3,9-bis(2,4-di-tert-butylphenoxy)-2,4,8,10-tetraoxa-3,9-diphosphaspiro[5.5]undecane

Endpoint summary

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

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 or test system 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

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.