Santicizer 278®

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

No skin sensitisation data are available on S278. The structurally related compound, Santicizer 160 (butyl benzyl phthalate, BBP), showed no skin sensitisation potential in a human repeated insult patch test. During the induction phase, 200 healthy volunteers were exposed to 0.2 ml of the undiluted test material applied to an occlusive patch for 24 hours on fifteen separate occasions; after a 2 -week period, the same dose was applied as a challenge (24 -hour covered contact) to a new area of the skin. The skin was assessed for irritation after each induction exposure and for sensitisation 0, 24, 48 and 72 hours after the challenge. No evidence of sensitisation was observed by the investigators or reported by any of the volunteers during the study (Product Investigations Inc, 1980).

In a reliable study, no skin sensitisation was seen in guinea pigs after intradermal induction and epicutaneous challenge with BBP.

Induction involved intradermal injection of BBP (1 mM) with Freunds Complete Adjuvant into the four footpads of each of 4 guinea pigs. Epicutaneous challenges were applied, 14 days later, to the shaved abdominal skin of each animal, with three concentrations of BBP (3.6, 36 and 360 mM) and of the vehicle (acetone/corn oil). The skin was washed after 18 hours and skin reactions were read 24 and 48 hours after the start of the challenge exposure. Approximately 5 weeks later, a rechallenge using the highest concentration was made and skin reactions read at 48 hours. Four guinea pigs were treated with a positive control substance, 2,4 -dinitrofluorobenzene, in the same way. BBP did not induce skin reactions at any of the challenge sites, whereas clear positive responses were seen in the positive control animals (Washington University School of Medicine, 1983a).

Two other reliable studies, both ear swelling tests involving epicutaneous administration of BBP to the skin of AKR and BALB/c mice and subsequent challenge application to the ears, showed no evidence of skin sensitisation (Washington University School of Medicine, 1983b,c).

Migrated from Short description of key information:
No skin sensitisation data are available on S278. The structurally related compound, benzyl butyl phthalate, has shown no evidence of skin sensitisation potential in a human repeated insult patch test or in laboratory animal studies (a guinea-pig footpad test and two mouse ear swelling tests). Although none of these are guideline studies, all appear to be reliable with restrictions (reliability code 2).

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

No respiratory sensitisation data are available on S278. However, the potential for respiratory tract sensitisation by butyl benzyl phthalate (BBP) and certain other phthalate esters (DEHP, DINP and di-isohexyl phthalate) was investigated in B6C3F1 mice using an experimental procedure developed by Dearman et al. (1992). Repeated dermal applications of these four phthalates did not increase serum levels of IgE or of the interleukins IL-4 or IL-13, in contrast to the effects observed with the known respiratory sensitiser, trimellitic anhydride. Based on these results, it was concluded that these phthalates "have little, if any, potential to produce antibody-mediated respiratory allergy" (Butala et al., 2004). It is expected that a similar conclusion can be drawn for phthalates with a higher molecular weight (such as S278).

A more recent study by Dearman et al. (2009) assessed the strength of immune responses induced in BALB/c mice immunised subcutaneously with the reference allergen ovalbumin, when they received a concurrent topical application of BBP. When the BBP was applied either near to or distant from the site of ovalbumin immunisation, it had no impact on anti-ovalbumin IgE antibody responses. However, when applied at the same site as the immunisation, the high dose of BBP (100 mg) did produce a modest increase in anti-ovalbumin IgG1 antibody production, in the absence of any effect on IgE antibody production. The investigators concluded that "the doses of phthalate [BBP] encountered in the home environment are unlikely to be a major factor contributing to the increased incidence of asthma and allergy in the developed world".

Migrated from Short description of key information:
No respiratory sensitisation data are available on S278. However, data on butyl benzyl phthalate and other phthalate esters do not indicate a potential for respiratory tract sensitisation (Butala et al., 2004; Dearman et al., 1992, 2009). In addition, as the high-molecular-weight phthalates have provided no indication of skin sensitisation, a respiratory sensitising effect is considered unlikely. The low vapour pressures of these substances provide additional reassurance, as exposure by inhalation is likely to be minimal.

Justification for classification or non-classification

Based on the available data on other phthalates, S278 does not need to be classified as a sensitiser.