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Key value for chemical safety assessment

Effects on fertility

Description of key information

To examine reprotoxicity of the test item a one generation study was conducted (no GLP, equivalent to OECD guideline 415). Male and female rats were administered at doses of 100 and 500 ppm for 12 weeks (fed in diet). At a dose of 100 ppm in the rat the product has no effect on fertility, whilst at the dose of 500 ppm a reduction in fertility of about 20% was observed. According the authors, the background variation is about 10% and these results are bordering on insignificance. The NOAEL for fertility is therefore considered to be 500 ppm (compound intake not given, therefore no calculation of mg/kg bw).

Link to relevant study records
Reference
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
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
Specific details on test material used for the study:
- Name of test material (as cited in study report): Weston XP 1452
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
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
Dose / conc.:
100 ppm
Dose / conc.:
500 ppm
No. of animals per sex per dose:
15
Control animals:
yes, plain diet
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
Gross pathological findings:
not examined
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
not examined
Histopathological findings: neoplastic:
not examined
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.
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
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
Behaviour (functional findings):
not examined
Developmental immunotoxicity:
not examined
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.
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
Reproductive effects observed:
not specified
Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

To examine reprotoxicity of the test item a one generation study was conducted (no GLP, equivalent to OECD guideline 415). Male and female rats were administered at doses of 100 and 500 ppm for 12 weeks (fed in diet). The animals were mated at the rate of 8 males for 15 females. 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 an days 1, 10 and 20. The young were examined for any possible malformation of limbs or palate or hydrocephalus. Mortalities did not occur, growth was considered to be normal. A reduction in fertility of 20% in the high dose group was noted. Fertility in the low dose group was not impaired. According the authors, the background variation is about 10% and these results are bordering on insignificance. The NOAEL for fertility is therefore considered to be 500 ppm (compound intake not given, therefore no calculation of mg/kg bw).

Effects on developmental toxicity

Description of key information

A teratogenicity study in rabbits (equivalent to OECD guideline 414) was conducted to determine toxicity to mother and embryo. The test material was administered by gavage at dose levels of 20, 50, 200 mg/kg bw from day 6 -18 of gestation. Application of the test item to gestating rabbits did not induce maternal toxicity. Sex ratio, implantation as well as number and weight of the foetuses was not affected by the treatment. Miscarriages (3/15) were observed at the high dose group. This result is bordering on insignificance and was therefore disregarded. In conclusion, the test material is not considered to be teratogenic.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
200 mg/kg bw/day
Species:
rabbit
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

A teratogenicity study in rabbits (equivalent to OECD guideline 414) was conducted to determine toxicity to mother and embryo. The test material was administered by gavage at dose levels of 20, 50, 200 mg/kg bw from day 6 -18 of gestation. Caesarian section and examination for malformations was performed on day 29 of gestation. Application of the test item to gestating rabbits did not induce maternal toxicity. Sex ratio, implantation as well as number and weight of the foetuses was not affected by the treatment. Food consumption was normal in all of the groups. The product does not affect the frequency of distribution of yellow bodies or implantation in the uterus or the number of live foetuses, and the distribution between male and female foetuses is normal. At 200 mg/kg bw, there was a slight reduction in the weight of the foetuses (insignificant). Any notable sign of malformation in the foetus were not observed. In the high dose group, 3 rabbits miscarried on days 18, 20 and 23 p.c. This result is bordering on insignificance and was therefore disregarded. In conclusion, the test material is not considered to be teratogenic.

Justification for classification or non-classification

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for reproductive toxicity under Regulation (EC) No. 1272/2008.