Registration Dossier

Administrative data

Description of key information

Skin irritation studies on ptBP in rabbits have demonstrated that the compound is a severe skin irritant.  PtBP was classified as an irritant according to EEC labelling regulations.  The compound has been determined to be non-corrosive according to EU classification criteria.
PtBP has been demonstrated to be highly irritating to rabbit eyes.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Skin Irritation

Skin irritation studies on ptBP in rabbits, two of which were performed according to OECD test guidelines, have demonstrated that the compound is a severe skin irritant. PtBP was classified as an irritant according to EEC labelling regulations. The compound also has been reported to be corrosive to the rabbit skin to a minor extent; however, the compound has been determined to be non-corrosive according to EU classification criteria (full thickness destruction of the skin on at least one animal/irreversible alteration of the skin).

A skin irritation study on ptBP has been performed in albino New Zealand White rabbits (Tuffnell et al., 1991). The study was performed in accordance with OECD Guidelines for the Testing of Chemicals No. 404 and in compliance with GLP, and therefore, was selected as the key study.  In this study, 3 rabbits (1 male and 2 females) were dermally exposed to 0.5 g of a fine powder of ptBP moistened with 0.5 mL of distilled water on clipped dorsal/flank areas under semi-occlusive conditions. Animals were exposed to the test compound for 4 hours and observations were recorded at 1, 24, 48, and 72 hours, as well as at 7 and 14 days after removal of the patch and residual test substance. Skin reactions were scored according to the method of Draize. Very slight to well-defined erythema was noted at all treated skin sites one hour after patch removal. Severe erythema, small areas of white-coloured necrosis (approximately 5 mm x 5 mm), and well-defined erythema surrounding scabs were noted at all treated skin sites at 24 and 48 hours and at two treated skin sites at 72 hours. Very slight to slight oedema was noted at two treated skin sites one hour after patch removal. Very slight to moderate oedema was noted at all treated skin sites at 24 hours with very slight to slight oedema at 48 and 72 hours. All incidences of erythema and oedema were fully reversible within 7 or 14 days. Other adverse skin reactions observed included hardened light brown-coloured scabs and thickening of the skin at two treated skin sites on day 7, with reduced re-growth of fur on day 14. Well-defined erythema noted at one treated skin site at 72 hours developed crust formation by day 7. The ptBP test material produced a primary irritation index of 5.5 and was classified as a severe irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were observed. The test material was also classified as an irritant according to EEC labelling regulations.

PtBP also was reported to be irritating to rabbit skin in a supportive skin irritation study performed according to OECD Guidelines for the Testing of Chemicals No. 404 (Mürmann, 1985). In this study, 3 male and 3 female small White Russian rabbits were dermally exposed to 0.5 g of ptBP on shaved dorsal/flank areas under semi-occlusive conditions. Animals were exposed to the test compound for 4 hours and observed over a 14-day period after removal of the patch and residual test substance. Skin reactions were scored according to the method of Draize. Erythema was observed at 24, 48, and 72 hours, with an average score of 2.39. Oedema also was observed at 24, 48, and 72 hours, with an average score of 1.56. All incidences of erythema and oedema were completely reversible within 14 days. Other effects observed included scab and scale formation after 6 days and desquamation from day 8 up to day 14. The results of this study indicated that ptBP was irritating to rabbit skin.

Klonne et al. (1988) also conducted a skin irritation study in New Zealand White rabbits. The study was not reported to be performed according to any test guideline, but was deemed reliable, and therefore, serves as a supportive study. A finely ground powder of ptBP was applied in an amount of 0.5 g, moistened with distilled water, to the clipped backs of 3 male and 3 female rabbits. The animals were exposed to the test substance for 4 hours under occlusive conditions. Skin reactions were scored according to the method of Draize at 1 hour, and 1, 2, 3, 7, 10, 14, and 17 days after removal of the bandage and residual test substance. Irritation was not observed in 4 out of the 6 rabbits tested. Minor, transient erythema was observed in 1 rabbit by day 1, with desquamation observed during days 10 to 17. The remaining 2 rabbits displayed minor to severe skin irritation, consisting of slight edema on days 1 through 3 and dermal necrosis on days 1 through 10. Scab formation was observed in these latter animals on days 7 through 10 and desquamation on days 10 through 14. All skin reactions were fully reversible by day 17. Based on the results of this study, ptBP was determined to be irritating to rabbit skin and possibly also corrosive.

In a screening study following an internal company standard, Vienna White rabbits were exposed to about 1 g of an 80% aqueous test substance preparation of ptBP (BASF, 1971). Using an occlusive dressing, the rabbits were exposed for 1 min, 5 min, 15 min or 20 h. After the exposure period, the test substance was washed off with 50% Lutrol and the rabbits observed for 8 days. Non reversible effects were observed. However, the use of occlusive dressings makes the results difficult to interpret.

Further information on the skin irritation potential of ptBP is available in the EU risk assessment on ptBP. In a depigmentation test, skin irritation was induced following exposure of guinea pigs to 0.1 mL solutions of ptBP in various solvents (Gellinet al., 1970). The test substance was applied daily to an area of 3x3 cm3on the shaved skin on the back of 12 randomly bred adult male and female, English, short-hair, black guinea pigs. A solution containing 1 mg ptBP did not produce irritation, whereas 5 mg ptBP produce moderate irritation. Moderate irritation also was observed following application of 10 mg ptBP in DMSO or propylene glycol. PtBP in an amount of 10 mg in acetone induced severe skin irritation, consisting of erythema and oedema extending beyond the area of application. 

Eye Irritation                                                                                               

PtBP has been demonstrated to be highly irritating to rabbit eyes. This finding was determined in an eye irritation test performed in New Zealand White rabbits (Klonne et al., 1988). The study was not reported to be performed according to any test guideline; however, the study was deemed reliable, and therefore, was considered as the key study. In this study, 10 or 80 mg of a finely ground, dry powder of ptBP was applied to the conjunctival sac of one eye of each of 3 males and 3 females. The eyelids were then held together for one second, and the eyes were not rinsed after exposure to the substance. The eyes were scored according to a scale based on the Draize method. Animals were observed for 21 days following exposure. Application of 80 mg ptBP produced severe corneal injury (with vascularization and surface bulges), iritis, and severe conjunctival irritation, which persisted through the 21-day observational period. Similar effects were observed in animals exposed to 10 mg ptBP. Although the severity of the effects in the 10 mg dose group decreased with time, irritation and injury persisted in most eyes for the entirety of the 21-day observational period.

In a screening study following an internal company standard, Vienna White rabbits were exposed to 50 mg of ptBP (BASF, 1971). The substance was not washed out and the rabbits were observed for 8 days. Non reversible effects were observed after 1 hour.

Respiratory Irritation

In the acute inhalational toxicity study conducted by Klonne et al. (1988), signs of respiratory distress were observed in male and female Sprague-Dawley rats exposed to a dust aerosol of ptBP at a concentration of 5.6 mg/L, or 5600 mg/m3, in a 120 L chamber for 4 hours. Observations included mucosal irritation (perinasal, perioral, and periocular encrustation) and signs of respiratory distress (audible respiration, gasping, and a decreased respiration rate) following exposure to ptBP.

In general, the signs of respiratory distress observed in this study are not considered to justify classification, namely due to the high dose used (5600 mg/m3).


Effects on skin irritation/corrosion: highly irritating

Effects on eye irritation: highly irritating

Justification for classification or non-classification

Skin irritation: according to CLP classification criteria, the substance does meet the criteria for classification and labelling for this endpoint (category II: causes skin irritation) as set out in Regulation (EC) No. 1272/2008.

Eye irritation: according to CLP classification criteria, the substance does meet the criteria for classification and labelling for this endpoint (category I: causes serious eye damage) as set out in Regulation (EC) No. 1272/2008.

In general, the signs of respiratory distress observed in two different animal studies are not considered to justify classification, namely due to the high dose used in an acute inhalation study (5600 mg/m3) and due to the administration procedure (gavage) used in a repeated dose study.