Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Acute/short term exposure
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
7.04 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
5
Dose descriptor:
NOAEC
AF for dose response relationship:
1
AF for differences in duration of exposure:
1
Justification:
Based on local effects, lower AF used.
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation route
AF for intraspecies differences:
5
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Acute/short term exposure
DNEL related information

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - workers

1 -Ethylpiperidine is a cyclic tertiary amine. Based on Regulation (EC) No. 1272/2008 (CLP), the test substance is self classified for acute oral toxicity with Cat 3 (H301 -Toxic if swallowed), acute inhalation toxicity with Cat 3 (H331 -Toxic if inhaled), for acute dermal toxicity based on a read across to CAS No. 626-67-5 (Methylpiperidine) with Cat 4 (312 - Harmful in contact with skin) and for skin corrosion with Cat 1B (H314 - Causes severe skin burns and eye damage). According to 67/548/EEC self classification, the test substance is classified with Xn, R20/21/22 (Harmful by inhalation, in contact with skin and if swallowed) and C, R34 (Causes severe burns).

 

The test item is a clear colorless liquid, a strong base with a pH of 12.2 (at a concentration of 50 g/L and 20 °C), and exhibits therefore severe corrosive properties. The moderate vapor pressure of about 12.76 hPa (20 °C) indicates that exposure by the inhalation route may be possible under ambient conditions.

Thus, the primary routes of anticipated industrial exposure to the substance may occur via inhalation and skin contact.

 

Acute / short-term exposure - local effects

There are no data on human exposure.

There is an acute inhalative toxicity study available (BASF, 85/207, 1970), but the data were not suitable to derive a NOAEC. Therefore, an acute toxicity DNEL could not be derived. However, short-term exposure is sufficiently covered by the DNEL derived for long-term exposure of 7.04 mg/m³.

 

Long-term exposure - local effects

There are animal data available concerning repeated oral dose toxicity for the test item. Exposure related slight inflammation with keratolysis in the forestomach, indicating evidence of a local irritation by the test substance was observed in rats exposed to 80 mg/kg bw. (Bayer, T8076401, 2006). There are no data available about repeated inhalative exposure. However, for local effects route-to-route extrapolation as necessary for evaluation of inhalative exposure is not an appropriate way as recommended by the "Guidance on information requirements and chemical safety assessment”, Chapter R.8. Accordingly, when substance-specific information is not available, data on analogues, which act with the same mode of action as the chemical under consideration, are proposed to be taken into account. Therefore, a read across to Piperidine (CAS 110-89-4) is proposed for deriving a long-term DNEL for local effects. Both, 1-ethylpiperidine and piperidine cause severe local effects such as irritation and corrosion, whereas no systemic effects were detectable. Thus, both are classified for skin irritation (Cat 1B, H314, Causes severe skin burns and eye damage). Classification for acute inhalative toxicity (Cat 3, H331, Toxic if inhaled) is based on a LC50 of 4.8 mg/L for piperidine and a LC50 of 2.42 mg/L for 1-ethylpiperidine.

Therefore, rat inhalative (6 hours per day, 5 days per week) subacute repeated dose study of piperidine conducted similar to OECD 412 (BASF 1993) was used as the endpoint for DNEL derivation. The no-observed adverse effect concentration (NOAEC) in this study for local toxicity of the read across substance was set to 20 ppm (70 mg/m³) for male and female rats. Similar to 1-ethylpiperidine, no NOAEC for systemic toxicity was observed.

 

As point of departure for DNEL derivation for local exposure following inhalation contact, the local NOAEC of 70 mg/m³ was taken.

 

DNEL inhalative long-term - local

For derivation of the inhalative DNEL, allometric scaling was performed as recommended in the "Guidance on information requirements and chemical safety assessment”, Chapter R.8. Thereby, due to the 6 h/d inhalatory rat study, the starting point was corrected for the different exposure duration of workers of about 8 h/d and for differences between the 8 -hour inhalation volume of workers in rest versus workers in light activity, by multiplying with the corresponding factors (* 6 h/d / 8 h/d * 6.7 m³/10 m³).

The resulting corrected starting point for inhalation DNEL derivation for workers is equal to 35.2 mg/m³.

For DNEL derivation, the following assessment factors (AF) were applied to the corrected starting point:

• Interspecies factor: 1

As recommended by the ECETOC TR 110, besides the applied allometric scaling factors no additional interspecies factor for remaining differences has been used based on the fact that concerning inhalation, rodents are in general more sensitive compared to humans as the rat's ventilation frequency is higher.

• Intraspecies factor: 5

• Exposure duration: 1

The assessment factor for exposure duration extrapolation of 1 was used as recommended by ECETOC TR 110 (2010).

• Dose-response: 1 (default)

• Quality of whole database: 1

Due to the good quality of database and the similar toxicological profile of the read across substance piperidine no additional uncertainty in the dose descriptor derived has to be considered, and a factor of 1 was used as recommended by the "Guidance on information requirements and chemical safety assessment”, Chapter R.8.

Total AF = 5

Based on this calculation the resulting local DNEL for long-term inhalation is 7.04 mg/m³.

 

This value is considered protective for local effects by the inhalation route.

 

DNEL calculation is based on  

• ECHA (2010). REACh Guidance Document R.8.

• ECETOC (2010). Guidance on Assessment Factors to Derive DNELs. ECETOC Technical Report No. 110.

 

 

General Population - Hazard via inhalation route

Systemic effects

Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Acute/short term exposure
DNEL related information

General Population - Hazard via oral route

Systemic effects

Acute/short term exposure
DNEL related information

General Population - Hazard for the eyes

Additional information - General Population

There are no identified uses concerning consumer exposure. Consequently no DNELs have been derived.