α-chlorotoluene

Endpoint summary

Additional information

Skin irritation:

Two studies are available on skin irritation of the benzyl chloride. They both are based on animal studies and based on an american standard methods. The levels of details for each study are similar.

In a study report from Birch (1975), the authors tested the skin irritation properties of benzyl chloride (CAS n° 100-44-7) with two different methodologies, one described in the F.H.S.A (16CFR1500.41) and one in the D.O.T (49CFR173 appendix A). They exposed an unknown number of New Zealand rabbits to 0.5 mL of pure benzyl chloride.Presence of erythema and edema were investigated, besides apparent injury in depth of the skin.

After 4h of exposure in the D.O.T experiment, the New Zealand rabbits displayed at time points 4h and 24h moderate erythema and edema. In ten to fourteen days a defatting effect was observed, but no injury in depth was observed. No reversibility of the observed effects is reported. The loosening of the edges of scabs after 17 days of exposure to benzyl chloride in the New Zealand rabbits indicated in the F.H.S.A experiment, that the test substance should be classified as corrosive according to F.H.S.A criteria. Based on the CLP regulation n° 1272/2008 EC, benzyl chloride should be classified as a skin irritant category 2 based on the defatting effect observed in the DOT experiment until the end of observation period (14 days).

In an other study report from Thyssen (1979), the authors tested the potential of benzyl chloride (CAS n° 100-44-7) to cause skin irritation by following a methodology which is also similar to the method described in the Code of Federal Regulation, title 16, section 1500.41. The shaved skin of two New Zealand white rabbits was exposed to approximately 0.5 mL of the test substance during 24h. Afterwards the patches containing the test substance were removed and the reaction of the skin to this exposure was observed for 7 days. Erythema and edema reactions were scored and recorded for seven days.

Under the test conditions, severe redness was observed during the entire observation period (i.e. untill 7d after removal of test substance) and moderate swelling was noted untill 2 days after removal of the test substance. Finally at the end of the observation period the treated skin was necrotic.

In both experiments, generally few details are available on the results. Neither individual scores, nor mean scores are reported in both experiments. The skin responses seem despite well evaluated and based on scientifc principles. However, the first expriment of Birch (1975) is the most relevant as one the method involved in the testing has a four hours exposure period and an observation period of fourteen days. This study design is also described in the OECD guideline 404 and is the first basis for classification. Besides, the defatting effect observed at the end with one method and the loosening of the scabs observed with the other method bring strong consistent evidences that benzyl chloride should be considered as a skin irritant according to the CLP regulation n° 1272/2008 EC. Hence, all these elements were the basis for the choice of the Birch study (1975) as a key study.

Eye irritation:

Two studies are available on eye irritation of the benzyl chloride. They both are based on animal studies and based on an american standard methods. The levels of details for each study are also similar.

In the study from Birch (1975), the authors tested also the eye irritation of New Zealand Albino rabbits exposed to benzyl chloride (CAS n° 100-44-7) following a methodology described in 16 CFR 1500.42 and a method similar to the OECD guideline 405 (Acute eye irritation/corrosion). Six rabbits were exposed for 24h to 0.1 mL undiluted benzyl chloride and the effects on the cornea, iris and conjunctivae were recorded at 1, 24, 48, 72, 120, 168 hours and 10 days, and graded according to FHSA scoring criteria.

Immediately after the exposure, the rabbits exhibited discomfort. The reaction to the test substance increased and the maximum mean total score (i.e. 23.8/110.0) was reached after 24h. At this time point the test specimens displayed areas of barely perceptible corneal dullness, severe erythema, slight to moderate edema and copious discharge. From 48 to 168 there was a gradual improvement and after 10 days all scored zero.

Thus results indicate that benzyl chloride should be considered as a mild irritant according to FHSA criteria.

In the study from Thyssen (1979), the authors tested also the potential of benzyl chloride (CAS n° 100-44-7) to cause skin irritation by following a methodology which is similar to the method of CFR, 16, 1500.42. One of the eyes of two New Zealand white rabbits was exposed to approximately 100 µL of the test substance and the reaction of the cornea, iris and conjuncivae was followed and recorded for seven days. In this experiment, the scoring system used may have been the same than the OECD scoring system but no further information is provided.

Immediately after application a moderate redness and slight swelling of the treated eye was observed which still could be observed after 24h. The test substance was however partially washed out by the almost simultaneous onset of tear flow at the start of the exposure. As a result two days after exposure only a very slight irritation of the conjunctivae could be noted and this persisted untill the end of the observation period. Furthermore in one of the two tested animals slight redness and swelling of the iris as well as slight and diffuse opacity was noted untill two days after application.

In both studies, the skin responses have been well studied and sufficiently documented. However, the study design gives more reliability to the study from Birch (1975) since six rabbits were tested. Besides, the observation period was longer in this experiment. In both experiments, evidences are brought that benzyl chloride may be considered as an eye irritant. Hence, all these elements were the basis for the choice of the Birch (1975) study as a key study.