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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.023 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
AF for dose response relationship:
1
Justification:
Starting point is a NOAEC. Thus standard assessment factor 1 is used as described in chapter R 8.4.3.3, Table R 8-6 of TGD.
AF for differences in duration of exposure:
1
Justification:
The assessment factor suggested by the ECHA TGD for exposure duration from subacute to chronic should be 6, but extrapolation factors for differences in duration of exposure of exposure are not always needed. In the depicted case only local effects (no systemic effects) were observed, and the 14-days repeated dose toxicity inhalation study (TNO, 2012) leads to nearly the same result as other subchronic 90-days studies with diamines with similar structural characteristics (e.g. 1,6-hexamethylenediamine). Therefore it is not expected that a longer duration of the study would change the outcome and a AF of 1 is warranted.
AF for interspecies differences (allometric scaling):
1
Justification:
An allometric scaling factor is not applicable for local effects, since local effects are independent of the basal metabolic rate (see section R.(.4.3.1. of TGD), therefore AF 1 is chosen.
AF for other interspecies differences:
1
Justification:
A factor 2.5 is suggested by the ECHA TGD for other interspecies differences, but justified deviations are possible. Rodens 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 factor of 1 for other interspecies differences provides sufficient protection.
AF for intraspecies differences:
3
Justification:
For intraspecies variability, the default assessment factor of 5 is recommended for workers for effects on respiratory tract (see Appendix R. 8 -9 of TGD). Furthermore chapter R.8.4.3.1 of the TDG states that in general the assessment factor for local (concentration-dependent) effects is very scarce and no attempt has therefore been made to refine the default intraspecies factors already used for systemic effects. So TGD proposes to use the same assessment factor (5 in case of workers sub-population) for local as well as for systemic effects as generic step but justified deviations are possible. In general the assessment factor should cover intraspecies differences which are a result of biological factors such as genetic polymorphism affecting e.g. toxicokinetic/metabolism, age, gender, health status and nutritional status as well as environmental influences as described in TGD. Regarding decamethylenediamine the mechanism of toxicity at the port of entry is still a mechanical destruction of membranes because of the corrosive effects of the substance. Metabolic activities are not involved in this mechanism. Hence intraspecies differences should not be related to metabolic differences between the individuals und thus these differences could be caused only by non-metabolic differences. The workers sub-population is more homogeneous than other populations also for non-metabolic effects like e.g. good health status, restricted age range, good nutrition status. Therefore a reduced AF of 3 for remaining intraspecies differences provides sufficient protection. The AF was refined according to ECETOC, 2003 and draft guidance 2010.
AF for the quality of the whole database:
1
Justification:
Because of good/standard quality of the database the standard assessment factor 1 is used as described in chapter R.8.4.3.1 of TGD.
AF for remaining uncertainties:
1
Justification:
According to TGD R 8.4.3.3, Table R 8-6, Factor 1, for effects on skin, eye and GI tract via simple distruction of membranes
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.046 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL extrapolated from long term DNEL

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
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

Derivation of DNELlong-term for workers for inhalation route - local effects

For workers which are exposed via inhalation, relevant DNELs for acute and long-term inhalation effects of decamethylenediamine have to be derived.

For repeated dose toxicity a subacute (14 -day) inhalation range finding study with vapour / aerosol exposure of decamethylenediamine to rats is available (TNO, 2012). Based on microscopic changes observed in the nasal passages of animals of the mid (0.62 mg/m3) and high concentration (5.7 mg/m3) groups and the absence of adverse effects in the low concentration group, the No-Observed-Adverse-Effect-Concentration (NOAEC) of decamethylenediamine was estimated to be 0.14 mg/m3 (actual concentration measured by chemical analysis). No indications of systemic toxicity effects were found within this study. Therefore, 0.14 mg/m3 was used as a starting point for the derivation of a DNEL for long-term local effects for inhalation.

The NOAEC was converted to a corrected NOAEC for the correction of the inhalation absorption in rats to the inhalation absorption in humans (derived from figure R.8 -2; Chapter R.8.4.2 of TGD "Chapter R.8: Characterisation of dose [concentration]-response for human health"):

For workers:

assumptions:

- 8 hours exposure/day

- inhalation absorption rat = inhalation absorption human

corrected NOAECinhalatory; rep. dose

= rat NOAECinhaltory; rep. dose* ((6 h/d) / (8 h/d))*(6.7 m3(8h) / 10 m3(8h))

= 0.14 mg/m3* 0.75 * 0.67 = 0.070 mg/m3

DNELlong-term for workers for inhalation route - local effects = NOAECcorr / Overall AF = 0.070 mg/m3 / 3 = 0.023 mg/m3

Discussion

Prenatal Development toxicity study (OECD 414, rat, oral route)

A prenatal developmental toxicity study in rats according to OECD 414 (oral exposure) (LPT, 2015) revealed no effects on prenatal development in doses that are non toxic to parental animals. All toxic effects observed in this OECD 414 study as well as in the DRF-study (LPT, 2015) were secondary effects as a consequence of the corrosive properties of decamethylenediamine. Due to these corrosive properties of the test item a very high level of protection is required and recommended and therefore repeated inhalative or dermal exposure is sufficient minimised by appropriate risk management measures (see CSR, chapter 9).

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

The use of decamethylenediamine is restricted only to industrial applications. A direct use of this substance is not known. The exposure of consumers to this substance is unlikely to occur via consumer products, because no consumer product is known to contain this substance. Hence there is no need to derive DNELs for general population (consumers).