Ferrate(1-), bis[4-[2-[5-chloro-2-(hydroxy-.kappa.O)phenyl]diazenyl-.kappa.N1]-3-(hydroxy-.kappa.O)-N-phenyl-2-naphthalenecarboxamidato(2-)]-, ammonium (1:1)

Endpoint summary

Description of key information

Repeated dose toxicity (oral, subacute): NOEL (male/female) = 250 mg/kg bw/day; NOAEL (male/female) = 1000 mg/kg bw/day (Annex V; Method B7)

Key value for chemical safety assessment

Toxic effect type:

dose-dependent

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

other: SNIF

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

All information in this endpoint has been provided by the ECHA using the 12-year rule, this is data not owned by the registrant. The reliability is assumed to be at level 2. Therefore the following reliability statement can be used: Study conducted in accordance with generally accepted scientific principles, possibly with incorect reporting or methodological deficiencies, which do not affect the quality of the relevant results.

Qualifier:

according to guideline

Guideline:

EU Method B.7 (Repeated Dose (28 Days) Toxicity (Oral))

Principles of method if other than guideline:

Information from migrated NONS file, as per inquiry number 06-0000021057-76-0000, permission to refer granted by ECHA.

GLP compliance:

not specified

Limit test:

no

Species:

rat

Strain:

other: Charles River Crl : CD(SD)BR strain

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

other: 1 % aqueous methyl cellulose

Duration of treatment / exposure:

Test duration: 28 days

Frequency of treatment:

7 days per week

Dose / conc.:

62.5 mg/kg bw/day (nominal)

Dose / conc.:

250 mg/kg bw/day (nominal)

Dose / conc.:

1 000 mg/kg bw/day (nominal)

No. of animals per sex per dose:

5 males
5 females

Control animals:

yes

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not specified

Haematological findings:

effects observed, treatment-related

Description (incidence and severity):

Mean haemoglobin concentration decreased (p <0.05) in top dose females relative to controls, and was marginally lower than the lower end of the historical value range.

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

no effects observed

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

no effects observed

Details on results:

One animal died during blood sampling (anaesthetic trauma).

Dose descriptor:

NOEL

Effect level:

250 mg/kg bw/day (nominal)

Sex:

male/female

Basis for effect level:

other: No effects noted

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day (nominal)

Sex:

male/female

Basis for effect level:

haematology

Critical effects observed:

no

Conclusions:

In a sub-acute toxicity study in Charles River Crl:CD(SD)BR rats, the NOEL (male/female) was 250 mg/kg bw/day and the NOAEL (male/female) was 1000 mg/kg bw/day.

Executive summary:

In a sub-acute toxicity study (Annex V; Method B7), DL-N33 was administered by oral gavage to Charles River Crl:CD(SD)BR rats (5/sex/group) in 1% aqueous methylcellulose at 0, 62.5, 250 or 1000 mg/kg bw/day for 28 days, 7 days per week.

No treatment-related deaths or clinical signs of toxicity. Mean haemoglobin concentration decreased (p <0.05) in top dose females relative to controls, and was marginally lower

than the lower end of the historical value range. No other treatment-related effects were observed. No gross or microscopic treatment-related effects were observed.

The NOEL (male/female) was 250 mg/kg bw/day and the NOAEL (male/female) was 1000 mg/kg bw/day.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

There is one study available and it has a Klimisch score of 2.

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 dose toxicity (oral)

There is one 28 day repeated dose toxicity study in rats available.

In a sub-acute toxicity study (Annex V; Method B7), DL-N33 was administered by oral gavage to Charles River Crl:CD(SD)BR rats (5/sex/group) in 1% aqueous methylcellulose at 0, 62.5, 250 or 1000 mg/kg bw/day for 28 days, 7 days per week. No treatment-related deaths or clinical signs of toxicity. Mean haemoglobin concentration decreased (p <0.05) in top dose females relative to controls, and was marginally lower than the lower end of the historical value range. No other treatment-related effects were observed. No gross or microscopic treatment-related effects were observed. The NOEL (male/female) was 250 mg/kg bw/day and the NOAEL (male/female) was 1000 mg/kg bw/day.

This study is acceptable to use in the human health risk assessment.

Justification for classification or non-classification

Based on the available information in the dossier, the substance DL-N33 (CAS No. 104815-18-1) does not need to be classified as specific target organ toxicity (repeated) when considering the criteria outlined in Annex I of 1272/2008/EC.