Registration Dossier

Administrative data

Description of key information

The key study for acute oral toxicity found the test substance harmful, when administered via oral gavage to rats, with acute oral LD50s of 986 (male), 1650 (female) and 1423 mg/kg bw (males and females) calculated. The study was performed in accordance with OECD Test Guideline 401 (ASTA Pharma 1987).
The key study for acute dermal toxicity reports an LD50 value of >4000 mg/kg bw, which was determined in a reliable study carried out according to current guideline and in compliance with GLP (Harlan 2011).
In accordance with Column 2 of REACH Annex VIII, the acute toxicity study via the inhalation route (required in Section 8.5.2) does not need to be conducted as reliable data via the oral and dermal routes are available.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 423 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
4 000 mg/kg bw

Additional information

The key study for acute oral toxicity reports an LD50 value of 1423 mg/kg bw in rat (ASTA Pharma 1987). Signs of toxicity included hypokinesia, clonic convulsions, decrease of muscle tone, salivation and strenuous breathing. Stilted gait, tonic convulsion, ptosis, mydriasis, lacrimation, epistaxis, diarrhoea, cold extremities and vocalisation on handling also occurred in individual animals. Ante mortem general loss of reflexes and dyspnea were observed. Symptoms of toxicity were observed 3 minutes after substance administration and generally lasted up to one day (epistaxis up to 4 days after administration). Observations at necropsy included: tympany in the stomach, red stomach and intestinal mucous membranes, liquid-filled intestine, red discolouration in the intestine of individual animals, red spotted/marbled lung of emphysematous consistency, reddened peritoneum, pancreas, spleen and external skin in individual animals.

Acute dermal toxicity study was carried out in compliance with GLP and in accordance with OECD Test Guideline 402, in which triethoxy(3-thiocyanatopropyl)silane was found to be of low toxicity to rats following a 24-hour dermal application (Harlan 2011). The acute dermal LD50 was determined to be greater than 4000 mg/kg bw. There were no deaths over the course of the study, and no significant gross macroscopic or body weight changes were reported. Dragging of limbs was noted in all animals within a day of application, and persisted in all but one (a female) to day two, and to day three in two males. Activity was significantly increased in all animals shortly after treatment, while decreased activity was noted on days two and three. More severe effects (severely decreased activity, reduced temperature, vocalisation and shivering) were seen in one female on day two. Some males demonstrated reversible skin effects (slight erythema and focal crusts, with slight desquamation in one), which reverted within eight days of application. Skin effects were more pronounced in females (slight to moderate erythema, slight to severe focal crusts, slight to severe desquamation, and slight to moderate necrosis), with some effects lasting up until day 15 (focal crusts in two animals, desquamation in one).


Justification for selection of acute toxicity – oral endpoint
The selected study is the only available acute oral toxicity study. It was conducted according to an appropriate OECD test guideline and in compliance with GLP.

Justification for selection of acute toxicity – dermal endpoint
The selected study is the only available acute dermal toxicity study. It was conducted according to an appropriate OECD test guideline and in compliance with GLP

Justification for classification or non-classification

Based on the available information, no classification is required for acute dermal toxicity. However, the reported acute oral LD50 value of 1423 mg/kg bw in male and females rats requires classification of Triethoxy(3 -thiocyanatopropyl)silane as Category 4, H302; Harmful if swallowed in accordance with Regulation (EC) No 1272/2008.