Tris(p-isocyanatophenyl) thiophosphate

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.047 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

30

Dose descriptor:

NOAEC

AF for dose response relationship:

1

Justification:

When the starting point for the DNEL delineation is a NOAEC, the default AF is 1.

AF for differences in duration of exposure:

6

Justification:

The default AF to be applied for the extrapolation of exposure duration subacute to chronic is 6.

AF for interspecies differences (allometric scaling):

1

Justification:

According to the ECHA TGD allometric scaling should not be applied for local effects, since local effects are independent of the basal metabolic rate, therefore AF 1 is chosen.

AF for other interspecies differences:

1

Justification:

A factor 2.5 is suggested by the ECHA TGD for remaining interspecies differences, but justified deviations are possible. Rodents like the rat are in general more sensitive compared to humans as the rat’s ventilation frequency is higher. Therefore, as a general rule a AF of 1 for remaining interspecies differences provides sufficient protection.

AF for intraspecies differences:

5

Justification:

The default AF to be applied for intraspecies differences in workers is 5.

AF for the quality of the whole database:

1

Justification:

The default AF to be applied for good/standard quality of the database, taking into account completeness, consistency and the standard information requirements, is 1.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - workers

Selection of the relevant starting point

Inhalation exposure is typically the most relevant route for assessing occupational hazard and risk in humans. Effects from repeated exposure of animals to tris(p-isocyanatophenyl) thiophosphate are limited to effects on the respiratory tract. In a subacute (4-week) inhalation study with aerosol exposure of rats to tris(p-isocyanatophenyl) thiophosphate a NOAEC of 2.8 mg/m³ was determined based on histopathological effects in the upper and lower respiratory tract (Pauluhn, 2012). These portal-of-entry effects were caused by deposits of the test article or its polymerized reaction products. As far as alterations in the respiratory epithelium occurred they appeared to follow a particle-overload phenomenon. No indication for systemic toxicity was found in this study and there was no indication that tris(p-isocyanatophenyl) thiophosphate is systemically available after inhalative exposure. Based on the unspecific effects observed in the subacute inhalation toxicity study it is not assumed that a longer treatment duration would substantially change the hazard assessment of the substance.

Therefore, the worker DNEL for long-term inhalation exposure - local effects is derived with the starting point 2.8 mg/m³ of the subacute study.

 

Derivation of the DNEL long-term inhalation exposure - local effects

Starting point: 2.8 mg/m³ (NOAEC from subacute inhalation study)

Correction of the starting point according to ECHA Guidance, Chapter R.8 (Dec. 2010), Figure R.8-2:

corrected NOAEC = 2.8 mg/m³ x (6 h/d : 8 h/d) x (6.7 m³ : 10 m³) ≈ 1.41 mg/m³

According to ECHA Guidance, Chapter R.8 (Dec. 2010), Section R.8.4 a series of assessment factors (AF) were applied to the corrected NOAEC from the subacute rat inhalation study, summarized in the table below, which result in the overall AF of 30.

 

Dividing the corrected NOAEC of 1.41 mg/m³ by the calculated overall AF of 30 results in a worker DNEL of 0.047 mg/m³ for long-term inhalation - local effects. This DNEL can be considered as highly conservative for the following reasons:

The DNEL is calculated using the default factors suggested under REACH. It is expected to be highly protective with regard to local effects to the respiratory tract since it is lower than the general threshold limit value for the respirable fraction of insoluble dusts* (0.3 mg/m³) and the general threshold limit value for the inhalable fraction of insoluble dusts* (4 mg/m³), as set by the German MAK Commission (see List of MAK and BAT Values 2012, DFG; *related to insoluble dusts with a density of 1g/cm³)

 

Type of assessment	Assessment factor (AF)
For interspecies differences rat vs. human (allometric scaling)^1	1
For remaining interspecies differences ^2	1
For intraspecies differences in workers^3	5
For extrapolation of exposure duration (subacute to chronic) ^4	6
For reliability of dose-response ^5	1
For quality of whole database ^6	1
Overall assessment factor	30

¹ According to the ECHA TGD allometric scaling should not be applied for local effects, since local effects are independent of the basal metabolic rate. In this case, substance deposition in the respiratory tract without any inflammatory response to deposited material was seen. Therefore AF 1 is chosen. 

² A factor 2.5 is suggested by the ECHA TGD for remaining interspecies differences, but justified deviations are possible. Rodents like the rat are in general more sensitive compared to humans as the rat’s ventilation frequency is higher. No interspecies differences are expected due to substance deposition in the respiratory tract. Therefore, as a general rule a AF of 1 for remaining interspecies differences provides sufficient protection.

 

³The use of the default AF 5 is a conservative approach because for the substance deposits with respective consequences is not to assume that there are great intraspecies differences.

⁴For DNEL derivation after long-term exposure a time extrapolation factor of 6 was used to take into account the exposure duration subacute to chronic.

 

⁵ When the starting point for the DNEL delineation is a NOAEC, the default AF is 1.

 

⁶ The default AF to be applied for good/standard quality of the database, taking into account completeness, consistency and the standard information requirements, is 1.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - General Population

Exposure of the General Population is expected to be negligible. The substance has a very low vapour pressure and is low volatile from surface waters (see section 5.4 of IUCLID). Emissions of the substance in the environmental compartments water, air and soil are negligible, the risk of exposure of the General Population via secondary poisoning can be considered as negligible as well.
The substance is not present in consumer available products (all consumer uses are strongly advised against).