Hexaphenoxycyclotriphosphazene

Endpoint summary

Description of key information

The NOEL and NOAEL were estimated as 1000 mg/kg/day.

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:

repeated dose toxicity: oral, other

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Qualifier:

according to guideline

Guideline:

other: Annex V

GLP compliance:

yes

Limit test:

yes

Species:

other: Rat (Sprague-Dawley)

Route of administration:

oral: unspecified

Vehicle:

olive 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: 10 animals at 0 mg/kg bw/day
Male: 5 animals at 50 mg/kg bw/day
Male: 5 animals at 250 mg/kg bw/day
Male: 10 animals at 1000 mg/kg bw/day
Female: 10 animals at 0 mg/kg bw/day
Female: 5 animals at 50 mg/kg bw/day
Female: 5 animals at 250 mg/kg bw/day
Female: 10 animals at 1000 mg/kg bw/day

Details on results:

Clinical observations:
Males: Salivation was noted in the control group.
Salivation and a reddish tear was noted in the 50
mg/kg group.
Salivation, scab formation and exudates on the neck
were noted in the 250 mg/kg group.
Females: Loss of hair was noted in the 250 mg/kg group.
Salivation and loss of hair was noted in the 1000
mg/kg group.
Laboratory findings:
Haematological examinations:
Males: No abnormalities were observed.
Females: Large unstained cells were decreased in the 1000
mg/kg group.
Blood chemical examination:
At termination of dosing period:
Males: Calcium was increased in the 50 and 1000 mg/kg
groups.
Females: No abnormailites were observed.
At termination of recovery period:
Males: Albumin:T-protein-Albumin ratio was increased in the
1000 mg/kg group.
Females: No abnormailites were observed.
Effects in organs:
Organ weights:
At termination of dosing period:
Males: No abnormalities were observed.
Females: Relative brain weight was increased in the 50
mg/kg group.
At termination of recovery period:
Males: No abnormalities were observed.
Females: Absolute heart and spleen weights were decreased
in the 1000 mg/kg group.
Necropsy:
At termination of dosing period:
Males: Whitish region in the heart was observed in the
vehicle group.
Females: Erosion on the skin was observed in the 250 mg/kg
group.
At termination of recovery period:
No abnormalities were observed in either males or females.
Histopathological examiniation:
At termination of dosing periods:
Males: Microgranuloma in the liver, focal myocarditis in
the heart, increased hyaline droplets, solitary cyst
in cortex and medulla in the kidney and aberran
craniopharyngael tissue in the pituitary gland were
noted in the vehicle control group.
Ulcer on skin was noted in the 250 mg/kg group.
Mineralisation in the glangular stomach was noted in
the 1000 mg/kg group.
Females: Mineralisation in corticomedullary junction of the
kidney and cyst formation in pars distalis gland
were noted in the vehicle control group.
Mineralisation in corticomedullary junction of the
kidney was noted in the 1000 mg/kg group.
At termination of recovery period:
No abnormalities were noted in either males or females.

Dose descriptor:

NOEL

Effect level:

1 000 mg/kg bw/day (nominal)

Basis for effect level:

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

Dose descriptor:

NOAEL

Effect level:

ca. 1 000 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

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

subacute

Species:

rat