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EC number: 250-284-7 | CAS number: 30674-80-7
Skin sensitisation (non-guideline study): sensitising
Respiratory sensitisation (no guideline available): sensitising
Results of test (ctd.)
Hours after challenge
No. with + reactions
Total no. in group
50% polymer with 0.01% monomer (test item)
2 animals showed mild erythema and 7 animals did not show any skin reactions.
50% polymer with 0.1% monomer (test item)
1 animal showed moderate erythema, 5 animals showed mild erythema, and 2 animals did not show any skin reactions.
50% polymer with 1% monomer (test item)
1 animal showed erythema plus oedema, 5 animals showed moderate erythema, 2 animals showed mild erythema, and 1 animal did not show any skin reactions.
50% polymer with 0. 1% monomer (test item)
6 animals showed mild erythema and 3 animals did not show any skin reactions.
8 animals showed mild erythema and 1 animal did not show any skin reactions.
3 animals showed mild erythema and 6 animals did not show any skin reactions.
1 animal showed moderate erythema, 5 animals showed mild erythema, and 3 animals did not show any skin reactions.
2 animals showed moderate erythema, 5 animals showed mild erythema, and 2 animals did not show any skin reactions.
1 animal showed mild erythema and 8 animals did not show any skin reactions.
1 animal showed moderate erythema, 6 animals showed mild erythema, and 2 animals did not show any skin reactions.
In the available key study (DuPont, 1976), which predates the appropriate OECD test guideline and GLP, the test item was investigated for skin sensitising properties. Male guinea pigs were induced with the test item by a series of 3 intradermal injections of a 1% test material solution in dimethyl phthalate, but no additional treatment with adjuvant was included into the study. After a 2 week rest period the animals received the epicutaneous challenge exposure with 0.01, 0.1, and 1% solutions in acetone, and following 2 further weeks of rest the animals were rechallenged with 0.05, 0.1, 0.5, and 1% solutions in acetone. After another 2 weeks, the animals received a challenge exposure with the respective polymer of the test item (50% solution in acteone), which was spiked with the monomer (the test item itself) at concentrations of 0.01, 0.1, and 1%. Naive animals were included as controls into the test. 24 and 48 h after challenge exposure with 1% test material solution, 8/9 and 7/9 animals, respectively, were observed with skin reactions, whereas 5 animals showed moderate erythema after both 24 and 48 h, and 3 animals and 2 animals showed mild erythema after 24 and 48 h, respectively. Animals treated with lower concentrations did not show any skin reactions. Rechallenge with 0.5 and 1% test item solutions revealed 4/9 and 9/9 animals with skin reactions 24 h post treatment, whereas the first exposure revealed 2 animals with moderate erythema and 2 animals with mild erythema, and the latter exposure resulted in 3 animals with moderate erythema and 6 animals with mild erythema. After 48 h 3/9 and 7/9 animals treated with 0.5 and 1% concentrations, respectively, still showed skin reactions, with 3 animals with mild erythema in the 0.5% dose group and 1 animal with moderate erythema and 8 animals with mild erythema in the 1% dose group. Treatment with 0.05 and 0.1% test substance solution again did not result in skin reactions. Exposure to the polymer spiked with the monomer also exhibited skin reactions. However, also the naive control animals showed comparable skin reactions when treated with the spiked polymer.
Based on the outcome of the study, the test material meets the criteria to be classified as a skin sensitiser (Xi, R43) according to 67/584/EEC and (Cat 1A, H317) according to EC/1272/2008.
In the available key study (Mullin et al., 1983) the test item was investigated for the risk of respiratory sensitisation after exposure via inhalation. No information is available, whether the study was performed in compliance with GLP, and no guideline is available, which adresses this endpoint. Several further test materials were prepared in addition to the submission substance (IEM, monomer) prior to the study: IEM was conjugated to bovine serum albumin (BSA-IEM) or to guinea pig serum albumin (GSA-IEM), and additionally a polymer (styrene/IEM/dodecyl mercaptan polymer (44/46/10) as a 20% solution in dimethyl phthalate), which contained less than 0.0004% total monomer, was prepared. Once daily for 5 days/week male albino guinea pigs were induced only with the BSA-IEM conjugate via inhalation at concentrations of 24, 72, 89, 90, 92, and 98% conjugation (with 37±10, 54±14, 31±9, 49±24, 47±7, 42±8 g/L average chamber protein concentration), respectively. Exposures were carried out until respiratory responses were observed. Challenge was carried out with GSA-IEM conjugate, the IEM monomer, or the polymer, respectively. Control animals were treated with BSA alone.
The study revealed that respiratory responses to the conjugate generally occurred after several minutes of exposure and subsided during the 5-min recovery period following exposure. The number of animals developing respiratory responses was related to the degree of IEM conjugation on protein. 2/4 animals exposed to the 24% conjugate, 3/4 animals exposed to the 72% conjugate, and all animals exposed to 89% and greater conjugates developed positive responses during the 2nd or 3rd week of exposure. Often the responses were transient and lasted only several days. However, the responses could be evoked again, if animals were rechallenged after a 1-week rest period. When animals were responsive to the BSA-IEM, 80% also responded to the GSA-IEM conjugate, while none responded to unconjugated BSA. Those challenged with GSA alone also responded negatively. The authors considered this result as a strong evidence that IEM portion of the molecule was critical for eliciting the response.
All animals exposed to the 90% BSA-IEM conjugate developed respiratory responses within 8-15 days after study initiation. They were treated with DSCG, which was administered 30 min prior to exposure on test days 10 and 16. None of the animals had positive respiratory responses on the days when DSCG was preadministered.1 animal responded on the subsequent day after DSCG preadministration again, while others responded several days later when challenged with the BSA-IEM conjugate aerosol. The authors conclude that DSCG diminished the respiratory response to BSA-IEM. No exposure related gross or histopathologic abnormalities were observed in any of these animals.
Two groups of animals exposed to the BSA-IEM conjugate (92 and 98%) were challenged with the IEM monomer. No immediate or delayed response occurred in animals challenged with 0.01 ppm monomer. Exposure to 0.1-0.4 ppm monomer vapour elicited repiratory responses in some of the BSA-IEM responsive animals. The responses were qualitatively identical to those induced by the conjugate, i.e. similar increases in respiratory rate. However, the responses to the monomer were delayed, occurring 1-5 h post exposure and generally lasted longer than those induced by the conjugates. No responses were seen, when control animals were exposed to the monomer. Challenge with 0.5 and 0.6 ppm monomer produced severe upper respiratory tract irritation, as indicated by a 30 and 50% decrease in respiration during exposure, respectively, in both control animals and and those previously induced with the conjugate. No delayed responses were detected at these concentrations. The authors stated that the recovery from irritation was slow and may have masked a positive respiratory response.
None of the animals responsive to BSA-IEM and challenged with the polymer displayed a positive response when monitored during exposure or the 6 h recovery period.
Based on the outcome of the study, the test material meets the criteria to be classified as a respiratory sensitiser (Xn, R42) according to 67/584/EEC and (Cat 1, H334) according to EC/1272/2008.
The available data are reliable and suitable for classification. Based on this data, the registered substance meets the criteria to be classified for skin sensitisation (Xi, R43) and respiratory sensitisation (Xn, R42) according to 67/584/EEC and skin sensitisation (Cat 1A, H317) and respiratory sensitisation (Cat 1, H334) according to EC/1272/2008.
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