Registration Dossier

Administrative data

Description of key information

FAT 40000 is not a skin sensitiser.

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

In total four studies have been conducted to investigate skin sensitization potential of Reactive Yellow 095.

The first two tests conducted in 1990 on batch FAT 40000/G and in 1992 on batch FAT 40000/F followed the testing protocol of the Guinea Pig Maximisation Test according to Magnusson & Kligman. The third test conducted in 2016 on batch FAT 40000/I was done in mice following the protocol of the Local Lymph Node Assay (LLNA). The last test performed in 1994 by Safepharm on “Kayacion Yellow P-7G” is again a study following the Magnusson and Kligman protocol but performed with a non-Huntsman test substance. 

 

Based on the analytical certificates available batch 40000/I consists of equivalent amounts of the meta- and para-isomere of the molecule. The para-isomer is sometimes also described by CAS 111850-26-1 and EC 402-480-0.

 

While the skin sensitization test according to the protocol of the LLNA gave a negative result in mice, the results of the GPM-tests of batch 40000/G and 40000/F gave contradictory results: The first test with batch 40000/F has been judged negative with no animals being sensitized in the test groups, while the second test with batch 40000/G showed a positive result with about 53% of the animals being judged "positive" after the first challenge at a test substance concentration of 25 %. In addition one animal of the test group died for unknown reasons on day 5 of the study. After necropsy no evidence was found that the death was substance related, therefore this result was excluded from the final evaluation and rated as incidental. Beside this further deviations are present within this study. During the epidermal pretest performed with 4 animals the substance was tested at 25, 15, 10 and 5 %. No local effects were noted in all animals for all four concentrations. Therefore, the 25 % concentration was selected as highest non-irritant concentration to be used for the challenge phase but was also used as highest applicable concentration to be used for the induction phase. This was correct.

However, as one can see after the induction phase performed with 25 %, 6 out of 19 test animals showed a skin reaction (edema grade 1), even if the erythema could not be evaluated, this showed that the 25 % concentration produced some effects and it is highly probable that the edema was associated with an erythema (unfortunately not possible to assess as animals are not depilated during the induction phase). The issue is that the same concentration was used during the challenge phase and again some animals showed reactions (erythema + edema in one case). It is not possible to judge if the reaction observed in the animals after challenge is related to irritation or sensitisation, given that some animals showed also effects during the induction phase.

Additionally, when comparing the results at the 24h reading and 48h reading, the number of animals showing effects is reduced at 48h and the animals showing effects at the 48h reading showed less severity than at the 24h reading. This is typical for irritation effects whereas sensitisation effects generally go in the opposite way, more animals after 48h and higher severity.

After the effects observed in the induction phase, the study director should have reduced the concentration to be used for the challenge phase or at least used two different concentrations like 25 and 15 %, as the concentration to be used for a challenge phase in the M&K test should be the highest non-irritant concentration, which is obviously not the case in this study given the edema observed during the induction phase.

In summary this deviation from the guideline in parallel with other uncertainties like great weight loss of one test animal during the acclimatization period, the death of on test group member in the course of the study, the overall reliability of the study is questionable. Consequently, the results of this study should be considered at least as equivocal if not completely invalid.

 

Last but not least two further Guinea Pig Maximization Tests are available.

The first test was conducted on test material FAT 40279/B (representing the pure para-form of the molecule) performed in 1987 according to the test protocol of the GPMT (Magnusson & Kligman) and also gave a negative response with no single animal showing signs of sensitziation, signs of toxicity or death in response to the challenge procedure.

The second test was performed in 1994 by Safepharm on a non-Huntsman test substance according to the test protocol of the GPMT (Magnusson & Kligman) and also gave a negative response with no single animal showing signs of sensitziation, signs of toxicity or death in response to the challenge procedure.

Taking all this information into account the reason why 1/5 tests involving two different test types, two different animal species, test materials from two different companies and different test material compositions regarding the composition of the meta- and para-isomere of the molecule is positive is difficult to judge.

Therefore in a weight of evidence approach the test material is judged not sensitizing to the skin and will therefore not be classified according to GHS.

Respiratory sensitisation

Link to relevant study records
Reference
Endpoint:
respiratory sensitisation
Remarks:
other: Letter
Type of information:
other: TSCA
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
GLP compliance:
no
Interpretation of results:
sensitising
Conclusions:
The substance is considered to be a respiratory sensitiser (classification as Xn, R42 resp. GHS: Resp. Sens. 1, H334).
Executive summary:

The read across substance, FAT 40277 has been considered to be the respiratory sensitiser on the basis of a report of allergic reactions in a worker.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

Adverse Reaction u TSCA section 8: classification as Xn, R42 resp. GHS: Resp. Sens. 1, H334

Justification for classification or non-classification

Based on the available information, FAT 40000 was classified as Resp. Sens.1 (H334) as per the CLP (Regulation 1272/2008) criteria.