Phenol, 2,4-bis[(dodecylthio)methyl]-6-methyl-

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.8 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

10

Modified dose descriptor starting point:

NOAEC

Acute/short term exposure

Hazard assessment conclusion:

exposure based waiving

DNEL related information

Local effects

Acute/short term exposure

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.25 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

40

Modified dose descriptor starting point:

NOAEL

Acute/short term exposure

DNEL related information

Additional information - workers

Industrial exposure to 4,6-bis(dodecylthiomethyl)-o-cresol is considered to be low in general, as the substance is a low melting point solid with a low vapour pressure.

Since the substance did not show adverse effects in limit tests for acute systemic and local toxicity, no DNELs were derived for these endpoints.

The most sensitive endpoint for long-term exposure is repeated dose toxicity. For the substance, no adverse effects were observed at the limit dose upon subacute oral exposure. A 90-day study is available for the analogue substance in rats and dogs. Both species showed responses of the liver. The DNEL is therefore derived from the NOEL of 10 mg/kg bw . The NOAEL may be 100 mg/kg bw, but effects are borderline, so 10 mg/kg bw is used for calculation. A quality factor of 1 is assigned because all studies are GLP and OECD testing guideline compliant studies. The remaining differences factor for intraspecies is not applied because two species were tested and the NOEL is used as a starting point. In addtion, the target substance was less hazardous upon subacute exposure. The NOEL is lower than tested doses in the studies for reproductive toxicity and therefore adequate for these endpoints as well.

DNEL Calculation - Workers

The derivation of DNEL is based on the above described NOAEC as described in R8 (ECHA, May 2008).

 

- Inhalative route – Long-term exposure.

For derivation of the worker inhalative DNEL, a route to route extrapolation of the above NOAEL was performed, and different assessment factors were applied as described below:

 

Long term systemic DNEL derivation (inhalation route)

Description	Values	Remark
Relevant dose descriptor	NOEL: 10 mg/kg bw/day	OECD Guideline 408; rat, 90 days
Modification of the starting point	0.38 m^3/kg bw	Conversion into NOAEC
	6.7 m^3/10 m^3	Light activity
Assessment factors
Exposure duration	2	Subchronic to chronic
Interspecies	1	Included in route-to-route extrapolation No remaining factor for interspecies taken, because two species tested and most sensitive species chosen.
Intraspecies	5	worker
DNEL	Derivation equation and value
For workers	10 mg/kg bw/day / 0.38m³/kg bw/day * 6.7m³/10m³ / (2 x 1 x 5 *1) = 1.8 mg/m³

  

- Dermal route

The DNELs for dermal long term exposure of workers are also derived from the NOELs obtained in a subchronic oral study mentioned above. Extrapolation from oral to the dermal route has been performed assuming that 100 % of the amount applied is systemically available.

 

Long term systemic DNEL derivation (dermal route)

Description	Values	Remark
Relevant dose descriptor	NOEL: 10 mg/kg bw/day	OECD Guideline 409; dogs, 90 days
Modification of the starting point	Not applicable
Assessment factors
Exposure duration	2	Subchronic to chronic
Interspecies	4	No remaining factor for interspecies taken, because two species tested and most sensitive species chosen
Intraspecies	5	workers
Route to route	1	Assuming equal absorption
DNEL	Derivation equation and value
For workers	10 mg/kg bw/day / (2 x 4 x 5 x 1) = 0.25 mg/kg bw/day

 

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

exposure based waiving

Acute/short term exposure

Hazard assessment conclusion:

exposure based waiving

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

exposure based waiving

Acute/short term exposure

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.13 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

80

Modified dose descriptor starting point:

NOAEL

Acute/short term exposure

DNEL related information

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.13 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

80

Modified dose descriptor starting point:

NOAEL

Acute/short term exposure

DNEL related information

Additional information - General Population

Exposure to 4,6-bis(dedecylthiomethyl)-o-cresol is considered to be low in general, as it is embeddded at a low percentage in articles and is non volatile. Since it is did not show adverse effects in limit tests for acute systemic and local toxicity, no DNELs were derived for these endpoints. The most sensitive endpoint for long-term exposure is repeated dose toxicity. A 90-day study is available for rats and dogs with an analogue substance. The DNEL is therefore derived from the NOEL of 10 mg/kg bw. This is conservative because the target substance caused no adverse effects upon subacute oral exposure at 1000 mg/kg bw. A quality factor of 1 is assigned because all studies are GLP and OECD testing guideline compliant studies. The remaining differences factor for intraspecies is not applied because two species were tested and the NOEL is used as a starting point.

Long term systemic DNEL derivation (oral/dermal route)

Description	Values	Remark
Relevant dose descriptor	NOEL: 10 mg/kg bw/day	OECD Guideline 408; rat, 90 days
Modification of the starting point	Not applicable
Assessment factors
Exposure duration	2	Subchronic to chronic
Interspecies	4	-
Intraspecies	10
Route to route	1	Assuming equal uptake
DNEL	Derivation equation and value
For general population	10 mg/kg bw/day / (2 x 4 x 10x 1)= 0.13 mg/kg bw/day