Registration Dossier

Administrative data

Description of key information

Subacute NOAEL (rat): 1000mg/kg bw (Method B7 of directive 92/69/EEC; GLP) 

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:
key study
Reliability:
2 (reliable with restrictions)
Qualifier:
according to
Guideline:
other: Method B7 of directive 92/69/EEC and Japanese Ministry of Health and Welfare (MHW) and Ministry of International Trade and Industry (MITI) Guideline 1986.
GLP compliance:
yes
Limit test:
no
Species:
other: rat (Sprague-Dawley)
Sex:
male/female
Route of administration:
oral: unspecified
Vehicle:
other: Polyethylene glycol 400
Details on oral exposure:
Method of administration:

gavage
Duration of treatment / exposure:
28 days
Frequency of treatment:
7 days/week
No. of animals per sex per dose:
Male: 10 animals at 0 mg/kg bw/day
Male: 5 animals at 15 mg/kg bw/day
Male: 5 animals at 150 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 15 mg/kg bw/day
Female: 5 animals at 150 mg/kg bw/day
Female: 10 animals at 1000 mg/kg bw/day
Details on results:
Clincal observations:
No clinical observable signs of toxicity were detected in test or control animals throughout the study. No adverse effects on body weight gain, food consumption or water consumption were observed.

Laboratory findings:
No treatment realted effects were observed in hematology, blood chemistry or urinalysis.

Effects in organs:
No effect on organ weights were detected and no macroscopic abnormalitites were observed at necropsy. No treatment related findings were observed during histopathology.
Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day (nominal)
Basis for effect level:
other: original NCD unit is mg/kg/day
Dose descriptor:
NOEL
Effect level:
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

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

The repeated oral dose toxicity of (1-methylethylidene)di-4,1-phenylenetetraphenyl diphosphate (CAS No. 5945-33-5) has been evaluated in 3 studies. In the first guideline subacute study, the substance was administered in the diet (dissolved in acetone) for 28 days (high dose groups: 1862mg/kg bw to ten male rats and 1968mg/kg bw to ten female rats). No signs of toxicity were observed.

The study chosen as the key study was conducted in accordance with Method B7 of directive 92/69/EEC and GLP. The substance was administered by gavage (in Polyethylene glycol 400) up to a maximum dose of 1000mg/kg bw in 10 male and 10 female rats for 28 days. In addition, two recovery groups, each of five males and five females, were treated with the high dose (1000 mg/kg/day) or vehicle alone for 28 consecutive days and then maintained without treatment for a further 14 days. No toxicity was evident (clinical changes, laboratory findings or organ changes). NOEL and NOAEL values of 1000mg/kg bw were assigned and a NOAEL of 1000mg/kg bw will be used as the key value for repeated dose oral toxicity.

Justification for classification or non-classification

Based on the available information in the dossier, the substance(1-methylethylidene)di-4,1-phenylenetetraphenyl diphosphate (CAS No.5945-33-5) does not need to be classified as specific target organ toxicity (repeated) when considering the criteria outlined in Annex I of 1272/2008/EC.