(chloromethyl)vinylbenzene

Endpoint summary

Description of key information

Skin irritation/corrosion

Key: In vitro skin irritation (in vitro EpiDerm skin irritation assay, Settivari 2017, OECD Guideline 439): positive, potential irritant

Supporting:

In vivo skin irritation (albino rabbit, Morris 1971): positive, potential irritant

In vitro skin corrosion (in vitro EpiDerm skin corrosion assay, Settivari 2017, OECD Guideline 431): negative, non corrosive

In vivo skin corrosion (albino rabbit, Rampy 1973, acc. to paragraph 191.11 of 21 CFR, Part 191 (rev. as of January 1, 1970): negative, non corrosive

Eye irritation/corrosion

Key: In vitro eye irritation/severe eye damage (in vitro EpiOcular eye irritation assay, Settivari 2017, OECD Guideline 492): positive, potential ocular irritant

Supporting:

In vivo eye irritation (rabbit, Wolf 1955): positive, mild results and indication on reservibility, potential eye irritant

In vivo eye irritation (rabbit, Biggs 1969): positive, potential eye irritant

In vivo eye irritation (albino rabbit; Rampy 1973): positive, potential eye irritant

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)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In vitro skin irritation

Vinylbenzyl chloride was evaluated for skin irritation potential in an non-GLP in vitro EpiDerm skin irritation assay (MatTek Corporation; Ashland, MA) according to OECD Guideline 439 (KS_Skin irritation_RHE EpiDerm tissue model_in vitro_2017).

The EpiDerm tissue model consists of normal human epidermal keratinocytes that are cultured to form a multilayered, differentiated model of human epidermis. In this assay, vinylbenzyl chloride was topically applied to the EpiDerm tissue for 60 minutes, followed by a 42-hour post-exposure recovery. Following recovery, the cell viability was measured in treated and control tissues using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay and the data reported as a percentage of the mean of negative control. A test chemical is considered to possess skin irritation potential (Cat 1 or 2) if the relative cell viability is less than or equal to 50%. In this study, Dulbecco’s Phosphate Buffered Saline (DPBS) and 1% TRITON™ X-100 served as the negative and positive controls, respectively.

The mean relative cell viability of vinylbenzyl chloride and positive control-treated tissues were 2.3% and 3.2% (i.e. ≤ 50%), respectively, therefore, vinylbenzyl chloride was interpreted as a potential irritant (Cat 1. or 2) in the EpiDerm irritation assay.

In vitro skin corrosion

Vinylbenzyl chloride was evaluated for skin corrosion potential in an non-GLP in vitro EpiDerm skin corrosion assay (MatTek Corporation; Ashland, MA) according to OECD Guideline 431 (SS_Skin corrosion_EpiDerm reconstituted humen epidermis model_in vitro_2017). The EpiDerm tissue model consists of normal human epidermal keratinocytes that are cultured to form a stratified, squamous epithelium similar to that found in human epidermis. In this assay, vinylbenzyl chloride was topically applied to the EpiDerm tissue model for 3 and 60 minutes. The cell viability was then measured in treated and control tissues using MTT (3-(4,5 - dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay and the data reported as a percentage of the mean of negative control. Skin corrosion potential of the test substance was classified according to tissue viability following the two exposure times. The test substance is considered corrosive if the mean viability is ≤ 50% at three minutes or ≥ 50% at three minutes but less than 15% at one hour. Sterile water and 8N potassium hydroxide served as the negative and positive controls, respectively.

The mean tissue viabilities of vinylbenzyl chloride-dosed tissues following the three minute exposure period was 113.5% and following the one hour exposure period was 123.8%. Therefore, under these conditions, vinylbenzyl chloride was interpreted as non-corrosive in the EpiDerm corrosion assay.

In vivo skin irritation

Tests in albino rabbits revealed irritation properties of the test substance vinylbenzyl chloride. Prolonged skin contact may result in moderate redness and swelling accompagnied by a superficial burn. Repeated contact may result in a moderate to severe burn (SS_Skin irritation study_in vivo_rabbit_1971).

In vivo skin corrosion

The skin corrosion study approved for use by the DOT (U.S. Department of Transportation) was described in Paragraph 191.11 of 21 CFR, Part 191 (revised as of January 1, 1970). Due to the absence of observable irreversible changes or destruction of the initially intact skin of an albino rabbit after an exposure period of four hours vinylbenzyl chloride was considered to be non-corrosive (SS_skin_corrosion study_in vivo_rabbit_1973).

In vitro eye irritation

Vinylbenzyl chloride was evaluated for eye irritation potential in an in vitro EpiOcular eye irritation assay according to OECD Testing Guideline 492 (KS_EpiOcular eye irritation assay_RhCE_in vitro_2017). The EpiOcular tissue model consists of normal, human-derived epidermal keratinocytes that are cultured to form a stratified, squamous epithelium similar to that found in the cornea. In this assay, vinylbenzyl chloride was topically applied to the EpiOcular tissue for 2, 15, or 30 minutes followed by a 120 ± 15 minute post-exposure recovery. Following recovery, the cell viability was measured in treated and control tissues using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay and the data reported as a percentage of the mean of negative control. An ET-40 value was calculated for vinylbenzyl chloride, which is the time of exposure that resulted in reduction in cell viability to 40% of negative control level. The test substance is considered a (severe) irritant (UN GHS Cat 1 or 2) if the mean relative cell viability is <= 60%. The test substance was considered a nonirritant (UN GHS Cat NC) if the relative mean cell viabiliy is >60%. In this study, Dulbecco’s Phosphate Buffered Saline (DPBS) and 0.3% TRITON™ X-100 served as the negative and positive controls, respectively.

The mean relative cell viability of the positive control-treated tissue was 13.7%. Exposure of the tissue model to the test material vinylbenzyl chloride for 30 min reduced the mean relative cell viability to 30.8 %. Therefore, under these conditions, vinylbenzyl chloride was interpreted as a potential ocular irritant (UN GHS Category 1 or 2) in the EpiOcular assay.

In vivo eye irritation

When rabbit eyes were treated with undiluted vinylbenzyl chloride or 10 % vinylbenzyl chloride in propylene glycol, each unwashed and washed with H2O, the following results were obtained (SS-Range Finding Toxicological Tests_in vivo_rabbit_1955):

Material	Treatment	Response - Remarks
100%	Unwashed	Moderate pain, slight conjuctival irritation and trace of corneal injury. Almost completely healed in 24 hours.
100%	Washed H2O	Trace of pain, trace of conjuctival irritation. Completely healed in 24 hours.
10 % in propylene glycol	Unwashed	Slight pain, marked conjunctival irritation and marked corneal injury healing in 7 days.
10 % in propylene glycol	Washed H2O	Slight conjuctival irritation, trace of corneal injury. Completely healed in 24 hours.

It was concluded that the undiluted material has a slight effect on the eye. Pain and conjunctival inflammation may persist for several days. Transient corneal injury may occur, but is expected to heal completely within a few days.

Contact of the liquid test material with the eye of albino rabbits resulted in slight effect on the eye (Biggs, 1969). It was concluded that pain and conjunctival inflammation may persist for several days after eye contact. Transient corneal injury may occur, but is expected to heal completely within a few days.

In another experiment, direct contact of the material with the eye of a single albino rabbit resulted in discomfort, not pain, slight conjunctival membrane inflammation, corneal haziness, very slight iritis and lacrymation (SS_Eye irritation in vivo_rabbit_1971).

Overall, eye contact with the undiluted material may result in moderate pain, slight conjunctival irritation, and transient corneal injury. The material is a lacrimator.

Justification for classification or non-classification

Effects on the skin

In the in vitro skin irritation assay (KS_Skin irritation_RHE EpiDerm tissue model_in vitro_2017) the mean relative cell viabilities of vinylbenzyl chloride- and positive control-treated tissues were 2.3% and 3.2% (i.e. ≤ 50%), respectively. Therefore, vinylbenzyl chloride was interpreted as a potential irritant (Cat 1 or 2) in the EpiDerm irritation assay.

In the subsequent in vitro skin corrosion assay (SS_Skin corrosion_EpiDerm reconstituted human epidermis model_in vitro_2017) the mean tissue viabilities of vinylbenzyl chloride-treated tissues following the three minute exposure period was 113.5% and following the one hour exposure period was 123.8%. Therefore, under these conditions, vinylbenzyl chloride was interpreted as non-corrosive in the EpiDerm corrosion assay.

As overall result for the irritation/corrosion potential of vinylbenzyl chloride to skin it is concluded, that the substance is classified according to Regulation (EC) No 1272/2008 (CLP Regulation) as irritating to skin Cat. 2 (Skin Irrit. 2, H315: Causes skin irritation).

Effects on the eye

Based on the findings in an in vitro EpiOcular eye irritation assay according to OECD Testing Guideline 492, vinylbenzyl chloride was interpreted as a potential ocular irritant (KS_EpiOcular eye irritation assay_RhCE_in vitro_2017).

Contact of the undiluted liquid material with the rabbit eye induced moderate pain, sligth conjuctival irritation and trace of corneal injury that almost completely healed within 24 hours. 10% in propylene glycol caused slight pain, marked conjunctival irritation and marked corneal injury healing in 7 days (SS_Range Finding toxicological Tests_in vivo_rabbit_1955). Thes findings were confirmed by Biggs (SS_Eye irritation in vivo_Rabbit_1969) and Morris (SS_Eye irritation in vivo_rabbit_1971) leading to the interpretation that vinylbenzyl chloride is irritating to the eye.

As overall result for the serious eye damage/eye irritation potential of vinylbenzyl chloride it is concluded that the substance is classified according to Regulation (EC) 1272/2008 (CLP Regulation) in Category 2 as irritating to eyes (Eye Irrit. 2, H319: Causes serious eye irritation).