Registration Dossier

Administrative data

Description of key information

In a 90-day oral toxicity study in rats the NOAEL was determined to be 1.05 mg/kg/day, based on hematological effects and effects in the mesentheric lymph nodes. Dosing up to 50 mg/kg/day caused severe body weight reduction, and lymphoid depletion of spleen and thymus.
In a 5-day mouse inhalation study with exposures for 6 hours per day, at 100, 300 and 750 mg/m3 air caused significant mortality but exposure was too short to see organ effects. No NOAEL was established indicating that the NOAEL is < 100 mg/m3 air.
In a 26-week skin -tumour promotion study no toxic effects were observed apart from acanthosis at the application site indicating that TGIC did not penetrate the skin in significant amounts except to cause irritqtion and sensitization.
A study with mice , dogs, guinea pigs and white rabbits using the intravenous route of exposure, showed mortality, reduced organ weights, haematological effects and signs of neurotoxicity especially in dogs. However, dosing was too short (5 daily injections) to get a clear picture of the neurological effects.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
1.05 mg/kg bw/day

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Dose descriptor:
LOAEC
25 mg/m³

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
200 mg/kg bw/day

Additional information

The effects observed in studies with oral, inhalation and intravenous exposure to various concentrations of TGIC showed as major effects mortality, body weight and organ weight reductions ( due to palatability effects in the oral study), hematological effects (reduced leucocyte and lymphocyte numbers), effects on the mesenteric lymph system and depletion of lymphocytes in the thymus and spleen, as well as some clinical signs in dogs which could be interpreted as neurological effects at high dose levels..

As TGIC is rapidly hydrolysed and excreted, no accumulation of the substance is to be expected in the organism, and delayed effects are unlikely.

Alltogether TGIC is harmfull by the oral and inhalation route, but no significant organ effects are to be expected by the dermal route, apart from skin sensitization and skin irritation.


Repeated dose toxicity: via oral route - systemic effects (target organ) cardiovascular / hematological: hematopoiesis

Repeated dose toxicity: inhalation - systemic effects (target organ) cardiovascular / hematological: hematopoiesis

Repeated dose toxicity: dermal - systemic effects (target organ) other: skin

Justification for classification or non-classification

Based on the effects observed in the 90 -day oral toxicity study and in the short-term inhalation study the classification as Harmful (Xn) and R48/22 is fully justified.