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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information

Alpha-amylase is not an reproductive toxicant.

Link to relevant study records
Reference
Endpoint:
multi-generation reproductive toxicity
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Reproductive effects observed:
not specified
Effect on fertility: via oral route
Endpoint conclusion:
no study available
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

Short description of key information:
Alpha-amylase does not affect fertility.

Justification for selection of Effect on fertility via oral route:
Toxicokinetic data together with the molecular structure of alpha-amylase and the weight of evidence from animal studies and human exposure provides no evidence for toxicity on fertility.

Justification for selection of Effect on fertility via inhalation route:
Toxicokinetic data together with the molecular structure of alpha-amylase and the weight of evidence from animal studies and human exposure provides no evidence for toxicity on fertility.

Justification for selection of Effect on fertility via dermal route:
Toxicokinetic data together with the molecular structure of alpha-amylase and the weight of evidence from animal studies and human exposure provides no evidence for toxicity on fertility.

Effects on developmental toxicity

Description of key information

Alpha-amylase is not a teratogen.

Link to relevant study records
Reference
Endpoint:
developmental toxicity
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because the substance is of low toxicological activity (no evidence of toxicity seen in any of the tests available), it can be proven from toxicokinetic data that no systemic absorption occurs via relevant routes of exposure (e.g. plasma/blood concentrations below detection limit using a sensitive method and absence of the substance and of metabolites of the substance in urine, bile or exhaled air) and there is no or no significant human exposure
Abnormalities:
not specified
Developmental effects observed:
not specified
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
Additional information

Justification for selection of Effect on developmental toxicity: via oral route:
Toxicokinetic data together with the molecular structure of alpha-amylase and the weight of evidence from animal studies and human exposure provides no evidence for developmental toxicity.

Justification for selection of Effect on developmental toxicity: via inhalation route:
Toxicokinetic data together with the molecular structure of alpha-amylase and the weight of evidence from animal studies and human exposure provides no evidence for developmental toxicity.

Justification for selection of Effect on developmental toxicity: via dermal route:
Toxicokinetic data together with the molecular structure of alpha-amylase and the weight of evidence from animal studies and human exposure provides no evidence for developmental toxicity.

Toxicity to reproduction: other studies

Additional information

From the toxicokinetic information available, it can be concluded that the bioavailability of enzymes is low due to the fact that no significant absorption can be expected through the respiratory and/or gastrointestinal tract and/or through the skin. Exposure to enzymes will be limited because of the DMEL (derived minimum exposure levels) settings for workers, professionals and consumers to prevent respiratory allergy (supported by exposure scenarios and DMEL values) (ref. 58). Apart from the irritation potential of some proteases, respiratory allergy is generally considered to be the only human health hazard of enzymes indicating that this is the most sensitive endpoint considering enzyme toxicity. Concentrations that are not expected to result in respiratory allergy will certainly not result in any other toxic effect (ref. 59). This conclusion is substantiated by the information that follows.

Although endocrine disrupting chemicals are a broad group of chemicals consisting of man-made and natural compounds it is unlikely that enzymes have the potential to cause endocrine disruption. The enzymatic structure is different from any endocrine disrupter known to date (ref 1). Indeed, enzymes are much larger than endocrine disrupters in general excluding mechanisms such as direct action on hormone receptors (EDSTAC (Endocrine Disruptor Screening and Testing Advisory Committee, US EPA), (Ref. 2)). Due to the high biodegradability of enzymes, it is highly unlikely that they could reach target organs or sites to any significant amount or of any significant period of time. Testing of enzymes in currently available screening assays typically based on hormone receptor binding cannot be expected to provide any evidence for endocrine disruption due to the specific features of enzymes.

Data from acute and subchronic oral toxicity studies provide evidence that enzymes are of very low toxicological activity (ref. 3;4-53, 59, 60). Typically, the derived NOAEL values are significantly higher than the maximum doses applied. None of the oral toxicity studies performed by members of the consortium in the past 40 years, as well as published data from other studies revealed any effect that indicates that enzymes could have an adverse effect on the reproduction system in males or females.

Complementing the above information is data from 26 industrial studies (Novozymes, unpublished data) on fertility and/or teratogenicity and/or reproduction studies primarily in rodents but also other species like dogs and rabbits which did not identify any evidence for reproductive toxicity of enzymes. Both proteolytic and non-proteolytic enzymes have been investigated for their teratogenic and reproductive toxicity potential. Several of these studies have been published in peer reviewed articles (ref. 24;29;33;54). Enzymes have been produced and used for many years without any evidence for reproductive potential in humans. OEL for workers is set to be 60 ng/m3 to protect against respiratory sensitization. Considering that endocrine disrupting chemicals in general are a factor of 100 000 less potent than physiologically relevant hormones (ref. 55), the low worker exposure to enzymes due to rigorous application of airborne limit and very low exposure to consumers (below 15 ng/m3, which is the highest known consumer exposure and only the case when using pre-spotters (ref. 56)) and the low bioavailability together with the high biodegradability of enzymes, no reproductive toxicity effect can be expected in humans. Furthermore, enzymes have been used for decades to treat pancreatic insufficiency in both children and adults without any evidence of reproductive toxicity (ref. 57).

In conclusion, toxicokinetic data together with the enzymatic structure and the weight of evidence from animal studies and human exposure provide no evidence for reproductive toxicity of enzymes.  

 

References

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Justification for classification or non-classification

Alpha-amylase is not classified as it is not a reproductive toxicant. (For further justification see discussion above)

Additional information