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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
one-generation reproductive toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1983
Report Date:
1983

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 415 [One-Generation Reproduction Toxicity Study (before 9 October 2017)]
Deviations:
yes
Remarks:
only two doses used; only 15 animals per dose used, reporting details
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
no further data provided
Specific details on test material used for the study:
- Name of test material (as cited in study report): Weston XP 1452

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: animals weighing about 50 g
- Housing: two animals per cage

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24 - 26

Administration / exposure

Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Details on exposure:
PREPARATION OF DOSING SOLUTIONS:
It was preferred to use the product in conditions close to its utilization, i.e. being heated in plastics. For practical mixing reasons and for technical reasons, the product was mixed with the food which was shaped into small biscuits in accordance with the normal preparation technique for rats' diets; the product was therefore heated.
Details on mating procedure:
The animals were mated at the rate of 8 males selected at random from each group for 15 females from each group. After 3 weeks, the females were separated and placed in individual cages. At birth, the number of young per litter was counted and each litter was weighed and days 1, 10 and 20. The young were examined for any possible malformation of limbs or palate or hydrocephalus.
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
12 weeks
Frequency of treatment:
daily
Doses / concentrationsopen allclose all
Dose / conc.:
100 ppm
Dose / conc.:
500 ppm
No. of animals per sex per dose:
15
Control animals:
yes, plain diet

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
no effects observed
Dermal irritation (if dermal study):
not examined
Mortality:
no mortality observed
Description (incidence):
No mortality in any case of treated or untreated animals was observed.
Body weight and weight changes:
no effects observed
Description (incidence and severity):
Growth was normal.
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 examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
not examined
Histopathological findings: non-neoplastic:
not examined
Histopathological findings: neoplastic:
not examined

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
not examined
Reproductive function: sperm measures:
not examined
Description (incidence and severity):
The number of gravid females was identical in the control group and the treated group receiving food containing 100 ppm of the test substance. However, we noted a reduction in fertility of 20% in the case of the diet containing 500 ppm of test substance, although the results are bordering on insignificance.

Effect levels (P0)

open allclose all
Dose descriptor:
NOAEL
Effect level:
100 ppm
Based on:
test mat.
Sex:
female
Basis for effect level:
other: no adverse findings
Dose descriptor:
LOAEL
Effect level:
500 ppm
Based on:
test mat.
Sex:
female
Basis for effect level:
reproductive performance

Results: F1 generation

General toxicity (F1)

Clinical signs:
no effects observed
Dermal irritation (if dermal study):
not examined
Mortality / viability:
not examined
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
The weight of the young was reduced at 500 ppm.
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 examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Sexual maturation:
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
not examined
Histopathological findings:
not examined

Developmental neurotoxicity (F1)

Behaviour (functional findings):
not examined

Developmental immunotoxicity (F1)

Developmental immunotoxicity:
not examined

Details on results (F1)

Whilst the number of young per litter is the same for the first two groups, it is 10% less in the last group. We did not observe any difference in the average weight of the young on days 1, 10 and 20. The ratio between males and females differs from group to group and is particularly marked between the control group and the group treated with 500 ppm, this last group having a lower number of females. lt is difficult to judge the significance of these results, because in our conditions we often see variations of over 10% in sex distribution among animals not having received any treatment; we have therefore disregarded this result.

Effect levels (F1)

Dose descriptor:
NOAEL
Generation:
F1
Effect level:
500 ppm
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: no adverse finding at this level

Overall reproductive toxicity

Reproductive effects observed:
not specified

Applicant's summary and conclusion