Solsperse 22000-Wirksubstanz

Endpoint summary

Description of key information

The test substance was administered daily for at least 90 days by oral gavage to SPF-bred Wistar rats. One control group and three treated groups were used. each consisting of 10 males and 10 females. The following parameters were evaluated: Clinical signs, functional observations, body weight, food consumption and opthalmoscopy. Urine and faeces samples were collected in week 13. At termination: clinical pathology, macroscopy and organ weights. Histopathology was performed on a selection of tissues.

Since the findings in the adrenal cortex were also seen in one of the control females, the histiocytosis in the mesenteric lymph nodes was not accompanied by adverse tissue reaction and the post dosing salivation considered due to the bad taste of the substance, a No Observed Adverse Effect Level (NOAEL) of 200 mg/kg/day may be considered for males and females.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Qualifier:

according to guideline

Guideline:

other: Annex V - method B.7

GLP compliance:

yes

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

Method of administration:Gavage

Duration of treatment / exposure:

Test duration: 28 days

Frequency of treatment:

Dosing regime: 7 days/week

No. of animals per sex per dose:

Male: 5 animals at 0 mg/kg bw/dayMale: 5 animals at 50 mg/kg bw/dayMale: 5 animals at 250 mg/kg bw/dayMale: 5 animals at 1000 mg/kg bw/dayFemale: 5 animals at 0 mg/kg bw/dayFemale: 5 animals at 50 mg/kg bw/dayFemale: 5 animals at 250 mg/kg bw/dayFemale: 5 animals at 1000 mg/kg bw/day

Details on results:

Clinical observations:There were no mortalities or clinical observations seenduring the study that could be attributed to administrationas Substance H109368Laboratory findings:Changes considered to be related to treatment were recordedfor animals receiving 1000mg/kg/day. Slight reductions ingroup mean haemoglobin, haematocrit and red cell count wereseen for males and females. minor reductions in group meanplasma triglyceride levels for males and increases in plasmaaspartate transaminase and/or alanine transaminaseactivities for males and/or females were possiblyindicative of a mild hepatic response, althoug this couldnot be correlated with histopathological changeEffects in organs:Pathological changes included mononuclear cell infiltrationin the kidney, adrenal gland, heart and liver, and anincrease in extramedullary haemopoiesis of the spleen. Thetoxicological significance of these findings is uncertain.Organ weight parameters were not affected.

Dose descriptor:

NOAEL

Effect level:

250 mg/kg bw/day (nominal)

Basis for effect level:

other: original NCD unit is mg/kg/day.

Dose descriptor:

NOEL

Effect level:

250 mg/kg bw/day (nominal)

Basis for effect level:

other: original NCD unit is mg/kg/day.

Critical effects observed:

not specified

Conclusions:

Classified as: Not classified

Executive summary:

Changes considered to be related to treatment were recorded for animals receiving 1000mg/kg/day. The no-observed effect level for the substance in the rat is therefore 250mg/kg/day for males and females, following daily oral administration over a 28 -day period.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

200 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

reliable

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

Repeated oral toxicity:

An OECD test guideline and GLP-compliant 90-day toxicity study was performed with test item in Wistar rats. Groups of 10 male and 10 female rats received 0, 50, 200 and 1000 mg/kg/day by oral gavage in polyethylene glycol 400 for 90 days. The No-observed-adverse-effect level (NOAEL) of test item was 200 mg/kg bw/day in both sexes.

This study is supported by a 28 day oral dosing study (GLP-compliant) in Wistar rats (Alpk:APfSD). Groups of 5 male and 5 female rats received 0, 50, 250 and 1000 mg/kg/day by oral gavage in corn oil for 28 days. The No-observed-adverse-effect level (NOAEL) of test item was 250 mg/kg bw/day in both sexes.

Repeated dermal toxicity:

The dermal route was waived; substance is not classified for this endpoint. The substance is considered not to exert any local or systemic adverse effects.

Repeated inhalation toxicity:

The inhalation route was waived; substance is not classified for this endpoint. When aerosolized in respirable form; when aerosolized in respirable form, the substance is considered likely to behave like an inert dust.     

Justification for classification or non-classification

not classified

Criteria for SOTS classification not met.