats): 4130 mg/kg
Oral LD50 (male mice): 4130 mg/kg
Oral LD50 (female mice): 5620 mg/kg
EFFECTS OF SKIN
TDI was applied separately to the intact and
abraded skin of albino rabbits at single dosage levels of 2.5, 3.9, 6.0
and 9.4 g/kg as described by the International Research and Development
Corp. (January, 1964). No pharmacodynamic signs were observed at any
time during the 14-day observation period following the single
application of TDI. All rabbits survived the course of study. The
application of TDI at all dosage levels resulted in delayed dermal
irritation, including moderate-to-marked erythema, oedema, atonia and
coriaceousness, followed by desquamation and fissuring of the skin. All
skin lesions had repaired by the 14th day of observation.
EFFECTS ON EYES
Investigations by the International Research
and Development Corp. (March, 1964) gave the following results.
Application of TDI to the eyes of rabbits produced corneal opacity in
two animals which failed to clear in 30 days. All seven other rabbits
appeared normal by the seventh post-treatment day. Circumcorneal
injection of the iris was observed in all groups treated. In some
animals this continued through the seventh day post-treatment, but
cleared by the eighth day. Irritation of the conjunctivae appeared
within a few hours after instillation of TDI and persisted in some
animals from 18 to 20 days. Purulent ocular discharge was exhibited in
all animals treated. In a few animals purulent discharge continued for
20 days after treatment. TDI was also observed to cause a loss of hair
around the treated eyes of 7 of the 9 rabbits subjected to this chemical.
MUTAGENITY AND CARCIONOGENITY
A publication by Anderson et al. (1980)
reports that TDI is mutagenic to Salmonella typhimurium strains
TA1538 and TA98 after activation. The authors ascribe the effect to the
amine analogue (TDA) formed during the hydrolysis of the isocyanate.
Earlier reports by the U.S. Department of Health, Education and Welfare
(1978) show that TDI is not mutagenic to Salmonella lyphimurium
in the presence of a mammalian liver activating system.
The report reviews different publications
and international research reports concerning animal toxicity test
results for toluene diisocyanate (TDI). Effects of inhalation,
ingestion, skin, eyes as well as mutagenicity and carcinogenicity are
considered and compared to one another.
The LC50 value of 10 ppm/4h for mice
(inhalation) and the LD50 value of 4130 mg/kg for female rats as well as
male mice (oral) are described as the most critical ones. The exposure
of 2.5 g/kg (single dose) TDI to the intact and abraded skin of albino
rabbits caused delayed dermal irritation, including moderate-to-marked
erythema, edema, atonia and coriaceousness, followed by desquamation and
fissuring of the skin. In addition, skin lesions occur. Eye effects such
as irritation and loss of hair around treated eyes were observed.
Contradictory results referring to mutagenicity were provided by
different publications applying Ames test. Furthermore, no evidence of
carcinogenicity, teratogenicity or reproductive effects in humans or
animals were reported.
Furthermore, the NIOSH (National Institute
for Occupational Safety and Health) has set the TLV (Threshold Limit
Value) for diisocyanates at 0.005 ppm for a time-weighted average for up
to a 10 -hour workshift, 40 -hours workweek and 0.02 ppm as a ceiling
concentration for any 10 -minute sampling period.
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