Registration Dossier

Administrative data

Endpoint:
two-generation reproductive toxicity
Remarks:
based on generations indicated in Effect levels (migrated information)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
February 1976 to May 1977
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Test procedure in accordance with scientific standard methods, before GLP guidelines). No information on test substance purity. Very limited information on experimental procedures. Limited endpoints examined and no statistics reported. Only a single, low, dose was used.
Cross-reference
Reason / purpose for cross-reference:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1977

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
1 male and 5 female Wistar rats were mated after 6 months of test substance administration in diet at dose level of 100 ppm (approximately 5 mg/kg bw/day). Of the F1 animals, 5 males and 5 females were administered test substance through diet until the end of the study. 1 treated male and 5 treated females from the F1 were mated in order to obtain a second generation from which 5 males and 5 females were also treated with test substance through diet until the end of the study.
All the new born animals were subjected to a detailed macroscopic examination and 10 F1 and 10 F2 offspring were sacrificed for autopsy.
GLP compliance:
no
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Reaction mass of 1-phenyloctadecane-1,3-dione and phenylicosane-1,3-dione
EC Number:
915-316-2
Molecular formula:
C50H80O4
IUPAC Name:
Reaction mass of 1-phenyloctadecane-1,3-dione and phenylicosane-1,3-dione

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
- Source: institut de Médecine du Travail
- Age at study initiation:
- Weight at study initiation:
- Fasting period before study:
- Housing: metal cages
- Diet (type + e.g. ad libitum): no data, ad libitum
- Water (type + e.g. ad libitum): no data
- Acclimation period: rats used were bred in the institute where the study was conducted

Administration / exposure

Route of administration:
oral: feed
Vehicle:
not specified
Details on exposure:
- Preparation of dosing solutions: no data
- Diet preparation:no data
- Vehicle: no data
Details on mating procedure:
- M/F ratio per cage:1 male/5 females
- Length of cohabitation: no data
- Proof of pregnancy: no data
- After ... days of unsuccessful pairing replacement of first male by another male with proven fertility: no data
- Further matings after two unsuccessful attempts: no data
- After successful mating each pregnant female was caged (how): no data
- Any other deviations from standard protocol:no data
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
6 months for males and females
Frequency of treatment:
no data , but assumed daily
Details on study schedule:
- F1 parental animals not mated until [...] weeks after selected from the F1 litters: no data
- Selection of parents from F1 generation when pups were [...] days of age: no data
- Age at mating of the mated animals in the study: no data
Doses / concentrations
Remarks:
Doses / Concentrations:
100 ppm
Basis:
nominal in diet
No. of animals per sex per dose:
1 male, 5 females in each generation
Control animals:
yes, historical
Positive control:
no

Examinations

Parental animals: Observations and examinations:
* Cage side observations: No data
* Detailed clinical observations: No data
* Body weight: No data
* Food consumption and compound intake (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: YNo data
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data
* Water consumption and compound intake (if drinking water study): No data
- Time schedule for examinations: no data
Oestrous cyclicity (parental animals):
not examined
Sperm parameters (parental animals):
not examined
Litter observations:
- Standardisation of litters: no data
- Parameters examined
The following parameters were examined in [F1 / F2] offspring: presence of gross anomalies
- Gross examination of dead pups: no data
Postmortem examinations (parental animals):
- Sacrifice:
* Male animals: All surviving animals
* Maternal animals: All surviving animals
- Gross necropsy: Gross necropsy consisted of external and internal examinations including cranio-cerebral, digestive, thoraco-visceral abdominal or genital organs.
- Histopathology / organ weights: no data
Postmortem examinations (offspring):
- Sacrifice:
* The F1 offspring not selected as parental animals and all F2 offspring were sacrificed at [unknown] days of age.
* These animals were subjected to postmortem macroscopic examinations as follows: all the new born animals
- Gross necropsy: Gross necropsy consisted of external and internal examinations without reported details.
- Histopathology / organ weights: no data reported on organ weight. Lungs, liver, spleen and kidneys were analysed by histopathological examination only for 10 animals from the F1 and 10 of the F2
Statistics:
no data
Reproductive indices:
no data
Offspring viability indices:
no data

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
no effects observed
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Organ weight findings including organ / body weight ratios:
not specified
Histopathological findings: non-neoplastic:
not specified
Other effects:
not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
not specified
Reproductive performance:
not specified

Results: F1 generation

General toxicity (F1)

Clinical signs:
not specified
Mortality / viability:
not specified
Body weight and weight changes:
not specified
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
no effects observed
Histopathological findings:
no effects observed

Effect levels (F1)

Dose descriptor:
NOAEL
Generation:
F1
Effect level:
100 ppm (nominal)
Sex:
male/female
Basis for effect level:
other: No macroscopic or microscopic abnormalities reported

Results: F2 generation

Effect levels (F2)

Dose descriptor:
NOAEL
Generation:
F2
Effect level:
100 ppm (nominal)
Sex:
male/female
Basis for effect level:
other: No macroscopic or microscopic abnormalities reported

Overall reproductive toxicity

Reproductive effects observed:
not specified

Any other information on results incl. tables

The mating of 1 treated male and 5 treated female P generation rats gave rise to a first generation (F1) of 38 rats (13 males and 25 females).

The mating of 1 treated male and 5 treated females from the F1 generation gave rise to 44 F2 offspring (20 males and 24 females).
All the new born animals were subjected to a detailed macroscopic examination in which no abnormalities were found.

10 pups from each of the F1 and F2 generation were autopsied, revealing no microscopic abnormalities.

Applicant's summary and conclusion

Conclusions:
No effects on parental animals or offspring. NOAEL (parental & developmental) = 100 ppm (corresponding to approximately 5 mg/kg b.w./day). However, this single test concentration was too low to draw a definitive conclusion on the potential of the test substance for effects on reproduction at high concentrations in the diet.
Executive summary:

In a satellite 2-generation reproduction study combined with a chronic/carcinogenic study conducted before guidelines (1977), one male and five female Wistar rats were mated after 6 months of SAP RP test substance (corresponding to stearoylbenzoylmethane) administration through diet at dose level of 100 ppm (corresponding to approximately 5 mg/kg bw/day). The pairings gave rise to a first generation (F1) of 38 rats (13 males and 25 females). Of the F1 animals, five males and females were administered SAP RP test substance through diet until the end of the study. One treated male and five treated females from the F1 were mated in order to obtain a second generation. This generation was composed of 44 rats (20 males and 24 females) from which five males and females were also treated with SAP RP test substance through diet until the end of the study.
All the new born animals were subjected to a detailed macroscopic examination and 10 animals of the F1 and 10 rats of the F2 were sacrificed for autopsy. No abnormalities (cranio-cerebral, digestive, thoraco-visceral abdominal or genital) were observed.
 The histological examination (lungs, liver, spleen and kidneys) of these animals showed no abnormalities.

Under these test conditions,
SAP RP showed no adverse effects on parental animals or histological or macroscopic abnormalities in the new born animals from exposed parents: the test substance SAP RP is not considered as toxic to reproduction or teratogenic.

This reproduction study in the rat is acceptable as part of a weight of evidence approach because little information on protocol was reported, the endpoints examined were limited and only a single, low, dose level was tested.
 The study does not satisfy the guideline requirement for a reproduction study OECD 416 in rat.