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Key value for chemical safety assessment

Effects on fertility

Description of key information

In an OECD422 study, fertility indices and any other reproductive parameters for male and female animals were not impaired by test-substance administration at dose levels up to 100 mg/kg bw/d (highest dose tested).

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
100 mg/kg bw/day
Study duration:
subacute
Species:
rat
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

In a GLP-compliant OECD422 study (28 days repeated dose + reproduction/developmental toxicity screening) 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.

Effects on developmental toxicity

Description of key information

No developmental toxicity was observed in a GLP-compliant OECD422 screening study (2018).

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
100 mg/kg bw/day
Study duration:
subacute
Species:
rat
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available

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 reprotoxicity according to the EU Classification, Labelling, and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

Additional information