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Description of key information

In a GLP-compliant OECD422 study in rats, the oral administration by gavage of TMG revealed signs of local toxicity at dose levels of 30 mg/kg bw/d and above in female animals indicated by erosions in the glandular stomach. However, the no observed adverse effect level (NOAEL) for general systemic toxicity was set to 100 mg/kg bw/d for male and female rats; the local NOAEL was set to 10 mg/kg bw/d.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
10 mg/kg bw/day
Study duration:
subacute
Species:
rat
System:
other: local effects at the point of entry; systemic NOAEL = 100 mg/kg bw/day

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 GLP-compliant OECD 422 study TMG was given to rats orally ba gavage (2018). TMG was given daily as a solution to groups of 10 male and 10 female Wistar rats (F0 animals) at dose levels of 0, 10, 30, and 100 mg/kg bw/d. Deionized water served as vehicle. The duration of treatment covered a 2-week premating period and mating in both sexes (mating pairs were from the same test group) as well as entire gestation and lactation period in females up to one day prior to the day of schedule sacrifice of the animals. The test substance preparation analyses confirmed: Stability of the test-substance preparations for a period of 7 days at room temperature, homogeneous distribution of the test substance in the vehicle, correctness of the prepared concentrations. Effects: The following test substance-related, relevant findings were noted: Local effects on the glandular stomach in individual female animals related to the corrosive potential of the test item. For all other organs/endpoints/parameters exmanied: No treatment-related, adverse effects were observed.

CONCLUSION: Under the conditions of this Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test, the oral administration by gavage of 1,1,3,3-Tetramethylguanidine to Wistar rats revealed signs of local toxicity at dose levels of 30 mg/kg bw/d and above in female animals indicated by erosions in the glandular stomach. However, the no observed adverse effect level (NOAEL) for general systemic toxicity was set to 100 mg/kg bw/d for male and female Wistar rats, the local NOAEL to 10 mg/kg bw/d. The NOAEL for reproductive performance and fertility was also set to 100 mg/kg bw/d for male and female Wistar rats. The NOAEL for developmental toxicity was 100 mg/kg bw/d.

Justification for classification or non-classification

Based on the results of the oral OECD422 study in rats, TMG does not need to be classified for STOT RE according to the EU Classification, Labelling, and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008. The local effects (erosion in glandular stomach in some mid and high dose females) are covered by the classification for Skin Corr. 1B.