Bis(1,2,2,6,6-pentamethyl-4-piperidyl) [[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]methyl]butylmalonate

Endpoint summary

Description of key information

Based on the available experimental data, the substance is taken up after ingestion and to a lesser extent by skin contact. The physico-chemical properties and the two ester functions indicate that there is little potential for bioaccumulation.

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential

Additional information

A specific toxicokinetic study is not available, but the subacute oral toxicity studies in rat show a rather specific hazard profile. It appears that the substance is taken up after ingestion because it causes adverse effects on mesenteric lymph nodes at lower doses and on spleen and liver at higher doses. It causes granulomatous inflammation of the intestinal tract which indicates uptake into the macrophages. As part of the micronucleus study in vivo, the substance was measured and detected in a total of six plasma samples taken from each three mice 1h and 4h after a single gavage dose of 2000 mg/kg bw (BASF 2015).

Regarding dermal absorption, little information is available. The molecular weight of > 500 and the n-octanol-water partition coefficient of > 4 are in the range for which low dermal absorption (10%) can be assumed (EU guidance document on dermal absorption, Sanco/222/2000 rev. 7, 19 March 2004). The substance is of moderate solubility in artificial perspiration fluid (16 mg/L, 37°C) and acute oral toxiciy is higher than acute dermal toxicity: LD 50 (oral) = 1490 mg/kg bw compared to absence of toxicity upon acute dermal expsoure at 3170 mg/kg bw.

In the study for skin sensitization, a skin reaction was observed for intradermal challenge, but not for the epidermal challenge (Ciba 1977). All indicators taken together, systemic availability by skin contact is possible but less good than by the oral route.

A 14 -day study with dermal exposure was performed in mice in order to investigate certain immunologic parameters. This study is of limited value to assess skin permeability as no precautions against preening was taken, and indeed it was recorded in the report that animals were licking the treated areas (abdomen). Under this regime, increase in spleen weight and changes in haematology were observed as for the oral route. As to the effective dose levels, a comparison is not possible because of the spacing and of the shorter duration. The 14 -day "dermal" route caused no effects on body weight and no mortality at dose levels, that were effective in rats at oral dosing. Considering that the effects were less severe and are at least in part due to oral exposure, this also indcates that skin permeability is lower than oral absorption.

Regarding systemic availability after inhalation, this needs to be assumed. The available acute inhalation study does not show adverse effects but was performed at a dose level about ten times lower than the limit dose.

Experimental data on reversibility on effects or metabolism is not available.

The substance contains two ester functions that are prone to enzymatic hydrolysis. It also contains a phenolic hydroxy group which is however sterically blocked by two teriary butyl groups and is therefore unlikely to become conjucated.

Ester hydrolysis products would be sufficently small for elimination via the kidney.

Other degradation products may be formed from oxidative destruction in macrophages.

Both the potential for enzymatic ester hydrolysis and the moderate solubility in water indicates that the substance does not have a significant potential for bioaccumulation.