2,6-di-tert-butyl-4-nonylphenol

Endpoint summary

Description of key information

The toxicokinetics of 2,6-di-tert-butyl-4-nonylphenol (CAS No. 4306-88-1) was assessed qualitatively based on physicochemical and toxicological data according to chapter R.7c of the endpoint specific guidance of REACH.

-  Based upon the molecular weight, logP and available oral toxicity data, oral absorption is considered to be substantial.

-   Based upon the low vapor pressure, evaporation to the airways is unlikely. However for aerosol particles, if applicable, 10% respiratory absorption is considered.

-   Based upon the molecular weight & structure, liquid form with low vapour pressure and skin irritation/sensitization data, the absorption into the dermis is likely. However due to high log P value and limited systemic toxicity after dermal exposure, systemic availability is considered to be limited. From a realistic conservative viewpoint, 10% dermal absorption is used.

For the assessment of distribution, metabolism and excretion physicochemical and toxicological properties are also taken into account according to ECHA guidance 7c.

-   Based upon the molecular weight and Log P as well on signs of toxicity, distribution into the body is considered to be likely. 

-  Based on high Log P, predilection organs are adipose tissue, lungs and stratum corneum after oral, inhalation and dermal exposure, respectively

- Based on high Log P, excretion via the milk, but also urine and bile after metabolisation in the liver, might be expected after oral exposure. As the substance has a low vapour pressure, exhalation via the lungs is not expected. After dermal exposure, exfoliation from the skin is most likely.

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential

Absorption rate - oral (%):

100

Absorption rate - dermal (%):

10

Absorption rate - inhalation (%):

10

Additional information

The toxicokinetics of 2,6-di-tert-butyl-4-nonylphenol (CAS No. 4306-88-1) was assessed qualitatively based on physicochemical and toxicological data according to chapter R.7c of the endpoint specific guidance of REACH.

The registered substance is a monoconstituent with 90-100% of 2,6-di-tert-butyl-4-nonylphenol with the molecular formula as given below.

The substance is a clear colourless liquid at room temperature with molecular formula C23-H40-O and molecular weight 332.568. The log P >6.5 (based on OECD 117 test), and water solubility was 0.376 mg/L (based on OECD 105 test). Vapour pressure is 0.008 Pa.at 20°C (based on OECD 104 test). The substance is moderately irritating (not corrosive) to rabbit skin (based on OECD 404 testing) and classified as a dermal sensitizer (based on OECD 429 assay). Oral and dermal LD50 > 2000 mg/kg (based on OECD 401, 402 testing), and oral LOAEL = 100 mg/kg (based on OECD 422 test). Effects on body weight, food consumption, haematology, coagulation and clinical biochemistry were seen at 300 and 1000 mg/kg. Liver weight and histopathological changes were observed at 100, 300 and 1000 mg/kg.

 According to chapter R.7c of the endpoint specific guidance of REACH, physicochemical and toxicological data may be used for a qualitative TK assessment. The data below were used for a qualitative toxicokinetic assessment.

-        Oral/GI absorption:

Based upon the molecular weight, logP and available oral toxicity data, oral absorption is considered to be substantial. From a conservative viewpoint, a 100% oral absorption is considered.

-        Respiratory absorption:

Based upon the low vapor pressure, evaporation to the airways is unlikely. However for aerosol particles, if applicable, 10% respiratory absorption can be considered as realistic worst case value. Once particles are deposited in the alveoli, absorption is supported by the high LogP value and observations seen in oral toxicity studies.

-        Dermal absorption:

Based upon the molecular weight & structure, liquid form with low vapour pressure and skin irritation/sensitization data, the absorption into the dermis is likely. However due to high log P value and limited systemic toxicity after dermal exposure, systemic availability is considered to be limited. When Dermwin was applied (see below), dermal penetration rate seems to be rather high, which confirms dermal penetration. However, it is more expected that the test material is retained in the dermis than that it is absorbed. From a realistic conservative viewpoint, a 10% dermal absorption can be used.

For the assessment of distribution, metabolism and excretion physicochemical and toxicological properties are also taken into account according to ECHA guidance 7c.

-        Distribution:

Based upon the molecular weight and Log P as well on signs of toxicity, distribution into the body is considered to be likely. 

-        Metabolism & accumulation potential:

Based on high Log P, predilection organs are adipose tissue, lungs and stratum corneum after oral, inhalation and dermal exposure, respectively.

-        Excretion:

Based on high Log P, excretion via the milk, but also urine and bile after metabolisation in the liver, might be expected after oral exposure. As the substance has a low vapour pressure, exhalation via the lungs is not expected. After dermal exposure, exfoliation from the skin is most likely.

 A more detailed assessment is attached to the dossier: 'CAS4306-88-1 Toxicokinetics 201700205'.