(1S,7S,8S,8aR)-8-{2-[(2R,4R)-4-hydroxy-6-oxotetrahydro-2H-pyran-2-yl]ethyl}-7-methyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl(2S)-2-methylbutanoate

Repeated dose toxicity: oral

Administrative data

Endpoint:

repeated dose toxicity: oral

Remarks:

other: QSAR

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: no OECD test method was used

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Data source

Reference

Reference Type:

other: literature review

Title:

Unnamed

Year:

2012

Materials and methods

Test guideline

Qualifier:

no guideline followed

Guideline:

other: not applicable

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

75330-75-5

EC Number:

616-212-7

Cas Number:

75330-75-5

IUPAC Name:

75330-75-5

Details on test material:

Lovastatin

Results and discussion

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Repeated dose toxicity

Here, reference is made to human data from clinical use in the treatment of hypercholesterinemia (see Summary of Product Characteristics/SPC for lovastatin, "New class warnings for statins", and review article "Lovastatin for hypercholesterinemia").

Myositis/Rhabdomyolysis (reversible/irreversible):

Lovastatin occasionally causes myopathymanifested as muscle pain, tenderness or weakness with creatine kinase above 10 fold the upper limit of normal. Myopathy sometimes takes the form of rhabdomyolysis with or without acute renal failure secondary to myoglobinuria, and rare fatalities have occurred.

Hepatopathia (reversible)

Histologically verified inflammation and increase of transaminases have been observed in some patients.

Impairment of sexual function

Induction of Diabetes Mellitus

So you may consider classifying mevastatin for target organ toxicity (Cat. 1, toxicity on the muscoskeletal system).

Repeated dose toxicity

Rhabdomyolysis was observed in rare cases in patients treated with mevastatin or lovastatin.

Consider classification as repeated dose Cat. 1/2, hazard statements H372: Causes damage to organs through prolonged or repeated exposure/H373: May cause damage to organs through prolonged or repeated exposure.

IST FDA v3b Maximum Recommended Daily Dose 0.00504 mmol, Confidence 0.163

Applicant's summary and conclusion

Conclusions:

Repeated dose toxicity
Here, reference is made to human data from clinical use in the treatment of hypercholesterinemia (see Summary of Product Characteristics/SPC for lovastatin, "New class warnings for statins", and review article "Lovastatin for hypercholesterinemia").
Myositis/Rhabdomyolysis (reversible/irreversible):
Lovastatin occasionally causes myopathy manifested as muscle pain, tenderness or weakness with creatine kinase above 10 fold the upper limit of normal. Myopathy sometimes takes the form of rhabdomyolysis with or without acute renal failure secondary to myoglobinuria, and rare fatalities have occurred.
Hepatopathia (reversible)
Histologically verified inflammation and increase of transaminases have been observed in some patients.
Impairment of sexual function
Induction of Diabetes Mellitus
So you may consider classifying mevastatin for target organ toxicity (Cat. 1, toxicity on the muscoskeletal system).

Repeated dose toxicity
Rhabdomyolysis was observed in rare cases in patients treated with mevastatin or lovastatin.
Consider classification as repeated dose Cat. 2, hazard statements H373: May cause damage to organs through prolonged or repeated exposure.
IST FDA v3b Maximum Recommended Daily Dose 0.00504 mmol, Confidence 0.163

Executive summary:

Repeated dose toxicity

Rhabdomyolysis was observed in rare cases in patients treated with mevastatin or lovastatin.

Consider classification as repeated dose Cat.2, hazard statements H373: May cause damage to organs through prolonged or repeated exposure.