Nitrapyrin

Endpoint summary

Description of key information

SKIN

Not-irritating (rabbit); EPA OPPTS 870.2500, OECD 404, EU Method B.4 and JMAFF 12 -Nouan-8147; Durando (2006)

EYES

Irritating (rabbit); similar to OECD 405; Carreon (1986)

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

Skin

In the key study, the skin irritation potential of the registered substance (purity: 98.6 %) was investigated by Durando (2006) under GLP conditions and in accordance with the standardised guidelines EPA OPPTS 870.2500, OECD 404, EU Method B.4 and JMAFF 12 -Nouan-8147.

During the study 0.5 g of test material was moistened with distilled water and then applied to the clipped skin of three healthy New Zealand White rabbits for 4 hours in a semi-occlusive fashion. Following exposure, dermal irritation was evaluated by the method of Draize. One hour after patch removal, well-defined erythema and very slight oedema were noted for all three treated sites. The overall incidence and severity of irritation decreased with time. All animals were free from dermal irritation within 72 hours.

All animals appeared active and healthy during the study. There were no signs of gross toxicity, adverse clinical signs, or abnormal behaviour.

Under the conditions of the study, the test material was found to be not irritating to the skin of New Zealand White rabbits.

 

Supporting information (Norris, 1971) is available in the form of a study which investigates the skin irritation potential of the registered substance (purity: 90% min) using a method similar to that outlined in the standardised guideline OECD 404.

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, 1 g test material was applied to intact and abraded skin of 3 New Zealand White rabbits in a semi-occlusive fashion. In the case of intact skin, the test material was applied 5 days per week for 2 weeks (which represents a continuous exposure of 14 days). The exposure to abraded skin was for a duration of 3 days. Observations were performed daily, 5 days per week, during the exposure period and also at the end of the 3 week study. The animals were weighed at weekly intervals and were frequently observed to detect any changes in behaviour and general appearance.

Under the conditions of the study, single and multiple applications of test material to intact and abraded abdominal skin of rabbits, under conditions of confinement and in accordance with the prescribed procedure, resulted in very slight or slight erythema and slight exfoliation. There were no detectable signs of toxicity noted during the exposure or the two week observation period. The body weights taken after the 2 week application period were greater than the pre-exposure body weight in two rabbits and less than the pre-exposure weight in one rabbit. The terminal body weights of all rabbits were greater than the pre-exposure body weights.

Further supporting information is available in the form of a study, reported by Lowe (2007) in which the skin irritation potential of a formulation (containing the registered substance at 17.9 %) was investigated under GLP conditions and in accordance with the standardised guidelines EPA OPPTS 870.2500, OECD 404, EU Method B.4 and JMAFF 12 -Nouan-8147.

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).

During the study, 0.5 mL of test material was applied to the clipped skin of three healthy New Zealand White rabbits for 4 hours in a semi-occlusive fashion. Following exposure, dermal irritation was evaluated by the method of Draize at approximately 30-60 minutes, 24, 48, and 67 hours and at 7 and 10 days after patch removal.

For the first 48 hours after test substance instillation, well-defined to moderate erythema and very slight to slight oedema were noted for all three treated dose sites. The overall severity of irritation decreased thereafter. All animals were free from dermal irritation by Day 10. All animals gained body weight and appeared active and healthy during the study. There were no signs of gross toxicity, adverse clinical signs, or abnormal behaviour.

Under the conditions of the study, the test material was found to be not irritating to the skin of New Zealand White rabbits.

Eyes

In the key study, the eye irritation potential of the registered substance (purity: 93.4 %) was investigated by Carreon (1986) in a study which was conducted under the intent of GLP and following a method similar to that which is outlined in the standardised guideline OECD 405. Since this study was not conducted under GLP conditions, but followed a method deemed equivalent to a standardised guideline, it was assigned a reliability score of 2 in line with the criteria of Klimisch et al. (1997).

During the study 0.1 g of test material was instilled once into the right eye of six New Zealand White rabbits. The eyes were not washed. The left eye remained untreated and served as a control. Both eyes of all rabbits on test were examined using a penlight at 1, 24, 48 and 72 hours post-instillation and again at 7, 14 and 21 days for conjunctival redness, chemosis, discharge, corneal opacity and reddening of the iris.

Following application, rabbits appeared to experience moderate discomfort. Examination of the eyes revealed marked conjunctival redness, moderate chemosis, marked discharge, reddening of the iris and in 2 rabbits, scattered/slight opacity of the cornea. All signs of irritation were resolved 21 days post-exposure.

Therefore, under the conditions of the study, the test material was found to be irritating to the eyes of New Zealand White rabbits.

Supporting information (Norris, 1971) is available in the form of a study which investigates the eye irritation potential of the registered substance (purity: 90 % minimum) using a method similar to that which is outlined in the standardised guideline OECD 405. 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).

The test procedure consisted of instillation of approximately 0.1 mg of undiluted test material (dust) or 0.1 mL of a 10 % propylene glycol solution of test material into the conjunctival sac of the right eye of two New Zealand White rabbits. Following a 30 second exposure period the eye was washed for 2 minutes with tepid, flowing tap water. The dust and the 10 % propylene glycol solution of test material were then instilled in a similar manner in the left eye which was left unwashed. At this time both eyes were examined for conjunctival irritation, corneal injury and internal effects such as iritis. The behaviour of the animals was observed for indications of pain or discomfort. Observations of both eyes are made at 2, 24 and 48 hours and 7 days after test material installation. Both eyes are stained with fluorescein (5 % solution in water) for these observations.

Instillation of undiluted test material dust into the eyes of a rabbit resulted in very slight or slight pain, and moderate conjunctival inflammation, slight transient iritis and transient corneal haziness in the unwashed eye. The washed eye displayed slight transient conjunctival inflammation. Both eyes appeared normal 48 hours post-instillation of the material.

Instillation of a 10 % propylene glycol solution of test material resulted in slight or moderate pain and moderate conjunctival inflammation in the unwashed eye. The washed eye displayed slight conjunctival inflammation. Both eyes appeared normal one week post-instillation of the material.

 

Further supporting information is available in the form of a study, reported by Lowe (2007) in which the eye irritation potential of a formulation (containing the registered substance at 17.9 %) was investigated in a study which was conducted under GLP conditions and in accordance with the standardised guidelines EPA OPPTS 870.2400, OECD 405, EU Method B.5 and JMAFF 12-Nouan-1847. 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).

During the study, 0.1 mL of test material was instilled into the right eye of three healthy New Zealand White rabbits. The left eye remained untreated and served as a control. Ocular irritation was evaluated in accordance with the Draize scale at 1, 24, 48, and 72 hours post-instillation

There was no corneal opacity or iritis observed in any treated eye during this study. One hour after test material instillation, all three treated eyes exhibited positive conjunctivitis. The overall incidence and severity of irritation decreased with time. All animals were free of ocular irritation by 72 hours.

All animals appeared active and healthy. There were no signs of gross toxicity, adverse clinical signs, or abnormal behaviour.

Under the conditions of the study the test material was found not to be irritating to the eyes of New Zealand White rabbits.

Justification for selection of skin irritation / corrosion endpoint:

The key study was conducted on the registered substance, under GLP conditions and according to standardised guidelines; it was therefore assigned a reliability score of 1 in line with the criteria of Klimisch et al. (1997).  

Justification for selection of eye irritation endpoint:

The key study was selected as the methodology used was most closely related to the method outlined in standardised guidelines. According to guideline, and classification and labelling requirements, a sufficient number of test animals were included, observations were performed at the required time points, and the required amount of test material was instilled in the eye.

Conversely, the study by Norris (1971) did not include a sufficient number of test animals, or a sufficient quantity of test material. The study by Lowe (2007) was not conducted on the registered substance itself, rather a formulation containing the registered substance at 17.9 %.

Effects on eye irritation: irritating

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 does not require classification with respect to either skin corrosion or skin irritation

In accordance with the criteria for classification as defined in Annex VI, Directive 67/548/EEC (DSD), the substance does not require classification with respect to either skin corrosion or skin irritation.

For eye damage/eye irritation:

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No. 1272/2008, the substance should be classified as Category 2 H319 (Causes serious eye irritation) 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 R36 (Irritating to eyes) with the symbol Xi.