Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Endpoint conclusion:
no study available
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available

Effects on developmental toxicity

Description of key information
NOAEL for effect on developmental toxicity: 1000 mg/kg bw/day (OECD 414, rat; GLP)
Link to relevant study records
Reference
Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Qualifier:
according to
Guideline:
other: Annex V (Developmental toxicity study)
GLP compliance:
yes
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on mating procedure:
Dosing regime: 7 days/week
No. of animals per sex per dose:
Number of dams and doses
25 at 0 mg/kg or mg/l
14
25 at 125 mg/kg or mg/l
25 at 500 mg/kg or mg/l
25 at 1000 mg/kg or mg/l
Details on maternal toxic effects:
Details on maternal toxic effects:
From a preliminary dose range finding study, dose levels of
125 mg/kg, 500 mg/kg and 1000 mg/kg were used.
All maternal animals survived to the scheduled necropsy on
gestation day 20. Treatment related clinical signs included
salivation immediately following dosing in all 3 treatment
groups between gestation days 10 and 19. Changes in general
appearance was also noted following dosing during the same
period in the 125 mg/kg, 500 mg/kg and 1000 mg/kg treatment
groups with animal rubbing their faces on the cage surface,
and excessive grooming and clonic tremors of the forelimbs.
In the 500 mg/kg and 1000 mg/kg treatment groups, animals
were observed to erratically paw the cage following dosing
between gestation days 11 and 19. All these findings had
subsided by 1 hour post dosing. Other clinical signs such
as hair loss on various body surfaces occurred also in the
control group and was not indicative of being treatment
related
At necropsy there were no macroscopic findings thought to be
treatment related.
Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day (nominal)
Basis for effect level:
other: maternal toxicity
Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day (nominal)
Basis for effect level:
other: other:
Details on embryotoxic / teratogenic effects:
Details on embryotoxic / teratogenic effects:
Effects on fetus - Gross:
Gravid litter weights, litter size and fetal body weights
were unaffected by the test substance administration. In
the 500 mg/kg dose group one foetus had bilateral
anophthalmia and one foetus had unilateral anophthalmia. No
other external malformations and no external developmental
variations were observed in foetuses at any dose levels
Effects on fetus - Soft tissue:
In the 500mg/kg dose group one foetus had hydrocephaly
consisting of increased cavitation of both lateral
ventricles and the third ventricle. One foetus in the 1000
mg/kg group had a retroesophageal aortic arch. No other
soft tissue malformations were noted.
Effects on fetus - Skeletal:
No skeletal malformations were observed in foetuses at any
dose level.
Abnormalities:
not specified
Developmental effects observed:
not specified
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subacute
Species:
rat
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

In the only one prenatal reproductive toxicity study carried out in rats at dose of 0, 125, 500, 1000 mg/kg or mg/ml according to OECD 414 with GLP compliance, the NOAEL for maternal toxicity and embriotoxicity was both established as 1000 mg/kg bw/day.


Justification for selection of Effect on developmental toxicity: via oral route:
Only one key study available

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 for reproductive toxicity when considering the criteria outlined in Annex I of 1272/2008/EC.