α,α,α',α'-tetramethylxylene-α,α-diol

Endpoint summary

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

basic toxicokinetics, other

Remarks:

G.I. human passive absorption

Type of information:

calculation (if not (Q)SAR)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a (Q)SAR model, with limited documentation / justification, but validity of model and reliability of prediction considered adequate based on a generally acknowledged source

Objective of study:

absorption

Guideline:

other: REACH Guidance on QSARs R.6

Principles of method if other than guideline:

Model to predict either high or low fraction absorbed for an orally administered, passively transported substance on the basis of a new absorption parameter. The model includes only two inputs: the octanol-water partition coefficient (Kow) and the dimensionless oversaturation number (OLumen). The latter is the ratio of the concentration of drug delivered to the gastro-intestinal (GI) fluid to the solubility of the drug in that environment.

Species:

other: Human

Type:

absorption

Results:

Absorption from gastrointestinal tract for 1 mg dose: 95%

Type:

absorption

Results:

Absorption from gastrointestinal tract for 1000 mg dose: 90%

Reference 2

Endpoint:

dermal absorption, other

Remarks:

Mathematical simulation

Type of information:

calculation (if not (Q)SAR)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a (Q)SAR model, with limited documentation / justification, but validity of model and reliability of prediction considered adequate based on a generally acknowledged source

Guideline:

other: REACH Guidance on QSARs R.6

Principles of method if other than guideline:

IH SkinPerm mathematical tool for estimating dermal absorption

Doses:

1000 mg/hour

Time point:

8 h

Dose:

1000 mg/hour

Parameter:

percentage

Absorption:

0 %

Reference 3

Endpoint:

dermal absorption, other

Remarks:

QSAR

Type of information:

(Q)SAR

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a (Q)SAR model, with limited documentation / justification, but validity of model and reliability of prediction considered adequate based on a generally acknowledged source

Guideline:

other: REACH Guidance on QSARs R.6

Principles of method if other than guideline:

The Dermal Permeability Coefficient Program (DERMWIN) v2.00 estimates the dermal permeability coefficient (Kp), the dermally absorbed dose per event (DAevent) and Dermal Absorbed Dose (DAD) of organic compounds via water contact.

Specific details on test material used for the study:

CAS: 1999 -85 -5; SMILES : C(C)(C)(O)c1cc(C(C)(C)O)ccc1
CAS: 2948 -46 -1; SMILES : C(C)(C)(O)c1ccc(C(C)(C)O)cc1

Parameter:

rate

Remarks:

Kp

Absorption:

0.001 cm/h

Remarks on result:

other: CAS: 1999-85-5

Parameter:

rate

Remarks:

Kp

Absorption:

0.001 cm/h

Remarks on result:

other: CAS: 2948-46-1

CAS: 1999 -85 -5

                 Kp (est): 0.00147 cm/hr

SMILES : C(C)(C)(O)c1cc(C(C)(C)O)ccc1

CHEM   :

MOL FOR: C12 H18 O2

MOL WT : 194.28

------------------------------ Dermwin v2.01 ----------------------------------

Log Kow  (estimated)  :  2.31

Log Kow (user-entered):  1.60   (used in Kp calculations)

GENERAL Equation:   log Kp = -2.80 + 0.66 log Kow - 0.0056 MW

   Kp (predicted): 1.47e-003  cm/hr

Dermally Absorbed Dose per Event for Organic Compounds - Water Contact:

  Water Conc (mg/cm3): 2  (estimated by program)

  Fraction Absorbed  : 1.0000

  DA(event):  7.14e-003 mg/cm2-event (using eqn 3.2 & 3.3)

                  (tau = 1.31 hr,  t* = 3.14 hr)

Dermally Absorbed Dose (70 kg Adult) - Water Contact:

  DAD:  7.54e-001 mg/kg-day (using eqn 3.1)

----------------------------------------------------------------------------------------------------------------------------------------------

CAS: 2948 -46 -1

                 Kp (est): 0.00147 cm/hr

SMILES : C(C)(C)(O)c1ccc(C(C)(C)O)cc1

CHEM   :

MOL FOR: C12 H18 O2

MOL WT : 194.28

------------------------------ Dermwin v2.01 ----------------------------------

Log Kow  (estimated)  :  2.31

Log Kow (user-entered):  1.60   (used in Kp calculations)

GENERAL Equation:   log Kp = -2.80 + 0.66 log Kow - 0.0056 MW

   Kp (predicted): 1.47e-003  cm/hr

Dermally Absorbed Dose per Event for Organic Compounds - Water Contact:

  Water Conc (mg/cm3): 2  (estimated by program)

  Fraction Absorbed  : 1.0000

  DA(event):  7.14e-003 mg/cm2-event (using eqn 3.2 & 3.3)

                  (tau = 1.31 hr,  t* = 3.14 hr)

Dermally Absorbed Dose (70 kg Adult) - Water Contact:

  DAD:  7.54e-001 mg/kg-day (using eqn 3.1)

Description of key information

No data on toxicokinetics, metabolism and distribution are available for m/p-DIOL.

Absorption

The assessment of the toxicokinetics of m/p-DIOL is based on the available toxicological data and the physicochemical properties of m/p-DIOL as suggested by the REACH Guidance Chapter R.7c.

The reaction mass is a white powder at room temperature with a molecular weight of 194.3 g/mol for the m/p-DIOL alone. The m/p-DIOL are soluble in water (2.66 g/L). The logKow of both meta and para DIOL is 1.6. Based on this log Kow a logBCF of 0.72 was calculated. The reaction mass of m/p-DIOL has a very low vapour pressure (0.2 Pa at 25 °C).

The powder is made of agglomerates of small particles, of few microns or tens of microns size (5-50 µm), plate shaped. The mean diameter of the test sample is determined to be close to 200 µm (the desagglomeration of the constitutive particles leads to a mean diameter measured at 69 µm).

Based on physico–chemical properties of m/p-DIOL, the substance is not likely to penetrate skin to a large extent as it is a powder. Nevertheless, after dissolution in an aqueous solution, the DIOL could penetrate the skin as their molecular weight, their water solubility and their Log Kow are rather in favor of dermal uptake. Therefore, the rate of absorption was estimated using the IH SkinPerm model using a Kp derived from the EPI Dermwin model. For a skin deposition of 1000 mg/h four 8 h, m/p-DIOL is virtually not absorbed (0%).

Based on the low vapour pressure and on the high granulometry, inhalation exposure is unlikely. Nevertheless, once in the respiratory tract, m/p-DIOL could be solubilized in contact of residual humidity, reach pulmonary alveoli and then be absorbed.

Based on the moderate solubility in water and in oil, the substance could be absorbed in a large extent following oral exposure. Using a model to predict either high or low fraction absorbed for an orally administered, passively transported substance, the rates of absorption were 95 and 90% for a dose of 1 and 1000 mg of m/p-DIOL, respectively.

Therefore, according to the REACH Guidance, default values of 100, 10 and 100% will be used for oral, dermal and inhalation absorptions of m/p-DIOL, respectively.

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential

Absorption rate - oral (%):

100

Absorption rate - dermal (%):

10

Absorption rate - inhalation (%):

100