oligomeric Reaction products from Hydrogenation and Hydrolysation of Starch

Endpoint summary

Key value for chemical safety assessment

Toxic effect type:

dose-dependent

Effects on fertility

Description of key information

Predictions of the reproductive effects of the identified constituents have been performed using OECD QSAR Toolbox.

The majority of source substances were tested to different top doses without showing effects. Therefore the derived regression presents a worst-case assumption, as data with qualifiers (">") was used.

In addition, the carbohydrate monomers of the substance, Glucose and Glucitol are listed in Annex IV of REACH.

Although Maltotriose and Maltrotetraose are typically hydrogenated in
the manufacturing process of MG-60 and only small amounts can be present in MG-60,
these oligosaccharides are included in the prediction approach to cover also
representatives of the starting materials of MG-60.

Link to relevant study records

Reference

Endpoint:

screening for reproductive / developmental toxicity

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

weight of evidence

Study period:

May 2021

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Prediction from OECD QSAR Toolbox

Justification for type of information:

REPORTING FORMAT FOR THE CATEGORY APPROACH
[Please provide information for all of the points below addressing endpoint-specific elements that were not already covered by the overall category approach justification made available at the category level. Indicate if further information is included as attachment to the same record, or elsewhere in the dataset (insert links in 'Cross-reference' table)]

1. HYPOTHESIS FOR THE CATEGORY APPROACH (ENDPOINT LEVEL)
The OECD QSAR Toolbox is designed to create categories of substances based on defined similarity criterions. The category consists of similar substances and experimental data for category members is available. Therefore a prediction for the target chemical is possible based on the experimental data of the source substances. For details, please refer to attached documentation.

2. CATEGORY APPROACH JUSTIFICATION (ENDPOINT LEVEL
[Summarise here based on available experimental data how these results verify that the read-across is justified]
The OECD QSAR Toolbox is designed to create categories of substances based on defined similarity criterions. Data is gathered from internationally recognised inventories and databases. For details, please refer to attached documentation.

1. SOFTWARE
OECD QSAR Toolbox
2. MODEL (incl. version number)
4.4.1
3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
OC[C@H](O)[C@@H](O)[C@H](O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O)[C@H](O)CO
4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
[[Explain how the model fulfils the OECD principles for (Q)SAR model validation. Consider attaching the QMRF and/or QPRF or providing a link]
- Defined endpoint: for this prediction, any studies on reproductive effects were considered. Therefore the defined endpoint is "reproductive toxicity"
- Unambiguous algorithm: the prediction is done based on categorising similar chemicals with known experimental data
- Defined domain of applicability: the category is build up around the target substance. Therefore the substance is within the domain of applicability
- Appropriate measures of goodness-of-fit and robustness and predictivity: given in reports
- Mechanistic interpretation: when effects are predicted, an analysis of the category members contributing to the prediction will be done and a mechanistic interpretation will be performed.

5. APPLICABILITY DOMAIN
[Explain how the substance falls within the applicability domain of the model]
The category build up with QSAR toolbox considers the structural, empirical and/or mechanistical (including metabolism) properties of the substance. Therefore the category which is used for predicition is unique to the substance and it can be concluded that the substance falls within the applicability domain.

6. ADEQUACY OF THE RESULT
[Explain how the prediction fits the purpose of classification and labelling and/or risk assessment]
No adverse effects for the substance are predicted. Therefore information are available to conclude on classification.

Qualifier:

no guideline followed

Principles of method if other than guideline:

Prediction using OECD QSAR Toolbox.

GLP compliance:

no

Limit test:

no

Specific details on test material used for the study:

not applicable for in silico

Species:

rat

Strain:

not specified

Details on species / strain selection:

experimental data from various studies using mainly rats is considered.

Sex:

not specified

Key result

Dose descriptor:

NOAEL

Effect level:

3 130 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

not specified

Basis for effect level:

reproductive performance

Remarks on result:

other: predicted value

Key result

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

3 130 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

not specified

Basis for effect level:

other: any toxicological effects

Key result

Reproductive effects observed:

no

Lowest effective dose / conc.:

3 130 mg/kg bw/day (nominal)

Treatment related:

no

Conclusions:

A NOAEL of 3130 mg/kg bw/day for Reproductive effects is predicted using OECD QSAR Toolbox.

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

The carbohydrate monomers, which build up the constituents of the substance are Glucose and Glucitol, both substances which are listed in Annex IV of REACH. These two substance are exempted from Registration as sufficient information is available that they are considered to cause minimum risk because of their intrinsic properties. The constituents of the substance will be readily metabolised by specialised enzymes in the gastro-intestinal tract (enzymatic cleavage of glycosidal 1,4-bond) to yield Glucose and Glucitol.

 

Effects on developmental toxicity

Description of key information

Predictions of the reproductive effects of the identified constituents have been performed using OECD QSAR Toolbox.

The majority of source substances were tested to different top doses without showing effects. Therefore the derived regression presents a worst-case assumption, as data with qualifiers (">") was used.

In addition, the carbohydrate monomers of the substance, Glucose and Glucitol are listed in Annex IV of REACH.

Under REACH Annex VII or VIII, no specific information on developmental toxicity is requested. However, the available predictions give hints to the absence of developmental effects.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Mode of Action Analysis / Human Relevance Framework

The carbohydrate monomers, which build up the constituents of the substance are Glucose and Glucitol, both substances which are listed in Annex IV of REACH. These two substance are exempted from Registration as sufficient information is available that they are considered to cause minimum risk because of their intrinsic properties. The constituents of the substance will be readily metabolised by specialised enzymes in the gastro-intestinal tract (enzymatic cleavage of glycosidal 1,4-bond) to yield Glucose and Glucitol.

 

Therefore no Mode of Action can be identified as the substance enters the general carbohydrate metabolism and will be ultimately metabolised to Carbondioxide and water.

Justification for classification or non-classification

The available information is conclusive but not sufficient for classification.