Registration Dossier

Administrative data

Link to relevant study record(s)

Description of key information

In order to fulfil the requirements for submission of a REACH dossier according to Annex IX of REACH Regulation (EC) No.1907/2006 (for substances >100 tonnes/year) and in absence of data on the toxicokinetics and dermal absorption, an assessment of toxicological behaviour is required. No studies are available on the toxicokinetics, metabolism and distribution of 1,1,3,3-tetramethylbutyl 2-ethylperoxyhexanoate.  

The available physico-chemical and toxicological information of the substance has been evaluated and used to assess the toxicological behaviour. The results of this analysis will address the question on how the chemical will react in the body. The ECHA “Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance May 2008” document provides guidance, which physico-chemical properties commonly determine oral, inhalatory and dermal absorption, distribution, metabolism and elimination of substances.

While toxicokinetic data is not available on 1,1,3,3-tetramethylbutyl 2-ethylperoxyhexanoate, if absorbed, it is expected to breakdown rapidly. There is no information on the actual breakdown products formed under physiological conditions. 1,1,3,3-tetramethylbutyl 2-ethylperoxyhexanoate has a high log kow 6.2 low molecular weight, these are properties that give concern for bioaccumulation. However the substance is readily biodegradable and hydrolysis quickly. Because half-lives are <12h under environmental conditions hydrolysis products have been indentified. 2-Ethylhexanoic acid (CAS 149-57-5, log Kow = 2.64), Neopentyl alcohol (CAS 75-84-3, log Kow = 1.31) and Acetone (CAS 67-64-1, log Kow = -0.24) were formed. These products do not have bioaccumulation potential.

Key value for chemical safety assessment

Bioaccumulation potential:
low bioaccumulation potential
Absorption rate - oral (%):
100
Absorption rate - dermal (%):
25
Absorption rate - inhalation (%):
100

Additional information

Basic Toxicokinetics for 1,1,3,3-tetramethylbutyl 2-ethylperoxyhexanoate (CAS# 22288-43-3)

In order to fulfil the requirements for submission of a REACH dossier according to Annex IX of REACH Regulation (EC) No.1907/2006 (for substances >100 tonnes/year) and in absence of data on the toxicokinetics and dermal absorption, an assessment of toxicological behaviour is required. No studies are available on the toxicokinetics, metabolism and distribution of 1,1,3,3-tetramethylbutyl 2-ethylperoxyhexanoate.  

 

While toxicokinetic data is not available on 1,1,3,3-tetramethylbutyl 2-ethylperoxyhexanoate, if absorbed, it is expected to breakdown rapidly. There is no information on the actual breakdown products formed under physiological conditions. Once absorbed however, the peroxide would undergo thermal decomposition at body temperature, SADT 30°C. There is no information on the actual breakdown products formed under these conditions.

1,1,3,3-tetramethylbutyl 2-ethylperoxyhexanoate has a high log kow 6.2 low molecular weight, these are properties that give concern for bioaccumulation. However the substance is readily biodegradable and hydrolysis quickly. Because half-lives are <12h under environmental conditions hydrolysis products have been indentified. 2-Ethylhexanoic acid (CAS 149-57-5, log Kow = 2.64), Neopentyl alcohol (CAS 75-84-3, log Kow = 1.31) and Acetone (CAS 67-64-1, log Kow = -0.24) were formed. These products do not have bioaccumulation potential (See: hydrolysis).

 

Below are some physical chemical properties of 1,1,3,3-tetramethylbutyl 2-ethylperoxyhexanoate.

Endpoint

1,1,3,3-tetramethylbutyl 2-ethylperoxyhexanoate

MW

272.4

WS

306 µg/L

Log Pow

6.2

VP

<<0.01Pa 25°C

Skin irritation

Not irritating

 

NOTE:

1,1,3,3-Tetramethylbutyl 2-ethylperoxyhexanoate is classified as a peroxidetype D. Flammability is an intrinsic hazard in this class. The Self-Accelerating Decomposition Temperature (SADT) of the substances is 30°C (reference SADT: CLP regulations 2.15.2.3 and UN Recommendations on the Transport of Dangerous Goods, Manual of Tests and Criteria, 5th revised edition, sub-sections 28.1, 28.2, 28.3 and Table 28.3.)

 

The available physico-chemical and toxicological information of the substance has been evaluated and used to assess the toxicological behaviour. The results of this analysis will address the question on how the chemical will react in the body. The ECHA “Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance May 2008” document provides guidance, which physico-chemical properties commonly determine oral, inhalatory and dermal absorption, distribution, metabolism and elimination of substances.

 

Dermal Absorption

The molecular weight of the substance is 272.4, this means dermal uptake is possible. The water solubility is very low and based on this limited absorption is expected.

Based on the log Pow of 6.2 limited absorption across the skin is expected. The vapour pressure is very low and the substance will not evaporate from the skin to a great degree. the substance is not expected to penetrate the skin to a significant degree. The substance is not irritating to skin and increased absorption due to damaged skin is therefore not likely. Although the substance has been identified as a moderate skin sensitizer and therefore some uptake must have occurred. An LLNA study was performed in this study the dermal absorption is strongly enhanced by applying the substance to skin in an acetone/olive oil mixture 4:1. The substance is positive at 100% and 50% but negative at 25% concentration, respectively. No effects on the skin were observed. As a worst case 25% skin absorption is assumed.

 

Once absorbed however, the peroxide would undergo thermal decomposition at body temperature. There is no information on the actual breakdown products formed under these conditions.

 

Inhalation Absorption

The vapor pressure is<<0.01Pa 25°C. Based on the low vapor pressure and pattern of use, inhalation is not expected to be a major route of exposure. If inhalation of the peroxide does occur, as stated above it will rapidly decompose. There is no information on the actual breakdown products formed under these conditions.

 

Oral Absorption

An OECD422 and OECD 408 oral gavage study in rats, resulted in effects on the kidneys of males (alpha 2μglobulin), livers of males and females (increase liver weights, diffuse hepatocellular hypertrophy) and thyroid follicular hypertrophy and minimally-slightly increased extramedullary hemopoiesis. The liver effects were considered adaptive and the alpha 2μglobulin is specific to the male rat. The effects on the thyroid are a secondary effect due to increased metabolism of T3/T4 and the observations in the spleen are caused by an increased demand.

 

The theoretical breakdown product 2,4,4-trimethylpentan-2-ol has been associated with α2u-globulin-associated nephropathy in male rats[1].

 

While it is not possible to establish the causative agent of the effects noted in the OECD422 and OECD408 study with the peroxide, (i.e. peroxide or breakdown products), the peroxide is expected to quickly decompose at body temperature. There is no information on the actual breakdown products formed.

 

Conclusion

While toxicokinetic data is not available on 1,1,3,3-tetramethylbutyl 2-ethylperoxyhexanoate, if absorbed, it is expected to breakdown rapidly. There is no information on the actual breakdown products formed. 1,1,3,3-tetramethylbutyl 2-ethylperoxyhexanoate is not expected to bioaccumulate.

 

 

1.     -Formation of the metabolic intermediate 2,4,4-trimethyl-2-pentanol during incubation of a Sphingomonas sp. strain with the xeno-estrogenic octylphenol. Tanghe, T., Dhooge, W., Verstraete, W. Biodegradation (2000)

-Alpha 2u-globulin is the only member of the lipocalin protein superfamily that binds to hyaline droplet inducing agents. Lehman-McKeeman, L.D., Caudill, D. Toxicol. Appl. Pharmacol. (1992)

-Involvement of reversible binding to alpha 2u-globulin in 1,4-dichlorobenzene-induced nephrotoxicity. Charbonneau, M., Strasser, J., Lock, E.A., Turner, M.J., Swenberg, J.A. Toxicol. Appl. Pharmacol. (1989)

-2,2,4-Trimethylpentane-induced nephrotoxicity. I. Metabolic disposition of TMP in male and female Fischer 344 rats. Charbonneau, M., Lock, E.A., Strasser, J., Cox, M.G., Turner, M.J., Bus, J.S. Toxicol. Appl. Pharmacol. (1987)

-A physiological model for ligand-induced accumulation of alpha 2u globulin in male rat kidney: roles of protein synthesis and lysosomal degradation in the renal dosimetry of 2,4,4-trimethyl-2-pentanol. Kohn, M.C., Melnick, R.L. Toxicology (1999)