Hydrazinium nitrate

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

exposure based waiving

Acute/short term exposure

Hazard assessment conclusion:

DMEL (Derived Minimum Effect Level)

Value:

0.13 mg/m³

Most sensitive endpoint:

carcinogenicity

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

exposure based waiving

Acute/short term exposure

Hazard assessment conclusion:

no-threshold effect and/or no dose-response information available

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

exposure based waiving

Acute/short term exposure

Hazard assessment conclusion:

no-threshold effect and/or no dose-response information available

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

exposure based waiving

Acute/short term exposure

Hazard assessment conclusion:

no-threshold effect and/or no dose-response information available

Additional information - workers

Due to data point waiving, no data are available for hydrazine mono-nitrate. Please see each individual endpoint for details of the waiver.

All toxicological data required for hydrazine mono-nitrate under REACH Annexes VII and VIII has been waived (apart from anin vitrobacterial mutagenicity test) due to existing classification or exposure control. Therefore, it is not possible to derive DN(M)EL(s) for mammalian endpoints as test data are absent.

 

REACH (Annex 1) states that if a DN(M)EL cannot be derived “this shall be clearly stated and justified”.

 

Hydrazine mono-nitrate is a category 1b carcinogen. For carcinogens and mutagens, the Carcinogens and Mutagens Directive (2004/37/EC) requires that workplace exposures are avoided/minimised as far as technically feasible. As REACH does not overrule the Carcinogens and Mutagens Directive, the approach to controlling workplace exposure should therefore comply with this minimisation requirement.

 

As hydrazine mono-nitrate is a carcinogen and a positive result has been obtained in a bacterial mutagenicity testin vitro, a DMEL should be derived, if possible.

 

For workplace exposure, there may already exist occupational exposure limits (OELs) and/or the underlying information used for setting the OELs can be used to derive DNELs.

 

An indicative Occupational Exposure Limit for hydrazine mono-nitrate or hydrazine does not exist.

 

A registrant cannot use a national OEL in place of a DNEL without an evaluation of the scientific background for the setting of the national OEL. In cases where the evaluations of health effects used for setting the national OEL are documented this may be taken into account in deriving the DNEL.

 

Aworkplace Exposure Limit (WEL) exists for hydrazine of0.03 mg/m³ (8-hr TWA) and 0.13 mg/m³ (STEL, 15-minute reference period) with ‘Sk’ notation and ‘Carc’ notation added.

 

It is proposed that thesefor hydrazine are used as DMELs and read-across to hydrazine mono-nitrate for short-term inhalation exposure and that the Carcinogens Directive is invoked.

 

Basis for setting the Limit

 

Human data on the toxicity of hydrazine are limited, and in particular it is not possible to correlate the effects observed with specified doses/exposure levels. Hence suitable occupational exposure limits must be based largely on the results of animal studies.

 

Hydrazine is clearly carcinogenic in animals, producing tumours in the nasal cavity on inhalation and in the liver following repeated oral administration. These findings are considered relevant to human health; the significance of the other tumours seen in animal experiments is less certain. Chronic tissue damage is likely to have been a very influential factor in the aetiology of these tumours. However, in view of the genotoxicity of hydrazine in vitro and the possibility that this activity id expressed in vivo, it cannot be discounted that such effects could contribute to the carcinogenic process.

 

Furthermore, a clear NOAEL for repeated inhalation exposure in animals has not been identified. Hydrazine is also a developmental toxicant in animals, dose-response relationships for these effects being poorly characterised.

 

In view of these factors it was concluded that an OES cannot be set for hydrazine and a WEL is considered appropriate. The main uses of hydrazine in theare in boiler water treatment, particularly in the electricity generating industry, and in chemical manufacture. In boiler water treatment there is potential for exposure when hydrazine is transferred from drums to the dosing tanks. This operation is of short duration and all firms specify the use of protective clothing and some use of RPE. Limited exposure data suggests that the short-term exposures are less than 0.1 ppm. Recent contacts with the chemical manufacturing industry indicate that exposure to airborne hydrazine is controlled by process enclosure and provision of LEV at the bund hole of the drum during reactor charging. The limited background monitoring data supplied by industry that personal; exposure are likely to be below 0.1 ppm during these operations.

 

In view of the hygiene data supplied by industry the short duration of exposure and the string irritative effects of hydrazine a short term MEL was set of 0.1 ppm for a 15 minute reference period. However, the rat carcinogenicity study showed tumours occurring following inhalation exposure at 0.05 ppm for 30 hours per week for a year. WATCH considered that the tumours at this concentration could not be discounted. In view of the control that can be achieved it was proposed that total exposure should be limited by a MEL of 0.02 ppm 8-hour TWA.

 

Toxicokinetics show that significant skin absorption can occur, and thus a skin notation was set.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

exposure based waiving

Acute/short term exposure

Hazard assessment conclusion:

no-threshold effect and/or no dose-response information available

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

exposure based waiving

Acute/short term exposure

Hazard assessment conclusion:

no-threshold effect and/or no dose-response information available

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

exposure based waiving

Acute/short term exposure

Hazard assessment conclusion:

no-threshold effect and/or no dose-response information available

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

exposure based waiving

Acute/short term exposure

Hazard assessment conclusion:

no-threshold effect and/or no dose-response information available

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

exposure based waiving

Acute/short term exposure

Hazard assessment conclusion:

no-threshold effect and/or no dose-response information available

DNEL related information

Additional information - General Population

Due to data point waiving, no data are available for hydrazine mono-nitrate.