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Administrative data

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:
other toxicological threshold
Value:
0.05 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
DNEL derivation method:
other: The Indicative Occupational Exposure Limit (IOEL) 8 h TWA value recommended by the Scientific Committee on Occupational Exposure Limits (SCOEL) is used as toxicological threshold for long term local inhalation effects.
Acute/short term exposure
Hazard assessment conclusion:
other toxicological threshold
Value:
0.1 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
DNEL derivation method:
other: The Indicative Occupational Exposure Limit (IOEL) 15 min STEL value recommended by the Scientific Committee on Occupational Exposure Limits (SCOEL) is used as toxicological threshold for acute/short term local inhalation effects.

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:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - workers

Overview of the toxicological database

 

The large database of animal studies, human studies, human cases and observations are consistent in demonstrating the critical (and essentially) the only effect of sulphuric acid to be local corrosivity/irritancy at the site of contact. Studies have not shown any systemic effect resulting from exposure to sulphuric acid, with the possible exception of cases involving oral ingestion of large amounts.

 

Critical endpoint

 

The most sensitive endpoint of sulphuric acid exposure in animals and humans is local irritation of the respiratory tract. This endpoint has been investigated in numerous studies performed in a number of different animal species. It is clear from the results of these studies and from experiments and observations in human subjects that the response to sulphuric acid aerosols is influenced by many variables including duration of exposure, species investigated, age and particle size. The critical study is the 28-day rat inhalation study by Kilgour et al (2000) which identified laryngeal effects in the rat at low levels of exposure. This study would therefore appear to be the appropriate basis for derivation of the DNEL/DMEL values, however it has been argued that the findings in this study are not of clear toxicological significance (Osimitz et al, 2007) therefore this is likely to represent a conservative position. It is noted that the SCOEL has recently discussed the sulphuric acid data base, and these discussions are shown below. Due to the toxicity profile of sulphuric acid, DNEL/DMEL values for systemic effects and for dermal exposure are not relevant and are therefore not proposed. No systemic toxicity is predicted; dermal effects will be dominated by local corrosivity/irritation and will be limited by the use of appropriate protective equipment.

 

SCOEL consideration

 

The extensive database of animal studies, human studies and observations with sulphuric acid have recently been reviewed by the SCOEL (2007). SOEL discussions included the recent (and guideline-compliant) study of repeated inhalation exposure to sulphuric acid performed by Kilgour et al (2002). SCOEL's conclusions are shown below.

 

Reference:

 

Osimitz TG, Droege W & Finch JM (2007). Toxicologic significance of histologic change in the larynx of the rat following inhalation exposure: a critical review. Toxicol. Appl. Pharmacol. 225(3): 229 -237

 

Concern about the toxicity of sulphuric acid in the workplace atmosphere is focussed on its potential, as an inhaled aerosol, to exert local effects on the respiratory tract, as a consequence of low pH. Such effects can be manifested as sensory irritation of nerve endings, acute or longer term inflammation at various sites along the length of the respiratory tract epithelium and ultimately the possibility of tumour formation in the respiratory tract, believed to be a consequence of sustained tissue inflammation and repair processes. Human carcinogenicity data and the findings of a recent 28-day inhalation study in rats suggest that the larynx is a site of particular concern, in relation to epithelial inflammation, damage and ultimately cancer.

 

The identification of a clear NOAEL for this range of potential respiratory tract effects is difficult, from the available data. However, the recent 28-day inhalation study in rats (using a 50% sulphuric acid aerosol) provides evidence of slight changes in the laryngeal epithelium at the lowest concentration tested, 0.3 mg/m3. Other experimental studies in a range of animal species suggest respiratory tract effects on repeated exposure to concentrations around 0.3 mg/m3, with the possibility of effects of some health significance even at concentrations down to about 0.1 mg/m3.

 

Taking into account the overall database, and with the concern for potential human carcinogenicity in mind, SCOEL concluded that long-term exposure should be maintained below 0.1 mg/m3 in order to provide sufficient reassurance of avoidance of possible adverse consequences for the respiratory tract epithelium. Hence SCOEL recommends an 8h TWA limit of 0.05 mg/m3 in order to satisfy this requirement. SCOEL appreciates that the reliable measurement of exposures at and around the limit value proposed is challenging. In some circumstances there might be interference from sulphate salts also present in the atmosphere. However, from the most recent evidence presented to SCOEL and from the assessment made in the Annex it appears that there are measurement techniques available that are compatible with the proposed limit. In terms of health protection, SCOEL considered that it would be desirable to recommend a STEL of 0.1 mg/m3 to avoid short-term irritant effects. However, at present there is no available measurement method which can accommodate a short-term limit at this value.

 

SCOEL therefore proposed an 8 -hour TWA limit of 0.05 mg/m3 and a 15 -minute STEL of 0.1 mg/m3, based on the weight of evidence from the large available database of findings in animals and humans. The values were not based on single key studies using an assessment factor, although the critical factor was local irritation of the respiratory tract and the study by Kilgour et al (2002) was cited. The TWA and STEL values can be used for the long-term (local) and acute/short-term (local) DNEL values, as shown above. The TWA of 0.05 mg/m3 is adopted (Directive 2009/161/EC) as an EU IOEL value (sulphuric acid mist, defined as the thoracic fraction). The use of IOEL values is justified as there is no new scientific information which indicates that the IOEL values do not provide an appropriate level of protection under REACH.

 

Reference: Osimitz TG, Droege W & Finch JM (2007).

 

Derivation of DNEL according to REACH guidance

 

According to REACH guidance, the use of a number of assessment factors need to be considered when deriving the DNEL. These include factors for interspecies differences, intraspecies differences, duration of exposure, dose-response and the quality of the database. The use of these assessment factors for the derivation of a DNEL for sulphuric acid is considered in turn:

 

Correction of starting point:

 

The LOAEC of 0.3 mg/m3 should be corrected for the duration of exposure (6 hours/day in the study) to 8 hours (relevant for worker exposure) and also for breathing rate (6.7 m3/10 m3), relevant for workers potentially exposed for 8 hours/day. The corrected inhalatory LOAEC is 0.15 mg/m3.

 

Interspecies differences:

 

For local irritant effects differences in toxicodynamic factors are not relevant, however a default factor of 2.5 is recommended to cover possible differences in regional airflow and deposition. However given the large amount of data for different species including the monkey, which is more relevant in terms of respiratory tract structure and does not show any greater sensitivity than other species, an assessment factor of 1 for interspecies differences is considered to be applicable.

 

Intraspecies differences:

 

A default assessment factor of 5 is recommended in the REACH guidance for workers for systemic and local effects in the absence of specific information.

 

Differences in duration of exposure:

 

The use of various assessment factors is discussed when deriving DNEL values relevant to long-term exposure from studies of shorter duration. In the case of sulphuric acid, the use of an additional factor is not considered to be warranted as the starting point is based on the weight of evidence from all studies, including those of chronic exposure. In addition, the available data do not indicate any significant differences resulting from different exposure periods. A lower assessment factor of 1 can therefore be used in this case.

 

Dose-response relationship:

 

There are no specific concerns for sulphuric acid that would warrant the use of an assessment factor of greater than 1 (the default).

 

Quality of the database:

 

The data available for sulphuric acid are comprehensive. The use of a default assessment factor of 1 is therefore appropriate.

 

Using the NOAEC of 0.3 mg/m3 from the study of Kilgour et al (2002) as the point of departure, corrected for duration and breathing rate to 0.15 mg/m3, and applying an overall assessment factor of 5 results in a DNEL of 0.03 mg/m3. This is comparable to the OEL proposed by SCOEL.

 

Exposure to sulphuric acid at the DNEL: physiological context

 

Assuming 8 -hour occupational exposure to sulphuric acid mist at the DNEL of 0.05 mg/m3 and a breathing rate of 1.25 m3/h, the estimated total daily exposure of a worker is 0.5 mg sulphuric acid. If all of the inhaled sulphuric acid is retained in the lung, systemically absorbed and dissociates to sulphate, the amount of absorbed sulphate (~0.5 mg) is a small fraction of the total serum sulphate level of 80 -96 mg (based on published values for serum sulphate levels of 2.9 -3.5 mg/dl, blood volume of 5l and serum 55% of blood volume). It is important to note that this figure does not include any estimation of intracellular sulphate concentrations, which are reported to be higher than the serum concentration. It is therefore clear that the 'additional' (i.e. above physiological) levels of sulphate resulting from occupational exposure to sulphuric acid are minimal and will therefore be readily controlled by homeostatic mechanisms. It can be confidently predicted that this minimal additional exposure to sulphate will not have any systemic toxicity, including effects on reproduction/fertility, any effects on the developing foetus or any carcinogenicity. Further testing for systemic effects is therefore not required.

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:
high hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
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:
high hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion

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:
high hazard (no threshold derived)

Additional information - General Population

Significant additional inhalation exposure (over and above background levels resulting from other sources including combustion of fossil fuels) of the general population is not predicted; DNEL/DMEL values are therefore not proposed.

Dermal exposure of the general population is not predicted.

Oral exposure of the general public is not relevant and in any case would be indistinguishable from naturally occurring ionic species.

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