2-Propenoic acid, reaction products with pentaerythritol

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

Skin sensitisation

A study was conducted to evaluate the skin sensitization potential of C-171 in Hartley guinea pigs according to Buehler test method. In the range finding test, test animals (2 animals/sex/dose) were applied with 10, 25 or 50 % (v/v) solution of the substance in propylene glycol. In the main study, animals (5/sex) were applied with 0.2 mL of undiluted substance via occluded patch for 6 h, thrice weekly for 3 weeks, followed by a challenge patch of 50 % (v/v) of C-171after 2 weeks of rest period. Control groups included: 100 % propylene glycol (negative control); 0.1 % 2,4-dinitrochlorobenzene (DNCB) in 80 % ethanol (positive control); 0.1 % DNCB in acetone (irritation control), 50 % test material (irritation control). The application sites were graded with irritation scores at 6 (30 min after patch removal), 24 or 48 h after challenge. Results of the initial challenge (at a 50 % concentration) indicated evidence of dermal irritation. Since dermal scores greater than 2 occurred, in both test groups and irritation control animals, a second challenge, at lower concentrations (25 % and 10 %) was, therefore, performed. Although results of this challenge revealed evidence of slight irritation, incidence of response was comparable in control and treated animals. Scores of 2 or greater were exhibited by one of ten test animals and two of eight control animals dosed at 25 %; no dermal scores of 2 or greater occurred in animals treated with 10 %. Animals treated with DNCB (positive control) exhibited evidence of sensitization, thus confirming the susceptibility of this group of animals to dermal sensitization. In conclusion, the test substance was not sensitising in this guinea pig skin sensitisation test (Auletta, 1981).

A study was conducted to evaluate the skin sensitization potential of the C-78 in guinea pigs according to Buehler test method. In the range finding test, no skin reactions were observed when test animals were exposed to a 10, 20, 30, 50, 60, 75, 90, 95 and 100 % solution of the substance in acetone. In the main study, ten animals were applied with 0.5 mL of 95 % of the substance via occluded patch for 6 h, once weekly for 2 weeks, followed by a challenge patch of 95 % (v/v) of the substance after a 2 weeks rest period. Ten animals in the control group were exposed to a challenge patch of 95 % (v/v) of the substance. The application sites were graded (Draize scoring system) with irritation scores 24 and 48 h after challenge. No skin irritation or positive skin sensitization reactions were observed at the application sites in the control and test groups and all animals appeared normal throughout the study. In conclusion, the test substance was not sensitising in this guinea pig skin sensitisation test (Wolfe, 1979).

A study was conducted to evaluate the skin sensitization potential of SN-1462 in albino guinea pigs according to the Buehler test method. In the range finding test, minimal erythema was observed in two animals applied with undiluted test material. No skin irritation reaction was observed when test animals were applied with 1 or 10 % (v/v) solution of the substance in propylene glycol. In the main study, ten animals were applied with 0.5 mL of undiluted substance via occluded patch for 5 h for a total of nine times, followed by a challenge patch of 1% (v/v) of the substance after 2 weeks of rest period. Four animals in the control group were applied with challenge patch of 1% (v/v) of the substance. The application sites were graded with irritation scores 24 and 48 h after challenge. No skin irritation or positive skin sensitization reactions were observed at the application sites in the control and test groups. In conclusion, the test substance was not sensitising in this guinea pig skin sensitisation test (Brett, 1974).

PETIA was negative for skin sensitization in three separate Buehler studies according to methods similar or equivalent to OECD 406. However, the skin sensitizing potential of pentaerythritol triacrylate (PETA), one the main constituents of PETIA, in studies in animals, volunteers and workers has been well documented (reviewed in: MAK, 2012; NTP, 1991). Skin sensitization reactions following exposure to pentaerythritol tetraacrylate, the other main constituent of PETIA, have also been reported, albeit with less potency compared to PETA (for review see NTP, 1991).

PETA has been implicated in a number of cases of allergic contact dermatitis reported in workers exposed to ultraviolet curing inks (Björkner et al., 1980; Dahlquist et al.1983; Emmett, 1977; Emmett and Kominsky, 1977; Smith, 1977) and paint hardeners (Cofield et al., 1985; Saval et al., 2007) containing multifunctional acrylates. Cross-sensitization to multifunctional acrylates such as trimethylol propane triacrylate (TMPTA), pentaerythritol tetraacrylate and PETA has been reported in an animal study (reviewed in MAK, 2012 and NTP, 1991), and suggested in reported incidences of dermatitis in workers, although in these cases previous exposure to PETA cannot be ruled out (Björkner et al., 1980; Estlander et al., 1996). PETA (0.1%) tested positive in a patch test in 4/6 workers exposed to UV curing ink containing the multifunctional acrylate trimethylol propane triacrylate (TMPTA). The workers had previously worked with other UV curing inks, although the presence of PETA in these products is unknown (Björkner et al., 1980). Positive patch tests to PETA (at 0.01% in one subject) were also observed in 2/4 workers who had developed dermatitis following exposure to a floor top coat containing TMPTA; all four workers tested positive in a patch test to TMPTA (Dahlquist et al.,1983). Five out of 26 employees of a printing ink formulation facility developed dermatitis following introduction of a new formulation of printing ink containing TMPTA and PETA (Emmett, 1977). Positive sensitization reactions to PETA (0.2%) were evident in 4 of the 5 subjects evaluated by patch test, confirming an allergic response (Emmett, 1977). Smith (1977) also reported positive patch tests to PETA (0.1%) in two print workers with dermatitis on the hands and face following the introduction of UV cured inks containing PETA.

In summary, the main constituent of PETIA, PETA has been confirmed as a skin sensitizer in a number of case studies and controlled studies in animals and volunteers. Pentaerythritol tetraacrylate, the other main constituent of PETIA, is also considered to be a skin sensitizer of comparably lower potency (NTP, 1991). The reported use of gloves and protective clothing in some of the case studies in workers was found to effectively reduce exposure and limit sensitization reactions to only those exposed areas of skin (Emmett and Kominsky, 1977; Estlander et al., 1996), and the introduction of PPE as a risk reduction measure was found to effectively minimize sensitization reactions in already sensitized subjects and limit new cases of sensitization (Saval et al., 2007).

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information:

No information could be found on the respiratory sensitization potential of PETIA. The substance has relatively low vapour pressure so that normal processing and use conditions will not generate inhalation exposure. Uses creating aerosols or vapours (e.g. spraying, elevated temperature/pressure), are not covered in this registration.

Under such conditions, the risk to humans of respiratory sensitization can be considered minimal and further testing involving vertebrate animals may be omitted, in accordance with Annex XI (1.2) of the REACH regulation.

Justification for classification or non-classification

PETIA was tested in three separate Buehler studies and found to be not sensitising under the experimental conditions. However, skin sensitization/allergic contact dermatitis has been observed after exposure at the workplace, suggesting that PETIA is a skin sensitizer in humans. Hence, it qualifies for classification as Skin Sens. 1 - H317 (May cause an allergic skin reaction) according to EU CLP (EC 1272/2008) criteria. The workplace exposure data is not sufficiently robust to categorize potency as 1A or 1B.