Reaction mass of 7-azatridecane-1,13-diamine and hexamethylenediamine

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:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.42 mg/m³

Most sensitive endpoint:

irritation (respiratory tract)

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

37.5

Dose descriptor:

LOAEC

AF for dose response relationship:

3

Justification:

adequate factor for steep dose-response funtion

AF for differences in duration of exposure:

1

Justification:

no additional factor is required for time duration since the effect observed is not dependent on the time of exposure

AF for interspecies differences (allometric scaling):

1

Justification:

local effects, starting point is inhalation concentration

AF for other interspecies differences:

2.5

Justification:

according to ECHA Guidance

AF for intraspecies differences:

5

Justification:

according to ECHA Guidance

AF for the quality of the whole database:

1

Justification:

adequate database, default according to ECHA Guidance

AF for remaining uncertainties:

1

Justification:

adequate database, default according to ECHA Guidance

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.84 mg/m³

Most sensitive endpoint:

irritation (respiratory tract)

DNEL related information

DNEL extrapolated from long term DNEL

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

Acute/short term exposure

DNEL related information

Additional information - workers

Worker DNEL long-term for dermal route -systemic effects:

No repeated-dose toxicity with dermal application exist for the submission substance. The only effects observed in oral repeated dose studies were seen in the respiratory tract, with subsequent mortality at higher doses. As these effects possibly are attributable to inhalation uptake in these studies, no systemic effects were observed in these studies, which might serve as a basis for deriving a DNEL for dermal exposure. In addition, the substance is corrosive to the skin and any exposure to the skin has to be avoided. Respective RMM are expected to effectively prevent any significant dermal exposure.

Worker-DNEL long-term for inhalation route- local effects:

In a 13 week toxicity study (6 hours a day, 5 days a week) rats were exposed to an aerosol containing various concentrations of the submission substance (EHL, 1985, Report No. 85 -220). In this study a LOAEC of 15.8 mg/m³ was determined (analytically determined concentration of BHMT corrected for total concentration submission substance, findings: lesions in the respiratory tract).

Correction of starting point for DNEL derivation: no correction of the starting point is needed since the effect observed (irritation of respiratory tract) is not driven by the time of exposure (see various studies in IUCLID section 7.5.2)

Assessment factors applied were for:

·        Interspecies differences:                         no allometric scaling, 2.5 (remaining differences)

·        Intraspecies differences:                           5

·        Differences in duration of exposure:         1 ( no additional factor isrequired for time duration since the effect observed is not dependent on the time of exposure)

·        Issues related to dose-response:                3 (starting point is LOAEC instead of NOAEC)

·        Quality of whole database:                      1 (no deficiencies)

Overall assessment factor: 75

Calculation DNEL = 15.8 mg/m³/37.5 resulting in the DNEL = 421 µg/m³≈0.4 mg/m³

 

Please note: Benchmark modeling, which was applied to these data, did not lead to an improved situation compared to extrapolation from LOAEL to NOAEL by the default factor of 3.

Worker-DNEL short-term for inhalation route- local effects:

No dose-response data exist for acute inhalation exposure, which would allow to derive a short-term DNEL. Effects after repeated application of the submission substance by inhalation to rats were restricted to the respiratory tract with target organs damaged by local irrititation being the nasal passages, the trachea and lungs. After repeated inhalation of HMD, a main component of the submission substance, effects observed in rats and mice are limited to effects on the upper respiratory tract caused by local irritation in the nasal passages and the larynx. Therefore, an acute DNEL inhalation for local effects was established from the WORKER DNEL LONG-TERM FOR INHALATION ROUTE, LOCAL EFFECTS by using a multiplying factor of 2 considering that the observed adverse effects are mainly driven by the exposure concentration of the submission substance with respect to its corrosive properties.

Calculation DNEL = 0.42 mg/m³ * 2 resulting in the DNEL = 842 µg/m³ ≈ 0.84 mg/m³

Concerning quantitative assessment of acute/short term exposure local and systemic effects:

Worker-DNELs for short term duration (short term event, peak exposure) for dermal route- local and systemic effects were not established as the available data are not sufficient for quantitfication. A qualitative risk assessment will be performed due to the identified short term toxicity hazard leading to Classification (i.e. Acute Tox. 4 (dermal and oral), Skin Corr. 1 A, Eye damage 1, Skin sens. 1B, STOT SE 3).

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

Additional information - General Population

No DNELs for the general population were derived due to the fact, that the substance is not intended to be used by the general population, thus the submission substance reaches the end of the lifecycle without exposure of the general population.