Registration Dossier
Registration Dossier
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EC number: 270-337-8 | CAS number: 68425-17-2
Toxicological Summary
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 5 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 2 000 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - workers
Acute DNELs:
Worker: Production of sorbitol/maltitol is in excess of 10 t/y. According to the REACh "Guidance on information requirements and chemical safety assessment, Part B: Hazard Assessment", above 10 t/y, the establishment of acute toxicity DNEL is unnecessary in most cases, as the DNEL based on long-term exposure is normally sufficient to ensure that adverse effects do not occur. Thus, as long term DNELs are available for sorbitol/maltitol and these substances are not classified for acute toxicity via any route of exposure, separate acute DNELs were not derived; default to systemic DNEL for local effects.
Long-term DNELs:
Dermal:
Metabolic data demonstrate that the notifiable substance, as well as the read-across substances [maltose, maltitol, sorbitol, wheat glucose syrup (WGS), and dextrin] share a common metabolic pathway as they are converted to D-glucose and/or sorbitol via hydrolysis of their glycosidic linkages by the intestinal brush border carbohydrases. On the basis of their common mono- and disaccharide metabolites, the properties of the notifiable substance, is expected to be similar to the read-across substances maltose, sorbitol, maltitol, WGS, and dextrin. Considering this, it is anticipated that exposure to any of the aforementioned saccharides would ultimately result in the formation of D-glucose and/or sorbitol. As such, maltose, sorbitol, maltitol, WGS, and dextrin may be used as appropriate surrogates for the notifiable substance, considering their common metabolic products.
Therefore, the dermal DNELs are based on the European Food Safety Agency's (EFSA) Opinion (Request N° EFSA-Q-2004-091, adopted on 19 October 2004) that states the following: For coeliac disease, assessment of the evidence provided indicates that wheat-based glucose syrups including dextrose are unlikely to cause an adverse reaction in individuals with coeliac disease provided that the provisional value of gluten considered by Codex Alimentarius for foods rendered gluten-free (currently 200 mg/kg) is not exceeded. As this is a limit based on a sensitive patient population, healthy individuals could exceed this value.
Based on the information provided in the Merck Index and the Roquette Safety Data Sheets, the calculated water solubility is at least 901530 mg/L and it is scientifically reasonable to expect the solubility of the notifiable substance to be > 10000 mg/L. Based on this information, it is scientifically reasonable to expect the log Kow to be less than -2. Therefore as per Reach Guidance Chapter R.7C, a value of 10% skin absorption can be chosen if the log P values is outside the range [-1, 4].
Final DNEL:
200 x 1/10 (adjustment factor for dermal absorption of 10%) = 2,000 mg/kg bw
Inhalation: The United States Occupational Safety and Health Administration have a limit of 15 mg/m3 for total dust and 5 mg/m3 for respirable dust for “Particulates not otherwise regulated”. The US OHSA has applied these dust limits to food-related items such as sucrose, cellulose, and vegetable oil mist (29CFR1910.1000 TABLE Z-1 (Limits for Air Contaminants)].
The final DNEL was based on the respirable dust (5 mg/m3), while a higher level of 15 mg/m3 was recommended for total dust.
References:
European Chemicals Agency. Chapter R.7C – Endpoint Specific Guidance. Guidance on information requirements and chemical safety assessment. Adopted May 2008.
European Food Safety Agency. Opinion of the Scientific Panel on Dietetic Products, Nutrition and Allergies on a request from the Commission related to a notification from AAC on wheat-based glucose syrups including dextrose pursuant to Article 6 paragraph 11 of Directive 2000/13/EC (Request N° EFSA-Q-2004-091) (adopted on 19 October 2004).
Talbot, JM (1978) "The Need for Special Foods and Sugar Substitutes by Individuals with Diabetes Mellitus", Life Sciences Research Office Federation of American Societies for Experimental Biology, Bethesda, Maryland.
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.89 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 2
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 2 000 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 200 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - General Population
Acute DNELs:
General Population: Production of sorbitol/maltitol is in excess of 10 t/y. According to the REACh "Guidance on information requirements and chemical safety assessment, Part B: Hazard Assessment", above 10 t/y, the establishment of acute toxicity DNEL is unnecessary in most cases, as the DNEL based on long-term exposure is normally sufficient to ensure that adverse effects do not occur. Thus, as long term DNELs are available for sorbitol/maltitol and these substances are not classified for acute toxicity via any route of exposure, separate acute DNELs were not derived; default to systemic DNEL for local effects.
Long-term DNELs:
Oral:
Metabolic data demonstrate that the notifiable substance, as well as the read-across substances [maltose, maltitol, sorbitol, wheat glucose syrup (WGS), and dextrin] share a common metabolic pathway as they are converted to D-glucose and/or sorbitol via hydrolysis of their glycosidic linkages by the intestinal brush border carbohydrases. On the basis of their common mono- and disaccharide metabolites, the properties of the notifiable substance, is expected to be similar to the read-across substances maltose, sorbitol, maltitol, WGS, and dextrin. Considering this, it is anticipated that exposure to any of the aforementioned saccharides would ultimately result in the formation of D-glucose and/or sorbitol. As such, maltose, sorbitol, maltitol, WGS, and dextrin may be used as appropriate surrogates for the notifiable substance, considering their common metabolic products.
Therefore, DNELs are based on the European Food Safety Agency's (EFSA) Opinion (Request N° EFSA-Q-2004-091, adopted on 19 October 2004) that states the following: For coeliac disease, assessment of the evidence provided indicates that wheat-based glucose syrups including dextrose are unlikely to cause an adverse reaction in individuals with coeliac disease provided that the provisional value of gluten considered by Codex Alimentarius for foods rendered gluten-free (currently 200 mg/kg) is not exceeded. As this is a limit based on a sensitive patient population, healthy individuals could exceed this value.
Considering the above, and according to the Talbot, 1978 document "The Need for Special Foods and Sugar Substitutes by Individuals with Diabetes Mellitus", daily sorbitol intake from food (for other than coeliac disease patients) may exceed 50 g provided it bears the statement "Excess consumption may have a laxative effect".
Dermal:
DNELs for dermal exposure are the same as for worker, as previously discussed.
Inhalation:
The United States Occupational Safety and Health Administration have a limit of 15 mg/m3 for total dust and 5 mg/m3 for respirable dust for “Particulates not otherwise regulated”. The US OHSA has applied these dust limits to food-related items such as sucrose, cellulose, and vegetable oil mist (29CFR1910.1000 TABLE Z-1 (Limits for Air Contaminants)]. No adjustments required for interspecies, exposure duration, dose response or quality of whole database as DNEL is based on an occupational limit for workers. An AF of 2 applied for differences between workers and general population (basis: when extrapolating from animal to human, the recommended AF is 10 for general population and 5 for worker – since the starting dose is amortized for continuous exposure an additional 2 fold AF for differences was considered sufficient)
Final DNEL:
5 mg/m3(based on occupational exposure of 8 hours/day, 5 days/week) (amortized below for continuous exposure)
5 mg/m3 x (10/6.7) x (8/24) x (5/7)/2 = 0.89 mg/m2
References:
European Chemicals Agency. Chapter R.7C – Endpoint Specific Guidance. Guidance on information requirements and chemical safety assessment. Adopted May 2008.
European Food Safety Agency. Opinion of the Scientific Panel on Dietetic Products, Nutrition and Allergies on a request from the Commission related to a notification from AAC on wheat-based glucose syrups including dextrose pursuant to Article 6 paragraph 11 of Directive 2000/13/EC (Request N° EFSA-Q-2004-091) (adopted on 19 October 2004).
Talbot, JM (1978) "The Need for Special Foods and Sugar Substitutes by Individuals with Diabetes Mellitus", Life Sciences Research Office Federation of American Societies for Experimental Biology, Bethesda, Maryland.
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