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Description of key information

The acute oral toxicity in rats is between 400 and 800 mg/kg bw for male and female. LD50 for acute oral toxicity is 400 mg/kg bw.
The acute dermal toxicity of TGIC is low , the LD50 is >2000 mg/kg bw for both genders.
The lowest acute inhalation toxicity value in rats is 1083 mg/m3 air for female rats while for male rats the value is 5040 mg/m3 air. Then the LC50 for acute inhalation is 3400 mg/m3 air.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
400 mg/kg bw
Quality of whole database:
Several studies available. The main deficiency is the lack of analytical data for the older studies.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study is selected as the key study because it includes both males and females, used the test material with the smaller particle size, has been performed according to current Guidelines and according to GLP regulation.
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
The exact name of the rat strain is Crl:HanWist(GlxBRL)BR
The rats were acclimatized for about 5 days in an animal room with 12-hour dark/light cycle, 21 - 23°C, and a rel. humidity of 55 - 65%.
Route of administration:
inhalation: dust
Type of inhalation exposure:
head only
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
4-hour inhalation , followed by a 14-day observation period.
Temperature in the exposure chamber was 17 - 24°C with a rel. humidity of 20 - 65% for control and treated groups.Air flow was 12 litre/min for all groups, oxigen concentration was 19.5 - 21.4 %
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
ca. 4 h
Concentrations:
Nominal: 2.80 mg/L ; measured 1.14 mg/L (group 1)
Nominal: 4.62 mg/L; measured 2.76 mg/L (group 2)
Nominal: 8.16 mg/L; measured: 5.04 mg/L (group 3)
No. of animals per sex per dose:
group 1: 0 males / 5 females
group 2: 0 males / 5 females
group 3: 5 males / 5 females
Control animals:
yes
Statistics:
none
Preliminary study:
none
Sex:
female
Dose descriptor:
LC50
Effect level:
ca. 1.14 mg/L air (analytical)
Exp. duration:
4 h
Sex:
male
Dose descriptor:
LC50
Effect level:
ca. 5.04 mg/L air (analytical)
Exp. duration:
4 h
Mortality:
Group 1: 1/5 females (day 1)
Group 2: 5/5 femlaes (1 on day 1, 3 on day 2, 1 on day 5)
Group 3: 3/5 females (all on day 3) and 1/5 males (day 7)
Clinical signs:
other: Coldness , gasping , paleness, piloerection, hunched posture, prostration, noisy respiration, nasal discharge, lethargy, tremors, vocalisation, and semi-closed eyes were observed among all dose groups.
Body weight:
Treated rats lost more weight during the day of exposure than the control rats, but by the end of the observation period all gained similar weight as controls except high dose group animals
Gross pathology:
Lung weights of dead or in extremis killed animals were heavier than those of the controls, but the lungs of surviving rats were comparable to those of the control group.
Other findings:
Apart from discoloration of the lungs and distention of parts of the intestinal tract, no substance -related findings were recorded.

The four - hour acute median lethal dose for female rats was calculated (probit method) to be 1.83 mg/l air.

For Male rats no such value was calculated , but as 2/5 males died at 5.04 mg/L air. The LC 50 is approximately 5 - 6 mg/L

Interpretation of results:
moderately toxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LC50 of female rats (most sensitive sex) is calculated to be 1.83 mg/L.
The LC50 of male rats is approximately 5-6 mg/L, as only a dose of 5.04 mg/L was tested with 2/5 male rats showing lethal effects
Executive summary:

The LC50 of femlae rats (most sensitive sex) is calculated to be 1.83 mg/L. The LC50 of male rats is approximately 5-6 mg/L, as only a dose of 5.04 mg/L was tested with 2/5 male rats dying upon inhalation of TEPIC-SP with a median aerodynamic diameter of 1.70 - 2.06 micrometers.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
3 400 mg/m³
Quality of whole database:
Several studies available. The main deficiency is the lack of analytical data for some of the older studies and the testing of only one sex. T

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Three studies available. All show an LD50> 2000 mg/kg bw without clinical signs.The most recent study is the key study due to highest quality.

Additional information

Triglycidyl isocyanurate is toxic to laboratory animals following acute oral administration and inhalation exposure. The oral LD50 for triglycidyl isocyanurate ranges from 400 to 800 mg/kg body weight in rats. Clinical signs of toxicity observed prior to death included hunched appearance, squinting eyes, rough haircoat, discolored red skin on the nose, and/or general debilitation. Pathological findings included enlarged stomach in female given 800 mg/kg bw.

The acute inhalation study was performed with a 4-hour lasting exposure to particles, followed by a 14-day observation period. The mass median aerodynamic diameter of the inhalable particles in the atmosphere was 1.70 - 2.06 micrometer. Air flow was 12 litre/min for all groups, the oxygen concentration was 19.5 - 21.4 %. Group 1 was exposed to analytically determined 1.14 mg/L and consisted of 0 males and 5 females. Group 2 was exposed to analytically determined 2.76 mg/L and consisted of 0 males and 5 females. Group 3 was exposed to analytically determined 5.04 mg/L and consisted of 5 males and 5 females. Clinical signs: Gasping , paleness, piloerection, hunched posture, prostration, noisy respiration, nasal discharge, lethargy, tremors, vocalisation, and semi-closed eyes were observed among all dose groups. Treated rats lost more weight during the day of exposure than the control rats, but by the end of the observation period group 1 and 2 animals gained similar weight as controls. The bodyweight effect was still present in the high dose group animals at the end of the observation period. Lung weights of dead or in extremis killed animals were heavier than those of the controls, but the lungs weights of surviving rats were comparable to those of the control group. Apart from discoloration of the lungs and distension of parts of the intestinal tract, no substance -related findings were recorded. The LC50 of female rats (the more sensitive sex) is 1.83 mg/L, the LC50 of male rats is approximately 5-6 mg/L.

The dermal LD50 for rats was >2000 mg/kg body weight. There were no deaths or exposure-related adverse clinical signs; at necropsy, no gross organ changes were observed.


Justification for selection of acute toxicity – oral endpoint
Several studies available. The key study selected is the most recent one performed with TGIC and is of the highest quality.

Justification for selection of acute toxicity – inhalation endpoint
Several studies available. The key study selected is the most recent one performed with TGIC and is of the highest quality. The key study shows a significant difference between males and females LC50 values. The LC50 used is the mean of female and male LC50 values.

Justification for classification or non-classification

As the dermal LD50 is > 2000 mg/kg bw , there is no reason to classify the substance; however, the oral LD50 is between 400 and 800 mg/kg bw and the inhalation toxicity (LD50 = 650 mg/m3air) justify to classify the substance with T; R23/25.