Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Additional information

The substance is expected to be hydrolysed into glycerin and glucose which are nutrients and not suspected to be toxic for reproductive organs.


Short description of key information:
The substance is expected to be hydrolysed into glycerin and glucose which are nutrients and suspected to be toxic for reproductive organs.

Effects on developmental toxicity

Additional information

Glycerin Glucoside is composed of glucosides with glycerine. The chemical is therefore expected to be hydrolyzed and metabolised in mammals to the nutrients glucose and glycerine which are not suspected to be reproductive toxicants. In addition, the toxicological profiles of Glycerin Glucosides and structural related substances like alkyl polyglucosides do not indicate any hazard concern. These arguments are explained in the following chapters:

Hydrolysis:

Toxicokinetic and toxicity studies have been carried out with the structurally related alkyl polyglucosides (registered substance, CAS 110615-47-9) which are non-ionic surfactants used e.g.in personal care products. The substance is composed of a glucoside which bound to a fatty alcohol via an ether bond. Glycerin Glucoside is also composed of a glucoside which is bound to glycerin via an ether bound. Toxicokinetic studies in the mouse proved that alkyl polyglucosides are readily cleaved into glucose and fatty alcohol (Weber and Benning, 1984; cf. EAS, 2007, and US FDA, 2008). The same can be expected for glycerin glucoside as the mechanism should be comparable.

In addition, for digoxin, an endogenic glucoside which is also bound via an ether bound, a complete hydrolysis can occur in within 60-90 min (Gault et al 1977, see chapter 5.1.2).

In summary, it is expected that gylcerin glucoside is hydrolyzed into glycerin and glucoside.

Toxicity profile of Glycerin Glucoside:

Registration data show a low toxicity profile of Glycerin Glucoside. Accordingly, the substance has not been classified. An oral NOAEL of 1000 mg/kg bw/d has been derived from a sub-chronic study. At the dose level of 1000 mg/kg bw/d minor effects were noted which were considered to be non-adverse. In the study reproductive organs were also examined without considering any adverse effects. This is an additional evidence of the absence of effects related to the reproductive organs.

Read-across data:

The structural analogue C12-14 alkylpolyglucoside (CAS CAS 110615-47-9) was tested in a teratogenicity study (OECD 414) and a reproductive screening study (OECD 421).

In the OECD 414 study, teratogenic effects potentially induced by C12-14 alkylpolyglycoside were investigated. The test substance was administered orally by gavage once daily from day 6 to day 15 of gestation The dams tolerated the applied dose levels of up to 1000 mg/kg bw/day without any signs of clinical toxicity. Maternal body weight gain was not affected by the treatment. For maternal toxicity, embryo toxicity and teratogenicity, a NOAEL of 1000 mg/kg bw was deduced. From the studies presented, there is no indication for any impairment of reproduction, either with regard to the development of the progeny or to the effects on fertility both of the structural and functional level. Therefore, a hazard of reproductive toxicity for C12-14 alkylpolyglycoside is not expected.

In a one-generation screening assay according to OECD 421, C12-14 alkylpolyglycoside was applied to 40 males and 40 females Sprague-Dawley rats prior to mating, throughout the gestation and lactation period until post partum day 3. Treatment by gavage with 0, 100, 300 and 1000 mg/kg bw/day began 7 days after allocation for both males and females. Treatment commenced when males and females were approximately 12 weeks of age, 2 weeks before pairing and continuously thereafter, up to the day before sacrifice (study day 53, day 4 post partum). Matings were monogamous. During the study, parameters of general toxicity like clinical signs, food consumption and body weight gain were recorded in the parental generation and in the pups. Effects related to reproduction and hormone balance such as oestrous cycle, mating performance, pregnancy rates and the number of embryo resorptions were registered. Pup losses were recorded and the filial generation was examined for behavioural abnormalities and external growth abnormalities. No effects on the fertility were observed up to the highest dose of 1000 mg/kg bw/day. Under the conditions of a state-of-the-art reproduction/developmental toxicity screening testing according to the OECD guideline 421, no adverse effects were observed regarding male and female reproductive organs even at the very high dose of 1000 mg/kg bw/day.

Conclusion:

Due to hydrolysis data of structural related glucosides, Glycerin Glucoside is expected to be hydrolyzed to glycerin and glucose which are both nutrients. Glycerin and glucose are not suspected to be reproductive compounds. In addition, Glycerin Glucoside was tested in a subchronic toxicity study including additional examinations on the reproductive organs. No adverse effects have been observed. Furthermore, the structural related substance C12-14 alkyl polyglucoside was tested in an OECD 414 and OECD 421 study. The substances were applied via gavage. As no adverse effects were noted up to the maximum dose, a NOAEL of 1000 mg/kg was deduced for embryo/fetotoxicity, teratogenicity and maternal toxicity.

In summary, based on this weight-of evidence approach Glycerin Glucoside is not suspected to be toxic for the reproductive system of humans. A study to investigate the developmental toxicity of the registered substance is therefore scientifically unjustified.

Justification for classification or non-classification

There is no indication for toxicity to reproduction from existing data.