Phosphoric acid, mono- and di-C6-10-alkyl esters

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

5.87 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

Modified dose descriptor starting point:

NOAEC

Value:

440.5 mg/m³

Explanation for the modification of the dose descriptor starting point:

Route to route extraploation required for oral to inhalation route as no long term inhalation study available.

AF for dose response relationship:

1

Justification:

When the starting point for the DNEL calculation is a NOAEL the default assessment factor is 1

AF for differences in duration of exposure:

6

Justification:

Default AF for subacute to chronic studies (an OECD 422 study)

AF for interspecies differences (allometric scaling):

1

Justification:

AF for allometric scaling not required as the differences in allometry (respiration rate and rat to human body sizes) were considered in the conversion from oral to inhalation starting point.

AF for other interspecies differences:

2.5

Justification:

Default AF for remaining differences

AF for intraspecies differences:

5

Justification:

Default AF for worker population

AF for the quality of the whole database:

1

Justification:

All studies conducted to GLP and reliability 1.

AF for remaining uncertainties:

1

Justification:

None applicable.

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

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.67 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

Modified dose descriptor starting point:

NOAEL

Value:

500 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Route to route extraploation required for oral to dermal route as no long term dermal study available.

AF for dose response relationship:

1

Justification:

When the starting point for the DNEL calculation is a NOAEL the default assessment factor is 1.

AF for differences in duration of exposure:

6

Justification:

Default AF for subacute to chronic studies (an OECD 422 study)

AF for interspecies differences (allometric scaling):

4

Justification:

Default AF for allometric scaling based on rats

AF for other interspecies differences:

2.5

Justification:

Default AF for remaining differences

AF for intraspecies differences:

5

Justification:

Default AF for worker population

AF for the quality of the whole database:

1

Justification:

All studies conducted to GLP and reliability 1.

AF for remaining uncertainties:

1

Justification:

None applicable.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

acute toxicity

Route of original study:

Dermal

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

low hazard (no threshold derived)

Additional information - workers

The substance is classified for human health as a Category 2 skin irritant and Category 2 eye irritant.

Inhalation

Systemic effects:

Long term systemic DNEL:

A DNEL has been derived for long-term systemic effects by the inhalation route. The DNEL is derived by route-to-route extrapolation from an oral NOAEL. An Oral (Gavage) Combined Repeat Dose Toxicity Study With Reproduction / Developmental Toxicity Screening Test in the Rat resulted in a NOAEL of 500 mg/kg bw/day.

A modification of the dose dsecrptior starting point (oral to inhalation) was conducted. It is assumed that the oral absorption rate is 50% of that of the inhalation absorption.

The corrected 8 hr inhalation NOAEC was 440.5 mg/m³.

The corrected dose descriptor (NOAEC) for inhalation was calculated in accordance with the ECHA Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health.

The conversion of an oral rat NOAEL into a corrected inhalatory NOAEC to assess human inhalatory exposure was performed using the modification of starting point equation as given in Figure R. 8-3 (see below) for workers (in the case of 8 hour exposure/day).

Default parameters for rats and human (for 8 hour exposure) were used for the modification of starting point under the allometric scaling principle as given in Table R. 8-2 of the above ECHA guidance.

Figure R.8-3 Modification of the starting point:

Conversion of an oral rate N(L)OAEL into a correct inhalatory N(L)OAEC to assess human inhalatory exposure:

For workers (in case of 8h exposure/day):

Corrected inhalatory N(L)OAEC = oral N(L)OAEL x (1 / sRVrat) x (ABSoral-rat / ABSinh-human) x (sRVhuman / wRV)

 

 

Corrected inhalatory N(L)OAEC= 500 mg/kg bw/day x (1 / 0.38 m³/kg/d) x (1 / 2) x (6.7 m³(8h) / 10 m³(8h))

                                                         = 440.5 mg/m³

 

Where:

ABS: Absorption

sRV: standard Respiratory Volume

wRV: worker Respiratory Volume (light activity)

 

Default parametrs:

sRVrat (8 h) : 0.38m³/kg bw

sRVhuman (8 h) : 6.7 m³/ person

wRV (8 h): 10 m³/ person

The appropriate assessment factors were then applied to give an overall assessment factor of 75.

DNEL (inhalation)= Inhalatory NOAEC / Overall assessment factor = 440.5 mg/m³/ 75 = 5.87 mg/m³

This long-term inhalation systemic effect DNEL is used in the quantitative assessment of risk for systemic toxicity to workers via the inhalation route.

Acute/short term systemic DNEL:

No acute DNEL has been derived for systemic effects.

The substance is not considered to be volatile taking into account the vapour pressure of the substance (0.31 Pa at 25°C), boiling point and viscosity of the substance. It is considered that the substance has low potential to become airborne from the organic preparations in which the substance is used and that the potential for exposure to workers to aerosols, particles or droplets of an inhalable size is unlikely based on the vapour pressure and use of the substance. Therefore, inhalation is not considered to be a significant route of exposure and no significant short term 'peak' exposures to workers anticipated.

The inhalation DNEL derived for long-term systemic effects will therefore be used for the assessment of risk for systemic toxicity to workers via the inhalation route.

In case significant exposure via the inhalation route did occur, it is anticipated that local effects would be more prominent then any possible systemic effects based on the irritant properties of the substance and the lack of systemic toxicity seen in acute oral and dermal toxicity studies.

Local effects:

Long-term local DNEL:

No DNEL has been derived for long-term inhalation local effects as no long-term inhalation study has been conducted. The substance is not considered to be volatile taking into account the vapour pressure of the substance (0.31 Pa at 25°C), boiling point and viscosity of the substance. It is considered that the substance has low potential to become airborne from the organic preparations in which the substance is used and that the potential for exposure to workers to aerosols, particles or droplets of an inhalable size is unlikely based on the vapour pressure and use of the substance. No exposure to dust containing the substance is expected under the conditions of use. Therefore, inhalation is not considered to be a significant route of exposure.

In case significant repeated exposure via the inhalation route did occur, it is anticipated that local effects would be more prominent then any possible systemic effects based on the irritant properties of the substance, i. e. irritation of the respiratory tract would be a likely local effect.

Acute/short-term local DNEL:

No DNEL has been derived for short-term inhalation local effects as no inhalation study has been conducted. The substance is not considered to be volatile taking into account the vapour pressure of the substance (0.31 Pa at 25°C), boiling point and viscosity of the substance. It is considered that the substance has low potential to become airborne from the organic preparations in which the substance is used and that the potential for exposure to workers to aerosols, particles or droplets of an inhalable size is unlikely based on the vapour pressure and use of the substance. Therefore, inhalation is not considered to be a significant route of exposure and no significant short term 'peak' exposures to workers anticipated.

In case significant exposure via the inhalation route did occur, it is anticipated that local effects would be more prominent then any possible systemic effects based on the irritant properties of the substance,i. e. irritation of the respiratory tract would be a likely local effect.

Dermal

Systemic effects:

Long-term systemic DNEL:

A DNEL has been derived for long-term systemic effects by the dermal route. The substance is a skin irritant and therefore effects following dermal exposure will be characterised by local irritant effects that are related to duration, quantity and concentration of the substance, rather than by systemic toxicity due to dermal intake. Appropriate PPE should been used by all workers and therefore repeated substantial dermal exposure is unlikely.

However, a long-term systemic DNEL has been derived by route-to-route extrapolation from an oral NOAEL obtained in a

Oral (Gavage) Combined Repeat Dose Toxicity Study With Reproduction / Developmental Toxicity Screening Test in the Rat. Appropriate assessment factors were applied to give an overall assessment factor of 300.

The derived DNEL is 1.67 mg/kg bw/day.

This long-term dermal systemic effect DNEL is used in the quantitative assessment of risk for systemic toxicity to workers via the dermal route.

Acute/short-term systemic DNEL:

It is considered to be unnecessary to derive an acute systemic dermal DNEL as an acute dermal toxicity study showed no signs of systemic toxicity and gave an LD50 of >2000 mg/kg bodyweight. The substance is not classified for acute dermal toxicity. It is considered that dermal effects will be characterised by local tissue damage (skin irritation) rather than by systemic effects due to dermal absorption.

For substances which are classified as irritating to the skin, appropriate PPE should be used by all workers. As a result, direct dermal contact should only occur infrequently or accidentally.

Local effects:

Long-term local DNEL:

No DNEL has been derived for long-term dermal local effects. No long-term dermal study has been conducted and available short-term studies do not give adequate dose-response data. The substance is a skin irritant therefore effects following repeated dermal exposure will be characterised by local irritant effects that are related to duration, quantity and concentration of the substance.

Appropriate PPE should been used by all workers and therefore repeated substantial dermal exposure is unlikely.

Acute/short-term local DNEL:

The substance is classified as a skin irritant (Category 2) based on the results of an in-vivo skin irritation study, which showed effects for erythema and edema. An acute dermal toxicity study also showed evidence of dermal irritation. However, the skin irritation study does not provide suitable dose-response information to derive a DNEL for local effects. Dermal effects will be characterised by local tissue damage and irritation.

For substances which are classified as irritating to the skin, appropriate PPE should be used by all workers. As a result, direct dermal contact should only occur infrequently or accidentally.

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:

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)

General Population - Hazard via oral 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

Additional information - General Population

DNELs have not been derived for the general public as there will be no exposure to the general public/consumers.

The substance will only be used by industry and not by the public. Due to minimal release of the substance from industrial use, exposure to the general public is not anticipated.