1,3,5-triallyl-1,3,5-triazine-2,4,6(1H,3H,5H)-trione

Endpoint summary

Description of key information

Oral (OECD 401), rat: LD50 (female): 812 mg/kg bw; LD50 (male): 707 mg/kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Dose descriptor:

LD50

Value:

707 mg/kg bw

Additional information

Oral

The acute oral toxicity of triallyl isocyanurate was examined in a GLP study according to OECD guideline 401 (2003-0758-FGT). The test substance was administered via gavage to Crj:CD(SD)IGS rats (5/sex/dose) at concentrations of 250, 500, 1000 and 2000 mg/kg bw. A control group received the vehicle olive oil. All animals of the high dose group died within 5 days after administration. In the 1000 mg/kg bw group the death of all males and 4 females occurred. In the animals that died, reduced locomotor activity, staggering gait, tremors, clonic convulsions, hypothermia, mydriasis and smudging in the peri-genitourinary area were observed the day following administration or in females of the 1000 mg/kg bw group from day 2 after administration. In addition, body weights decreased until death. Necropsy of animals that died revealed malnutrition, small thymi and spleens, small mesenteric lymph nodes, white foci in the forestomach and dark red foci in the glandular stomach. The white foci in the forestomach were noted on the fundal end and indicative of histopathological erosion/ulceration in the mucosa and thickening of mucosal epithelium of the forestomach. The surviving animals of the 250 and 500 mg/kg bw showed suppressed body weight gain until day 2 of administration, but no abnormal behaviour. Necropsy revealed white foci in the forestomach of one female rat of the 500 mg/kg bw group and in the female surviving the single application of 1000 mg/kg bw. LD50 values of 707 mg/kg bw for males and 812 mg/kg bw for females were determined, respectively.

In another acute oral toxicity study performed in 1976, male rats (3/dose) were given a single dose of triallyl isocyanurate at concentrations of 126, 253, 500, 1000 and 2000 mg/kg bw (TSCA Section 8(e), Doc-ID 88-920002607). 2 rats at 2000 mg/kg bw and one rat at 1000 mg/kg bw died within 7 days after dosing. Thus, the LD50 was considered to be ca. 1000 mg/kg bw. In the two high dose groups lethargy, inability to walk, convulsions, tremors and red secretions around the nose were noted. Pathology of one surviving animal of each dose group at day 6 p.a. revealed overdistended stomachs in rats dosed with 500, 1000, 2000 mg/kg bw. In addition, in the rat administered 2000 mg/kg bw diffuse pale discoloration of the liver was examined and in the glandular mucosa of the stomach multiple gastric ulcerations covered by hemolyzed blood clots were noted. In the small intestine of rats at 1000 and 2000 mg/kg bw more fluid ingesta was observed.

In a not-reliable publication by Bidnenko (1969), LD50 values for triallyl isocyanurate of ca. 700 mg/kg bw for rat and ca. 437 mg/kg bw for mouse were reported, respectively. The animals were administered the test substance in aqueous solutions via gavage at different concentrations. Toxic concentrations revealed weakness, apathy and increased respiratory rate. 20 - 30 minutes after administration of toxic doses animals had convulsions. Some animals showed coordination disturbance. In most cases death occurred 1.5 and 4 h after administration of the test solution. At a concentration of 400 mg/kg bw for rat and 300 mg/kg bw for mouse, respectively no mortality occurred. No signs of toxicity were observed in surviving animals during the 3 weeks observation period.

Inhalation

Rats (six males/dose) were exposed head only to particles of triallyl isocyanurate on synthetic calcium silicate at concentrations of 1.09, 1.28, 1.42 and 1.86 mg/L for 4 hours(78-0306-FKT). The content of triallyl isocyanurate in the inhaled particles was 74% and the mass median diameter of the particles ranged between 1.20 µm and 3.5 µm. No animals died during the 14-day observation period. Discharge from nose and eyes and redness around eyes were observed in all dose groups. In the 1.42 mg/L and 1.86 mg/L dose group sporadic salivation were noted. One animal of the high dose group showed irregular respiration and lethargy immediately after exposure. Weight loss to different extents was observed in all dose groups. The LC50 was considered to be > 1.86 mg triallyl isocyanurate on synthetic calcium silicate/L. 1.86 mg/L represented the maximum attainable concentration with the used generating facility.

Triallyl isocyanurate has a very low vapour pressure at room temperature (0.00017 Pa at 20 °C)at which exposure via the inhalation route can be considered negligible and formation of aerosols is unlikely.By following appropriate risk management measures and operational conditions, the inhalative exposure to triallyl isocyanurate in industrial settings is adequately controlled and the exposure levels are considered to be safe (for details refer to CSR Section 9 and 10).Due to the low vapour pressure, exposure considerations und animal welfare considerations, further testing by the inhalation route does not need to be conducted.

Dermal

In a non-reliable study by Bidnenko (1969), dermal application of triallyl isocyanurate for 2 hours caused general toxic effects including death of rats. According to the method by Behrens and Schlosser a LD50 value of 2750 mg/kg bw was calculated.

Only insufficient documentation is provided in the publication by Bidnenko and the exposure period of 2 h differs significantly from the proposed 24 h exposure period in dermal acute toxicity studies according to current OECD Guidelines. Thus, the LD50 value is inappropriate for classification purposes.

A general prerequisite for systemic toxicity after dermal application is the permeability of the skin for the applied substance. The dermal permeability constant Kp of triallyl isocyanurate was estimated to be 0.00198 cm/h using the QSAR published by Potts and Guy (1992) considering the log Pow of 2.2 at pH 5 - 6 and the molecular weight of 249.27 g/mol. Further on the maximum flux Imax (Imax = Kp [cm/h] x water solubility [mg/cm³]) was calculated similar to the approach taken by Kroes et al. (2007) and resulted in a value of 6.947 µg/cm²/h for triallyl isocyanurate. This flux value represents a moderate dermal absorption potential and can be assigned to a dermal absorption of 50 % (Mostert and Goergens, 2011). Therefore, the dermal bioavailability is definitely lower than after oral administration. The gastrointestinal absorption is reported as 100% for a dose of 1 mg (Danish (Q)SAR Database Report, 2005)

Since triallyl isocyanurate does not cause local effects and specific first-pass effects are excluded, extrapolation from oral data can be considered appropriate for the evaluation of dermal systemic effects. Taking into account an oral LD50 of 707 mg/kg bw for male rats and an dermal absorption of 50 %, extrapolation results in a dermal LD50 value triggering a classification as "Acute Dermal 4 (H312)" according to Regulation (EC) 1272/2008 and as "Xn (R21)" according to Directive 67/548/EEC.

As shown by the risk assessment the dermal exposure levels of workers can be considered adequately controlled (for details refer to CSR Section 9 and 10), since relevant operational conditions are implemented and workers are wearing protective gloves at the respective worker scenarios in industrial applications , where exposure to triallyl isocyanurate may occur.

Route-to-route extrapolation can be considered adequate for the purpose of classification and labeling and for the risk assessment of acute dermal toxicity of triallyl isocyanurate. Moreover, taking into account exposure and animal welfare considerations, further testing by the dermal route is not appropriate.

Justification for classification or non-classification

Oral:

The available data on acute oral toxicity of the test substance meet the criteria for classification as "Acute Oral 4 (H302)" according to Regulation (EC) 1272/2008 and as "Xn (R22)" according to Directive 67/548/EEC.

Inhalation:

The available data on acute inhalation toxicity is inconclusive.

Dermal:

Based on extrapolation from the oral route, triallyl isocyanurate meets the criteria for classification as "Acute Dermal 4 (H312)" according to Regulation (EC) 1272/2008 and as "Xn (R21)" according to Directive 67/548/EEC.