Registration Dossier

Administrative data

Description of key information

Subchronic (rat, 13 weeks): All the rats given the 2.5% and lower concentrations of 2,3-didehydro-3-O-sodio-D-erythro-hexono-1,4-lactone survived to the end of 13 weeks (Combined repeated dose and carcinogenicity study).
Subchronic (mouse, 10 weeks): The maximum tolerated dose (MTD) of 2,3-didehydro-3-O-sodio-D-erythro-hexono-1,4-lactone in drinking water was 2.5% for male mice and 5.0% for female mice (Combined repeated dose and carcinogenicity study).

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Study duration:
subchronic
Quality of whole database:
A rat subchronic (13 weeks) study and mouse subchronic (10 week) study are presented as weight of evidence.

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Mode of Action Analysis / Human Relevance Framework

Additional information

Two combined repeated dose and carcinogenicity studies were presented as weight of evidence. In the first study (Abe, 1984), the substance was administered to 10 Fischer 344/DuCrj rats/sex/dose in water at dose levels of 0, 0.625, 1.25, 2.5, 5 and 10% for 13 weeks. All the rats given the 10% solution refused to drink and died in 2 to 5 weeks. Three males and one female out of the 10 given the 5% solution died during the first 4 days. All the rats given the 2.5% and lower concentrations survived to the end of 13 weeks. The 2.5% solution suppressed body weight gains by 12% in males and by 6% in females as compared with nontreated controls. No NOAEL value was identified. This dosing information was used in a subsequent chronic carcinogenicity study (52 male/50 female Fischer 344/DuCrj rats in water at dose levels of 1.25 and 2.5% for 104 weeks). At the doses tested, there was not a treatment related increase in tumor incidence when compared to controls. The pattern of occurrence of the various types of tumors was similar among the groups.

In the second study (Andersen, 1999), the substance administered to 10 B6C3F1 mice/sex/dose in drinking water at dose levels of 0, 0.625, 1.25, 2.5, 5 and 10% for 10 weeks. Six male mice and one female mouse of the 10% dosing group had died by the end of week 1. In male mice given 5.0% 2,3-didehydro-3-O-sodio-D-erythro-hexono-1,4-lactone, the average weekly body weight gain was slightly less than 90% that of the control female mice. Body weight gain was increased in female mice given 2,3-didehydro-3-O-sodio-D-erythro-hexono-1,4-lactone at a concentration of 5.0%, compared to that of control mice. No significant changes were observed in the visceral organs of untreated mice or mice given the dose less than or equal to the maximum tolerated dose (MTD) of 2,3-didehydro-3-O-sodio-D-erythro-hexono-1,4-lactone. Mice given doses greater than the MTD had marked atrophy of both hepatocytes and splenic lymphoid follicles, as well as hydropic degeneration of the renal tubular epithelium. The MTD of Sodium Erythrobate in drinking water was 2.5% for male mice and 5.0% for female mice. No NOAEL value was identified. This dosing information was used in a subsequent chronic carcinogenicity study (50 B6C3F1 mice in water at dose levels of 1.25 and 2.5% (males) and 2.5 and 5% (females) for 96 weeks). The average body weights of the treated mice were similar to controls. Of the male mice (without tumors) that survived beyond week 43, dose-dependent reductions in the heart and brain weights were observed. The weights of the heart, lungs, kidneys, and brain of female mice (without tumors) were significantly different between the high dose group and the control group.At the doses tested, there was not a treatment related increase in tumor incidence when compared to controls.

The results from these studies together were deemed acceptable to use in the human health risk assessment.


Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
Two studies are presented as weight of evidence.

Justification for classification or non-classification

Based on available information in the dossier, the substance 2,3-didehydro-3-O-sodio-D-erythro-hexono-1,4-lactone (CAS No. 6381-77-7) was given a classification of ‘inconclusive’ for specific target organ toxicity (repeated) when considering the criteria outlined in Annex I of 1272/2008/EC.