Reaction Products of Diphosphorus Pentaoxide with n-Alcohols, C8-10 (even), salted with Amines, C12-14, Tert-alkyl

Endpoint summary

Description of key information

- Skin irritation: EPA guideline, rabbits; irritating (undiluted), not irritating (conc. of 50 % and lower);
- Eye irritation: EPA guideline, rabbits; severe irritant (undiluted); not irritating (conc. of 50 % and lower).

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

In a primary dermal irritation study (EPA OPP 81-5), young adult New Zealand White rabbits (2 females, 4 males) were dermally exposed to 0.5 ml of the undiluted test item for four hours to an area of approx. 1 inch² (Bonnette, 1995; Study No. 3663.87). Animals then were observed for 14 days.

Exposure to the test article produced very slight to well-defined erythema on 6/6 test sites and very slight edema on 5/6 test sites at the 1 hour scoring interval which progressed to focal/pinpoint to mild blanching on 3/6 test sites by the 48 hour scoring. The dermal irritation generally diminished during the remainder of the test period and resolved completely in all animals by study day 14. Additional dermal findings noted during the period included desquamation which was noted on 6/6 test sites.

In this study, the undiluted test item is a dermal irritant.

In another primary dermal irritation study (equivalent to EPA OPP 81-5), young adult New Zealand White rabbits (6 males) were dermally exposed to 0.5 ml of the diluted test item (concentrations: 50%, 25%, 12.5%, 6.25% in the vehicle) for four hours under a semi-occlusive binder to an area of approx. 1 inch² (Bonnette, 1995; Study No. 3263.116). Following the exposure period, the binder was removed and the remaining test article was wiped from the skin using gauze moistened with the vehicle followed by dry gauze. Test sites were subsequently examined and scored for dermal irritation for up to 14 days following patch removal.

50% solution: Exposure to the test article produced well-defined erythema and very slight to slight edema on 6/6 test sites and focal/pinpoint blanching on 3/6 test sites at the 1 hour scoring interval. The dermal irritation resolved completely in all animals by study day 14. Additional dermal observations noted during the test period included desquamation, which was noted on 6/6 test sites.

25% solution: Exposure to the test article produced well-defined erythema and very slight to slight edema on 6/6 test sites and focal/pinpoint blanching on 3/6 test sites at the 1 hour scoring interval. The dermal irritation resolved completely in all animals by study day 10. Additional dermal observations noted during the test period included desquamation, which was noted on 6/6 test sites.

12.5% solution: Exposure to the test article produced very slight to well-defined erythema and very slight to slight edema on 6/6 test sites at the 1 hour scoring interval. The dermal irritation resolved completely in all animals by study day 10. Additional dermal observations noted during the test period included desquamation, which was noted on 6/6 test sites

6.25% solution: Exposure to the test article produced very slight to well-defined erythema and very slight to slight edema on 6/6 test sites at the 1 hour scoring interval. The dermal irritation resolved completely in all animals by study day 10. Additional dermal observations noted during the test period included desquamation, which was noted on 6/6 test sites.

In this study, the diluted test item is not a dermal irritant in concentrations up to 50%.

Eye irritation

In a primary eye irritation study (EPA OPP 81-4), young adult New Zealand White rabbits (6 females) were exposed to 0.1 ml of the undiluted test item via single instillation into the conjunctival sac with wash-out after 24h during examination with fluorescein (Bonnette, 1995; Study No. 3263.86). Animals then were observed for 21 days.

Exposure to the test article produced corneal opacity in 6/6 test eyes at the 1 hour scoring interval. The corneal opacity was confirmed by positive fluorescein dye retention at the 24 hour scoring interval. The corneal opacity resolved completely in 5/6 test eyes by study day 21. Iritis was noted in 6/6 test eyes at the 1 hour scoring interval. The iridal irritation resolved completely in all animals by study day 7. Conjunctivitis (redness, swelling and discharge) was noted in 6/6 test eyes at the 1 hour scoring interval. The conjunctival irritation resolved completely in all animals by study day 21. Additional ocular findings included sloughing, corneal neovascularization and raised area on the cornea, which were noted in 4/6, 2/6 and 1/6 test eyes, respectively.

A normal background finding of superficial stippling was observed in 1 /6 test eyes during the fluorescein examination. This finding was transient and was not considered significant. No corneal opacity, iritis or conjunctivitis was observed in the control eyes.

In this study, the undiluted test item is severe irritant to the ocular tissue of the rabbit. According to the EEC Ocular Evaluation Criteria, the test item is considered to be an irritant for corneal opacity, a nonirritant for iris lesion, a nonirritant for conjunctival redness and a nonirritant for conjunctival edema.

In another primary eye irritation study young adult New Zealand White rabbits (m/f, 6 rabbits/concentration) were exposed to 0.1 ml of the test item (12.5%, 25%, 50% w/w in the vehicle) via single instillation into the conjunctival sac with wash-out after 24h during examination with fluorescein (Bonnette, 1995; Study No. 3263.115). Animals then were observed for 7 days.

12.5% w/w solution: Exposure to the test article produced conjunctivitis (redness, swelling and discharge) in 6/6 test eyes at the 1 hour scoring interval. The conjunctival irritation resolved completely in all animals by the 48 hour scoring interval.

A normal background fluorescein finding was observed in 1/6 test eyes (mechanical abrasion). This finding was considered to be transient and was not considered significant. No corneal opacity, iritis or conjunctivitis was observed in the control eyes.

25% w/w solution: Exposure to the test article produced iritis in 3/6 test eyes at the 1 hour scoring interval. The iridal irritation resolved completely in the affected test eyes by the 72 hour scoring interval. Conjunctivitis (redness, swelling and discharge) was noted in 6/6 test eyes at the 1 hour scoring interval. The conjunctival irritation resolved completely in 6/6 animals by study day 4.

No corneal opacity, iritis or conjunctivitis was observed in the control eyes.

50% w/w solution: Exposure to the test article produced corneal opacity in 1 /6 test eyes at the 24 hour scoring interval which was confirmed by positive fluorescein dye retention. The corneal opacity resolved in the affected eye by the 72 hour scoring interval. Iritis was observed in 5/6 test eyes at the 1 hour scoring interval. The iridal irritation resolved completely by the 24 hour scoring interval. Conjunctivitis (redness, swelling and discharge) was noted in 6/6 test eyes at the 1 hour scoring interval. The conjunctival irritation resolved completely in all animals by study day 7.

No corneal opacity, iritis or conjunctivitis was observed in the control eyes.

According to the Ocular Evaluation Criteria, the test item is considered to be a moderate irritant to the ocular tissue of the rabbit when applied as 50% solution, a mild irritant when applied as 25% solution and a slight irritant when applied as 12.5% solution. According to the EEC Ocular Evaluation Criteria, the test item is considered to be a nonirritant for corneal opacity, iris lesion, conjunctival redness and conjunctival edema when applied in solutions up to 50%. According to FHSA criteria, a 12.5% solution of the test item is not an irritant, a 25% solution of the test item may cause irritation and a 50% solution of the test item is an irritant.

Justification for selection of skin irritation / corrosion endpoint:
The study with the undiluted test material is the key study.

Justification for selection of eye irritation endpoint:
The study with the undiluted test material is the key study.

Effects on skin irritation/corrosion: moderately irritating

Effects on eye irritation: highly irritating

Justification for classification or non-classification

Skin irritation

According to the classification criteria outlined in the section 3.2.2.3.2.2. (Guidance on the Application of CLP criteria, November, 2013), classification as skin irritant into Category 2 applies if at least 4 out of 6 rabbits show a mean score (from gradings at 24, 48 and 72 hours) per animal of ≥ 2.3 ≤ 4.0 for erythema/eschar or for oedema.

In the first skin irritation study with the undiluted test material, there were 5 out of 6 positive responders for both erythema and oedema formation. The mean values were 3.6, 2.0, 2.3, 3.3, 2.3 and 4.0 for erythema and 4.0, 3.7, 4.0, 4.0, 1.7 and 3.0 for oedema in animal 1, 2, 3, 4, 5 and 6, respectively.

In the second study with the diluted test material, the substance was not irritating in concentrations up to 50 %. In details, only 1/6 of the animals treated with the 50 % - diluted test material responded positively (reached the cut-off value of 2.3), i.e. the animal had score of 2.7 for oedema. The other animals had the mean values under the cut-off value of 2.3. No positive responders were observed in the groups of animals treated with 25 %, 12.5 %, and 6.25 % solutions of the test material.

In accordance with EU CLP (Regulation (EC) No. 1272/2008) classification of this substance is required for skin irritation in Cat 2 (H315) with specific concentration limit (SCL) of 50 % and higher. No classification is required for the test substance in concentrations lower than 50 %.

Eye irritation

According to the classification criteria outlined in the section 3.3.2.3.2.2. (Guidance on the Application of CLP criteria, November, 2013), classification as serious eye damage into Category 1 applies if at least in one animal effects on the cornea, iris or conjunctiva that are not expected to reverse or have not fully reversed within an observation period of normally 21 days; and/or(ii) at least 4 out of 6 rabbits show a mean score per animal of ≥ 3 for corneal opacity and/or > 1.5 for iritis.

Classification as eye irritation – Category 2 applies, if at least 4 out of 6 rabbits show a mean score per animal of:

i. ≥ 1 for corneal opacity and/or

ii. ≥ 1 for iritis and/or

iii. ≥ 2 conjunctival erythema (redness) and/or

iv. ≥ 2 conjunctival oedema (swelling) (chemosis)

and which fully reverses within an observation period of normally 21 days. The calculated values should be the mean scores following grading at 24, 48 and 72 hours after instillation of the test material.

In the first study with the undiluted test material, the corneal opacity did not resolve in one animal during 21 days. Therefore, in accordance with EU CLP (regulation (EC) No. 1272/2008), classification of this undiluted substance is required for eye irritation or corrosion: seriously damaging to eyes (Category 1, H318).

In the second study, the diluted test substance as 12.5 5, 25 % or 50 % solution did not cause positive responders. The mean scores for corneal opacity, iritis, conjunctival erythema and oedema were all under the cut-off values triggering classification for eye irritation.

In accordance with EU CLP (Regulation (EC) No. 1272/2008) classification of the diluted substance in concentrations up to 50 % is not required for eye irritation. However, classification of this undiluted substance is required for eye irritation or corrosion: seriously damaging to eyes (Category 1, H318).