Registration Dossier

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:
high hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.2 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
3
Dose descriptor:
NOAEC
Value:
25 mg/m³
AF for dose response relationship:
1
Justification:
The dose response relationship is considered unremarkable, therefore no additional factor is used.
AF for differences in duration of exposure:
1
Justification:
When comparing the effects observed in the 14-Day Range Finding study with the effects observed in the 90-Day Repeated Dose study an increase of the incidence or severity of adverse effects in relation to exposure duration were not observed. Thus, a lower extrapolation factor for exposure duration is used as local effects in the respiratory tract are considered to be concentration-driven rather than dependent on exposure duration.
AF for interspecies differences (allometric scaling):
1
Justification:
Local effects are independent of the basal metabolic rate, allometric scaling should not be applied.
AF for other interspecies differences:
3
Justification:
According to Bruening et al. (2014) 3 is the most reasonable factor for extrapolating animal data concerning local irritating effects.
AF for intraspecies differences:
1
Justification:
No additional AF for intraspecies differences for local effects.
AF for the quality of the whole database:
1
Justification:
The quality of the whole data base is considered to be sufficient and uncritical.
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative. No further assessment factors are required.
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information

Local effects

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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - workers

General

DNEL derivation for the test substance is performed under consideration of the recommendations of ECHA. In view of the data used for evaluation, the "quality of whole database factors", “remaining uncertainties” and "dose-response factors" are considered to amount each to a value of 1, and are thus not shown in the calculations presented below.

 

Workers – Hazard via inhalation route

Long term systemic inhalation DNEL, worker

A subchronic repeated dose toxicity study is available for the inhalation route. Inhalation exposure of 5, 25 and 125 mg/m³ 2-Ethylhexylamine for 90 days (65 exposures) caused clearly treatment-related adverse histological changes in the nasal cavity levels I and II. Moreover, slight but significantly lower body weight and body weight gain was observed in male animals of the high concentration group. No signs of systemic toxicity were observed in the study at the highest tested concentration (125 mg/m³), while a NOAEC of 25 mg/m³ was established for local effects. Therefore, local effects are considered to be more critical and the derived DNEL for local effects by inhalation exposure is considered to be sufficient to protect against possible systemic effects.

Short term systemic inhalation DNEL, worker

The substance is classified as cat. 2 (H330) for acute inhalative toxicity.

Following 4 h exposure to the test substance, at necropsy, macroscopic dark red spots were found on the lungs, and when the lungs were opened small quantities of white foam were detected. Exposed animals showed impairment of respiration, salivation, nasal discharge and periodically arising tonic spasms.

As no dose-response-relationship for acute toxicity and corrosivity can be established and according to the REACH guidance on information requirements and chemical safety assessment, Part E: Risk Characterization, a qualitative risk characterization was performed for this endpoint. In order to guarantee "adequately control of risks", it is necessary to stipulate risk management measures that minimize exposure.

Long term local inhalation DNEL, worker

A subchronic repeated dose toxicity study for inhalation according to OECD 413 is available for DNEL derivation. The appropriate assessment factors were set based on the publication of Bruening et al (2014). In this publication the sensory irritation pathway in humans was compared to the tissue irritation pathway in animals. Experimental exposure studies with human volunteers provided the empirical basis for effects along the sensory irritation pathway and thus, sensory NOAEChuman was derived. In contrast, inhalation studies with rodents investigated the second pathway that yielded an irritative NOAECanimal. The comparison of the sensory NOAEChuman with the irritative NOAECanimal (chronic) resulted in an interspecies extrapolation factor (iEF) of 3 for extrapolating animal data concerning local sensory irritating effects.

Step 1: Selection of the relevant dose descriptor (starting point):

No route to route extrapolation is required as a reliable repeated inhalation toxicity study is available. In this study, the NOEAC (local) for inhalation is 25 mg/m³.

Step 2: Modification into a correct starting point:

The NOAEC (local) obtained from study has to be adapted considering different exposure times of laboratory animals (6h) and humans (8h), and respiratory volumes of humans at rest and with physical light activity for 8 hours.

Relevant dose descriptor (NOAEC): 25 mg/m³

exposure time of rats: 6 h

exposure time of human workers: 8 h

Standard respiratory volume of humans (sRVhuman) for 8 hours: 6.7 m³

Worker respiratory volume (wRV) for 8 hours with light physical activity: 10 m³

 

Corrected inhalatory NOAEC for workers

= 25 mg/m³ * (6 h/8 h) * (6.7 m³/10 m³)

= 12.56 mg/m³

 

Step 3: Use of assessment factors: 3

Interspecies differences (allometric scaling): 1 (Local effects are independent of the basal metabolic rate, allometric scaling should not be applied)

Interspecies AF, remaining differences: 3 (according to Bruening et al., 2014)

Intraspecies AF (worker): 1

 

In conclusion, long term local systemic inhalation DNEL, workers = 4.2 mg/m³

 

Workers – Hazard via dermal route

Long term and short term dermal DNEL, worker

The test item is classified for skin irritation/corrosion (cat. 1A, H 314) according to Regulation (EC) No 1272/2008 (CLP) and thus belongs to the high hazard band.

A qualitative risk assessment is conducted to minimize potential exposure.

Worker – Hazard for the eyes

The test item is classified for eye irritation/corrosion (cat. 1, H 318) according to Regulation (EC) No 1272/2008 (CLP). Thus, a qualitative risk assessment is conducted.

References

(not included as endpoint study record)

- ECHA (2012). Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health. Version 2.1. November 2012.

- ECHA (2017). Guidance on information requirements and chemical safety assessment. Chapter R.7.12: Endpoint specific guidance: Guidance on Toxicokinetics. June 2017.

- ECHA (2012) Practical Guide 15: How to undertake a qualitative human health assessment and document it in a chemical safety report, November 2012.

- ECHA (2016). Guidance on information requirements and chemical safety assessment. Part E: Risk Characterisation, Version 3.0, May 2016.

- Bruening T. et al (2014). Sensory irritation as a basis for setting occupational exposure limits. Arch Toxicol 88:1855–1879

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

Since 2-ethylhexylamine is used at industrial and professional domains only, no exposure of the general population to 2-ethylhexylamine is expected. Therefore, no DNELs for the general population were calculated.