Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
68.24 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Modified dose descriptor starting point:
other: adjusted NAEC
DNEL value:
3 412 mg/m³
Explanation for the modification of the dose descriptor starting point:
no route to route extrapolation needed
AF for dose response relationship:
1
Justification:
Data support the confidence in the dose descriptor
AF for differences in duration of exposure:
2
Justification:
The NOAEC was determined from a sub-chronic test. Default AF for 90-day to chronic according to REACH guidance R.8.4.3.1
AF for interspecies differences (allometric scaling):
1
Justification:
A factor of 1 is appropriate since the adjusted starting point was in mg/m3
AF for other interspecies differences:
2.5
Justification:
Default AF according to REACH guidance R.8.4.3.1
AF for intraspecies differences:
5
Justification:
Default AF for workers according to REACH guidance R.8.4.3.1
AF for the quality of the whole database:
1
Justification:
guideline tests with GLP
AF for remaining uncertainties:
2
Justification:
Although no adverse test substance-related effects have been observed in the reproduction /developmental screening study (OECD 422) and no alerts on reproductive organs have been observed in the rat 90-day study, an AF of 2 for remaining uncertainty is applied for taking into account the lack of developmental and explicit reproductive toxicity studies, which have not been conducted because the lack of human exposure and because of the absence of any alert for reproductive and developmental toxicity.
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
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

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

There is no available data concerning effects of the test substance on humans.

An approximate lethal concentration (ALC) of 10000 ppm at which a pulmonary oedema was observed is significantly greater than that of the repeated dose toxiciy test (i.e. NOAEC: 1000 ppm) used to apply the DNEL of long-term exposure by inhalation derivation. Furthermore, as the long-term DNEL is normally sufficient to ensure that these effects do not occur, and under normal operating conditions no peak exposure is expected, the DNEL for acute effects by inhalation is not necessary. As the existing data shows the test substance is not an eye irritant, the DNEL of eye effects does not need to be derived.

As the test substance is a gas at room temperature, the test is not technically feasible through oral and dermal routes, so the DNEL for dermal and oral effects does not need to be derived. However, detailed data through inhalation route is available. A GLP test (Report No. DUPONT-20813, 2007) following OECD guideline 422 combined repeat dose toxicity study with the reproduction/development toxicity shows that exposure to the test substance did not result in adverse clinical signs or mortality. Test substance-related reductions in weight gain, food consumption, and/or food efficiency occurred in 1500 ppm males and females, however, they were transient and did not adversely affect the health of the animals. Meanwhile, test substance-related, minimal regeneration of renal tubular epithelium was observed in 1500 ppm males and females, and was accompanied by increased absolute and relative kidney weights in 1500 ppm females. However, there were no adverse or test substance-related effects on reproductive function, clinical pathology parameters, and no effects on offspring body weight, clinical observations, or survival.

In the follow-up study, a GLP 90 -day inhalation study in rats conducted at 0, 80, 280 and 1000 ppm, only few clinical signs were observed, and were limited to non-adverse test substance-related effects consisting of yellow material around the urogenital area in the 280 and 1000 ppm group females and slightly lower mean body weights in the 1000 ppm group females. There were no remarkable histopathological findings in males and females at the highest dose. Therefore, the no observed adverse effect concentration (NOAEC) was 1000 ppm.

Based on the results, the NOAEC for reproduction toxicity in the screening assay was 1500 ppm (10185,40 mg/m3), above that of systemic toxicity at 1000 ppm ( 6790.26 mg/m3). Therefore, the NOAEC of 6790.26 mg/m3was selected as starting point for the derivation of the Long-term DNEL inhalation toxicity

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
16.97 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
other: adjusted NOAEC
DNEL value:
1 697.56 mg/m³
Explanation for the modification of the dose descriptor starting point:
no route to route extrapolation
AF for dose response relationship:
1
Justification:
Data support the confidence in the dose descriptor
AF for differences in duration of exposure:
2
Justification:
The NOAEC was derived from a sub-chronic test. Default AF for extrapolation from a 90-day to chronic exposure according to REACH guidance R.8.4.3.1
AF for interspecies differences (allometric scaling):
1
Justification:
A factor of 1 is appropriate since the adjusted starting point was in mg/m3
AF for other interspecies differences:
2.5
Justification:
Default AF according to REACH guidance R.8.4.3.1
AF for intraspecies differences:
10
Justification:
Default AF for general population according to REACH guidance R.8.4.3.1
AF for the quality of the whole database:
1
Justification:
Based on the validity of the study performed
AF for remaining uncertainties:
2
Justification:
Although no adverse test substance-related effects have been observed in the reproduction /developmental screening study (OECD 422) and no alerts on reproductive organs have been observed in the rat 90-day study, an AF of 2 for remaining uncertainty is applied for taking into account the lack of developmental and explicit reproductive toxicity studies, which have not been conducted because the lack of human exposure and because of the absence of any alert for reproductive and developmental toxicity.
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information
DNEL extrapolated from long term DNEL

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

The test substance is a gas at room temperature, so the test is not technically feasible through the oral and dermal routes, no exposure is normally expected and a DNEL for dermal/oral effects does not need to be derived. However, detailed data through the inhalation route is available. A GLP test (Report No. DUPONT-20813, 2007) following OECD guideline 422 showed that no test treatment-related reproductive toxicity was observed at 1500 ppm. Furthermore, no substance related adverse effects (systemic toxicity) occurred at moderate doses (60ppm, 300 ppm).

In the follow-up study, a GLP 90-day inhalation study in rats conducted at 0, 80, 280 and 1000 ppm, only few clinical signs were observed, and were limited to non-adverse test substance-related effects consisting of yellow material around the urogenital area in the 280 and 1000 ppm group females and slightly lower mean body weights in the 1000 ppm group females. There were no remarkable histopathological findings in males and females at the highest dose. Therefore, the no observed adverse effect concentration (NOAEC) was 1000 ppm.

Based on the available animal data, the NOAEC for reproduction toxicity in the screening assay was 1500 ppm (10185.40 mg/m3), above that of systemic toxicity at 1000 ppm (6790.26 mg/m3) observed in the 90-day study. Therefore, the NOAEC of 6790.26 mg/m3 was selected as starting point for the derivation of the Long-term DNEL inhalation toxicity.