Registration Dossier

Administrative data

Description of key information

In a K1 acute oral toxicity study (up-and down procedure) in Sprague-Dawley rats, performed according to OECD Guideline 425 (acute toxic class method) and EPA OPPTS 870.1100 - Acute Oral Toxicity, an LD50 value of 1000 mg/kg bw was observed (René E Vasquez (2012)).
In a K1 acute dermal toxicity study in Sprague Dawley rats, performed according to OECD Guideline 402, EPA OPPTS 870.1200, and EEC Method B.3, an LD50 value greater than 2000 mg/kg bw was observed (René E Vasquez (2011)).

No acute inhalation toxicity study is performed.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
1 000 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
2 000 mg/kg bw

Additional information

Acute toxicity: oral

René E Vasquez (2012) assessed the acute oral toxicity of XTJ 568 in Sprague-Dawley rats (up-and-down procedure). The study was carried out based on the guidelines described in: EPA OPPTS 870.1100 "Acute Oral Toxicity" and OECD No. 425, "Acute Oral Toxicity - Up-and-Down procedure". This study is selected as key study.

The first animal was dosed at an initial dose level of 550 mg/kg. Since this animal survived, the second animal received a higher dose (1000 mg/kg). Two additional animals were dosed at 1000 mg/kg, one at 320 mg/kg and one at 2000 mg/kg. The dose for each successive animal was adjusted up or down, depending on the previous result.

Mortality was not observed in any of the animals dosed at 320 or 550 mg/kg of the test article. Two or three animals receiving the test article at 1000 mg/kg were found dead as well as the single animal dosed at 2000 mg/kg.

Clinical observations observed included piloerection at 30 minutes in the single animal at 320 mg/kg and in the surviving animal at 1000 mg/kg. No clinical signs were observed prior to death in the two other animals at 1000 mg/kg. Piloerection, decreased activity, decreased body tone and abnormal gait and stance were observed at 4 hours in the animal treated at 550 mg/kg. At 2000 mg/kg, decreased body tone and abnormal gait were observed at 30 minutes and death was observed at 4 hours.

No biological significant effect was seen on body weights of the surviving animals on Days 8 and 15.

Terminal necropsy revealed no visible lesions in the animals at 320, 550 or the surviving animal at 1000 mg/kg. Necropsy of two animals found dead at 1000 and 2000 mg/kg revealed dark red fluid-filled intestines. The third animal found dead had no visible lesions.

Based on the results of this study, the oral LD50 for the substance in rats was estimated to be 1000 mg/kg.

In addition, in another acute oral toxicity study (class method), F.M. van Otterdijk (2003) observed an LD50 value between 200 and 2000 mg/kg.

Acute toxicity: dermal

Based upon the results of the Acute Dermal Toxicity Study in rats with the substance, the estimated LD50 was considered to be greater than 2000 mg/kg. Mortality was observed in two female animals at 2000 mg/kg. Abnormal gait and stance, hunched posture, decreased activity, decreased body tone, piloerection, black fur around eyes, yellow wet fur of the lower ventral area were observed throughout the study. All animals exhibited necrosis at the application site during the study. Gross necropsy revealed following information: no visible lesions were observed in the surviving animals at terminal necropsy. Dark red intestines were observed in the animal found dead on Day 5 of the study. No lesions were observed in the animal found dead on Day 3 of the study.

Acute toxicity: inhalation

No further acute toxicity studies (inhalation and dermal) were performed as the substance is concluded to be corrosive to the skin.

Justification for classification or non-classification

Based on the available acute oral toxicity study, the LD50 is 1000 mg/kg bw/d. The substance should thus be classified as acute oral toxic category 4 (for substances having an LD50 value between 300 and 2000 mg/kg bw); H302 according to CLP Regulation criteria.

No classification is warranted for acute toxicity via the dermal route.