Registration Dossier

Administrative data

Description of key information

No data on the acute toxicity of wheat glucose syrups were identified; however, acute toxicity data on read-across substances, such as sorbitol or Lycasin® were available.  Thus, using a weight of evidence approach, these data were included as supportive data.
Sorbitol and Lycasin® are all of low acute toxicity following oral exposure. The oral LD50 for sorbitol was reported as 20.2 and 18.9 g/kg for male and female rats, respectively. LD50 values could not be determined for Lycasin® since no mortalities and no clinical signs were observed during the study period.
Sorbitol and Lycasin® also are of low acute toxicity following intravenous exposure. The LD50 values of sorbitol were reported to be 3.22 g/kg and 5.6 g/kg for male and female mice, respectively, and 7.31 and 7.39 g/kg in male and female rats, respectively. No mortalities and no clinical signs were observed in mice at an intravenous concentration of up to 6.39 and 8.15 g/kg body weight of Lycasin® in male and female mice, respectively. Thus, no LD50 value for Lycasin® could be determined.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50
18 900 mg/kg bw

Additional information

No data on the acute toxicity of wheat glucose syrups were identified; however, acute toxicity data on read-across substances, such as sorbitol or Lycasin® were available. Thus, using a weight of evidence approach, these data were included as supportive data.

 

Metabolic data demonstrate that the notifiable substance [wheat glucose syrup (WGS)], as well as the read-across substances (sorbitol and Lycasin® 80/55) 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, WGS is expected to be similar to the read-across substances sorbitol and Lycasin® 80/55. 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, sorbitol and Lycasin® 80/55 may be used as appropriate surrogates for WGS, considering their common metabolic products.

 

Acute oral:

The potential acute oral toxicity of sorbitol was evaluated in male and female Wistar rats in a study conducted similar in methodology to OECD Guideline for the Testing of Chemicals No. 423 (Tanaka and Gomi, 1972). Groups of rats were orally administered 12, 17, 24, or 30 g/kg of sorbitol and observed for a period of 2 weeks. A total of 0/10, 1/10, 9/10, and 10/10 male rats died within 1 day in the 12, 17, 24, or 30 g/kg dose groups, respectively. A total of 0/10, 4/10, 8/10, and 10/10 female rats died within 1 day in the 12, 17, 24, or 30 g/kg dose groups, respectively. No information on clinical signs, body weight, or gross pathology was reported. Based on the results, the authors reported an LD50 of 20.2 g/kg for male rats and 18.9 g/kg for female rats.  

Groups of male and female mice and rats were orally administered Lycasin® 80/55 by gavage in a study performed similar in methodology to OECD Guideline for the Testing of Chemicals No. 423 (Dupas, 1982). Groups of OF1 Swiss mice received a single dose of 14.62, 19.50, or 24.37 g/kg body weight of Lycasin® and groups of Sprague-Dawley rats received a single dose of 24.37 g/kg body weight of Lycasin®. All mice and rats were observed for 14 days. No significant clinical signs were observed in mice during the study period and no details on clinical signs were provided in rats. No compound-related changes in body weight were reported in mice or rats administered Lycasin® and their respective control groups. No mortalities were observed in mice or rats. Thus, the LD50 could not be determined.

 

Acute intravenous:

The acute intravenous toxicity of sorbitol was investigated in both ICR mice and Wistar rats (Tanaka and Gomi, 1972). Female mice received 3.0, 4.3, 6.0, or 9.4 g/kg body weight sorbitol and male mice received 2.1, 3.0, 4.3, or 6.0 g/kg body weight sorbitol, and all animals were observed for a 2-week period. From a total of 10 animals tested per dose group, 0, 1, 7, and 9 female mice died in the 3.0, 4.3, 6.0, and 9.4 g/kg body weight dose groups, respectively. From a total of 10 animals per dose group, 1, 4, 9, and 10 male mice died in the 2.1, 3.0, 4.3, and 6.0 g/kg body weight dose groups, respectively. No information regarding clinical signs, body weight, or gross pathology was provided. The authors determined the LD50 of sorbitol to be 3.22 g/kg body weight for male mice and 5.6 g/kg for female mice following intravenous exposure. In rats, females were administered 4.3, 6.0, 8.4, or 12.0 g/kg body weight of sorbitol whereas males were administered 6.0, 7.1, or 8.4 g/kg body weight of sorbitol, both of which were observed during a 2-week study period. A total of 0, 2, 7, and 10 female rats died out of the 10 animals tested per group in the 4.3, 6.0, 8.4, and 12.0 g/kg body weight dose groups, respectively. From a total of 10 animals per group, 0, 3, and 10 male rats died in the 6.0, 7.1, and 8.4 g/kg body weight dose groups, respectively. No information regarding clinical signs, body weight, or gross pathology was provided. Under the conditions of the study, the authors concluded that the LD50 was 7.31 g/kg body weight in male rats and 7.39 g/kg body weight in female rats following intravenous exposure.

 

Dupas (1982) investigated the potential intravenous toxicity of Lycasin® 80/55 in mice. Groups of male and female OF1 Swiss mice were intravenously administered Lycasin® at doses of 1.32, 2.56, 3.97, 5.17, or 6.39 g/kg body weight and 1.48, 3.08, 4.82, 6.25, or 8.15 g/kg body weight, respectively. Gross pathology was not examined in the study. No mortalities were reported during the study period and no significant clinical signs were observed during the 14-day observation period. Therefore, the LD50 could not be determined by the authors.

Justification for classification or non-classification

Acute Toxicity, oral: While no acute oral information is available for the notifiable substance, the read-across substance has an acute oral LD50 of greater 2000 mg/kg bw (lowest reported acute oral LD50 = 18900 mg/kg bw). As a result, the substance does not meet the criteria for classification according to Regulation (EC) No 1272/2008, Annex I section 3.1.

 

Acute Toxicity, dermal: While no acute dermal information is available for the notifiable substance, the intravenous data for the read-across compound (the minimum LD50 report is 3220 mg/kg bw) represent a worst-case scenario and supports the assumption that the acute dermal LD50 would be greater than 2000 mg/kg bw. Additionally, the log Kow value of less than –1 (log Kow <-2) suggest that the substance is not likely to be sufficiently lipophilic to cross the stratum corneum, therefore dermal absorption is likely to be low. As a result of expert judgement, the substance does not meet the criteria for classification according to Regulation (EC) No 1272/2008, Annex I section 3.1.

 

Acute Toxicity, inhalation: There is no information available concerning inhalation toxicity; data is lacking.

 

Specific Target Organ Toxicity– Single Exposure: Based on the data available on the read-across substances, the notifiable substance is not likely to exhibit significant toxic effects arising from a single exposure. As a result, the substance does not meet the criteria for classification according to Regulation (EC) No 1272/2008, Annex I section 3.8.