Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information

The reproductive toxicity of the target substance (EC 406-176-9) has been assessed by reading across the results of studies conducted on two structurally similar analogue substances.

It is proposed that these results can be used in the assessment of the target substance (EC 406-176-9).

Source Substance; 1,3:2,4-bis-O-(3,4-dimethylbenzylidene)-D-glucitol (EC-413 -110 -2):

: Reproduction/Developmental Toxicity Screening Test (OECD 421):

The purpose of the study was to generate preliminary information concerning the effects of Gel All DX on male and female reproductive performance such as gonadal function, mating behavior, conception and parturition.

 

The test item was administered once daily orally (by gavage) throughout pre-pairing, pairing and after pairing periods for a total of 46 days in males and pre-pairing, pairing, gestation and lactation periods for at least 40 days in females, up to the day before scheduled necropsy.

 

The following dose levels were used:

Group 1: 0 mg/kg body weight/day (control group)

Group 2: 100 mg/kg body weight/day

Group 3: 300 mg/kg body weight/day

Group 4: 1000 mg/kg body weight/day

 

A standard dose volume of 5 mL/kg body weight with a daily adjustment to the actual body weight was used. Control animals were dosed with the vehicle alone (olive oil).

Parent Animals

Mortality/Viability

No test item related deaths were noted during the study.

 

One male given 1000 mg/kg body weight/day was found dead on day 12 of the after pairing period. The cause of this death was unclear and, due to an isolated occurrence, unlikely to be related to toxicity of the test item.

Clinical Signs

There were no clinical signs seen in males or females at any dose level, over the course of the study that were considered to be related to the administration of the test item.

Food Consumption

There was no effect of the test test item on the group mean amount of food consumed by males or females at any dose level over the course of this study, when compared to control animals.

Body Weights

Group mean body weight and body weight gain for males and females were considered to be unaffected by administration of the test item over the duration of the study.

Reproduction and Breeding Data

Fertility, time course of mating, duration of gestation,corpora lutea count, number of implantation sites, post-implantation loss, liter size and post natal loss were unaffected by administration of the test item at any dose level.

Organs Weights

No changes in absolute testes and epididymides weights or weights of these organs relative to body weight were noted at any dose level.

Macroscopic/Microscopic Findings

No test item-related macroscopical or microscopical findings were recorded at any dose level.

Litter Data - F1 Pups

Findings at First Litter Check and During Lactation

No test-item related findings were noted in pups at first litter check or during lactation at any dose level.

 

Pups sex ratio was not affected by exposure to the test item at any dose level.

 

Pup Weights to Day 4Post Partum

No effects on pup body weights or body weight gain were noted at any dose level.

Macroscopic Findings

No test item-related findings were noted in pups at necropsy at any dose level.

Conclusion

Based on these results, NOEL (No Observed Effect Level) for both general toxicity in males and females for reproduction/ developmental toxicity was considered to be 1000 mg/kg bw/day, the highest dose level tested.

Source Substance; 1-(2,6-bis(4-tolyl)-1,3-dioxano(5,4-d)-1,3-dioxan-4-yl)ethane-1,2-diol (EC 402-950-5):

: OECD 415 One-Generation Reproduction Toxicity Study:

The study was designed to investigate the effects of the test material when administered throughout the reproductive cycle of the rat to assess prenatal and postnatal development, and complies with the OECD Guidelines for Testing of Chemicals No 415 "One Generation Reproduction Toxicity Study" (Adopted 26 May 1983).

The administration of the test material by oral gavage to rats for either a period of up to one hundred and thirty three consecutive days for males or at least seventeen consecutive days prior to mating and throughout the gestation and lactation phases of the reproductive cycle for female rats, did not result in any toxicologically significant reproductive effects at dose levels of 100, 300 or 1000 mg/kg/day. A ‘No Observed Adverse Effect Level’ (NOAEL) of 1000 mg/kg/day was established for reproductive toxicity including fertility and mating in adults and for developmental toxicity in their subsequent progeny.

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

It is proposed that the results from the read-across source substances can be used in the assessment of the target substance.

Effects on developmental toxicity

Description of key information

Refer to effects on fertility.

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

Justification for classification or non-classification

Based on the absence of adverse effects to reproduction/development in OECD 421 and OECD 415 studies conducted on structurally similar substances, the target substance is not classified for reproductive toxicity.