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Administrative data

Description of key information

Subacute toxicity was evaluated in a combined repeated dose toxicity / screening for reprotoxicity study according OECD 422 and GLP on an analogue substance. Male and female rats were exposed orally to 100, 300 or 1000 mg/kg bw of the compound for 28d. All animals survived until scheduled necropsy; signs of systemic toxicity or changes in organs and tissues were not observed. Repeated dermal application for 1 weeks or 4 weeks to male and female rats (non guideline, prior GLP), respectively, did not cause skin irritation or signs of systemic toxicity. 

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subacute
Species:
rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Read across justification

Toxicity after repeated dose administration 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 toxicity after repeated dose administration and toxicity to reproduction and development.

Procedure and observations

The test item was administered orally by gavage to groups of 10 male and 10 female Wistar rats (F0 animals) at dose levels of 0 mg/kg body weight/day (drinking water served as vehicle), 100 mg/kg bw/d, 300 mg/kg bw/d and 1000 mg/kg bw/d. The duration of treatment covered a 2-week premating and a mating period in both sexes, approximately 1 week post-mating in males, and the entire gestation period as well as 4 days of lactation and 2 weeks thereafter in females. A detailed clinical observation was performed in all animals. Body weights and food consumption were determined in F0 animals. Clinicochemical and hematological examinations as well as urinalyses and FOB were performed in all animals towards the end of the administration period. All animals were assessed by gross pathology; weights of selected organs were recorded and a histopathological examination was performed.

Clinical examinations, reproductive performance, clinical pathology, histopathology and gross pathology did not reveal any finding in treated animals.

Furthermore, a subacute dermal study was performed (Klimisch 4). The test item dissolved in gummi arabicum was applied onto skin of male and female rats (5/sex/dose) at a concentration of 150 mg/kg bw. Exposure duration was 3h/day and all working days for 4 weeks. Effects on skin were recorded daily. Dermal application did not provoke local or systemic effects.

Discussion

Thus, under the conditions of this Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test the oral administration by gavage to male and female Wistar rats did not reveal signs of toxicity. Thus, the no observed adverse effect level (NOAEL) for general systemic toxicity was 1000 mg/kg bw/d in both sexes.

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 notconsidered to be classified for repeated dose toxicity under Directive 67/548/EEC, as amended for the 30th time in Directive 2008/58/EC.

 

 

Classification, Labeling, 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 repeated dose toxicity under Regulation (EC) No. 1272/2008, as amended for the second time in Directive (EC 286/2011).