Registration Dossier

Administrative data

Description of key information

Acute oral and acute inhalative toxicity of the test material was examined in several studies (prior GLP, according to or similar to OECD guideline 401 and 403). Oral or inhalative administration of the test item to rats or mice did not cause mortalies; also clinical signs of toxicity or organ changes were not observed. An acute dermal study on a structural analogue did not cause any effect or mortalities. LD50 after oral administration is therefore > 5000 mg/kg bw. after dermal administration > 2500 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
1 000 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 500 mg/kg bw

Additional information

Read across justification

Acute toxicity after dermal application of the test item was not evaluated; reliable, experimental data of an analogue are available.

The substances share high similaritiy in structure and have comparable physico-chemical properties. Both substances are solids of poor water solubility and insoluble in most of the common organic solvents. The molecular weight of both compounds is higher than 600 g/mol. The molecules includes phthalimid-like structures, whereas only the analogue compound bears the potential to release chlorinated phthalimid after enzymatic or bacterial cleavage. Therefore, the analogue substance was choosen to examine acute dermal toxicity.

Procedure and observations

Several studies were conducted to determine acute toxicity of the test material.

In the course of the key study, acute oral toxicity was examined by single oral (gavage) administration of the test material dissolved in polyethylene glycol at doses of 2000, 3000, 4000 or 5000 mg/kg bw to male and female rats (5/sex/dose, fasted overnight). Prior to treatment the animals were adapted to the laboratories for a minimum of 4 days. Bodyweights were recorded immediately prior to dosing (control weights) and at 7 and 14 days. Physical condition and rate of deaths were monitored throughout the whole observation

period. All animals survived until scheduled day of necropsy, no substance related gross organ changes were seen.

Next to the key study mentioned above, several other acute oral toxicity studies in rats and mice were performed. All of the animals received single doses of the test substance up to 5000 or 7000 mg/kg bw, respectively, and were observed for minimum 8 days. Mortality did not occur in any of the studies; clinical signs or organ changes were also not observed. In two of the studies dyspnoe, curved position and ruffled fur were recorded; these symptoms were reversible within post observation period.

Acute inhalation toxicity was examined by a 4h dust exposure (1000 mg/m3, nose only) to 9 male and female rats. The exposure was started 15 minutes after onset of the dust production, when the dust had reached an even dispersal throughout the chamber. After a 4 hour inhalation the rats were returned to their cages. Physical condition and incidence of death were monitored throughout an observation period of 14 days. None of the animals died, organ changes or clinical signs of toxicity were not observed.

To determine acute dermal toxicity of an analogue substance, 2500 mg/kg bw of the material was applied onto dorsal skin of male and female rats for 24h under occlusive conditions. The animals were observed for 14 days and checked daily for mortalitiy and clinical signs of toxicity. None of the rats died; yellowish staining of the treatment site was observed.

Results and discussion

Oral or inhalative administration of the test material did not cause mortalities, organ changes or clinical signs of toxicity. Dermal application of a structural analogue resulted in yellowish staining of the skin, mortalities and local or systemic effects were not observed. Therefore, LD50 oral is considered to be greater than 5000 mg/kg bw, LD50 after dermal administration is > 2500 mg/kg bw and LC50 greater than 1000 mg/m3.

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available studies are considered reliable and suitable for classification purposes under 67/548/EEC. As a result the substance is not considered to be classified for acute toxicity under Directive 67/548/EEC, as amended for the 30th time in Directive 2008/58/EC.

                               

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for acute toxicity under Regulation (EC) No. 1272/2008, as amended for the second time in Directive (EC 286/2011).