Benzoic acid, 2-([1,1'-biphenyl]-4-ylcarbonyl)-

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

short-term repeated dose toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

data waiving: supporting information

Reference

In the absence of experimental data on the test substance, the weight of evidence assessment according to according to REACH guidance document R7.C suggests that the test substance is likely to have a low to moderate absorption potential through oral and dermal routes and a moderate absorption potential through the inhalation route. Further, based on the predicted physico-chemical properties, the test substance as such is expected to have a low distribution and bioaccumulation potential with a less likelihood of excretion by urine. Metabolism prediction for the representative structure of the test substance using Meteor® Nexus from Lhasa,indicated glucuronidation (highest likelihood score), reduction of aromatic ketones or oxidation in para position as first metabolic reactionsleading to the formation of polar metabolites, which would eventually then be excreted via urine.

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

50

Absorption rate - dermal (%):

50

Absorption rate - inhalation (%):

100

There were no studies available in which the toxicokinetic properties of test substance were investigated. However, as per REACH guidance document R7.C (2014), information on absorption, distribution, metabolism and excretion may be deduced from the physicochemical properties and with the help of QSAR modelling and information from other toxicity studies.

 

ABSORPTION

Oral absorption

Based on physico-chemical properties

According to REACH guidance document R7.C, oral absorption is maximal for substances with molecular weights below 500. Water-soluble substances will readily dissolve into the gastrointestinal fluids. However, absorption of hydrophilic substances via passive diffusion may be limited by the rate at which the substance partitions out of the gastrointestinal fluid. Absorption by passive diffusion is higher at moderate log Kow values (between -1 and 4). However, the varying pH of the gastro-intestinal tract can influence the extent of absorption of ionic substances, as they are typically not readily diffused across biological membranes. For these substances, the determination of their pKa values (pH at which 50% of the substance is in ionized and 50% in non-ionised form) can be advantageous, as absorption of acids is favoured at pHs below their pKa whereas absorption of bases is favoured at pHs above their pKa. The usual pH range of stomach of human’s ranges between 1.6 to 4.5 and that of small intestine ranges from 5 to 8 (ECHA, 2017).

 

The test substance is a mono-constituent with a molecular weight (MW) of 302.33 g/mol. It is an off-white fine powder with a low water solubility value of 13.5 mg/L and a moderate partition coefficient of 1.78. Given the presence of the ionic/acidic group, the pKa value of the test substance was predicted to be 3.47 using Chemicalize (ChemAxon, 2019).

 

Based on the low molecular weight (less than 500), low water solubility and moderate lipophilicity, the test substance is likely to have a low to moderate absorption potential. Further given its ionic nature with a pKa value of 3.47, the test substance it is likely to be absorbed from stomach (as its pH (1.4) < pKa; Tracy, 2004), where the absorption will be relatively lesser compared to small intestine due to influence of gastric emptying and lesser absorptive surface area. Therefore, based on the R7.C indicative criteria, the oral uptake of the test substance is overall considered to be low to moderate.

 

Based on QSAR prediction:

 

The “Lipinski’s rule OASIS”profiler of the OECD QSAR Toolbox v.4.3.1, which describes the molecular properties important for a drug's pharmacokinetics in the human body, including their absorption, distribution, metabolism, and excretion ("ADME"), predicted the test substance to be‘bioavailable’.

 

Based on ‘other toxicity’studies:

According to REACH guidance document R7.C (ECHA, 2017),other toxicity studies can be helpful to get information on occurrence of absorption without any specification of the extent or amount. For example:if signs of systemic toxicity are present in acute or repeated dose studies, then absorption has occurred.Also colored urine and/or internal organs can provide evidence that a colored substance has been absorbed.

A OECD 422 repeated dose and reproductive/development toxicity screening study available a the structural analogue, showed signs of systemic toxicity at doses >300 mg/kg bw/day, suggesting a likelihood of absorption to a certain extent (ECHA REACH dossier, 2019).

Conclusion:Overall, given the absorption potential via stomach based on its pKa value together with the other available weight of evidence suggests that the test substancecan be expected to have a low to moderate absorption potential. Therefore, amaximum of 50% oral absorption has been considered for a conservative risk assessment.

 

Dermal absorption

Based on physico-chemical properties

According to REACH guidance document R7.C (ECHA, 2017), dermal absorption is maximal for substances having MW below 100 together with log Kow values ranging between 2 and 3 and water solubility in the range of 100-10,000 mg/L. Substances with MW above 500 are considered to be too large to penetrate skin. Further, dermal uptake is likely to be low for substances with log P values <0 or <-1, as they are not likely to be sufficiently lipophilic to cross the stratum corneum (SC). Similarly, substances with water solubility below 1 mg/L are also likely to have low dermal uptake, as the substances must be sufficiently soluble in water to partition from the SC into the epidermis.

The test substance is an off-white fine powder, with a MW exceeding 100 g/mol, low water solubility (<100 mg/L) and an experimental log Kow of <2. This together with its ionization potential (due to skin pH: 4.0 to 7.0 (Lambers et al., 2006) being > pKa;) suggests that the test substance is likely to have a low penetration potential through the skin.

 

Based on QSAR prediction:

The two well-known parameters often used to characterise percutaneous penetration potential of substances are the dermal permeability coefficient (Kp[1]) and maximum flux (Jmax). Kp reflects the speed with which a chemical penetrates acrossstratum corneum (SC) and Jmax represents the rate of penetration at steady state of an amount of permeant after application over a given area of SC. Out of the two, although Kp is more widely used in percutaneous absorption studies as a measure of solute penetration into the skin. However, it is not a practical parameter because for a given solute, the value of Kp depends on the vehicle used to deliver the solute. Hence, Jmax i.e., the flux attained at the solubility of the solute in the vehicle is considered as the more useful parameter to assess dermal penetration potential as it is vehicle independent (Robert and Walters, 2007).

In the absence of experimental data, Jmax can be calculated by multiplying the experimental water solubility with the estimated Kp values from DERMWIN v2.01 application of EPI Suite^TMv4.11. Considering an estimated Kp value of 4.8E-4 cm/h EPI Suite^TMand water solubility of 13.5 mg/L, the Jmax was calculated to be 2.3E-7. As per Shen et al. 2014, the default dermal absorption for substance with Jmax is ≤0.1 μg/cm2/h is less than 10%. Based on these calculations, the test substance is overall predicted to have a low absorption potential via the dermal exposure route.

Based on 'other toxicity' studies:

According to REACH guidance document R7.C (ECHA, 2017),a test substance with skin irritant or corrosive potential may enhance penetration due to the damage to the skin surface. Also, if the substance is a skin sensitizer then, provided the challenge application was to intact skin, some uptake must have occurred although it may only have been a small fraction of the applied dose. Likewise, presence of signs of systemic toxicity in dermal toxicity studies indicate that absorption must have occurred. However, if steps have not been taken to prevent grooming, the substance may have been ingested and therefore signs of systemic toxicity could be due to oral rather than dermal absorption.

The absence of skin irritation, sensitization responses and clinical signs in acute dermal toxicity study and local lymph node assay available with the test substance, suggests a low likelihood of absorption through skin.

Conclusion:Overall, given the ionization potential of the test substance at the usual skin pH together with the other available weight of evidence suggests that the test substance is likely to havea low to penetration or absorption potential via skin. Nevertheless, amaximum of 50% dermal absorption (same as oral route) has been considered for a conservative risk assessment.

Inhalation absorption

Based on physico-chemical properties

According to REACH guidance document R7.C, inhalation absorption is maximal for substances with VP >25 KPa, particle size (<100 μm), low water solubility and moderate log Kow values (between -1 and 4). Very hydrophilic substances may be retained within the mucus and not be available for absorption.

Specifically, for substances which are solids particulates/powders, the quantitative deposition pattern of particles in the respiratory tract varies with the particle size distribution of the inspired aerosol and may further depend on physical and physico-chemical properties of the particles (e.g. shape, electrostatic charge). Particles with aerodynamic diameters below 50 μm may reach the thoracic region and those below 15 μm the alveolar region of the respiratory tract.

The test substance is fine off-white powder with particle size distribution ranging from 3.78 to 26.673 µm (i.e., D10 = 3.778 µm, D50 = 11.618 µm and D90 = 26.673 µm). Therefore, considering the particle size distribution the test substance will be highly inhalable in its powder form and most likely deposited in the thoracic as well as alveolar regions leading to maximal absorption potential.However, given the acidic pKa value and the higher bronchial (5.7 – 6.6; Fischer and Widdicombe, 2006) as well as blood pH (7.4; Tracy, 2004), the test substance is expected to be ionized, leading to low partitioning potential across the respiratory tract epithelium by passive diffusion. Therefore, absorption of the deposited material thereafter is expected to be similar to the oral route/gastro-intestinal tract.

Based on 'other toxicity' studies

According to REACH guidance document R7.C (ECHA, 2017), if signs of systemic toxicity are present in an oral toxicity study or there are other data to indicate the potential for absorption following ingestion it is likely the substance will also be absorbed if it is inhaled.

No inhalation studies were available with the test substance or its structural analogue. However, the presence of signs of systemic effects in the OECD 422 screening study conducted with a structural analogue, suggests a likelihood of absorption to a certain extent also through the inhalation route.

Conclusion: Overall, given the ionization potential of the test in the respiratory tract together with the other available weight of evidence suggests that the test substance is likely to havea moderate inhalation absorption potential at the maximum. Nevertheless,a default value of 100% inhalation absorption has been considered for a conservative risk assessment.

 

METABOLISM:

Based on QSAR modelling:

The predicted metabolism of the test substance was evaluated using Meteor® Nexus from Lhasa (Judson, 2015).

According to this tool, the test substance was predicted to undergo either glucuronidation (Metabolite 1; highest likelihood score), reduction of aromatic ketones (Metabolite 2) or oxidation in para position (Metabolite 3) as first metabolic reactions (seeFigure 1). The metabolite 2, resulting from the reaction of reduction is then expected to undergo either glucuronidation (Metabolite 4 with the highest likelihood score and Metabolite 6), or lactonization (Metabolite 5). The Metabolite 3 is predicted to undergo glucuronidation. While for the reactions of glucuronidation, reduction and oxidation, the similarity for the nearest neighbours is within acceptable ranges, this value is very low for the reaction of lactonization; therefore, this reaction has not been considered to occur for the target substance. For further details, refer to the read across justification.

Figure 1:Prediction diagram (Refer to the CSR)

Based on 'other toxicity' studies:

The results of acute toxicity or mutagenicity study with the test substance or the OECD 422 screening study with the structural analogue, suggest that no toxic metabolites are likely to be formed when the constituents of test substance are broken down.

DISTRIBUTION:

According to REACH guidance document R7.C (ECHA, 2017), the smaller the molecule, the wider the distribution. Small water-soluble molecules and ions will diffuse through aqueous channels and pores, although the rate of diffusion for very hydrophilic molecules will be limited. Further, if the molecule is lipophilic (log P >0), it is likely to distribute into cells and the intracellular concentration may be higher than extracellular concentration particularly in fatty tissues. Identification of the target organs in repeated dose studies are also indicative of the extent of distribution.

Given the pKa value and the blood pH (7.4; Tracy TS, 2004), the test substance is expected to be ionised, following absorption from the stomach region. Hence, the test substance is not likely to readily partition across the blood membranes into the different organs, leading to an overall low distribution potential. This is supported by the presence of only non-adverse adaptive effects in the kidneys (tubular vacuolation) and liver (hypertrophy, increased liver weights) without any histopathological correlations in the OECD 422 study in rats. Moreover, even if the test substance distributes to a certain extent, it is not expected to bioaccumulate based on the estimated BCF value of 3.16 L/kg wet-wt, generated for the test substance using ionic BCF regression-based equation from BCFBAF v. 3.02 program of EPISuite^TM.

EXCRETION:

According to REACH guidance document R7.C (ECHA, 2017), the characteristics favourable for urinary excretion are low molecular weight (below 300 in the rat), good water solubility, and ionization of the molecule at the pH of urine (4.5 to 8).

Given the low water solubility, MW just exceeding 300 g/mol together with the pKa value, which suggests that the test substance will be ionised in the small intestine, blood as well as in the urine, the test substance is expected to be primarily excreted via faeces. Nevertheless, there will be some urinary elimination following formation of water-soluble conjugates via Phase II reactions.

 

 

REFERENCES:

ECHA REACH dossier on read across substance (accessed in October 2019)

Chemicalize was used for prediction of Pka properties, August 2019,https://chemicalize.com/developed by ChemAxon (http://www.chemaxon.com).

Judson, P. N.,Long, A.,Murray, E., Patel, M. 2015. Assessing Confidence in Predictions Using Veracity and Utility – A Case Study on the Prediction of Mammalian Metabolism by Meteor Nexus. Molecular Informatics, 34, 284-291.

Lamber et al, 2006. Natural skin surface pH is on average below 5, which is beneficial for its resident flora.Int J Cosmet Sci. 2006 Oct;28(5):359-70.

Fischer and Widdicombe, 2006. Mechanisms of acid and base secretion by the airway epithelium. J Membr Biol. 2006; 211(3): 139–150.

Tracy TS, 2004. Drug absorption and distribution. Modern Pharmacology with Clinical Applications. 6^thedition. Lippincott Williams and Wilkings, Philadelphia PA, USA (2004): 20-47.

[1]Log Kp = -2.80 + 0.66 log kow – 0.0056 MW

Cross-reference 2

Reason / purpose for cross-reference:

data waiving: supporting information

Reference

Registration/ Notification status for the use:

use registered according to REACH Article 10; total tonnage manufactured/imported >=10tonnes/year per registrant

Use name:

Industrial use as a monomer in the production of polymeric resins

Name of activity / technique:

Industrial use as a monomer in the production of polymer

Environmental release category (ERC):

ERC6c: Use of monomer in polymerisation processes at industrial site (inclusion or not into/onto article)

Name of activity / technique:

Closed process without likelihood of exposure or processes with equivalent containment conditions

Process category (PROC):

PROC 1: Chemical production or refinery in closed process without likelihood of exposure or processes with equivalent containment conditions

Name of activity / technique:

Closed continuous process with occasional controlled exposure or processes with equivalent containment conditions

Process category (PROC):

PROC 2: Chemical production or refinery in closed continuous process with occasional controlled exposure or processes with equivalent containment conditions

Name of activity / technique:

Closed batch processes with occasional controlled exposure or processes with equivalent containment condition

Process category (PROC):

PROC 3: Manufacture or formulation in the chemical industry in closed batch processes with occasional controlled exposure or processes with equivalent containment conditions

Name of activity / technique:

Production process where opportunity for exposure arises

Process category (PROC):

PROC 4: Chemical production where opportunity for exposure arises

Name of activity / technique:

Mixing and blending in batch processes

Process category (PROC):

PROC 5: Mixing or blending in batch processes

Name of activity / technique:

Transfer of substance or mixture (charging and discharging) at dedicated facilities

Process category (PROC):

PROC 8b: Transfer of substance or mixture (charging and discharging) at dedicated facilities

Name of activity / technique:

Transfer of substance into small containers using dedicated filling line

Process category (PROC):

PROC 9: Transfer of substance or mixture into small containers (dedicated filling line, including weighing)

Name of activity / technique:

Sampling and analysis of in-process samples

Process category (PROC):

PROC 15: Use as laboratory reagent

Sector of end use:

SU 9: Manufacture of fine chemicals

Substance supplied to that use in form of:

as such

Subsequent service life relevant for this use:

no

Related assessment:

use assessed in an own CSR

Linked contributing activity:

30d4b62e-4a4f-4ada-92ac-56bcfe642cfd

Technical and organisational conditions and measures not related to biological sewage treatment:

On-site waste water treatment

Effectiveness (%):

98

Route affected:

water

Technical and organisational conditions and measures not related to biological sewage treatment:

On-site treatment of off-air: Incineration / thermal oxidation

Effectiveness (%):

100

Route affected:

air

Biological Sewage Treatment Plant (STP):

no

Particular considerations on the waste treatment operations:

no

Receiving surface water flow rate (m³/day):

290 000

Other conditions of use impacting on environmental exposure:

Discharge rate of effluent: >= 794.5 m3/day

Release from the site to::

surface water

Release estimation method:

estimated release factor

Remarks:

Site-specific information

Release factor from the site after on-site risk management (%):

0

Release from the site to::

ambient air

Release estimation method:

ERC

Release factor from the site after on-site risk management (%):

0

Release from the site to::

non-agricultural soil

Release estimation method:

estimated release factor

Remarks:

Site-specific information

Release factor from the site after on-site risk management (%):

0

Exposed compartment:

freshwater

Clocal:

0 mg/L

Predicted exposure concentration:

0 mg/L

Exposure estimation method:

exposure estimation tool

Exposure estimation tool name:

EUSES

Version of exposure estimation tool:

2.1.2

Exposed compartment:

sediment (freshwater)

Predicted exposure concentration:

0 mg/kg dw

Exposure estimation method:

exposure estimation tool

Exposure estimation tool name:

EUSES

Version of exposure estimation tool:

2.1.2

Exposed compartment:

marine water

Clocal:

0 mg/L

Predicted exposure concentration:

0 mg/L

Exposure estimation method:

exposure estimation tool

Exposure estimation tool name:

EUSES

Version of exposure estimation tool:

2.1.2

Exposed compartment:

sediment (marine water)

Predicted exposure concentration:

0 mg/kg dw

Exposure estimation method:

exposure estimation tool

Exposure estimation tool name:

EUSES

Version of exposure estimation tool:

2.1.2

Exposed compartment:

sewage treatment plant

Predicted exposure concentration:

0 mg/L

Exposure estimation method:

exposure estimation tool

Exposure estimation tool name:

EUSES

Version of exposure estimation tool:

2.1.2

Exposed compartment:

air

Clocal:

0 mg/m³

Predicted exposure concentration:

0 mg/m³

Exposure estimation method:

exposure estimation tool

Exposure estimation tool name:

EUSES

Version of exposure estimation tool:

2.1.2

Exposed compartment:

agricultural soil

Clocal:

0 mg/kg dw

Predicted exposure concentration:

0 mg/kg dw

Exposure estimation method:

exposure estimation tool

Exposure estimation tool name:

EUSES

Version of exposure estimation tool:

2.1.2

Exposed compartment:

predators' prey (freshwater)

Predicted exposure concentration:

0 mg/kg ww

Exposure estimation method:

exposure estimation tool

Exposure estimation tool name:

EUSES

Version of exposure estimation tool:

2.1.2

Exposed compartment:

predators' prey (marine water)

Predicted exposure concentration:

0 mg/kg ww

Exposure estimation method:

exposure estimation tool

Exposure estimation tool name:

EUSES

Version of exposure estimation tool:

2.1.2

Exposed compartment:

top predators' prey (marine water)

Predicted exposure concentration:

0 mg/kg ww

Exposure estimation method:

exposure estimation tool

Exposure estimation tool name:

EUSES

Version of exposure estimation tool:

2.1.2

Exposed compartment:

predators' prey (terrestrial)

Predicted exposure concentration:

0 mg/kg ww

Exposure estimation method:

exposure estimation tool

Exposure estimation tool name:

EUSES

Version of exposure estimation tool:

2.1.2

Daily intake via food consumption:

0 mg/kg bw/day

Exposure estimation method:

exposure estimation tool

Exposure estimation tool name:

EUSES

Version of exposure estimation tool:

2.1.2

Linked contributing activity:

b1f6fe98-b892-475e-abbb-d8ea15fa40b0

Percentage (w/w) of substance in mixture/article:

100

Physical form of the used product:

solid (material with medium dustiness)

Duration of activity (hour/day):

4

Technical and organisational conditions and measures:

General ventilation: Good general ventilation (3-5 air changes per hour)

Effectiveness (%):

30

Route affected:

inhalation

Technical and organisational conditions and measures:

Occupational Health and Safety Management System: Advanced

Technical and organisational conditions and measures:

Local exhaust ventilation: No

Effectiveness (%):

0

Route affected:

inhalation

Effectiveness (%):

0

Route affected:

dermal

Personal protection equipment:

Respiratory protection: No

Effectiveness (%):

0

Route affected:

inhalation

Personal protection equipment:

Dermal protection: Yes (Chemically resistant gloves conforming to EN374 with specific activity training) and (other) appropriate dermal protection

Effectiveness (%):

95

Route affected:

dermal

Place of use:

indoor

Operating temperature (°C):

40

Type of exposure:

inhalation (external) long-term exposure

Exposure estimate:

0.004 mg/m³

Exposure estimation method:

exposure estimation tool

Exposure estimation tool name:

ECETOC TRA workers

Version of exposure estimation tool:

3.0

Type of exposure:

inhalation (external) short-term exposure

Exposure estimate:

0.028 mg/m³

Exposure estimation method:

exposure estimation tool

Exposure estimation tool name:

ECETOC TRA workers

Version of exposure estimation tool:

3.0

Type of exposure:

dermal (external) long-term exposure

Exposure estimate:

0.002 mg/kg bw/day

Exposure estimation method:

exposure estimation tool

Exposure estimation tool name:

ECETOC TRA workers

Version of exposure estimation tool:

3.0

Type of exposure:

dermal (external) local concentration on skin

Exposure estimate:

0 mg/cm²

Exposure estimation method:

exposure estimation tool

Exposure estimation tool name:

ECETOC TRA workers

Version of exposure estimation tool:

3.0

Linked contributing activity:

346d5594-e7cb-44d2-8f5d-4f4097dfdd46

Percentage (w/w) of substance in mixture/article:

100

Physical form of the used product:

solid (material with medium dustiness)

Duration of activity (hour/day):

4

Technical and organisational conditions and measures:

Occupational Health and Safety Management System: Advanced

Technical and organisational conditions and measures:

General ventilation: Good general ventilation (3-5 air changes per hour)

Effectiveness (%):

30

Route affected:

inhalation

Technical and organisational conditions and measures:

Local exhaust ventilation: No

Effectiveness (%):

0

Route affected:

inhalation

Effectiveness (%):

0

Route affected:

dermal

Personal protection equipment:

Respiratory protection: Yes (Respirator with APF of 10)

Effectiveness (%):

90

Route affected:

inhalation

Personal protection equipment:

Dermal protection: Yes (Chemically resistant gloves conforming to EN374 with specific activity training) and (other) appropriate dermal protection

Effectiveness (%):

95

Route affected:

dermal

Place of use:

indoor

Operating temperature (°C):

40

Type of exposure:

inhalation (external) long-term exposure

Exposure estimate:

0.021 mg/m³

Exposure estimation method:

exposure estimation tool

Exposure estimation tool name:

ECETOC TRA workers

Version of exposure estimation tool:

3.0

Type of exposure:

inhalation (external) short-term exposure

Exposure estimate:

0.043 mg/m³

Exposure estimation method:

exposure estimation tool

Exposure estimation tool name:

ECETOC TRA workers

Version of exposure estimation tool:

3.0

Type of exposure:

dermal (external) long-term exposure

Exposure estimate:

0.069 mg/kg bw/day

Exposure estimation method:

exposure estimation tool

Exposure estimation tool name:

ECETOC TRA workers

Version of exposure estimation tool:

3.0

Type of exposure:

dermal (external) local concentration on skin

Exposure estimate:

0.01 mg/cm²

Exposure estimation method:

exposure estimation tool

Exposure estimation tool name:

ECETOC TRA workers

Version of exposure estimation tool:

3.0

Linked contributing activity:

0aa891b0-dcbb-4af9-9f61-e10191710b5c

Percentage (w/w) of substance in mixture/article:

100

Physical form of the used product:

solid (material with medium dustiness)

Duration of activity (hour/day):

4

Technical and organisational conditions and measures:

Occupational Health and Safety Management System: Advanced

Technical and organisational conditions and measures:

General ventilation: Good general ventilation (3-5 air changes per hour)

Effectiveness (%):

30

Route affected:

inhalation

Technical and organisational conditions and measures:

Local exhaust ventilation: No

Effectiveness (%):

0

Route affected:

inhalation

Effectiveness (%):

0

Route affected:

dermal

Personal protection equipment:

Dermal protection: Yes (Chemically resistant gloves conforming to EN374 with specific activity training) and (other) appropriate dermal protection

Effectiveness (%):

95

Route affected:

dermal

Personal protection equipment:

Respiratory protection: Yes (Respirator with APF of 10)

Effectiveness (%):

90

Route affected:

inhalation

Place of use:

indoor

Operating temperature (°C):

40

Type of exposure:

inhalation (external) long-term exposure

Exposure estimate:

0.042 mg/m³

Exposure estimation method:

exposure estimation tool

Exposure estimation tool name:

ECETOC TRA workers

Version of exposure estimation tool:

3.0

Type of exposure:

inhalation (external) short-term exposure

Exposure estimate:

0.043 mg/m³

Exposure estimation method:

exposure estimation tool

Exposure estimation tool name:

ECETOC TRA workers

Version of exposure estimation tool:

3.0

Type of exposure:

dermal (external) long-term exposure

Exposure estimate:

0.034 mg/kg bw/day

Exposure estimation method:

exposure estimation tool

Exposure estimation tool name:

ECETOC TRA workers

Version of exposure estimation tool:

3.0

Type of exposure:

dermal (external) local concentration on skin

Exposure estimate:

0.01 mg/cm²

Exposure estimation method:

exposure estimation tool

Exposure estimation tool name:

ECETOC TRA workers

Version of exposure estimation tool:

3.0

Linked contributing activity:

5e27b9dd-1b34-4883-a505-d180df2fd630

Percentage (w/w) of substance in mixture/article:

100

Physical form of the used product:

solid (material with medium dustiness)

Duration of activity (hour/day):

4

Technical and organisational conditions and measures:

General ventilation: Good general ventilation (3-5 air changes per hour)

Effectiveness (%):

30

Route affected:

inhalation

Technical and organisational conditions and measures:

Occupational Health and Safety Management System: Advanced

Technical and organisational conditions and measures:

Local exhaust ventilation: No

Effectiveness (%):

0

Route affected:

inhalation

Effectiveness (%):

0

Route affected:

dermal

Personal protection equipment:

Respiratory protection: Yes (Respirator with APF of 10)

Effectiveness (%):

90

Route affected:

inhalation

Personal protection equipment:

Dermal protection with 98% efficiency: 98

Place of use:

indoor

Operating temperature (°C):

40

Type of exposure:

inhalation (external) long-term exposure

Exposure estimate:

0.043 mg/m³

Exposure estimation method:

exposure estimation tool

Exposure estimation tool name:

ECETOC TRA workers

Version of exposure estimation tool:

3.0

Type of exposure:

inhalation (external) short-term exposure

Exposure estimate:

0.043 mg/m³

Exposure estimation method:

exposure estimation tool

Exposure estimation tool name:

ECETOC TRA workers

Version of exposure estimation tool:

3.0

Type of exposure:

dermal (external) long-term exposure

Exposure estimate:

0.137 mg/kg bw/day

Exposure estimation method:

exposure estimation tool

Exposure estimation tool name:

other: Modified TRA worker

Version of exposure estimation tool:

3.0

Linked contributing activity:

ed810037-1e28-4018-b755-683b13452823

Percentage (w/w) of substance in mixture/article:

35

Physical form of the used product:

solid (material with medium dustiness)

Duration of activity (hour/day):

4

Technical and organisational conditions and measures:

General ventilation: Good general ventilation (3-5 air changes per hour)

Effectiveness (%):

30

Route affected:

inhalation

Technical and organisational conditions and measures:

Occupational Health and Safety Management System: Advanced

Technical and organisational conditions and measures:

Local exhaust ventilation: No

Effectiveness (%):

0

Route affected:

inhalation

Effectiveness (%):

0

Route affected:

dermal

Personal protection equipment:

Respiratory protection: Yes (Respirator with APF of 10)

Effectiveness (%):

90

Route affected:

inhalation

Personal protection equipment:

Dermal protection with 98% efficiency: 98

Place of use:

indoor

Operating temperature (°C):

40

Type of exposure:

inhalation (external) long-term exposure

Exposure estimate:

0.043 mg/m³

Exposure estimation method:

exposure estimation tool

Exposure estimation tool name:

ECETOC TRA workers

Version of exposure estimation tool:

3.0

Type of exposure:

inhalation (external) short-term exposure

Exposure estimate:

0.043 mg/m³

Exposure estimation method:

exposure estimation tool

Exposure estimation tool name:

ECETOC TRA workers

Version of exposure estimation tool:

3.0

Type of exposure:

dermal (external) long-term exposure

Exposure estimate:

0.274 mg/kg bw/day

Exposure estimation method:

exposure estimation tool

Exposure estimation tool name:

other: Modified TRA worker

Version of exposure estimation tool:

3.0

Linked contributing activity:

154fe9fc-5c6f-4796-a591-a2644f0e877e

Percentage (w/w) of substance in mixture/article:

100

Physical form of the used product:

solid (material with medium dustiness)

Duration of activity (hour/day):

4

Technical and organisational conditions and measures:

General ventilation: Good general ventilation (3-5 air changes per hour)

Effectiveness (%):

30

Route affected:

inhalation

Technical and organisational conditions and measures:

Occupational Health and Safety Management System: Advanced

Technical and organisational conditions and measures:

Local exhaust ventilation: No

Effectiveness (%):

0

Route affected:

inhalation

Effectiveness (%):

0

Route affected:

dermal

Personal protection equipment:

Respiratory protection: Yes (Respirator with APF of 10)

Effectiveness (%):

90

Route affected:

inhalation

Personal protection equipment:

Dermal protection with 98% efficiency: 98

Place of use:

indoor

Operating temperature (°C):

40

Type of exposure:

inhalation (external) long-term exposure

Exposure estimate:

0.042 mg/m³

Exposure estimation method:

exposure estimation tool

Exposure estimation tool name:

ECETOC TRA workers

Version of exposure estimation tool:

3.0

Type of exposure:

inhalation (external) short-term exposure

Exposure estimate:

0.043 mg/m³

Exposure estimation method:

exposure estimation tool

Exposure estimation tool name:

ECETOC TRA workers

Version of exposure estimation tool:

3.0

Type of exposure:

dermal (external) long-term exposure

Exposure estimate:

0.274 mg/kg bw/day

Exposure estimation method:

exposure estimation tool

Exposure estimation tool name:

other: Modified TRA worker

Version of exposure estimation tool:

3.0

Linked contributing activity:

de819974-69a7-4a47-a803-20a37045c9af

Percentage (w/w) of substance in mixture/article:

100

Physical form of the used product:

solid (material with medium dustiness)

Duration of activity (hour/day):

0.25

Technical and organisational conditions and measures:

Occupational Health and Safety Management System: Advanced

Technical and organisational conditions and measures:

General ventilation: Good general ventilation (3-5 air changes per hour)

Effectiveness (%):

30

Route affected:

inhalation

Technical and organisational conditions and measures:

Local exhaust ventilation: No

Effectiveness (%):

0

Route affected:

inhalation

Effectiveness (%):

0

Route affected:

dermal

Personal protection equipment:

Respiratory protection: Yes (Respirator with APF of 10)

Effectiveness (%):

90

Route affected:

inhalation

Personal protection equipment:

Dermal protection with 98% efficiency: 98

Place of use:

indoor

Operating temperature (°C):

40

Type of exposure:

inhalation (external) long-term exposure

Exposure estimate:

0.035 mg/m³

Exposure estimation method:

exposure estimation tool

Exposure estimation tool name:

ECETOC TRA workers

Version of exposure estimation tool:

3.0

Type of exposure:

inhalation (external) short-term exposure

Exposure estimate:

0.043 mg/m³

Exposure estimation method:

exposure estimation tool

Exposure estimation tool name:

ECETOC TRA workers

Version of exposure estimation tool:

3.0

Type of exposure:

dermal (external) long-term exposure

Exposure estimate:

0.137 mg/kg bw/day

Exposure estimation method:

exposure estimation tool

Exposure estimation tool name:

other: Modified TRA worker

Version of exposure estimation tool:

3.0

Linked contributing activity:

107335c6-85cd-499e-b8bf-c5f244113a34

Percentage (w/w) of substance in mixture/article:

100

Physical form of the used product:

solid (material with medium dustiness)

Duration of activity (hour/day):

0.25

Technical and organisational conditions and measures:

General ventilation: Good general ventilation (3-5 air changes per hour)

Effectiveness (%):

30

Route affected:

inhalation

Technical and organisational conditions and measures:

Occupational Health and Safety Management System: Advanced

Technical and organisational conditions and measures:

Local exhaust ventilation: No

Effectiveness (%):

0

Route affected:

inhalation

Effectiveness (%):

0

Route affected:

dermal

Personal protection equipment:

Respiratory protection: Yes (Respirator with APF of 10)

Effectiveness (%):

90

Route affected:

inhalation

Personal protection equipment:

Dermal protection: Yes (Chemically resistant gloves conforming to EN374 with specific activity training) and (other) appropriate dermal protection

Effectiveness (%):

95

Route affected:

dermal

Place of use:

indoor

Operating temperature (°C):

40

Type of exposure:

inhalation (external) long-term exposure

Exposure estimate:

0.004 mg/m³

Exposure estimation method:

exposure estimation tool

Exposure estimation tool name:

ECETOC TRA workers

Version of exposure estimation tool:

3.0

Type of exposure:

inhalation (external) short-term exposure

Exposure estimate:

0.043 mg/m³

Exposure estimation method:

exposure estimation tool

Exposure estimation tool name:

ECETOC TRA workers

Version of exposure estimation tool:

3.0

Type of exposure:

dermal (external) long-term exposure

Exposure estimate:

0.017 mg/kg bw/day

Exposure estimation method:

exposure estimation tool

Exposure estimation tool name:

ECETOC TRA workers

Version of exposure estimation tool:

3.0

Type of exposure:

dermal (external) local concentration on skin

Exposure estimate:

0.005 mg/cm²

Exposure estimation method:

exposure estimation tool

Exposure estimation tool name:

ECETOC TRA workers

Version of exposure estimation tool:

3.0