Registration Dossier

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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

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:
0.345 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:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)

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 TDI Trimer are limited to effects on the respiratory tract. In a subacute (4-week) inhalation study with aerosol exposure of TDI Trimer (Desmodur RC, 25 % in ethyl acetate) to rats a NOAEC of 20.6 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 epithelial changes of the respiratory epithelium occurred they followed the typical anterior-posterior gradient of deposition intensity. Tissue inflammatory responses to deposited material did not occur. No indications of systemic toxicity were found in this study.

Therefore, a worker DNEL for long-term inhalation exposure - local effects have to be derived.

 

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

Starting point: 20.6 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 = 20.6 mg/m3 x (6 h/d : 8 h/d) x (6.7 m3 : 10 m3) = 10.35 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 and are summarized in the table below:

 

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)

6

For reliability of dose-response 4

1

For quality of whole database 5

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.

3 The 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.

 

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

 

5 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.

 

Dividing the corrected NOAEC of 10.35 mg/m3 by the calculated overall AF of 30 results in a worker DNEL of 0.345 mg/m3 for long-term inhalation - local effects.

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