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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:

0.5 mg/m³

Most sensitive endpoint:

irritation (respiratory tract)

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1 mg/m³

Most sensitive endpoint:

irritation (respiratory tract)

DNEL related information

Workers - 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:

high hazard (no threshold derived)

Most sensitive endpoint:

sensitisation (skin)

Acute/short term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

Most sensitive endpoint:

sensitisation (skin)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)

Additional information - workers

The most relevant route for assessing risk for the allophanate-type HDI oligomer in humans is via inhalation. In rats effects from acute aerosol exposure are limited to the respiratory tract caused by local irritation (BASF SE, 2003; Bayer AG, 2011; Bayer AG, 2013).

This distinct portal of entry toxicity can be assigned to the residual isocyanate (NCO)-groups of the substance which is amongst others also common to aliphatic diisocyanate monomers (e.g. HDI, CAS 822 -06 -0) and HDI homopolymers (e.g. Hexane, 1,6-diisocyanato-, oligomerisation product (isocyanaurate-type), CAS 28182-81-2). For these substances the toxicological database for inhalation toxicity uniformly demonstrates that toxicity is associated only with the portal of entry (respiratory tract), any other manifestations of toxicity are secondary to this. In conclusion it could be consistently demonstrated, that if a nonirritant threshold concentration is not exceeded, neither functional nor morphological indications of damage to the respiratory tract are observed.

For workers in industrial settings, which are exposed via inhalation, DNELs for local effects for acute and long-term inhalation exposure of the allophanate-type HDI oligomer have to be derived. In addition skin sensitisation and mild irritation after skin contact has to be assessed (in a quantitative manner).

According to REACH (ECHA Guidance, chapter R.8-13) a national occupational exposure limit (OEL) could be used as a surrogate for a DNEL. The German Federal Ministry of Labour and Social Affairs (Bundesministerium für Arbeit und Soziales, BMAS) published the Technical Rule for Hazardous Substances (Technische Regel für Gefahrstoffe, TRGS) for regulating the workplace exposure of isocyanates (TRGS 430, BMAS, 2009). ”This technical rule describes procedures for the assessment and surveillance of workplaces involved in the handling and use of polyurethanes and requires the assessment of isocyanates present either in the form of vapour, aerosol or both” (Pauluhn, J. Appl. Toxicol. 24, 2004, 231-247). In contrast to commonly employed workplace standards that focus solely on monomeric (di)isocyanates, the common unifying concept of TRGS 430 is to consider separate hazard assessment for monomeric and polymeric isocyanates, present as vapour and/or aerosol. The surrogate now used as DNEL for the allophanate-type HDI oligomer is the exposure assessment value (Expositionsbeurteilungswert, EBW). This value for polyisocyanate-aerosols is taking into account the lower irritant potential to the respiratory tract in comparison to the monomeric Diisocyanate, respectively. The EBW is either derived from the acute pulmonary irritant threshold concentration using a benchmark extrapolation of the concentration dependence of protein in bronchoalveolar lavage fluid (BALF) of an 1 x 6 h inhalation study (TRGS 430 study) or, alternatively, if available, from the NOAEC (no observed adverse effect concentration) of a subchronic (13-week) inhalation study according to OECD 413 (OECD, 1981) or OPPTS 870.3465 (1998). The approach suggested by TRGS 430 is inherently conservative, as a comparison of the irritant threshold concentration to the NOAEC from repeated inhalation studies show (Pauluhn, J. Appl. Toxicol. 24, 2004, 231-247).

If the irritant threshold concentration/NOAEC of the polymeric diisocyante from either of the two studies is ≤10 * AGW (Arbeitsplatzgrenzwert, German national OEL) of the monomeric diisocyanate then EBW = AGW, if the threshold concentration is >10 * AGW then EBW = 10 * AGW, respectively.

This means: For the monomeric hexamethylen-1,6-diisocyante (HDI) the AGW is 0.035 mg/m³.

 

Since for the allophanate-type HDI oligomer the pulmonary irritant threshold concentration is >10 * AGW (3 mg/m³, BASF SE, 2003; 3.4 mg/m3, Bayer AG, 2013), the EBW = 10 * AGW.

 

The pulmonary irritant threshold concentration derived from acute TRGS430 studies is almost identical for the allophanate-type HDI oligomer compared to the HDI, oligomerisation product (isocyanurate type) (3 mg/m³; Bayer AG, 2001). For the HDI, oligomerisation product (isocyanurate type, CAS 28182-81-2) a corresponding NOAEC of 3.4 mg/m³ was derived from a subchronic (13-week) inhalation study (Bayer AG, 1988). Accordingly, it was shown that for pulmonary irritation as well as for subchronic inhalation the respiratory damage is linked to the inhaled irritating concentration, and does not exacerbate during repeated exposure (Pauluhn, Inhal. Toxicol., 13, 2001, 513-532 and 14, 2002, 287-301). Since both substances (allophanate-type HDI oligomer and HDI, oligomerization product (isocyanurate type)) possess almost identical pulmonary irritant threshold concentrations, similarly low vapour pressures and a uniform portal of entry toxicity, a comparable NOAEC for subchronic exposure can be extrapolated for the allophanate-type HDI oligomer.

 

According to TRGS 430 there is even an option to set the EBW > 10 * AGW.

This was done for the allophanate-type HDI oligomer due to the reason that it can reliably be extrapolated, that the respiratory damage is linked to the inhaled irritating concentration, and does not exacerbate during repeated exposure.

Therefore the EBW = DNEL_{long-term local effects}for inhalation is set to 0.5 mg/m³. This is in line with a published proposed TLV-TWA of 0.5 mg/m³ for HDI homopolymers (Pauluhn and Mohr, Inhal. Toxicol., 13, 2001, 513-532). The value is further in the same order of magnitude compared to a DNEL delineated according to ECHA guidance, chapter R.8.4.

 

AGWs are based on 8-hour time weighted average exposure. According to the German rule for OELs (TRGS 900, BMAS, 2006/2009) for short-term ceiling concentrations an exposure limit could be established by multiplication to an exceeding factor (Überschreitungsfaktor), which is set per default 1 (could be adjusted to max. 8) . Pauluhn and Mohr proposed a maximum concentration limit of 1.0 mg/m³ (exceeding factor 2) for HDI-derived polyisocyanates. This value could be used as surrogate DNEL_{acute local effects}for inhalation for the allophanate-type HDI oligomer.

This procedure is in accordance to ECHA Guidance, Chapter R.8., Appendix R. 8-8, Box 6.

No DNEL for skin sensitization is calculated as the relationship between skin dose and response is not clear. There is no validated method of DNEL calculation for skin sensitization. According to the potency categorization approach the allophanate-type HDI oligomer is classified as a moderate skin sensitizer.

The DNEL acute/long-term for inhalation for workers covers also reproductive toxicity, as the local effects at the respiratory tract are the most sensitive effects.

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 substance is not used in the public domain and exposure of consumers is thus not to be expected.