Reaction products of phosphoryl trichloride and 2-methyloxirane

Endpoint summary

Description of key information

The skin sensitisation potential of the substance was investigated in vivo in accordance with OECD 429 (Safepharm Laboratories Ltd, 2005).  The substance was found to be non-sensitising as stimulation indices were <3 at all concentrations tested (25, 50 and 100 % (v/v)).

 

Hazards identified by EU Risk Assessment in May 2008:
"Evidence from a guinea pig study as well as from a local lymph node assay, indicates that TCPP does not possess significant skin sensitisation potential. No information is available on the respiratory sensitisation potential of TCPP."

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Reference 1

Endpoint:

skin sensitisation: in vitro

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro skin sensitisation study does not need to be conducted because adequate data from an in vivo skin sensitisation study are available

Reference 2

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

01 November 2004-24 November 2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study performed to GLP

Qualifier:

according to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

Qualifier:

according to guideline

Guideline:

EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)

GLP compliance:

yes (incl. QA statement)

Type of study:

mouse local lymph node assay (LLNA)

Specific details on test material used for the study:

Sponsors ID: TCPP
Description: pale straw coloured liquid
Batch no: TCPP 09-21-04
Date received: 30 Sept 2004
Storage conditions: approx 4C in dark

Species:

mouse

Strain:

CBA

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: B&K Universal Ltd Hull, UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 15-23g
- Housing:individually in solid floor polypropylene cages with softwood flakes
- Diet (e.g. ad libitum): Certified Rat and Mouse Diet 5LF2 ad libitum
- Water (e.g. ad libitum): mains tap water ad libitum
- Acclimation period:minimum of 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25C
- Humidity (%): 30-70%
- Air changes (per hr): apporx 15
- Photoperiod (hrs dark / hrs light) 12hrs light/dark cycle:


IN-LIFE DATES: From: 1 Nov 2004 To:24 Nov 2004

Vehicle:

acetone/olive oil (4:1 v/v)

Concentration:

100, 50, 25 and 0% v/v

No. of animals per dose:

four

Details on study design:

In a preliminary test, 25 µl of undiluted TCPP was applied topically to the dorsal surface of the ears of one CBA/Ca mouse for three consecutive days and observations were made up to day 6. No clinical signs were noted. In the main test, groups of CBA/Ca mice were treated with 25 µl undiluted TCPP or concentrations of 50% or 25% v/v in acetone: olive oil 4:1 for three days. A further group of mice received the vehicle alone. Five days following the first topical application, all mice were injected via the tail vein with 250 µl of phosphate buffered saline (PBS) containing a total of 20 µCi 3H-methyl thymidine (specific activity 2.0 Ci/mmol). All mice were terminated five hours after injection.
Draining auricular lymph nodes were excised and pooled for each experimental group. A single cell suspension was prepared and washed by repeated centrifugation and resuspension in PBS. Radioactive material was precipitated by resuspending the cells in 3ml of 5% trichloroacetic acid. HTdR incorporation was determined as dpm using liquid scintillation counting following an overnight incubation.
Proliferation resposne of lymph node cells was expressed as the number of radioactive disintegrations per minute per lymph node and as the ratio of HTdR incorporation into lymph node cells of test nodes relative to that recorded for the control nodes.

Positive control substance(s):

hexyl cinnamic aldehyde (CAS No 101-86-0)

Statistics:

Not reported

Positive control results:

10%v/v, SI =1.52;
25% v/v SI = 2.63
50% v/v SI= 5.07

Key result

Parameter:

EC3

Test group / Remarks:

No EC3 determined

Remarks on result:

not determinable

Remarks:

A stimulation index of <3 was recorded for all three tested concentrations of test item.

Parameter:

SI

Value:

1.56

Test group / Remarks:

100 % (v/v)

Parameter:

SI

Value:

1.97

Test group / Remarks:

50 % (v/v)

Parameter:

SI

Value:

1.55

Test group / Remarks:

25 % (v/v)

There were no mortalities or clinical observations and all bodyweights were comparable to those of the control animals.

Interpretation of results:

GHS criteria not met

Conclusions:

The substance was not found to be sensitising based on the results of the LLNA study.

Executive summary:

In a preliminary test, 25 µl of undiluted TCPP was applied topically to the dorsal surface of the ears of one CBA/Ca mouse for three consecutive days and observations were made up to day 6. No clinical signs were noted. In the main test, groups of CBA/Ca mice were treated with 25 µl undiluted TCPP or concentrations of 50% or 25% v/v in acetone: olive oil 4:1 for three days. A further group of mice received the vehicle alone. Five days following the first topical application, all mice were injected via the tail vein with 250 µl of phosphate buffered saline (PBS) containing a total of 20 µCi 3H-methyl thymidine (specific activity 2.0 Ci/mmol). All mice were terminated five hours after injection. Draining auricular lymph nodes were excised and pooled for each experimental group. A single cell suspension was prepared and washed by repeated centrifugation and resuspension in PBS. Radioactive material was precipitated by resuspending the cells in 3ml of 5% trichloroacetic acid. HTdR incorporation was determined as dpm using liquid scintillation counting following an overnight incubation. Proliferation resposne of lymph node cells was expressed as the number of radioactive disintegrations per minute per lymph node and as the ratio of HTdR incorporation into lymph node cells of test nodes relative to that recorded for the control nodes.

There were no mortalities or clinical observations and all bodyweights were comparable to those of the control animals. The substance was notfound to be sensitising.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

OECD 429 (2005): Not sensitising

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information:

Hazards identified by EU Risk Assessment in 2008:
"No information is available on the respiratory sensitisation potential of TCPP."

There are no indications that the substance has respiratory sensitisation potential.

Justification for classification or non-classification

The available data indicate that the substance does not meet the criteria for skin sensitisation (or respiratory sensitisation) in accordance with Regulation (EC) 1272/2008 (CLP).