Tris(2-hydroxyethyl)methylammonium methyl sulphate

Endpoint summary

Description of key information

OECD 408 (subchronic toxicity): NOEL of 406.4 and 495.5 mg/kg bw/d for male and female rats, respectively. (Colgate-Palmolive, 1991)

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Study duration:

subchronic

Species:

rat

Quality of whole database:

GLP and similar to guideline study.

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 repeated dose toxicity study, the test substance was administered to 10 Sprague-Dawley rats/sex/dosing group in drinking water at concentrations of 0 (control), 0.096, 0.32 and 1.6 % v/v for 90 consecutive days (Colgate-Palmolive, 1991). The mean substance intakes that were determined each week were used to estimate the percentages in mg /kg bw/d for male and female animals as follows:

Dose [% v/v]	Males [mg/kg bw/d]	Females [mg/kg bw/d]
0.096	115.3	139.6
0.32	406.4	495.5
1.6	2389.1	2703.3

The test animals were treated daily. The test was conducted equivalent to OECD guideline 408. Physical examinations, ophthalmoscopic examinations, body weight, food consumption and water consumption measurements were performed on study animals at selected intervals. Hematology, clinical chemistry, and urinalyses were performed on study animals at study termination.

After 91 or 92 days of treatment, depending on the day of termination, all animals were sacrificed, selected organs were weighed and organ/body and organ/brain weight ratios calculated. Complete gross postmortem examinations of selected tissues were conducted on all animals. At the highest concentration (1.6 %) administration of test substance produced diarrhea, which occurred earlier and with greater frequency in males than in females, and an apparent decrease in urinary pH. Only the males receiving the highest concentration (1.6 %) exhibited decreased body weight gains, increased water consumption and slightly increased kidney/body weight ratios. No unusual signs attributable to test material administration were seen in animals receiving the low (0.096 %) and intermediate (0.32 %) concentrations, and no effects on body weight gain, water consumption, urinary parameters or organ weights were seen in these groups. All animals survived throughout the study and evaluations of food consumption, ophthalmoscopic examinations, hematology and clinical chemistry studies and gross postmortem observations revealed no effect of the test material at any of the concentrations administered. Microscopic examinations of selected tissues revealed no abnormalities considered attributed to test material administration.

A NOAEL was not determined based on the results of this study due to precautionary reasons. Male animals of the highest dosing group showed a slightly lower body weight at the end of the study. The water intake was significantly increased compared to control animals. The kidney weights were slightly higher leading to a significant elevation of the kidney/body weight ratio. Both sexes of the high dose developed a significantly decreased urinary pH value. Due to these borderline effects in the highest dosing group a NOAEL was not determined.

Based on the ante mortem findings in the high-dose group, it is conservatively assumed that the no effect level (NOEL) for the test substance under conditions of this study was 0.32 %. Expressed as mg/kg bw/d doses these are 406.4 for males and 495.5 for females.

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
GLP and similar to guideline study.

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available study is considered reliable and suitable for classification purposes under 67/548/EEC. As a result, the substance does not need to be classified and labelled for repeated dose toxicity under Directive 67/548/EEC, as amended for the 31st time in Directive 2009/2/EC.

 

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

The available experimental test data is reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance does not need to be classified and labelled for repeated dose toxicity under Regulation (EC) No 1272/2008, as amended for the sixth time in Regulation (EC) No 605/2014.