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Description of key information

The  results of the 28-Day Repeated Dose Oral Toxicity Study of  Incozol EH in rats showed no significant toxicological changes related to administration of test  substance up to 200 mg/kg bw/day. Therefore the  NOAEL was 200 mg/kg bw/day under the conditions of this study.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
200 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
GLP study according to guideline. Reliable without restrictions.

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

Oral

The 28-Day Repeated Dose Oral Toxicity Study with Incozol EH in Rats was conducted according the OECD TG 407 (12 May 1981) and Directive 84/449/EEC, B.7 (19 September 1984).

Incozol EH was repeatedly administered by oral gavage at dose levels of 0 (control group), 40 (low dose), 200 (mid dose), and 1000 mg/kg bw/day (high dose) to male and female Wistar rats (Bor:WISW) for 29 consecutive days to assess the toxicological effects of Incozol EH. The control group was given 1,2-propandiol only. Each group consisted of 5 males and 5 females.

There was no mortality during the entire study period. No clinical signs were observed in all test item treated animals. Male and female animals of the high dose group (1000 mg/kg bw/day) showed ruffled fur from the 3rdweek of administration on. An increased water consumption compared to control group was observed in male and female animals of the high dose group. Food consumption was only increased in female animals of the 1000 mg/kg bw/day dose group.

In hematological and histopathological analysis, no test item related effects could be observed on blood parameters and hematopoietic organs up to 200 mg test item/kg bw/day in male animals and up to 1000 mg/kg bw/day in female animals. There was a significant decrease in hemoglobin concentration and hematocrit value and a lower reticulocyte count compared to control group in male animals of the 1000 mg/kg bw/day dose group. In addition a significant increase of the platelet count compared to control group was noted. Blood coagulation was not affected in all treatment groups.

As a result of the blood biochemical analysis and macroscopic and microscopic pathology, there was no treatment related effect on the intermediary metabolism and organ morphology in male and female animals up to a dose level of 200 mg/kg bw/day. Administration of 1000 mg/kg bw/day revealed an increased AST activity in female animals and a reduced ALT activity in male animals compared to control group. Albumin and total protein level were significantly increased in both sexes of the 1000 mg/kg bw/day dose group.

There was a significant increase of liver weights in male and female animals of the 1000 mg/kg bw/day dose group. In the same dose group, an increased adrenal gland and kidney weight was observed in male and female animals, respectively. As there was no macroscopic or microscopic pathological correlation a test item related kidney damage is not considered. Organ weights were not affected up to 200 mg test item/kg bw/day in male and female animals.

There was no test substance related change in urinalysis. In male animals of the high dose group protein concentration in urine was significantly increased compared to control. This observation was not considered to be test item related as there was no pathological correlation and female animals were not affected.

As a result, there was no test substance related change following 28-day repeated oral administration of Incozol EH up to a dose level of 200 mg/kg bw/day. Based on these results, a no-observed-adverse-effect-level (NOAEL) of Incozol EH was determined to be 200 mg/kg bw/day under the conditions of this study.


Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
Only one study available.

Justification for classification or non-classification

Based on the results of the subacute repeated oral toxicity study, the test item was not classified and labelled according to Directive 67/548/EEC (DSD) and to Regulation 1272/2008 (CLP).