HDI oligomers, uretdione

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:

0.35 mg/m³

Most sensitive endpoint:

irritation (respiratory tract)

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Dose descriptor:

NOAEC

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.7 mg/m³

Most sensitive endpoint:

irritation (respiratory tract)

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

DNEL extrapolated from long term DNEL

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:

no hazard identified

Additional information - workers

For HDI oligomers, uretdione type, the most relevant route for assessing risks in humans is via inhalation. In rats effects from repeated aerosol exposure to the substance are limited to the respiratory tract (report no AT06241, Bayer AG, 2011). No indications of systemic toxicity were found in the study. It was shown, 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 have to be derived. In addition, sensitisation after skin contact has to be assessed.

 

According to Guidance Document R.8 (ECHA, 2012) 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 430 (TRGS 430, last updated in 2009) for regulating the workplace exposure of isocyanates. ”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 HDI oligomers, uretdione type, is the exposure assessment value (Expositions­beurteilungswert, EBW). The EBW is either derived from the acute pulmonary irritant threshold concentration derived using a benchmark extrapolation of the concentration dependence of protein in bronchoalveolar lavage fluid of an 1 x 6 hours inhalation study (study recommended in TRGS 430) or, alternatively, if available, from the NOAEC of a subchronic (13-weeks) inhalation study according to OECD 413 or OPPTS 870.3465. 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 diisocyanate 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.

For HDI oligomers, uretdione type, the acute pulmonary irritant threshold concentration of 2.8 mg/m³ (report AT00075, Bayer AG, 2002) was used. No subchronic (90 days) study is available for the substance. A subacute (28 days) study reveals borderline changes in alveolar lavage and histopathology at 2.2 mg/m³ (= LOAEL) and a NOAEL of 0.41 mg/m³ (concentration levels 0.41, 2.2 and 10.1 mg/m³). The similarity of the borderline irritant threshold concentration of the repeated dose study (2.2 mg/m³) and the acute irritant threshold concentration from the "TRGS 430-study" (2.8 mg/m³) supports the conclusion that pulmonary effects are non-cumulative and justifies the applicability of the concept as described.

The AGW of the monomeric hexamethylen-1,6-diisocyante (HDI) is 0.035 mg/m³.

Since for HDI oligomers, uretdione type, the pulmonary irritant threshold concentration (2.8 mg/m³) is > 10 * AGW the EBW = 10 * AGW = 0.35 mg/m³ (= DNEL_{long-term, local effects}).

 

AGWs are based on 8-hour time weighted average exposure. According to the German rule for OELs (Technical Rule for Hazardous Substances 900, BMAS, 2006/2013) an exposure limit for short-term ceiling concentrations could be established by multiplication to an exceeding factor (Überschreitungsfaktor), which is set per default 1 (could be adjusted to max. 8). An exceeding factor of 2 is employed here to achieve a ceiling concentration limit of 0.6 mg/m³. This value could be used as surrogate DNEL_{acute, local effects} for workers for inhalation for HDI oligomers, uretdione type. This procedure is in accordance to Guidance Document R.8 (ECHA, Nov. 2012), Appendix R. 8 -8, Box 6.

 

For skin sensitization no DNEL is calculated as the relationship between skin dose and response is not clear. Furthermore, there is no validated method of DNEL calculation for skin sensitizers, therefore a quantitative risk assessment for this endpoint is not possible and a qualitative risk assessment is applied. As the substance is classified with R43/Cat. 1 for skin sensitisation (without sub-categorisation), it has to be allocated to the high hazard category (Guidance Document – Part E: Risk characterization, ECHA, November 2012). Consequently, the respective risk management measures (RMMs) at the workplaces have to be considered for risk assessment.

 

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