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Administrative data

Description of key information

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
900 mg/kg bw/day
Study duration:
subchronic
Species:
rat

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

Additional information

In a subchronic toxicity study (2003 -0842 -FGT) according to OECD TG 408 L-threonine was administered to rats in doses of 0 (control), 0.5, 1.5 and 5.0% in diet. Each group consisted of 10 rats/sex, the control group consisted of 20 rats/sex. Administration of the test substance did not reveal any treatment-related and toxicological relevant change in low- and mid-dose animals. However, in high-dose animals an increase in kidney weights and increased heart weights were considered to be treatment related. Although the observed changes were rather minor and histopathological examinations revealed no abnormalities, they were considered toxicologically relevant. The NOAEL after daily administration of L-threonine for 13 consecutive weeks can conservatively be placed at a dietary level of 1.5 % (equivalent to a mean test substance intake of 916 mg/kg bw in males and 962 mg/kg bw in females).    

In a second subchronic toxicity study (2009 -0252 -FGT) according to OECD TG 408 L-threonine was administered to rats in doses of 0 (control), 0.5, 1.5 and 5.0% in diet. The diets were fed ad libitum to Wistar rats (10 rats/sex/group) during 13 weeks, and provided an overall intake of 0.3, 0.9 and 3.0 g/kg body weight/day for males, and 0.3, 1.0 and 3.2 g/kg body weight/day for females

Based on the increase in relative kidney weight in the high-dose group, the NOAEL of L-Threonine was conservatively placed at the mid-dose level (1.5%). This level was equivalent to an overall intake of at least 0.9 g /kg body weight/day.

In a further subchronic toxicity study (94 -0630 -FGT) similar to OECD TG 408 L-threonine was administered to rats in doses of 0 (control group: basic diet), 1.25, 2.5 and 5.0% L-threonine in diet. Each group consisted of 12 or 18 male and female rats respectively. Even the highest dose used (5%) resulting in an average intake of 3266.9 and 3673.3 mg/kg bw for male and female, respectively produced no adverse effects and is therefore regarded as the NOAEL. However, a reliability score of 4 was assigned to this study and was used only as a supporting study as the full study report was not available to the registrant (only a summary of the results).

In a subacute toxicity study (2002 -0140 -DGT) according to OECD TG 407 performed under GLP L-threonine was given by gavage to 10 animals /dose (5 rats/sex) in doses of 100, 300, and 1000 mg/kg bw. The resulting NOAEL was 1000 mg/kg bw.

This result was confirmed in a publication (van de Mortel et al 2010). According to this publication l-threonine caused no adverse effects at a dose of 1000 mg/kg bw in a study according to OECD 407.

There are no studies available regarding repeated dose toxicity via the dermal route and via the inhalative route. However, although oral intake is not the most appropriate route of exposure it represents a worst case scenario in terms of bioavailability. No evidence for local effects is given. Therefore and due to animal welfare there is no need for further inhalative or dermal repeated dose testing.


Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
conservative approach - repeated dose study with toxicological relevant effects at lowest dose

Justification for classification or non-classification