Reaction product of Aminoguanidine bicarbonate and Tall Oil fatty acid

Endpoint summary

Description of key information

Two subacute toxicity studies of HiTEC 7134 via the oral route with ratsaare available.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEL

120 mg/kg bw/day

Study duration:

subacute

Species:

rat

Additional information

Two oral subacute toxicity studies of HiTEC 7134 with rats are available, which fulfils the legal requirements for this endpoint. According to REACH legislation one short-term (28 days) repeated dose toxicity is sufficient, provided that it is performed with the most appropriate route of administration. Performing a repeated-dose inhalation study would not be relevant for this specific test material due to its physical-chemical properties. The generation of vapors or aerosols is highly complex, or unfeasible, the log Kow is above 6.4, indicating that the substance is highly lipophilic and viscous, and the vapor pressure is very low, 0.00002 Pa. Overall, conduction of a repeated-dose inhalation study for this test material may be deemed superfluous.

The first study is a 28 -day oral study was performed in accordance with the OECD Guideline 407. H7134 was administered by gavage to groups of five male and five female Alpk: APfSD (Wistar-derived) rats for 28 consecutive days in the following doses: 0, 15, 150 or 250 mg/kg bw/day. Administration of 150 or 250 mg/kg bw H7134, resulted in decreased body weights and minor changes in clinical chemical parameters, as well as organ weights. However, there was no indication of major functional changes or severe organ damage at dose levels up to and including 250 mg H7134/kg bw. The NOAEL for this study was 15 mg/kg bw. 

 

An OECD 421 study titled “Reproductive/developmental toxicity screening test of H7134 in rats by oral gavage” (Zmarowski A, 2012) was performed that had a NOEAL of 120 mg/kg bw/day. Additional measurements particularly affecting clinical biochemistry were completed during this study so that it was similar to an OECD 422 study without the sensory reactivity to stimuli, assessment of grip strength, and other activity assessments. No toxicologically relevant effects were observed up to the highest dose level tested (120 mg/kg). The intial concentrations used were 0. 15, 60, and 250 mg/kg bw/day. However, the Group 4 animals, that were initially exposed to 250 mg/kg, had significantly reduced body weights, body weight gains, absolute and relative food consumption and adverse clinical signs were seen beginning after 4 days of treatment. After treatment was lowered to 120 mg/kg from Day 9 onwards, the condition of the animals improved substantially. While the body weights and body weight gains remained lower for these animals (except for body weight gains during post-coitum and lactation) through the treatment duration, this was not considered adverse since the body weight gains were substantially higher than controls when re-calculated from the time the dose level was lowered. There were several changes noted in clinical biochemistry parameters at 120 mg/kg bw/day, however these were not accompanied by any relevant changes in organ weights or macroscopic findings, and remained within the normal range of values available. Furthermore, increases were not observed in several endpoints that would be indicative of renal or hepatic toxicity. Furthermore, there were no toxicologically relevant effects on any of the remaining parental parameters investigated in this study (clinical observations, food consumption, clinical laboratory investigations, macroscopic examination, organ weights, and microscopic examination). Taken together, the body weight differences and the clinical biochemistry changes were not considered to be toxicologically relevant. No effects that were indictative of reproductive or developmental toxicity were seen. Therefore, the NOAEL was set at 120 mg/kg bw/day

Justification for classification or non-classification

On the basis of the aforementioned result and of the classification criteria laid down in the CLP Regulation, HiTEC7134 does not need to be classified for repeated-dose toxicity.