Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Skin irritation: not irritant based on OECD TG 439


Eye irritation: not irritant based on OECD TG 437

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:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation / corrosion
Skin irritation potential of test material was tested in accordance to OECD TG 439 in accordance with GLP. Undiluted test item was topically applied to EPISKIN-SMTM for 15 minutes. After a 42 hours post-incubation period, determination of the cytotoxic (irritancy) effect was performed using MTT conversion measurements. The tissue viability obtained after 15 minutes treatment with test material compared to the negative control tissues was 76.9% (84.7, 78.1 and 68.0%). The standard deviation value of the percentage viability of three tissues treated with positive or negative control was resp. 2.5 and 13.7%. Both the positive (6.8% viability) and the negative control were within the historical control data range for both assays and therefore considered valid, indicating that the test system functioned properly. The relative mean tissue viability of the test item is >50% and therefore, under the experimental conditions reported in this study, the test item was classified as non-irritant.


Supporting studies as presented in the EU-RAR (2008)


Several in vivo studies with solutions or mixtures of HHCB are performed and showed very slight to well-defined erythema and very slight oedema. (Haynes 1984, 1985, 1986 and Levenstein 1983 and 1985). In only one of the tests did the mean erythema score for Galaxolide 50 DEP exceed 2.0 (the calculated score was 2.1). For two of the studies it was concluded moderate and mild irritant, the observation period however was not sufficiently long to evaluate full reversibility of the effects. The overall results of the tests do not indicate that test item is a skin irritant.


Eye irritation / corrosion
The eye irritation/corrosion potential of the test item was tested in an OECD TG 437 test, in accordance with GLP. The undiluted test item was applied to bovine eyes for 10 minutes followed by an incubation period of 120 minutes. Negative (sodium chloride 0.9% w/v) and positive (ethanol) control items were tested concurrently, and all tests were performed in triplicate. The two endpoints decreased light transmission through the cornea (opacity) and increased passage of sodium fluorescein dye through the cornea (permeability) were combined in an empirically derived formula to generate an In Vitro Irritancy Score (IVIS). The corneas treated with the test item and with the negative control were clear post treatment and post incubation, while the corneas treated with the positive control were cloudy post treatment and post incubation. The positive and negative acceptance criteria were fulfilled. The IVIS observed for the test material was 1.5 (negative 0.4 and positive 47.7), therefore the substance is not an eye irritant in the BCOP test.


Other supporting studies as presented in the EU-RAR (2008)


Several in vivo studies with solutions or mixtures of HHCB are performed, (Saur 1980, Wolven & Levenstein 1983a, Levenstein 1985 and 1973b) testing for ocular irritation in rabbits are available. Some studies used ethanol, a known eye-irritant as solvent, and are not used. In other studies, some ocular irritation was found. The effects were not severe enough to indicate that the test item is an eye irritant.


 


Photo irritation


Because HHCB absorbs in the UV region, several studies to detect a possible photoirritation hazard have been conducted. 


In tests for photoirritation, results of in vivo studies in Rabbits and guinea pigs were slightly positive reactions at concentrations of 13 or 32% (Sato et al., 1978), positive in 5/20 animals at 6.5% for guinea pigs (Guillot et al., 1985), negative in mice at 65% (Forbes et al., 1978), and positive reactions were observed at >3.25% in rabbits and guinea pigs (Ogoshi et al., 1980, 1981).


There is no standardized protocol for conducting photoirritation screening in humans. Because of this, several tests were conducted in different laboratories using their standard protocol and standard operating procedures. Information on several studies is available, where results were negative at 65% (Lindstrum et al., 1978a, 1978b, 1978c), negative at 6.5% (Harrison and Stolman, 1986, Gabriel and Mark, 1987, Folk and Dammers, 1987, Shanahan and Alworth, 1987) and one negative at 25% (Mills, 1997).


Results found in in vitro studies of photoirritation of HHCB were negative for a Mouse Fibroblasts 3T3 Assay (Harbell et al., 2001), positive for Photohemolysis of human RBCs (Sugiyama et al., 1994), and studies in yeast where results were positive in three studies (Sugiyama et al., 1994, Forbes et al., 1978, Bagley et al., 1988) and negative in two (Tenenbaum et al., 1984, Weinberg and Springer, 1981).


In conclusion, there are some indications from animal studies that HHCB could be a photoirritant. The results in human tests do not indicate a photoirritating effect in humans. Also, an in vitro phototoxicity test (in compliance with test guideline B.41 (EU/COLIPA Test)) was negative.


 


Respiratory irritation


There are no occupational or consumer data indicating respiratory tract irritation. There are also no relevant experimental guidelines or results available that indicate respiratory irritation, therefore respiratory irritation is not anticipated. The ECHA guidance presents (R7a: 7.2.12.1, 2017) that respiratory irritation maybe be indicated when the substance is a severe irritant. The substance is not a skin or eye irritant and therefore it is not likely to be a respiratory irritant. 

Justification for classification or non-classification

The substance does not have to be classified for skin irritation/corrosion or eye irritation/corrosion according to EU CLP (EC No. 1272/2008 and its amendments).