Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard 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:
medium hazard (no threshold derived)
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)
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

Threshold values derivation:

In this section, data from all end-points are examined and analyzed in order to determine for which it is relevant and possible to establish a DNEL value. The method followed is that proposed in the guidance for the implementation of REACH (Chapter R.8: Characterization of dose (concentration) -response for human health, November 2012).

1. Acute / short-term exposure - systemic effects

Because no systemic effects were seen in any of the studies registered for phosphorous acid tri-C12 -14 -alkyl esters or triisodecyl phosphite as read across, and no acute toxicity hazard has been identified,it is not relevant to derive any DNEL for systemic effect.

2. Acute / short-term exposure - local effects

Cutaneous/ eye route

None of the available studies registered by dermal or inhalation routes provide relevant dose response data on irritation/ corrosion symptoms. That is why no DNEL could be derived for these endpoints, and a more qualitative approach was investigated:

Phosphorous acid, tri-C12-14-alkyl esters was tested in vivo for skin and eye irritation using OECD 404/ 405 test guidelines, but studies were not performed under GLP conditions. No deviation to the guidelines was noted and the studies were considered as reliable but quoted with reliability 2.

For skin irritation; three New Zealand white rabbits were tested with 0,5 mL pure test item and scoring was performed at 1, 24, 48 and 72 hour.

Slight erythema well defined were noted for 3 animals and very slight oedema on 2 animals after 24h observation. All were fully reversible within 6 days.

For eye irritation; three New Zealand white rabbits were tested with 0,1 mL pure test item and scoring was performed at 1, 24, 48 and 72 hour.

Slight conjunctivae effects were noted on 3 animals 1 hour after instillation (enanthema slight to moderate with slight chemosis) and were fully reversible within 48h after treatment.

In the two cases, no other clinical or systemic signs were noted.

With a primary skin irritation index of 1,8, and maximum mean irritation score of 9.3 for eyes, Phosphorous acid, tri-C12-14-alkyl esters was considered as slightly irritant for skin and eyes, according to French protocol and scaling but not classified according to GHS criteria.

In these conditions, no qualitative assessment is needed for Phosphorous acid, tri-C12-14-alkyl esters and good industrial hygiene practices are considered sufficient to ensure safety of workers. Moreover, a low hazard category could be used for a more proctective approach, but the sensitizing potential of Phosphorous acid, tri-C12-14-alkyl esters (see below the study summary) is the leading health effect for dermal route and its moderate hazard category associated covers the slight irritation effects showed in the rabbit studies. The risk managment measures and operational conditions linked with a moderate hazard would be then sufficient.

Inhalation

Triisodecyl phosphite used for read across was given to rats during the one-hour exposure period at the concentration of 12.6 mg/L air. Because neither adverse effects nor untoward signs and symptoms were observed during the 21-day post-exposure observation period, no threshold value could be derived for inhalation following acute exposure.

3. Long-term exposure - systemic effects

Because no systemic effects were seen in any of the studies registered for Phosphorous acid, tri-C12-14-alkyl esters

or triisodecyl phosphite as read across (combined repeated dose and reproductive toxicity study), and neither acute nor repeated toxicity hazard has been identified,it is not relevant to derive any DNEL based on these data. But sensitizing potential of the submitted substance could be taken into account for systemic effects as for local effects (point of contact of the substance on skin) and a qualitative assessment is therefore done : see the paragraph just below.

4. Long-term exposure - local effects

Cutaneous/eye route

As already described for short term exposure, no assessment is needed for Phosphorous acid, tri-C12-14-alkyl esters due to irritation/ corrosion effects.

But Phosphorous acid, tri-C12-14-alkyl esters was tested in a LLNA test for sensitization. The study followed the current guidelines and the small deviation did not affect the validity that was quoted to reliability 1 according to Klimlisch criteria.

Three groups each of four female mice were treated once daily with the test item at concentrations of 5, 10, and 25% (w/v) in acetone:olive oil (4+1, v/v) by topical application to the dorsum of each ear for three consecutive days. The highest concentration btested was the highest concentration that could be achieved whilst avoiding systemic toxicity and excessive local skin irritation as confirmed by a pre-experiment.

All treated animals survived the scheduled study period and no signs of systemic toxicity or local skin irritation were observed.

In this study Stimulation Indices of 1.00, 1.45 and 3.42 were determined with the test item at concentrations of 5, 10, and 25% (w/v) in acetone:olive oil (4+1, v/v). A clear dose response was observed. The EC3 value calculated was 21.8%, which indicates a moderate sensitizing potential.

As recommended in the guidance for the implementation of REACH (Chapter R.8: Characterization of dose (concentration) -response for human health, November 2012), the general approach to sensitizers could be viewed as a two-step procedure involving; 

1.  a qualitative approach (by using potency categorisation and following the approach described in Section E.3.4 to define the risk management measures (RMMs) and operational conditions (OCs), 

2.  and setting a DNEL (if possible) to judge the remaining/residual likelihood of risks after these RMMs and OCs are implemented

The qualitative approach aims at reducing/avoiding contact with the substance. However, implementation of risk management measures (RMMs) and operational conditions (OCs) needs to be proportional to the degree of concern for the health hazard presented by the substance. The purpose of this qualitative approach is to minimize the exposure considering the level of risk related to the hazard properties of the substance (indicated by R-phrases). 

For a moderate sensitizer as Phosphorous acid, tri-C12-14-alkyl esters, the medium hazard category is allocated on the basis that exposure should be adequately minimized.

This qualitative approach is considered as more relevant that deriving a DNEL from the EC3 value, which could result in an unrealistic to low value of substance/ µg/ cm²/ day, due to the considerable variability in determining each appropriate assessment factor. 

Inhalation

Triisodecyl phosphite used for read across was given to rats during the one-hour exposure period at the concentration of 12.6 mg/L air. Neither adverse acute effects nor local symptoms were observed during the 21-day post-exposure observation period. This substance was also tested by oral route in a combined repeated dose and reproductive toxicity study and showed that no effect due to the administration of triisodecyl phosphite. No threshold value could be then derived for repeated exposure by inhalation. 

 

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard 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:
no hazard identified
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)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

General Population - Hazard via oral route

Systemic 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 for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

See discussion for workers.