Propanamide, 3-amino-2,2-dimethyl-

Endpoint summary

Description of key information

rat, oral: NOEL = 316 mg/ kg bw/day; NOAEL >= 1000 mg/kg bw/day (OECD guideline 407)

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

subacute

Species:

rat

Additional information

There are valid data available for the assessment of the oral repeated dose toxicity of 3-amino-2,2-dimethyl-propionamide.

The study was performed to evaluate the toxicity of 3 -amino-2,2-dimethyl-propionamide after a repeated oral administration to rats, according to EC-guideline 96/54, method B.7, and to the OECD guideline 407. The test substance was administered as a freshly prepared aqueous solution, orally by gavage to 3 groups (100, 316, 1000 mg/kg bw/day) of 5 male and 5 female F344 rats each, once a day for 28 consecutive days. In addition, two groups of 5 males and 5 females each, i.e. one high dose satellite group and one control satellite group, were treated in the same way as their corresponding groups, but were kept for further 14 days without test substance administration in an attempt to observe the reversibility or persistence of test substance induced lesions. There was no test substance related mortality, all animals survived until their scheduled sacrifice. Signs of reduced well-being were noted shortly after dosing in the high dosed animals. Otherwise no test substance related effects were noted. The body weight gain of the high dosed recovery group males was significantly reduced in the first two weeks of dosing. No test substance related effects were noted in the body weights themselves or in the feed consumption. In the high dose group (males) a significant increase of platelets was observed. In the high dose group after recorvery female animals showed a decreased number of lymphocytes and an increase in alkaline phosphatase. The changes in platelet count may be due to the test substance, while both the differences in lymphocyte count and in alkaline phosphatase are of equivocal relevance. There were no significant differences in the organ weights. There were no significant differences nor any test substance related alterations noted at necropsy with gross pathological examination and histopathology.

There were a few scattered significant differences noted at the end of the satellite period. None of them can be attributed to the test substance, as to the lack of corresponding alterations at the end of the dosing period. None of the test substance related effects, noted during or at the end of the dosing period, persisted until the end of the recovery period.

In conclusion, 3-amino-2,2-dimethyl-propionamide was found to induce a few transient changes in life, regarded to be of low toxicological importance, together with a marginally reduced body weight gain and isolated haematological alterations at a dose of 1000 mg/kg bw/day. No test substance related effects were found at lower doses. None of the effects observed gave an indication for a mode of action of the test substance, none of the effects noted persisted until the end of the recovery period. None of the effects were severe or life threatening and therefore considered as not adverse. There was also no clear sex difference in the susceptibility to the test substance. The NOEL of 3 -amino-2,2-dimethyl-propionamide was at 316 mg/kg bw/day in both sexes. The NOAEL was considered to be >= 1000 mg/kg bw/day in both sexes.

Justification for classification or non-classification

Based on the results of the oral 28-day repeated dose toxicity study with rats the substance does not need to be classified according to Directive 67/548/EEC and according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.