Alkyl phosphites

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

The relevant studies for the assessment of skin sensitization are the Guinea Pig Maximization: Report No. 149221 (1996) and Buehler: Report No. 3575.1 2001. The guinea maximization test followed recognized guidelines (EU method B.6) and was conducted to GLP standards with a reliability rating of 2 according to the criteria of Klimisch, 1997. The test involved 0.1% intradermal induction and 5% topical induction with test substance dissolved in peanut oil, followed by 0.05% challenge in peanut oil. Dose levels took into account the irritancy of test material. Induction caused eschar at 5% ranging from slight to severe in grade. A mild response was seen at 24 hours on challenge, no responses were seen at 48 hours in any of the 20 animals. The supporting Buehler test in guinea pigs followed recognised guidelines (EPA OPPTS 870.2600) and was conducted to GLP standards with a reliability rating of 2 according to the criteria of Klimisch, 1997. Topical induction at 10% test material in mineral oil was followed by challenge at 5%. No sensitization occurred, dose levels were selected to take into account the irritancy of the test material.

A mouse LLNA Report No. CTL/GM7384/REG/REPT (2001) was conducted to GLP standards according to the methodology as described by Kimber and Basketter 1992 and Kimber 1994, because at the time the test was performed (2000) the OECD 429 test guideline was not yet available. The test was conducted on brown mice.Doses of 0.05, 0.1, 0.5, 1 and 5% were selected based on known irritancy seen in earlier guinea pig sensitization testing, threshold for this was around 5-10%. Weak positive reactions, expressed as an isotope incorporation being greater than 3-fold were seen at 5% test material concentration (dissolved in acetone in olive oil). From the data available on the test material, it would seem that EC 424-820-7 is at least mild-moderately irritating when dissolved in oil at levels of 5% and above. The in vivo skin irritation/corrosion tests established the neat registration material was corrosive to the skin, and also that a 10% w/w solution in water elicits a pH of 1.6. The material was tested after this in oil, producing mild-moderate irritation in most cases at concentrations in the region of 5%. According to the current OECD 429 test guideline (dated 22 July 2010), a pre-screen test should be performed in order to define the appropriate dose level to test in the LLNA in order to avoid an induction of systemic toxicity and/or excessive local skin irritation. To determine local irritation, both ears of each mouse are observed for erythema and scored. Ear thickness measurements are taken using a thickness gauge. In the LLNA study report, the authors state that in a preliminary irritation screen, a 5% dilution of the test material was used and the animals were observed for any signs of irritation. However, there was neither any description on the methodology how the level of irritancy response was determined, nor any information on erythema irritation scores or ear thickness values (which is in accordance with the former version of the 429 test guideline (dated 2002), but no longer with the requirements of the current version, dated 2010). As a consequence, in the absence of this crucial pre-screen information regarding the irritancy potential of the dilution used, it is not possible to distinguish between an irritant and a sensitising effect in the main study, based on the proliferation counts measured in the lymph nodes, if the non-irritancy of the 5% solution used cannot be proven by including appropriate irritation scores and/or ear thickness measurements in the study report. As a consequence, the results of the LLNA are considered inappropriate (Klimisch score 3) with regards to an assessment of the skin sensitisation potential of EC 424-820-7.

In conclusion, with only one concentration recording a questionable result in the LLNA, and taking into account the concerns that potential irritancy of the test material was not accounted for in the LLNA study design, coupled with the weight of evidence from other sensitisation test data provided for this material, EC 424-820-7 is not considered a sensitizer requiring the H317 label.

Migrated from Short description of key information:
Guinea Pig Maximization Test (EU B.6 Skin sensitization): not sensitising
Buehler Test (EPA OPPTS 870.2600): not sensitising
LLNA assay: sensitising (disregarded study)

Justification for selection of skin sensitisation endpoint:
Key study for this endpoint. However, other studies are available to confirm the result

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information:

Justification for selection of respiratory sensitisation endpoint:
Study not required according to Annex VII-X of Regulation (EC) No. 1907/2006.

Justification for classification or non-classification

In conclusion, with only one concentration recording a questionable result in the LLNA, and taking into account the concerns that potential irritancy of the test material was not accounted for in the LLNA study design, coupled with the weight of evidence from other sensitisation test data provided for this material, EC 424-820-7 is not considered a sensitizer requiring the H317 label and the data are therefore considered conclusive but not sufficient for classification.