Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 232-671-2 | CAS number: 9004-07-3
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Description of key information
The animals at all the tested doses (1060, 1591 and 2111 mg TOS/kg body weight) did not reveal any clinical signs of toxicity throughout the observation period and no mortality occurred. The body weight and percent change in body weight of animals at all the steps increased with respect to Day 1. A complete gross pathological examination was carried out for the animals and there were no gross pathological changes observed in any of the animals.
Based on the results of the experiment and under experimental conditions employed, it can be concluded that the test item Serine Endopeptidase, batch PPA 26797 cannot be classified based on the GHS criteria.
Key value for chemical safety assessment
Acute toxicity: via oral route
Link to relevant study records
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 25-06-2015 to 27-08-2015
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
- Version / remarks:
- Adopted 17 December 2001.
- Deviations:
- no
- GLP compliance:
- yes
- Test type:
- acute toxic class method
- Limit test:
- yes
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: BIONEEDS INDIA PRIVATE LIMITED (in-house bred)
- Females nulliparous and non-pregnant: Yes
- Age at study initiation: 10 weeks
- Weight at study initiation: 160.07 g to 170.45 g
- Fasting period before study: No
- Housing: Three animals were housed in a standard Polysulfone cage (size: L 430 x B 285 x H 200 mm) with stainless steel mesh top grill having facilities for holding pelleted food and drinking water in water bottle fitted with stainless steel sipper tube. Clean sterilized paddy husk was provided as bedding material. Sterilized paper shreds were provided as nesting material for enrichment.
- Diet: Ad libitum. Nutrilab rodent feed (Manufactured by Provimi Animal Nutrition India Pvt Ltd)
- Water: Ad libitum. Deep bore-well water passed through activated charcoal filter and exposed to ultraviolet rays in Aquaguard water filter purifier was provided in plastic water bottles with stainless steel sipper tubes.
- Acclimation period: Healthy and young adult animals used for step I, step II and step III were acclimatized for seven, nine and eleven days, respectively.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.6 to 22.4°C
- Humidity (%): 50-61%
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: 02 July 2015 To: 20 July 2015 - Route of administration:
- oral: gavage
- Vehicle:
- unchanged (no vehicle)
- Details on oral exposure:
- Undiluted test material for the top dose.
- Doses:
- The acute toxicity test was conducted with starting dose 1060 mg TOS/kg body weight, followed by 1591 mg TOS/kg body weight and the highest dose level of 2111 mg TOS/kg body weight. Three animals were used per step (total nine animals).
Fixed dose volume of 5.3 mL/kg body weight was used with increased frequency of administration to gain the final dose volume. - No. of animals per sex per dose:
- 3 (female only)
- Control animals:
- no
- Details on study design:
- The total quantity of test item to be administered per day was administered in divided doses of two (Step I), three (Step II) and four (Step III) times with approximately 4 hour interval between each administration. Test item administration was sequential and allowing at least 24 hours before dosing the next set of animals. The time interval between dosing at each level was determined by the onset, duration and severity of toxic signs.
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All the animals were observed for clinical signs of toxicity and mortality at 30 to 40 min, 1 hr (±10 min), 2 hrs (±10 min), 3 hrs (±10 min) and 4 hrs (±10 min) after each administration on Day 1 and thereafter, once daily for clinical signs of toxicity and twice daily for mortality during the 14 days observation period.
- Necropsy of survivors performed: At the end of observation period, all the animals were sacrificed by exsanguination in deep Isoflurane anaesthesia. A complete gross pathological examination was carried out for terminally sacrificed animals. - Statistics:
- No
- Key result
- Sex:
- female
- Dose descriptor:
- LD0
- Effect level:
- >= 2 111 mg/kg bw
- Based on:
- other: Total Organic Solids (TOS)
- Mortality:
- No mortality during 14 days of observation period.
- Clinical signs:
- other: The animals did not reveal any clinical signs of toxicity and mortality during 14 days of observation period.
- Gross pathology:
- There were no gross pathological changes observed in the animals dosed at 1060, 1591 and 2111 mg TOS/kg body weight for step I, step II and step III, respectively during necropsy.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The animals at all the tested doses (1060, 1591 and 2111 mg TOS/kg body weight) did not reveal any clinical signs of toxicity throughout the observation period and no mortality occurred. The body weight and percent change in body weight of animals at all the steps were increased with respect to Day 1. A complete gross pathological examination was carried out for the animals and there were no gross pathological changes observed in any of the animals.
Based on the results of the experiment and under experimental conditions employed, it was concluded that the test item serine endopeptidase, batch PPA26797 could not be classified based on the GHS criteria. - Executive summary:
The test item serine endopeptidase, batch PPA26797 was evaluated for Acute Oral Toxicity in Sprague Dawley Rats. The acute toxicity test was conducted with starting dose 1060 mg TOS/kg body weight, followed by 1591 mg TOS/kg body weight and the highest dose level of 2111 mg TOS/kg body weight. Three animals were used per step (total nine animals). Fixed dose volume of 5.3 mL/kg body weight was used with increased frequency of administration to gain the final dose volume.
All the animals were observed for clinical signs of toxicity at 30 to 40 minutes, 1 hr (±10 min), 2 hr (±10 min), 3 hr (±10 min) and 4 hr (±10 min) after each administration on Day 1 and once daily thereafter for clinical signs and twice daily for mortality.
The animals at all the tested doses (1060, 1591 and 2111 mg TOS/kg body weight) did not reveal any clinical signs of toxicity throughout the observation period and no mortality occurred.
Individual animal body weight was recorded at receipt, Day 1 before test item administration, Day 7 and Day 14 during the observation period for step I, step II and step Ill animals. The body weight and percent change in body weight of animals at all the steps were increased with respect to Day 1.
All the animals (step I, step II and step Ill) were observed for 14 days, sacrificed by exsanguination in deep Isoflurane anaesthesia on Day 15 and subjected to necropsy. A complete gross pathological examination was carried out for the animals and there were no gross pathological changes observed in any of the animals.
Based on the results of the experiment and under experimental conditions employed, it was concluded that the test item serine endopeptidase, batch PP A26797 could not be classified based on the GHS criteria.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
Acute toxicity: via dermal route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
In general, enzymes are of very low toxicity due to ready biodegradability and very low bioavailability. In traditional acute toxicity testing, mortality has been the endpoint. However, because enzymes show very low toxicity, extremely high doses that are far above human exposure levels typically have been applied. Therefore, acute toxicity studies are not considered to provide appropriate knowledge and are as such not a relevant test system for enzymes. Systemic exposure by the dermal route is unlikely based on the existing toxicokinetic knowledge of enzymes, which due to their relatively large molecular weight, are not expected to be absorbed through the skin (Basketter et al. 2008, Smith Pease et al. 2002). Therefore, it can be safely assumed that technical enzymes do not exert any acute dermal toxicity (Basketter et al 2012). This conclusion is confirmed by the toxicological data available. Sub-acute dermal toxicity studies with protease in rabbits (Novozymes, unpublished data) did not provide evidence for systemic effect to enzymes. This finding is confirmed by data from acute dermal toxicity studies (Novozymes, unpublished data) of other enzyme products in both rats and rabbits. None of these studies revealed any acute toxic effect through the dermal administration route. No clinical signs or adverse effects due to systemic exposure could be observed. Data waivers will further be established through exposure scenarios, i.e. no significant dermal exposure to consumers and professionals due to the toxicologically insignificant enzyme concentrations in end products and in the case of workers due to occupational hygiene measures associated with the prevention of respiratory allergy which includes protective clothing. In conclusion, toxicokinetic data together with evidence from animal studies and historical human experience derived from the use of detergent enzymes for decades confirm that exposure to technical enzymes will not result in any toxicologically relevant uptake by dermal route. Acute systemic exposure to a toxicologically significant amount of enzymes by this route can, therefore, be excluded and will further be prohibited by the obligatory setting of a DMEL value for enzymes, resulting in negligible exposure to enzymes (Basketter et al 2010). In vivo acute dermal toxicity studies will not add any value and cannot be expected to provide valuable knowledge and are considered scientifically and ethically unjustified. Therefore, in accordance with column 2 of REACH Annex VIII acute toxicity testing by the dermal route is inappropriate.
References:
- Basketter DA, English JS, Wakelin SH, White IR (2008). Enzymes, detergents and skin: facts and fantasies. Br. J. Dermatol., 158 (6):1177-1181.
- Smith Pease CK, White IR, Basketter DA (2002). Skin as a route of exposure to protein allergens. Clin. Exp. Dermatol., 27(4):296-300.
- Basketter D, Berg N, Broekhuizen C, Fieldsend M, Kirkwood S, Kluin C, Mathieu S, Rodriguez C (2012a). Enzymes in Cleaning Products: An Overview of Toxicological Properties and Risk Assessment/Management. Regul. Toxicol. Pharmacol., 64(1):117-123.
- Basketter DA, Broekhuizen C, Fieldsend M, Kirkwood S, Mascarenhas R, Maurer K, Pedersen C, Rodriguez C, Schiff HE (2010). Defining occupational and consumer exposure limits for enzyme protein respiratory allergens under REACH. Toxicology, 268(3):165-170.
Justification for classification or non-classification
GHS criteria not met.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.