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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.2 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
75
Dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
88.2 mg/m³
Explanation for the modification of the dose descriptor starting point:

NOAEC = systemic NOAEL (OECD422, rat) *abs. oral/abs. inhal. /0.38 m3/kg bw *6.7 m3/10 m3 = NOAEL /(2*0,38) *0.67 (see R.8.4.2)

AF for dose response relationship:
1
Justification:
GLP OECD guideline study with 3 doses
AF for differences in duration of exposure:
6
Justification:
default factor for subacute study
AF for interspecies differences (allometric scaling):
1
Justification:
default after extrapolation from oral route to inhalation
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
5
Justification:
default
AF for the quality of the whole database:
1
Justification:
default
AF for remaining uncertainties:
1
Justification:
default
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

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
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.33 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
300
Dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

NOAEL (dermal) = systemic NOAEL (oral, OECD 422 rat) * 1 (100 % resorption = worst case)

AF for dose response relationship:
1
Justification:
GLP OECD guideline study with 3 doses
AF for differences in duration of exposure:
6
Justification:
default factor for subacute study
AF for interspecies differences (allometric scaling):
4
Justification:
default for scaling from rat to man
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
5
Justification:
default
AF for the quality of the whole database:
1
Justification:
default
AF for remaining uncertainties:
1
Justification:
default
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

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

General considerations

1,1,3,3-Tetramethylguanidine (TMG), CAS 80-70-6 is a liquid with a MW of 115.1768 g/mol and a vapour pressure of 2.9 hPa @20 °C. Thus, the saturated vapour concentration is calculated to be 13.8 mg/L. It is miscible with water at any ratio and has a log Pow of -0.49 @20 °C. With a pH > 12.5 is is a strong alkaline substance.

In animal studies TMG is harmful after single ingestion (LD50 (oral, rat) = 835 mg/kg; 1982), and corrosive to the skin (study similar to OECD TG 404; 1982). TMG is not expected to be skin sensitizing (QSAR, 2017) and was not mutagenic in bacteria and mammalian cell culture (Ames: 2015; HPRT: 2018 and in vitro MNT, 2017).

For TMG an oral OECD422 study in rat is available with doses of 0, 10, 30 and 100 mg/kg bw /d administered per gavage (2018). The observed adverse findings were erosions in the glandular stomach of some females in the mid and high dose group and considered to be local effects resulting from the basic corrosive properties of TMG. Therefore, the systemic NOAEL in this study is 100 mg/kg bw/d and the local NOAEL is 10 mg/kg bw/d.

 

DNEL derivation: Point of departure

For the DNEL derivation the strong corrosivity of the substance is considered to be the most sensitive effect. Quantitative data (dose response) on this hazard are available for the oral route from acute and repeated dose toxicity, but not for the dermal or inhalation route. Therefore, no local (long term or acute/short term) DNELs and no systemic short term DNELs were derived. Systemic long-term DNELs for inhalation and dermal route were derived using the systemic NOAEL of the oral OECD422 study in rats as the dose descriptor starting point. These DNELs are only relevant in preparations when the corrosivity of the substance is not anymore the most prominent effect (concentration < 1%).

As TMG is classified as Skin Corr. 1B, H314 (GHS EU), it is attributed to the moderate hazard class according to ECHA Guidance E (v3.0, May 2016) and ECHA Guidance R.8 (v.2.1, Nov 2012). Appropriate OCs (operational conditions), RMMs (risk management measures) and PPE (personal protection equipment) should therefore be implemented, when developing exposure scenarios.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.3 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
150
Dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
43.5 mg/m³
Explanation for the modification of the dose descriptor starting point:

NOAEC = systemic NOAEL (OECD422, rat) / [sRV * time] *(abs. oral/abs. inhal.) = NOAEL / [0.8  L/min/kg bw rat * 24*60 min] *50%/100% = NOAEL /(1.15 m3/kg bw *2)

AF for dose response relationship:
1
Justification:
GLP OECD guideline study with 3 doses
AF for differences in duration of exposure:
6
Justification:
default for subacute study
AF for interspecies differences (allometric scaling):
1
Justification:
default after extrapolation from oral route to inhalation
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
10
Justification:
default for general population
AF for the quality of the whole database:
1
Justification:
default
AF for remaining uncertainties:
1
Justification:
default
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

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
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.17 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

100% resorption (worst case): *1

AF for dose response relationship:
1
Justification:
GLP OECD guideloine study with 3 doses
AF for differences in duration of exposure:
6
Justification:
default for subacute study
AF for interspecies differences (allometric scaling):
4
Justification:
default for scaling from rat to man
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
10
Justification:
default for general population
AF for the quality of the whole database:
1
Justification:
default
AF for remaining uncertainties:
1
Justification:
default
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

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

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.17 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Modified dose descriptor starting point:
other: no modification neccessary
AF for dose response relationship:
1
Justification:
GLP OECD guideline study
AF for differences in duration of exposure:
6
Justification:
default for subacute study
AF for interspecies differences (allometric scaling):
4
Justification:
default for scaling from rat to man
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
10
Justification:
default for general population
AF for the quality of the whole database:
1
Justification:
default
AF for remaining uncertainties:
1
Justification:
default
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population

see "Additional information - Workers"