Nitrapyrin

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

In the key study (Carreon, 1986), the skin sensitisation potential of the test material was investigated in a study which was conducted under the spirit of GLP and following a modified Maguire methodology. Since this study was not conducted to a standardised guideline, but followed sound scientific principles, it was assigned a reliability score of 2 in line with the criteria of Klimisch et al. (1997).

During the study, 10 male Hartley guinea pigs received 4 applications of the test material within 10 days. The test material was applied as a 10 % w/v solution. An additional group of 10 guinea pigs, used as a positive control, received an epoxy resin (positive control) as a 10 % v/v solution. Both solutions were prepared in dipropylene glycol monomethyl ether/Tween 80 (9:1). Each application consisted of 0.1 mL of the test material or the positive control resin applied to a gauze patch, placed on the back of the guinea pig, then secured and covered with adhesive tape.

Following a minimum 2-week rest period, the animals were challenged. Challenge with the positive control resulted in slight to marked erythema on all guinea pigs. Under identical conditions, three of the guinea pigs challenged with the test material revealed signs of slight to moderate erythema. The degree of erythema and/or oedema observed, along with the number of animals affected are taken into consideration in the evaluation of sensitisation potential. Therefore, based on these results, the test material should be considered as possessing some potential to induce skin sensitisation.

 

Supporting information is available in the form of a GLP study which was conducted in accordance with the standardised guidelines EPA OPPTS 870.2600, OECD 429 and EU Method B.42. However, since the study was conducted with a formulation, containing only 17.9 % w/w registered substance, the data have been used in a read-across approach and the study has been assigned a reliability score of 2 in line with the criteria of Klimisch et al. (1997).

The test was conducted using female CBA/J strain mice. During the irritation screening study three daily topical applications of 1, 5, 25, 50, 75, or 100 % test material were given to one animal at each dose level. Erythema was absent in all dose groups. Body weights were unaffected in the mice treated with 1, 5, 25, and 50 %, while the mice dosed with 75 and 100 % lost 0.4 and 1.7 grams respectively. Results from this study were used to determine the dosing concentrations for test material in the main sensitisation study (LLNA)

In the main study, six female mice/group received 5, 25, or 75 % test material, or vehicle (1 % L92), on days 1-3. On day 6, uptake of 3H-thymidine into the auricular lymph nodes draining the site of chemical application was measured five hours post administration.

Erythema was absent and body weights were unaffected in all dose groups.

The test material elicited proliferative responses with stimulation indices (SI) that were 1.2, 1.9 and 1.6 for mice treated with 5, 25 and 75 % solutions of test material, respectively, in comparison to the vehicle-treated mice. Proper conduct of the LLNA was confirmed via a positive response using 30 % α-hexylcinnamaldehyde (HCA), a moderate contact sensitiser, which elicited proliferation that was 12.2 in comparison to vehicle-treated mice.

The test material did not demonstrate dermal sensitisation potential in the mouse LLNA as the lymph nodes draining the area of topical application did not demonstrate a 3-fold proliferation when compared to vehicle-treated mice.

Migrated from Short description of key information:

Sensitising (guinea pig); modified Maguire method; Carreon (1986)

Justification for selection of skin sensitisation endpoint:

Only one study is available on the registered substance itself.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No. 1272/2008, the substance should be classified as Category 1B, H317 (May cause an allergic skin reaction) with the signal word "Warning".

In accordance with the criteria for classification as defined in Annex VI, Directive 67/548/EEC, the substance should be classified as R43 (May cause sensitisation by skin contact) with the symbol Xi.