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Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
49.8 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
30
Modified dose descriptor starting point:
NOAEC
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

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
14.1 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
120
Modified dose descriptor starting point:
NOAEL
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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

According to the REACH Guidance on information requirements and chemical safety assessment, a leading DN(M) EL needs to be derived for every relevant human population and every relevant route, duration and frequency of exposure, if feasible.

Short-term toxicity

Ammonium carbamate is classified as causing serious damage to eyes. As no qualitative data are available on this endoint, a DNEL can not be derived. A qualitative risk assessment will be performed.

The substance is not sensitising, therefore no DNEL has been derived for this endpoint.

 

Long-term toxicity

No substance-specific data on repeated dose toxicity of ammonium carbamate were available for assessment. Therefore the long-term DNELs for ammonium carbamate have been derived based on the 90-day oral toxicity study with rats with a structural analogue of ammonium carbamate, ammonium chloride. Route-to-route extrapolation was performed in order to derive DNELs for dermal and inhalation routes of exposure. As no quantitative information on absorption of ammonium carbamate was available, the default factors for route-to-route extrapolation suggested by Chapter R.8.4.2 of REACH Guidance on information requirements and chemical safety assessment were used.

Ammonium carbamate is not genotoxic, not carcinogenic and not toxic to reproduction and development, therefore no DNELs have been derived for these endpoints.

 

DNELs for workers:

 

Long-term – inhalation, systemic effects (based on the 90 days oral study in rats with a structural analogue ammonium chloride[1])

 

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL: 1695.6 mg/kg bw/day

The exposure of rats to ammonium chloride caused increased incidence of zona glomerulosa hypertrophy (adrenals) and significant body weight reduction in the high-dose animals

Step 2) Modification of starting point

2

 

 

 

0.38 m3/kg bw

 

 

 

6.7 m3/10 m3

The REACH guidance prescribes a default factor of 2 in case of oral to inhalation extrapolation.

 

Standard respiratory volume of a rat, corrected for 8 h exposure, as proposed in the REACH Guidance (R.8.4.2)

 

Correction for activity driven differences of respiratory volumes in workers compared to workers in rest (6.7 m3/10 m3)

Modified dose-descriptor

1695.6 x 6.7 / (10 x 0.38 x 2) = 1494.8 mg/m3

Step 3) Assessment factors

 

 

Interspecies

1

No factor for allometric scaling is needed in case of inhalation exposure

Intraspecies

 

 

5

 

Default assessment factor for workers according to Chapter R.8 of REACH Guidance on information requirements and chemical safety assessment

Exposure duration

2

Default assessment factor for extrapolation of exposure duration from subchronic to chronic

Dose response

1

 

Quality of database

3

An additional safety factor of 3 is introduced, as the data are based on the read-across approach

DNEL

Value

 

1494.8 / (1 x 5 x 2 x 3 x 1) =49.8 mg/m3

 

 

Long-term – dermal, systemic effects (based on the 90 days oral study in rats with a structural analogue ammonium chloride)

 

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL: 1695.6 mg/kg bw/day

The exposure of rats to ammonium chloride caused increased incidence of zona glomerulosa hypertrophy (adrenals) and significant body weight reduction in the high-dose animals

Step 2) Modification of starting point

1

 

  

 

 

On the assumption that, in general, dermal absorption will not be higher than oral absorption, no default factor should be introduced when performing oral to dermal extrapolation

Modified dose-descriptor

1695.6 mg/kg bw/day

Step 3) Assessment factors

 

 

Interspecies

4

Allometric scaling factor for rat

Intraspecies

 

 

5

 

Default assessment factor for workers according to Chapter R.8 of REACH Guidance on information requirements and chemical safety assessment

Exposure duration

2

Default assessment factor for extrapolation of exposure duration from subchronic to chronic

Dose response

1

 

Quality of database

3

An additional safety factor of 3 is introduced, as the data are based on the read-across approach

DNEL

Value

 

1695.6 / (4 x 5 x 2 x 3 x 1) = 14.1 mg/kg bw/day

 

[1] There is also a 90-day inhalation toxicity study available with ammonia with a NOAEC of 262 mg/m3 (24-hour exposure). Using this value as starting point for DNEL derivation results in the following DNEL for long-term exposure by inhalation: 262 x (24/8) x (6.7/10) / (1 x 5 x 2 x 1) = 52.7 mg/m3 for ammonia; assuming that the maximum quantity of NH3possibly released from ammonium carbamate would be 43.6%, this results in a long-term inhalation DNEL of 120.8 mg/m3 for ammonium carbamate.

 

 

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
12.3 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
60
Modified dose descriptor starting point:
NOAEC
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:
DNEL (Derived No Effect Level)
Value:
7.1 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
240
Modified dose descriptor starting point:
NOAEL
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:
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:
medium hazard (no threshold derived)

Additional information - General Population

According to the REACH Guidance on information requirements and chemical safety assessment, a leading DN(M) EL needs to be derived for every relevant human population and every relevant route, duration and frequency of exposure, if feasible.

Short-term toxicity

Ammonium carbamate is classified for acute oral toxicity (Xn, R22). However, oral uptake is not an anticipated route of exposure in the consumer uses described in the CSR (Use in washing and cleaning products, use in biocide formulations). Furthermore, it is unlikely that potential oral exposure via cross-contamination will lead to exposures exceeding the long-term systemic DNELs. Therefore, no short-term oral DNEL is derived. As the substance is not classified for acute dermal and inhalation toxicity, no short-term DNELs for these routes of exposure need to be derived.

Ammonium carbamate is classified as causing serious damage to eyes. As no qualitative data are available on these endpoints, a DNEL can not be derived. A qualitative risk assessment will be performed.

The substance is not sensitising, therefore no DNEL has been derived for this endpoint.

 

Long-term toxicity

No substance-specific data on repeated dose toxicity of ammonium carbamate were available for assessment. Therefore the long-term DNELs for ammonium carbamate have been derived based on the 90-day oral toxicity study with rats with a structural analogue of ammonium carbamate, ammonium chloride. Route-to-route extrapolation was performed in order to derive DNELs for dermal and inhalation routes of exposure. As no quantitative information on absorption of ammonium carbamate was available, the default values for route-to route extrapolation suggested by Chapter R.8.4.2 of REACH Guidance on information requirements and chemical safety assessment were used.

Ammonium carbamate is not genotoxic, not carcinogenic and not toxic to reproduction and development, therefore no DNELs have been derived for these endpoints.

DNELs for the general population:

Long-term – inhalation, systemic effects (based on the 90 days oral study in rats with a structural analogue ammonium chloride[1])

 

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL: 1695.6 mg/kg bw/day

The exposure of rats to ammonium chloride caused increased incidence of zona glomerulosa hypertrophy (adrenals) and significant body weight reduction in the high-dose animals

Step 2) Modification of starting point

2

 

 

1.15m3/kg bw

 

The REACH guidance prescribes a default factor of 2 in case of oral to inhalation extrapolation.

 

Standard respiratory volume of a rat, corrected for 24 h exposure, as proposed in the REACH Guidance (R.8.4.2)

Modified dose-descriptor

1695.6 / (2 x 1.15) = 737.2 mg/m3

Step 3) Assessment factors

 

 

Interspecies

1

No factor for allometric scaling is needed in case of inhalation exposure

Intraspecies

 

 

10

 

Default assessment factor for general population according to Chapter R.8 of REACH Guidance on information requirements and chemical safety assessment

Exposure duration

2

Default assessment factor for extrapolation of exposure duration from subchronic to chronic

Dose response

1

 

Quality of database

3

An additional safety factor of 3 is introduced, as the data are based on the read-across approach

DNEL

Value

 

737.2/ (1 x 10 x 2 x 3 x 1) = 12.3 mg/m3

 

Long-term – dermal, systemic effects (based on the 90 days oral study in rats with a structural analogue ammonium chloride)

 

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL: 1695.6 mg/kg bw/day

The exposure of rats to ammonium chloride caused increased incidence of zona glomerulosa hypertrophy (adrenals) and significant body weight reduction in the high-dose animals

Step 2) Modification of starting point

1

 

  

 

 

On the assumption that, in general, dermal absorption will not be higher than oral absorption, no default factor should be introduced when performing oral to dermal extrapolation

Modified dose-descriptor

1695.6 mg/kg bw/day

Step 3) Assessment factors

 

 

Interspecies

4

Allometric scaling factor for rat

Intraspecies

 

 

10

 

Default assessment factor for general population according to Chapter R.8 of REACH Guidance on information requirements and chemical safety assessment

Exposure duration

2

Default assessment factor for extrapolation of exposure duration from subchronic to chronic

Dose response

1

 

Quality of database

3

An additional safety factor of 3 is introduced, as the data are based on the read-across approach

DNEL

Value

 

1695.6 / (4 x 10 x 2 x 1 x 3) = 7.1 mg/kg bw/day

 

 


[1] There is also a 90-day inhalation toxicity study available with ammonia with a NOAEC of 262 mg/m3 (24-hour exposure). Using this value as starting point for DNEL derivation results in a comparable DNEL for long-term exposure by inhalation: 262 / (1 x 10 x 2 x 1) = 13.1 mg/m3 for ammonia; assuming that the maximum quantity of NH3 possibly released from ammonium carbamate would be 43.6%, this results in long-term inhalation DNEL of 30 mg/m3 for ammonium carbamate.