Registration Dossier

Administrative data

Description of key information

Acute oral and dermal LD50 value of 630 mg a.i./kg bw and 528 mg a.i./kg bw, respectively was determined from reliable guideline studies.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
630 mg/kg bw
Quality of whole database:
One reliable OECD guidelines as well as GLP compliant acute oral toxicity study available on a read-across substance, meeting the tonnage information requirements.

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
528 mg/kg bw
Quality of whole database:
One reliable OECD guidelines as well as GLP compliant acute dermal toxicity study available on a read-across substance, meeting the tonnage information requirements.

Additional information

Oral

An OECD guideline study was performed to assess the acute oral toxicity of the read-across subtance C16-C18 and C18 unsat., TMAC in Sprague-Dawley rats. Four groups of 10 fasted animals (five males and five females) were administered an oral gavage dose of the test substance (i.e., 50% active ingredient) at doses of 1,000, 1,260, 1,587 and 2,000 mg/kg bw. The animals were observed for 14 days and were then sacrificed and subjected to gross pathological examination. Mortality was observed at all doses with percentages ranging from 60-90 at ≥1,260 mg/kg bw. Major signs of toxicity noted in decedent and surviving animals were hunched posture, lethargy, pilo-erection, decreased respiratory rate and diarrhoea. All animals showed expected body weight gain during the second week of the study. Necropsy of decedents revealed abnormally red lungs, dark livers, haemorrhage and ulceration of the gastric mucosa and congestion of the small intestines. Surviving animals necropsied at termination showed white raised areas on the non-glandular region of the stomach or general white thickening of this region. Under the test conditions, the LD50was determined to be 1,260 mg/kg bw for males/females (i.e., equivalent to 630 mg a.i./kg bw) (Jones JR, Blackwell MP and Collier TA, 1987).

Dermal

An OECD 402 study was conducted to determine the acute dermal toxicity of the read-across substance C12-C18 TMAC (active ingredient 33%) in male or female albino rabbits. The test substance was applied (single application) to groups of 10 rabbits (five per sex) at dose levels of 0, 520, 1,020 and 2,000 mg/kg bw to shaved, intact skin under semi-occlusive conditions for 24 hours. Animals were observed at 1, 3 and 4 hours post-dosing. Following the 24 hour exposure period, animals were observed for mortality, clinical signs and skin response for 14 days. There was no mortality in the control or 520 mg/kg bw group. Two males died in the 1,020 mg/kg bw group while 4 males and 3 females died in the 2,000 mg/kg bw group. Under the conditions of the test, the acute dermal LD50for male and female albino rabbits was found to be 1,600 mg/kg bw (i.e., 528 mg a.i./kg bw) (95% confidence limits of 1,200 – 2,100 mg/kg bw) (Naas DJ, 1988).However it must be noted that the observed lethality is secondary to the local tissue damage, rather than the result of systemic toxicity through percutaneously absorbed material.


Justification for selection of acute toxicity – oral endpoint
One study available on a read-across substance. Study was conducted according to the OECD guideline as well as in compliance with GLP.

Justification for selection of acute toxicity – inhalation endpoint
The substance is a paste with a low vapour pressure. Due to its physical state and physical chemical properties, it is unlikely that it will form inhalable dust, mist or fumes when handled and used in solid form. In case inhalable forms of the substance (either pure or in aqueous solutions) are created under particular conditions (e.g., spraying, elevated temperature/pressure), appropriate risk management measures such as closed systems, exhaust ventilation or wearing of respirators are implemented to control exposure. Under such conditions, the risk to humans following inhalation exposure can be considered minimal and further testing involving vertebrate animals may be omitted, in accordance with Annex XI (1.2) of the REACH regulation.

Justification for selection of acute toxicity – dermal endpoint
One reliable study conducted according to the OECD guidelines.

Justification for classification or non-classification

Oral

Based on the oral LD50value of 699 mg a.i./kg bw from a guideline study, the R22 classification is warranted according to EC criteria (67/548/EEC). The corresponding classification according to CLP criteria (EC 1272/2008) is Category 4; H302: Harmful if swallowed.

Dermal

Based on the dermal LD50value of 528 mg a.i./kg bw from a guideline study, the R21 (harmful in contact with skin) classification is warranted according to EC criteria (67/548/EEC). The corresponding classification according to EC CLP criteria (EC 1272/2008) is Category 3; H311: Toxic in contact with skin. However, often the corrosive properties decrease with longer chain length (fully saturated) and therefore it is more realistic that C16 -18 TMAC is not corrosive (lower solubility; solid rather than liquid; less molecules per weight) but irritating. Unnecessary or over- classification leads to unnecessary use of risk reducing measures.