Piperidine

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:

low hazard (no threshold derived)

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

7.05 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

Value:

35.2 mg/m³

AF for dose response relationship:

1

Justification:

default value

AF for differences in duration of exposure:

1

Justification:

Based on the local effects, the assessment factor for exposure duration extrapolation of 1 was used as recommended by ECETOC TR 110 (2010).

AF for other interspecies differences:

1

Justification:

Besides the applied allometric scaling factors no additional interspecies factor for remaining differences has been used based on the fact that concerning inhalation, rodents like the rat are in general more sensitive compared to humans as the rat's ventilation frequency is higher. Also anatomical differences as well as air flow patterns between rodents and humans have to be taken into account.

AF for intraspecies differences:

5

Justification:

Concerning the intraspecies factor, an assessment factor of 5 as recommended by REACh Guidance Document R.8, ECHA (2010).

AF for the quality of the whole database:

1

Justification:

default value

AF for remaining uncertainties:

1

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)

Additional information - workers

Piperidine is a heterocyclic amine. Based on Annex VI to Regulation (EC) No. 1272/2008 (CLP), the test substance is classified for acute inhalation toxicity with Cat 3 (H331 -Toxic if inhaled), for acute dermal toxicity with Cat 3 (311 - Toxic in contact with skin) and for skin corrosion with Cat 1B (H314 - Causes severe skin burns and eye damage) and based on Annex I of Directive 67/548/EEC with R23/24 (Toxic by inhalation and in contact with skin) and R34 (Causes burns).

Piperidine is a clear colorless liquid, a very strong base with a pH of 12.6 (20 °C), and exhibit therefore severe corrosive properties. The moderate vapour pressure of about 19.58 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 few data on human exposure which are mostly cited from secondary sources and not verified. Thus, Bazarova and Migoukina (1975) reported that the irritation threshold for inhalation exposure to the test item was 90 mg/m³ (26 ppm). An odor threshold was reported to be less than 2 ppm (Nawakowski, 1980, cited by Trochimowicz et al., 1994) and estimated at 0.37 ppm (van Doorn et al. 2002; cited in NAC/AEGL Committee 2007). However, the data for irritation threshold were obtained from secondary sources. The primary sources were not available.

There is an acute inhalative toxicity study of BASF (77/283, 1980), but the data were not suitable to derive a NOAEC necessary for calculation of an acute toxicity DNEL. However, the derived DNEL for long-term exposure of 7.05 mg/m³ sufficiently covers short-term exposure.

Long-term exposure - local effects

There are animal data available concerning repeated dose toxicity for the test item. Exposure related nasal secretions, bloody or reddish encrustation/crust, indicating evidence for upper respiratory tract irritation, evidence of eye irritation, or reduced general state of health was observed in rats exposed to 50-200 ppm (HRC 1990a; BASF 30I0523/89017, 1990; BASF 46I0523/89065, 1993). The lowest concentration causing nasal irritation was 50 ppm for a 6-hour exposure in rats (BASF 1990), and no nasal irritation was observed in rats exposed to 20 ppm for 6 hours (BASF 1993). Other repeated dose studies reported by Bazarova 1973 found no effects after exposure to 0.58 or 2.9 ppm of the test item for 4 hours. In the developmental inhalation study reported by HRC (1990) observed eye closure, increased respiration, hunched posture, piloerection, salivation, a lack of response to a knock on the chamber door after the first exposure to 80 ppm in pregnant female rats exposed 6 hours/day during GD 6-15. A lack of response to a knock was also observed in pregnant rats exposed to 20 ppm for 6 hours, but the toxicological relevance of this observation is uncertain because a very extensive battery of neurofunctional tests showed no treatment-related effects after repeated exposures to 100 ppm for 6 hours (BASF 1993). The BASF (1990, 1993) and HRC (1990) studies were performed according to standard protocols for repeated exposure studies and were conducted under GLP.

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

As point of departure for DNEL derivation for local exposure following dermal and 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

Besides the applied allometric scaling factors no additional interspecies factor for remaining differences has been used based on the fact that concerning inhalation, rodents like the rat are in general more sensitive compared to humans as the rat's ventilation frequency is higher. Also anatomical differences as well as air flow patterns between rodents and humans have to be taken into account.

• Intraspecies factor: 5

Concerning the intraspecies factor, an assessment factor of 5 as recommended by REACh Guidance Document R.8, ECHA (2010).

• Exposure duration: 1

Based on the local effects, 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 (default).

Total AF = 5

Based on this calculation the resulting DNEL for long-term inhalation is 7.05 mg/m³.

DNEL calculation ist 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

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

No consumer uses have been identified, and exposure to the general population is not expected. Therefore, DNELs and/or DMELs for the general population have not been established.