Phosgene

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.4 mg/m³

Most sensitive endpoint:

irritation (respiratory tract)

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

2 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:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

Explanation for the modification of the dose descriptor starting point:

According to ECHA Guidance on information requirements and chemical safety assessment - Chapter R.8 (Dec. 2010), Appendix R.8-13 an EU occupational exposure limit (OEL) value could be used as a surrogate for a DNEL. This DNEL was delineated by the Scientific Committee on Occupational Exposure Limits (SCOEL) of the European Commission. For details see "Discussion".

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

Explanation for the modification of the dose descriptor starting point:

The toxicological database for inhaled phosgene demonstrates consistently that toxicity is associated only with the portal-of-entry (respiratory tract). No indications for systemic toxicity were observed. Therefore, any potential systemic toxicity effects are covered by the respective long-term exposure DNEL for inhalation exposure, local effects (= 0.4 mg/m3). For details see "Discussion".

Local effects

Long term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)

Additional information - workers

Inhalation exposure is typically the most relevant route for assessing occupational hazard and risk in humans. In case of phosgene this is especially true due to the physico-chemical properties (gas at room temperature and rapid hydrolysis) and the well know toxicological profile. Effects from available acute and repeated exposure of animals to phosgene are limited to effects on the respiratory tract caused by local irritation. No indications of systemic toxicity were found after acute or repeated exposure of phosgene.

 

According to the ECHA Guidance on information requirements and chemical safety assessment - Chapter R.8 (Dec. 2010), Appendix R.8-13 an EU occupational exposure limit (OEL) value was used as a surrogate for a DNEL. For phosgene the Scientific Committee on Occupational Exposure Limits (SCOEL) recommended an OEL of 0.4 mg/m3 referring to an 8-hour exposure period. This OEL is used as a surrogate DNEL for long-term exposure. A ceiling limit value of 2.0 mg/m3 was recommended for phosgene. This ceiling limit is used as a surrogate DNEL for short-term exposure. The justification of these OELs was based on the MAK documentation on phosgene (Greim, 2008), which includes the newest studies on acute inhalation effects of phosgene designed to verify the concentration x time = const. relationship and time-course changes in regard to pulmonary injury (lung edema probed by bronchoalveolar lavage) and to analyse species differences in rats and dogs, which are discussed extensively in the EC documentation SCOEL/SUM/004 (European Commission, 2011) with the following statements:

 

"The target organ/critical effect of phosgene is acute irritation of the mucous membranes of the respiratory tract and direct damage of the alveolar capillary membrane and subsequently delayed pulmonary oedema. Recent studies by Pauluhn (2006a, b,c) in rats and dogs have shown, that these effects are time and dose dependent and follow Haber’s law. It has been shown that dogs are less sensitive than rats (Pauluhn, 2006c). Since the dog lung is anatomically and physiologically closer related to the human lung compared to the rat (Pauluhn et al., 2007), studies in dogs are more relevant than studies in rats for deriving an OEL. In dogs, an exposure to 9 mg phosgene/m3 (2 ppm) for 30 minutes (270 mg/m3 x min) did not increase the protein concentration in the BAL fluid used as a sensitive marker for inflammatory reactions in the lung (Pauluhn 2006c). According to Haber's law, this dose corresponds to 0.14 ml/m3 for an 8 hour exposure. Interindividual differences in susceptibility, which might be due to different enzyme activities are not relevant, because phosgene reacts locally without prior metabolism. This assumption is verified by the similar protein concentration in the BAL fluid of the 4 dogs exposed to 270 mg/m3 x min. Due to the higher ventilation rate (dogs 0.4 L/kg, humans 0.2 L/kg) the same air concentration results in a higher lung exposure in dogs than in humans. This renders dogs more sensitive than humans so that an additional assessment factor is not needed and an OEL for phosgene of 0.1 ml/m3 (0.4 mg/m3) is derived. A STEL of 0.5 ppm (2.0 mg/m3) is proposed which is based on the NOEL of 2 ppm in dogs at 30 min exposure and considering 4 events per shift during 15 min each."

 

The DNELs acute/long-term for inhalation of workers covers also reproductive toxicity, as the local effects at the respiratory tract are the most sensitive effects and there is no indication of systemic toxicity.

 

 

References

 

European Commission (EC) 2011: Recommendation from the Scientific Committee on Occupational Exposure Limits for phosgene. SCOEL/SUM/004, September 2011.

 

Greim H. (ed.) 2008: Gesundsheitschädliche Arbeitstoffe, Toxikologisch-Arbeitsmedizinische Begründung von MAK-Werten, Loseblattsammlung, Phosgen, 45. Lieferung 2008, VCH-Verlagsgesellschaft, Weinheim.

 

Pauluhn J. 2006a: Acute nose-only exposure of rats to phosgene. Part I: Concentration x time dependence of LC50s, nonlethal-threshold concentrations, and analysis of breathing patterns. Inhalat Toxicol 18: 423-435.

 

Pauluhn J. 2006b: Acute nose-only exposure of rats to phosgene. Part II. Concentration x time dependence of changes in bronchoalveolar lavage during a follow-up period of 3 months. Inhalat Toxicol 18: 595-607.

 

Pauluhn J. 2006c: Acute head-only exposure of dogs to phosgene. Part III. Comparison of indicators of lung injury in dogs and rats. Inhalat Toxicol 18: 609-621.

 

Pauluhn J., Carson A., Costa D.L., Gordon T., Kodavanti U., Last J.A., Matthay M.A., Pinkerton K.E., Sciuto A.M., 2007: Workshop summary: phosgene-induced pulmonary toxicity revisited: appraisal of early and late markers of pulmonary injury from animal models with emphasis on human significance. Inhalat Toxicol. 19: 789-810.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Additional information - General Population

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