Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
18 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
18
Modified dose descriptor starting point:
NOAEC
AF for differences in duration of exposure:
6
AF for interspecies differences (allometric scaling):
1
AF for intraspecies differences:
3
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:
2.6 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
72
Modified dose descriptor starting point:
NOAEL
AF for differences in duration of exposure:
6
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
1
AF for intraspecies differences:
3
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

No acute hazards leading to acute toxicity have been identified for the submission substance by any route of exposure based on read-across data. The skin and eye irritation potential of the submission substance is minimal and the substance is not believed to be a skin sensitizer. There is no evidence of local irritation following long-term exposure. All available data indicate the submission substance is not genotoxic, it is not expected to be carcinogenic, and it is not expected to present a reproductive or developmental toxicity hazard. Based on the available read-across data, the submission substance was considered to be effectively non-hazardous for these endpoints. Since classification is not warranted for these endpoints the following DNELS were not calculated for workers:

1) Acute/short-term exposure-systemic effects dermal

2) Acute/short-term exposure-systemic effects inhalation

3) Acute/short-term exposure-local effects dermal

4) Acute/short-term exposure-local effects inhalation

5) Long-term exposure-local effects dermal

6) Long-term exposure-local effects inhalation

 

Repeated-dose exposures by the oral route to the structurally analogous material TOTM for 28 days showed changes in organ weights, clinical chemistry, and hematology at 650 mg/kg-bw/day with a NOAEL of 184 mg/kg/bw/day for systemic toxicity in one study (Chemical Manufacturers Association, 1984). No pathologic abnormalities were detected in the majority of the animals. The systemic changes observed in this study were not indicative of significant toxicity and occurred at doses above the CLP (EC Regulation 1272/2008) guidance values for classification. In a second 28 day oral feeding study in rats, no treatment related effects were observed at any dose tested resulting in a NOAEL of 1000 mg/kg/day (Ministry of Health & Welfare, Japan, 1996). Based on these data, the submission substance was considered to be effectively non-hazardous for these endpoints and no classification is warranted. Regardless, long-term exposure-systemic effects DNELS for both the inhalation and dermal routes were calculated for workers based on these data. DNELs were calculated in accordance with REACH regulations and the ECHA guidance document 'Guidance on Information requirements and chemical safety assessment: Chapter R.8: Characterisation of dose [concentration]-response for human health' (2008a).  All default values used in the calculations were obtained from this document. Assessment factor determinations followed the European Centre for Ecotoxicology and Toxicology of Chemicals recommendations (ECETOC Derivation of assessment factors for human health risk assessment. Technical Report No. 86, 2003).

 

LONG-TERM DERMAL EXPOSURE–SYSTEMIC EFFECTS WORKER DNEL

No repeated dose dermal data were available for this substance. Therefore, a NOAEL of 184mg/kg-bw/day from a 28d repeated-dose oral toxicity study in rats was used to calculate the long-term exposure–systemic effects dermal DNEL. Dosimetric exposure adjustments were not necessary as no data were available. An assessment factor of 72 was applied based on default assumptions (interspecies=1; intraspecies=3; study duration=6; allometric scaling=4 for rat). The resulting worker dermal systemic DNEL is 2.6 mg/kg-bw/day.

 

LONG-TERM INHALATION EXPOSURE–SYSTEMIC EFFECTS WORKER DNEL

No repeated dose inhalation data were available for this substance. Therefore, a NOAEL of 168 mg/kg-bw/day from a 28d repeated-dose oral toxicity study in rats was used to calculate the long-term exposure–systemic effects inhalation DNEL. The starting NOAEL was first modified into a corrected inhalatory NOAEC (324 mg/m3) for workers according to ECHA guidance (ECHA, 2008a). An assessment factor of 18 was applied based on default assumptions (interspecies=1.0; intraspecies=3; study duration=6). The resulting worker inhalation DNEL for systemic effects is 18.0 mg/m3.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
120
Modified dose descriptor starting point:
NOAEL
AF for differences in duration of exposure:
6
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
1
AF for intraspecies differences:
5
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
120
Modified dose descriptor starting point:
NOAEL
AF for differences in duration of exposure:
6
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
4
AF for intraspecies differences:
5
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

Additional information - General Population

For the general population, relevant routes of exposure include dermal and limited oral exposures. The physical and chemical properties of the substance limit inhalation exposures to aerosols or droplets of inhalable size only under certain use conditions. The general population is not anticipated to be subject to these uses and therefore is not subject to these types of exposures. In accordance with REACH (Annex I, 1.4.1) DNELS shall be established for the substance reflecting the likely route(s) of exposure. Therefore the following DNELS were not calculated for the general population:

1) Acute/short-term exposure-systemic effects inhalation

2) Long-term exposure-systemic effects inhalation

3) Acute/short-term exposure-local effects inhalation

4) Long-term exposure-local effects inhalation

 

No acute hazards leading to acute toxicity have been identified for the submission substance by any route of exposure. The skin and eye irritation potential of the submission substance is minimal.  There is no evidence of local irritation following long-term exposures. All available data indicate the submission substance is not genotoxic and it is not expected to be carcinogenic. Based on the available read-across data, the submission substance was considered to be effectively non-hazardous for these endpoints. Since classification is not warranted for these endpoints the following DNELS were also not calculated for the general population:

5) Acute/short-term exposure-systemic effects dermal

6) Acute/short-term exposure-systemic effects oral

7) Acute/short-term exposure-local effects dermal

8) Long-term exposure-local effects dermal

 

Repeated-dose exposures by the oral route to the structurally analogous material TOTM for 28 days showed changes in organ weights, clinical chemistry, and hematology at 650 mg/kg-bw/day with a NOAEL of 184 mg/kg/bw/day for systemic toxicity in one study (Chemical Manufacturers Association, 1984). No pathologic abnormalities were detected in the majority of the animals. The systemic changes observed in this study were not indicative of significant toxicity and occurred at doses above the CLP (EC Regulation 1272/2008) guidance values for classification. In a second 28 day oral feeding study in rats, no treatment related effects were observed at any dose tested resulting in a NOAEL of 1000 mg/kg/day (Ministry of Health & Welfare, Japan, 1996). Based on these data, the submission substance was considered to be effectively non-hazardous for these endpoints and no classification is warranted. Regardless, long-term exposure-systemic effects DNELS for both the oral and dermal routes were calculated for the general population based on these data. DNELs were calculated in accordance with REACH regulations and the ECHA guidance document 'Guidance on Information requirements and chemical safety assessment: Chapter R.8: Characterisation of dose [concentration]-response for human health' (2008a).  All default values used in the calculations were obtained from this document. Assessment factor determinations followed the European Centre for Ecotoxicology and Toxicology of Chemicals recommendations (ECETOC Derivation of assessment factors for human health risk assessment. Technical Report No. 86, 2003).

 

LONG-TERM DERMAL EXPOSURE–SYSTEMIC EFFECTS GENERAL POPULATION DNEL

No repeated dose dermal data were available for this substance. Therefore, a NOAEL of 184mg/kg-bw/day from a 28d repeated-dose oral toxicity study in rats was used to calculate the long-term exposure–systemic effects dermal DNEL. Dosimetric exposure adjustments were not necessary as no data were available. An assessment factor of 120 was applied based on default assumptions (interspecies=1; intraspecies=5; study duration=6; allometric scaling=4 for rat). The resulting general population dermal systemic DNEL is 1.5 mg/kg-bw/day.

 

LONG-TERM ORAL EXPOSURE–SYSTEMIC EFFECTS GENERAL POPULATION DNEL

A NOAEL of 184mg/kg-bw/day from a 28d repeated-dose oral toxicity study was used to calculate this DNEL. No modification of the starting NOAEL was needed, an assessment factor of 120 was applied (interspecies=4; intraspecies=5; study duration=6; allometric scaling=4 for rat). The resulting general population oral systemic DNEL is 1.5 mg/kg-bw/day.