Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5.49 mg/m³
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
56.25
Dose descriptor starting point:
NOAEL
DNEL value:
125 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
308 mg/m³
Explanation for the modification of the dose descriptor starting point:

The dose descriptor starting point oral rat NOAEL of 125 mg/kg bw for toxicity to reproduction was converted into the inhalation NOAEC:

Inhalation NOAEC = oral NOAEL x (1/sRVrat) x (ABS oral-rat/ABS inhal-human) x (6.7 m³/10 m³) x (exposure of animals per week) = 125 mg/kg bw x (1/0.38 m³/kg/day) x (100%/100%) x (6.7/10) x (7/5) = 308.5 mg/m³

AF for dose response relationship:
1
Justification:
default (three doses were tested, using a spacing range of 2-4 fold)
AF for differences in duration of exposure:
4.5
Justification:
since it is a subacute-subchronic study (54 days)
AF for interspecies differences (allometric scaling):
1
Justification:
No allometric scaling should be applied in case of oral-to-inhalation extrapolation
AF for other interspecies differences:
2.5
Justification:
default; no substance and route specific information on toxicokinetic and toxicodynamic is available for animals and humans
AF for intraspecies differences:
5
Justification:
default for workers
AF for the quality of the whole database:
1
Justification:
default
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties are identified
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:
7.78 mg/kg bw/day
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
225
Dose descriptor starting point:
NOAEL
DNEL value:
125 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
1 750 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

For the oral rat NOAEL of 125 mg/kg bw derived for toxicity to reproduction the following conversion was necessary:

dermal NOAEL = oral NOAEL x (ABS oral-rat/ABS dermal-rat) x (ABS dermal-rat/ABS dermal-human) x (exposure of animals per week) = 125 x (100 %/10%) x (10 %/ 10 %) x (7/5) = 1750 mg/kg bw

AF for dose response relationship:
1
Justification:
default (three doses were tested, using a spacing range of 2-4 fold)
AF for differences in duration of exposure:
4.5
Justification:
since it is a subacute-suchronic study (54 days)
AF for interspecies differences (allometric scaling):
4
Justification:
default for rats
AF for other interspecies differences:
2.5
Justification:
default; no substance and route specific information on toxicokinetic and toxicodynamic is available for animals and humans
AF for intraspecies differences:
5
Justification:
default for workers
AF for the quality of the whole database:
1
Justification:
default
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties are identified
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:
no hazard identified

Additional information - workers

The calculation of the DNELs magnesium metaborate (CAS 13703 -82 -7) is performed in accordance with the principles given in ECHA (2012) “Guidance of Information Requirements and Chemical Safety Assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health.”

Available dose descriptors:

There are data available on dermal irritation (Warren, 2017; Sanders, 2016b)) and sensitisation (Richeux, 2018) as well as on acute oral and dermal toxicity (Sanders, 2016; Sanders, 2017) and a combined 28-Day Repeated Dose Oral (Gavage) Toxicity Study with the Reproduction/Developmental Toxicity Screening Test in Rats, with Recovery was assessed (Herberth, 2017) of the test item.

Acute/short-term exposure – systemic effects (dermal DNEL):

There are acute oral and dermal studies in rats and also dermal irritation studies in rabbits available for the test substance.

The results show that the substance is non-toxic by ingestion and by skin contact; no remarkable systemic toxicity is reported. Oral LD50 values LD50 > 2,000 mg/kg bw/day and dermal LD50 values LD50 > 2000 mg/kg bw/day were reported.

The DNEL for acute systemic effects by the dermal route is unnecessary since the long-term DNEL covers sufficiently the risk of short-term exposure, so no DNEL for acute systemic effects needs to be derived.

Acute/short-term exposure – systemic effects (inhalation DNEL):

No acute inhalation study is available for the substance. However, magnesium metaborate is not expected to pose an inhalation hazard due to its low vapour pressure (0.0365 Pa @ 25°). Therefore an acute exposure hazard via inhalation route is not relevant and no DNEL is derived. The long-term DNELs are sufficient to ensure that acute effects do not occur.

Acute/short-term exposure – local effects (dermal DNEL):

The substance magnesium metaborate is not irritating to the skin of rabbits after 24-hour application of test material. LD50 values above 2000 mg/kg bw were reported for the magnesium metaborate in the dermal studies. Thus, the short-term dermal DNEL needs not to be derived and is sufficiently covered by the long-term DNEL for systemic and local effects.

Acute/short-term exposure – local effects (inhalation DNEL):

The magnesium metaborate substance does not pose an airborne hazard, due to its low vapour pressure. The long-term inhalation DNEL for systemic effects covers sufficiently local effects.

Long-term exposure – systemic effects (dermal DNEL):

A Combined 28-Day Repeated Dose Oral (Gavage) Toxicity Study with the Reproduction/Developmental Toxicity Screening Test in Rats, with Recovery (Herberth, 2017) is available for the test substance. The long-term systemic DNEL for the dermal route has been derived from the NOAEL for toxicity to reproduction. A NOAEL of 125 mg/kg bw/day was established. The starting point for the DNEL derivation is the oral NOAEL (route-to-route extrapolation necessary).

Long-term exposure – systemic effects (inhalation DNEL):

There are no dose-response and route-specific information on repeated dose toxicity via inhalation. The substance does not pose a hazard for humans by the inhalation route of exposure. The inhalation DNEL can be derived from the oral NOAEL of 125 mg/kg bw established in the Combined 28-Day Repeated Dose Oral (Gavage) Toxicity Study with the Reproduction/Developmental Toxicity Screening Test in Rats, with Recovery, by route-to-route extrapolation.

Long-term exposure – local effects (dermal DNEL):

Magnesium metaborate is not expected to be irritating to the skin. Although the substance is a moderate skin sensitiser (1B), no quantitative assessment can be performed, because no reliable dose descriptor can be set for this endpoint and thus no NOAEL can be derived. A DNEL is therefore not quantifiable. Local effects are covered sufficiently by the long-term DNEL for systemic effects and via a qualitative approach to assessing and controlling the risk. Moderate skin sensitisers (classified in Sub-category 1B in CLP) are allocated to the moderate hazard category band on the basis that exposure to these moderate skin sensitising substances should be well-controlled.

Long-term exposure – local effects (inhalation DNEL):

No long-term inhalation DNEL for local effects is needed since magnesium metaborate is not expected to be irritating or sensitising to respiratory system. Local effects are covered sufficiently by the longterm DNEL for systemic effects.

For the other non-threshold endpoints (mutagenicity, eye and skin irritation/corrosion) no DNELs can be derived because no No-Observed-Effect-Level could be established from the relevant studies. However, any other than reproductive toxicity hazard does not exist as no classification of magnesium metaborate was necessary for another category.

 Modification of the starting point:

From all available data on the magnesium metaborate for the different human health endpoints, it is clear that the substance exerts its effects by a threshold mode of action. Thus, DNELs can be calculated for the different threshold endpoints based on the most relevant dose descriptors per endpoint. DNELs are derived based on the available toxicity data for the target reflecting the routes, the duration and the frequency of exposure. DNELs are derived for workers and the general population. The general population includes consumers and humans exposed via the environment.

Bioavailability (absorption):

Magnesium metaborate is expected to be moderately absorbed after oral exposure, based on its moderate water solubility and low molecular weight. As worst-case 100 % oral absorption is considered appropriate. Concerning absorption exposure via inhalation, the substance is poorly available for inhalation, due to its low vapour pressure. However, the low water solubility is favourable for penetration in the alveolar regions of the lung. Absorption, after dissolving in the mucus lining the respiratory tract (most probably in the form of boric acid) cannot be ruled out. Therefore, 100 % inhalation absorption is considered as worst-case. Magnesium metaborate can potentially be absorbed by the Stratum corneum. Partition into the deeper viable parts of the epidermis is unlikely due to the low water solubility. This was also demonstrated in a key study with rats, where no systemic absorption after dermal exposure was observed. 10 % absorption is considered. Magnesium metaborate occurs in the body most likely in the un-dissociated form as boric acid and magnesium ion. Boric acid and magnesium ion are not further metabolised. They are expected to be distributed widely with the blood circulation. Boric acid is suggested to accumulate in the bones. Magnesium and boric acid are excreted mainly via the kidneys as urine.

Oral absorption:

Borates and boric acid have similar absorption potentials (IPCS, 1998; WHO, 2009). Based on these findings, it is likely, that magnesium metaborate will dissociate in the acidic environment of the stomach to boric acid and magnesium ion. Due to the known toxicity of borates (EFSA 2013, WHO 1998 and others), the toxic effects of magnesium metaborate are expected to be mainly caused by the metaborate moiety, occurring as boric acid at physiological pH (HERA 2005). With a log P value of 0.175 (EVM, 2002) and a molecular weight of 62 g/mol the absorption route of boric acid is most likely via passive diffusion through aqueous pores of the gastrointestinal epithelial by the bulk passage of water. The absorption of borates has shown to be essentially complete (approximately 95% in humans and rats), and boron appears rapidly in the blood and body tissues of several mammalian species following ingestion (IPCS 1998Magnesium is absorbed from the gastrointestinal tract by the blood at an amount of about 50 % (WHO, 2009) via passive diffusion through aqueous pores of the gastrointestinal epithelial by the bulk passage of water.

Based on this information, the worst case absorption value of 100 % is considered appropriate for the purposes of hazard assessment for this compound.

Dermal absorption:

No significant dermal absorption is expected for the Magnesium metaborate , as outlined in the in vitro assay on dermal aborption (see toxicokinetic statement). The log Pow of 6.01, the water solubility of < 1 mg/L and the molecular weight of 702.5 g/mol point to a poor absorption through the skin. According to the TGD, Part I, Appendix IV, and ECHA guidance R.7C, 2014, 10% of dermal absorption can be considered in this case, since the criteria for molecular weight and Log Pow are met (MW above 500 g/mol and log Pow > 4). Moreover, a critical assessment of all available data (toxicity effects in the available studies and physicochemical properties) should be taken into account before using default assumptions (ECETOC, TR No. 110). The absorption after dermal exposure is generally more gradual and slower than oral absorption and a lower bioavailability is expected due to the presence of the absorption hindering outer skin layer stratum corneum and a comparatively smaller surface area. Schuhmacher et al. recommended that a low dermal penetration (< 10%) can be assumed for substances with a logPow value >5 or for substances with a Kp value <0.0001 (cm/h). (Schumacher et al., 2003). Hence a dermal absorption of 10% is assumed.

Dermal absorption in rats, rabbits and in humans is assumed to be the same since no information for dermal absorption of magnesium metaborate in humans is available.

 Reference:

1.      Schuhmacher-Wolz U., Kalberlach F., Oppl R., van Hemmen J.J. (2003).A toolkit for dermal risk assessment: toxicological approach for hazard characterization. Ann. Occup. Hyg., Vol 47 No.8, pp. 641 -652.

 Inhalation absorption

Absorption by inhalation is considered to be negligible (low vapour pressure of 0.0365 Pa at 25°C) and not to be higher than absorption by oral route. However, 100% absorption is assumed for inhalation route and considered to be equal in rats and in humans since no substance specific information is available and worst-case assumption should be made for route-to-route extrapolation according to ECHA guidance R.8, 2012.

Route-to-route extrapolation:

Oral-to-inhalation extrapolation is performed to obtain a long-term inhalation NOAEC for systemic effects. The following formula was used: corrected inhalatory NOAEC = oral NOAEL x (1/sRVrat) x (ABSoral-rat/ABSinh-human) x (6.7 m³/10 m³) where sRV is standard respiratory volume of rats during 8 hours (= 0.38 m³/kg/day); ABS-absorption and 6.7 m³ and 10 m³ are standard respiratory volumes for workers under normal conditions and by light activity.

Oral-to-dermal extrapolation is performed to obtain long-term dermal NOAEL for systemic effects. The following formula was used: corrected dermal NOAEL = oral NOAEL * (ABS oral-rat/ABS dermal-rat) * (ABS dermal-rat/ ABSs dermal-human), where ABS is absorption.

 Exposure conditions:

No modification of the starting points for exposure conditions was necessary since the systemic dose after oral administration of the test material was already assessed in respiratory volume taken for rats during 8 h (0.38m³).

Differences in the respiratory volumes between experimental animals and humans were used when an oral rat NOAEL from the subacute oral combined repeated dose toxicity study in rats was used to assess inhalation exposure in humans. 0.38 m³/kg/day is the standard respiratory volumes in rats during 8h exposure. 6.7 and 10 m³ are standard respiratory volumes for workers under normal conditions and by light activity, respectively.

Applying of assessment factors and calculation of DNELs:

The assessment factors have been applied to the corrected starting point to obtain the endpoint specific DNELs. Assessment factors (AFs) correct uncertainties and variability within and between species in the effect data.

Interspecies differences:

The species-specific default assessment factor of 4 for allometric scaling for rats was applied in the case of employment of the oral NOAEL from the subacute oral toxicity to reproduction study in rats , which was used to derive the dermal long-term DNEL.

No allometric scaling factor was applied when the oral NOAEL from the toxicity to reproduction screening study in rats was used for the derivation of inhalation long-term DNEL. An assessment factor of 2.5 was applied for remaining interspecies differences in toxicodynamics between rat and human in all cases.

Intraspecies differences:

An assessment factor of 5 was applied for workers for all endpoints and for all exposure routes.

Extrapolation of duration:

An assessment factor of 4.5 was applied for duration of exposure (subacute-subchronic study, 54 day duration).

Quality of whole data base:

An assessment factor of 1 was used since all data is obtained from guideline studies with the test item.

Issues related to dose response:

A default assessment factor of 1 was applied when the NOAEL from the subacute oral one-generation reproductive toxicity screening study was used.

Calculation of DNELs:

Long-term exposure – systemic effects (dermal DNEL):

For the oral rat NOAEL of 125 mg/kg bw the following conversion was necessary:

dermal NOAEL = oral NOAEL x (ABS oral-rat/ABS dermal-rat) x (ABS dermal-rat/ABS dermal-human) x (exposure of animals per week) = 125 x (100 %/10%) x (10 %/ 10 %) x (7/5) = 1750 mg/kg bw

DNEL = 1750 mg/kg bw/(4 x 2.5 x 5 x 4.5 x 1 x 1) = 7.78 mg/kg bw. Assessment factors are: 4 – interspecies, 2.5 – remaining interspecies differences, 5 – intraspecies, 4.5 – study duration (subacute-subchronic study), 1 – dose response, 1 – quality of data base. The total AF amounts to 225.

Long-term exposure – systemic effects (inhalation DNEL):

The dose descriptor starting point oral rat NOAEL of 125 mg/kg bw for toxicity to reproduction was converted into the inhalation NOAEC:

Inhalation NOAEC = oral NOAEL x (1/sRVrat) x (ABS oral-rat/ABS inhal-human) x (6.7 m³/10 m³) x (exposure of animals per week) = 125 mg/kg bw x (1/0.38 m³/kg/day) x (100%/100%) x (6.7/10) x (7/5) = 308.5 mg/m³

DNEL = 308.5 mg/m³/(2.5 x 5 x 4.5 x 1 x 1)= 5.49 mg/m³. Assessment factors are: 2.5 – remaining interspecies differences, 5 – intraspecies, 4.5 – study duration (subacute-subchronic study), 1 – dose response, 1 – quality of data base. The total AF amounts to 56.25.

Selected DNELs

DNEL systemic dermal = 7.78 mg/kg bw

DNEL systemic inhalation = 5.49 mg/m³

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.82 mg/m³
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
450
Dose descriptor starting point:
NOAEL
DNEL value:
125 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
92.59 mg/m³
Explanation for the modification of the dose descriptor starting point:

The oral NOAEL of 125 mg/kg bw was converted into the inhalation NOAEC:

Corrected inhalation NOAEC = oral rat NOAEL x (1/1.35 m³/kg bw/day) x (ABS oral-rat/ABS inhal-human), where 1.35 is the standard respiratory volume (m³/kg bw) of rats during 24 h exposure (according to Functionalities of IUCLID 6 DNEL calculator), ABS is absorption (values are the same as described for workers).

Corrected Inhalation NOAEC = 125 mg/kg bw x (1/1.35 m³/kg/day) x (100%/100%) = 92.59 mg/m³

AF for dose response relationship:
1
Justification:
default (three doses were tested, using a spacing range of 2-4 fold)
AF for differences in duration of exposure:
4.5
Justification:
since it is a subacute-subchronic study (54 days)
AF for interspecies differences (allometric scaling):
1
Justification:
No allometric scaling should be applied in case of oral-to-inhalation extrapolation
AF for other interspecies differences:
2.5
Justification:
default; no substance and route specific information on toxicokinetic and toxicodynamic is available for animals and humans
AF for intraspecies differences:
10
Justification:
default for general population
AF for the quality of the whole database:
1
Justification:
Good quality due to guideline studies with the test item
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties are identified
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:
0.278 mg/kg bw/day
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
450
Dose descriptor starting point:
NOAEL
DNEL value:
125 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
1 250 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

For the oral rat NOAEL of 125 mg/kg bw the following conversion was necessary:

dermal NOAEL = oral NOAEL x (ABS oral-rat/ABS dermal-rat) x (ABS dermal-rat/ABS dermal-human) = 1250 mg/kg bw

AF for dose response relationship:
1
Justification:
default (three doses were tested, using a spacing range of 2-4 fold)
AF for differences in duration of exposure:
4.5
Justification:
since it is a subacute-suchronic study (54 days)
AF for interspecies differences (allometric scaling):
4
Justification:
default factor for rats
AF for other interspecies differences:
2.5
Justification:
default; no substance and route specific information on toxicokinetic and toxicodynamic is available for animals and humans
AF for intraspecies differences:
10
Justification:
default for general population
AF for the quality of the whole database:
1
Justification:
since the data is obtained from guideline studies conducted with the test item
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties are identified
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:
DNEL (Derived No Effect Level)
Value:
0.28 mg/kg bw/day
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
450
Dose descriptor starting point:
NOAEL
DNEL value:
125 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
125 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Not applicable: oral study and oral exposure

AF for dose response relationship:
1
Justification:
(three doses were tested, using a spacing range of 2-5 fold)
AF for differences in duration of exposure:
4.5
Justification:
since it is a subacute-subchronic study (54 days)
AF for interspecies differences (allometric scaling):
4
Justification:
default for rats
AF for other interspecies differences:
2.5
Justification:
default; no substance and route specific information on toxicokinetic and toxicodynamic is available for animals and humans
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:
No remaining uncertainties are identified
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

The principles of the DNEL calculation for the general population are the same as already described for workers. However, there are additional considerations or deviations for:

Modification of the starting point:

Bioavailability (absorption):

The oral absorption in rats and in humans is assumed to be the same since no information for oral absorption for target chemical in rats and in humans is available.

Respiratory volumes:

Adaptions in the respiratory volumes under normal conditions and by light activity in humans were taken into account. A default respiratory volume of 1.35 m³/kg bw for rats (general poulation) was used to convert dermal NOAEL into inhalation NOAEC, referring to 24h exposure instead of 8h (worker).

Applying of assessment factors:

A higher assessment factor of 10 (in place of 5 for workers) for intraspecies variation/differences of human population was used.

Calculation of endpoint-specific DNELs for general population

Long-term exposure - systemic effects (oral):

The oral NOAEL of 125 mg/kg bw had not to be converted.

The oral NOAEL of 125 mg/kg bw was not modified for differences in absorption by oral route since no substance- and route specific information is available: Oral NOAEL rat = oral NOAEL human = 125 mg/kg bw.

DNEL = 125 mg/kg bw/(4 x 2.5 x 10 x 4.5 x 1 x 1) = 0.28 mg/kg bw. Assessment factors are: 4 – interspecies, 2.5 – remaining interspecies differences, 10 – intraspecies, 4.5 – study duration, 1 – dose response (clear dose response), 1 – quality of data base (default).The total AF amounts to 450.

Long-term exposure - systemic effects (dermal):

For the oral rat NOAEL of 125 mg/kg bw the following conversion was necessary:

dermal NOAEL = oral NOAEL x (ABS oral-rat/ABS dermal-rat) x (ABS dermal-rat/ABS dermal-human) = 1250 mg/kg bw

DNEL = 1250 mg/kg bw/(4 x 2.5 x 10 x 4.5 x 1 x 1)= 2.8 mg/kg bw. Assessment factors are: 4 – interspecies, 2.5 – remaining interspecies differences, 10 – intraspecies, 6 – study duration (subacute study), 1 – dose response, 2 – quality of data base. The total AF amounts to 450.

 Long-term exposure - systemic effects (inhalation):

The oral NOAEL of 125 mg/kg bw was converted into the inhalation NOAEC:

Corrected inhalation NOAEC = oral rat NOAEL x (1/1.35 m³/kg bw/day) x (ABS oral-rat/ABS inhal-human), where 1.35 is the standard respiratory volume (m³/kg bw) of rats during 24 h exposure (according to Functionalities of IUCLID 6 DNEL calculator), ABS is absorption (values are the same as described for workers).

Corrected Inhalation NOAEC = 125 mg/kg bw x (1/1.35 m³/kg/day) x (100%/100%) = 92.59 mg/m³

DNEL =92.59 mg/m³/(2.5 x 10 x 4.5 x 1 x 1) = 0.82 mg/m³. Assessment factors are: 2.5 – remaining interspecies differences, 10 – intraspecies, 4.5 – study duration, 1 – dose response (clear dose response), 1 – quality of data base (default). The total AF amounts to 112.5.

Selected DNELs

DNEL systemic oral = 0.28 mg/kg bw

DNEL systemic dermal = 2.8 mg/kg bw

DNEL systemic inhalation = 0.82 mg/m³