1,3-Propanediaminium, N1-[3-[[2-[dimethyl[3-[(2-methyl-1-oxo-2-propen-1-yl)amino]propyl]ammonio]acetyl]amino]propyl]-2-hydroxy-N1,N1,N3,N3,N3-pentamethyl-, chloride (1:3)

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

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

DNEL related information

Local effects

Acute/short term exposure

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

40.33 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

600

Modified dose descriptor starting point:

NOAEL

Acute/short term exposure

Hazard assessment conclusion:

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

DNEL related information

Additional information - workers

Because the substance has a low acute toxicity hazard profile, and no classification for the acute oral and dermal routes, as well as no irritating effects to the skin and eyes, the following DNEL could not be derived:

- DNEL for acute/short-term - systemic effects

- DNEL for acute/short-term - local effects

There was no relevant data from the available studies to allow the derivation of an appropriate DNEL values for long-term exposure - local effects (dermal and inhalation routes). However, these potential effects are considered addressed by the long-term systemic assessment.

A 28-day repeated dose toxicity study by the oral route was available in rats, as well as a reproductive/developmental toxicity study. In both studies the NOAEL was at or above 1000 mg/kg bw/day (as expressed for the main constituent). The NOAEL determined in the 28 -day study was used to derive the DNEL for systemic effects for the dermal and the inhalation routes.

The NOAEL expressed for the substance as registered (i.e. including the residual water necessary to the stability, and impurities) is therefore 2420 mg/kg bw/day and is used as a starting point to derive DNEL for the risk assessment.

1) Dermal DNEL syst long-term :

Based on phys-chem properties (MW of 537 and logKow < -1.98), the default dermal absorption value of 10% is used.

ABS: absorption

Corrected Dermal NOAEL _syst = NOAEL_oral x [ABS_oral-rat/ABS_derm-hum] = 2420*[100/10]

Corrected Dermal NOAEL_syst = 24200 mg/kg bw/day

Assessment Factors:

Allometric scaling : 4

Interspecies : 2.5

Intraspecies : 5 (workers)

Duration : 6 (subacute to chronic)

Dose response : 1 (no adverse effects observed)

Quality of the database : 2 (an additional uncertainty factor is applied to take into account the incomplete data corresponding to Annex IX)

Total Assessment Factors, AF = 600

Dermal DNEL _{long-term/syst}= 40.33 mg/kg/day

2) Inhalation DNEL long-term syst:

Corrected NOAEL oral to NOAEC inhal.

Worker Respiratory Volume, Worker light activity – wRV = 10 m³for a 8-h work day.

Human SRV, standard Respiratory Volume: 6.7 m3 (8h)

Rat SRV, standard Respiratory Volume: 0.38 m³/kg

ABS: Absorption

Corrected Oral NOAEC =oral NOAEL * (1/ sRVrat) * (ABSoral rat / ABS inhal human) * (SRVhuman / wRV)

CorrectedOralNOAEC = 2420 * 1/0.38 * (1/1)* (6.7/10) = 4266.8 mg/m3

Assessment Factors:

Intraspecies: 5 (workers)

Duration: 6 (subacute to chronic)

Dose response: 1 (no adverse effects observed)

Quality of the database: 2 (an additional uncertainty factor is applied to take into account the omitted data corresponding to Annex IX requirements)

Total Assessment Factors, AF : 60

Inhalation DNEL_{long-term syst} = 71.1 mg/m3

For inhalation, the allometric scaling is included in the conversion to the inhalation NOAEC. No further assessment factors is applied for interspecies differences, as the absorption by the inhalation route is also expected to be limited due to the structure of the molecule, MW, logKow, and cationic charge that are not in favor of absorption across the respiratory tract epithelium, independently of the species.

In addition, Vapour pressure was determined for the substance including the residual water necessary for the stability. However, the estimate result is likely an overestimate because of the high water content, and the negligible contribution of the main Triquat constituent. Indeed, a QSAR estimate indicated a negligible vapour pressure of 8.86E-09 Pa for the main structure. Using the estimated vapour pressure for the registered substance therefore provides a very conservative exposure assessment. Thus, no further uncertainty factor was applied concurently to derive the inhalation DNEL.

For the inhalation exposure estimates in the external tool ART for workers, the exposure levels were expressed for the solid fraction [see Section 9 of the CSR]. In that case, a DNEL corrected for the solid content was used for the calculation of the RCR, i.e., 35.55 mg/m³.

Because the Triquat fraction has a low volatility and is dissolved in water [which is considered of non significant toxicity], the substance type “powders dissolved in a liquid” was selected to better assess the tasks with potential aerosol formation. In that case, the tool does not use the physico-chemical properties of the substance (i.e. the vapour pressure which is mainly related to that of water) but instead focuses on the activity types and their related potential aerosol formation. Thus, the air concentration estimates refer to the weight fraction of substance in the liquid matrix [45% for the product handled in the site]. These values have then to be compared to the DNEL for the corresponding fraction. To simplify the calculations, the DNEL was thus corrected for the solid fraction in the registered substance (50%), but the slight difference is not expected to affect significantly the conclusions.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

17.54 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

120

Modified dose descriptor starting point:

NOAEC

Acute/short term exposure

DNEL related information

Local effects

Acute/short term exposure

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Acute/short term exposure

DNEL related information

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

2.016 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

1 200

Modified dose descriptor starting point:

NOAEL

Acute/short term exposure

DNEL related information

Additional information - General Population

There is no expected exposure of the general population to the registered substance described in section 1.2. The monomer is only used as an intermediate in industrial setting, and is chemically transformed when used in polymer synthesis. Only traces amounts are expected to be present as an impurity in the end-products.

DNEL for the general population were derived for assessment of potential secondary exposure of the Human via the Environment.

A 28-day repeated dose toxicity study by the oral route was available in rats, as well as a reproductive/developmental toxicity study. In both studies the NOAEL was at or above 1000 mg/kg bw/day (as expressed for the main constituent).

The NOAEL determined in the 28 -day study and expressed for the substance as registered (i.e. including the residual water necessary to the stability, and impurities) is 2420 mg/kg bw/day and was the starting point to derive the DNEL for systemic effects via the oral and inhalation routes used in the risk assessment of the Human via the Environment.

1) Oral DNEL syst long-term :

No correction is made for the oral absorption differences between rat and human.

ABS: absorption

Corrected Oral NOAEL_syst= NOAEL_oralx [ABS_oral-rat/ABS_oral-hum] = 2420*[100/100]

Corrected Oral NOAEL_syst= 2420 mg/kg bw/day

Assessment Factors: Default AF from Guidance R8 Guidance document are used.

Allometric scaling : 4

Interspecies : 2.5

Intraspecies : 10 (general population)

Duration : 6 (subacute to chronic)

Dose response : 1 (no adverse effects observed)

Quality of the database : 2 (an additional uncertainty factor is applied to take into account the incomplete data corresponding to Annex IX)

Total AF = 1200

Oral DNEL_{long-term/syst}= 2.02 mg/kg

2) Inhalation DNEL long-term syst:

Corrected NOAEL oral to NOAEC inhal.

General population, 24 hours: 20 m³/person for a 24-h day.

Rat SRV, Standard Respiratory Volume: 1.15 m³/kg

ABS: absorption

Corrected Oral NOAEC =NOAEL_oral* (1 / sRVrat) * (ABS_{oral rat}/ABS_{inhal human}) = 2420 * (1 / 1.15) = 2104.34 mg/m3

Assessment Factors:

Intraspecies: 10 (general population)

Duration: 6 (subacute to chronic)

Dose response: 1 (no adverse effects observed)

Quality of the database: 2 (an additional uncertainty factor is applied to take into account the incomplete data corresponding to Annex IX)

Total Assessment Factors : 120

Inhalation DNEL_{long-term syst}= 17.54 mg/m3

 

For inhalation, the allometric scaling is included in the conversion to the inhalation NOAEC. No further assessment factors is applied for interspecies differences, as the absorption by the inhalation route is also expected to be limited due to the structure of the molecule, MW, logKow, and cationic charge that are not in favor of absorption across the respiratory tract epithelium, independently of the species.

In addition, Vapour pressure was determined for the substance including the residual water necessary for the stability. However, the estimate result is likely an overestimate because of the high water content, and the negligible contribution of the main Triquat constituent. Indeed, a QSAR estimate indicated a negligible vapour pressure of 8.86E-09 Pa for the main structure. Using the estimated vapour pressure for the registered substance therefore provides a very conservative exposure assessment. Thus, no further uncertainty factor was applied concurrently to derive the inhalation DNEL.