Registration Dossier

Administrative data

Description of key information

A number of skin irritation and eye irritation studies are available.  Studies are of variable design but indicate that acrylonitrile is a skin irritant (but not corrosive) and a severe eye irritant.  The animal data are also consistent with experiences of accidentally exposed workers.  Findings from animal studies and human experience also indicate that the substance is a respiratory irritant.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
: scores for erythem and oedema combhined; intact and abraded skin sites used; 24-hour exposure
GLP compliance:
no
Remarks:
Tests prior to GLP
Species:
rabbit
Strain:
New Zealand White
Type of coverage:
occlusive
Preparation of test site:
other: sites were shorn, intact and abraded sites were used
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 ml
Duration of treatment / exposure:
24 hours
Observation period:
72 hours
Number of animals:
Six
Irritation parameter:
other: combined mean score for oedema and erythema
Basis:
mean
Time point:
other: 24-72h
Score:
3.6
Reversibility:
not fully reversible within: 72h

The mean score both erythema and oedema was 3.6, with slightly higher scores reported for abraded skin.

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
The results of this study indicate that acrylonitrile is a skin irritant, but is not corrosive.
Executive summary:

In this guideline-comparable study, 0.5 mL acrylonitrile was applied for 24 hours under occlusive conditions to the shorn (intact and abraded) dorsal skin of six New Zealand White rabbits. Dermal reactions were assessed at 24 and 72 hours following application and mean scores (24 and 72 hour) scores (on a scale of 0 to 4) for both erythema and oedema are reported. The mean score for both erythema and oedema was 3.6, with slightly higher scores reported for abraded skin. This study that acrylonitrile is a skin irritant and should be classified as such.

Endpoint:
skin irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Remarks:
EU RAR assessed all exisiting data and provided classification
Qualifier:
no guideline followed
Principles of method if other than guideline:
The EU RAR summarises the results of two skin irritation studies in rabbits
GLP compliance:
not specified
Remarks:
: review of published studies
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Two studies are reported; one study uses young adult New Zealand White rabbits (Vernon et al, 1969), there is limited information available for the second study, rabbits were used (Zeller et al, 1969).
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
Vernon et al (1969) applied 0.5 ml acrylonitrile to the shaved skin. Zeller et al (1969) applied an unspecified amount of liquid acrylonitrile soaked onto a cotton pad.
Duration of treatment / exposure:
Vernon et al. applied acrylonitrile occlusively for 24 hours.
Zeller et al. applied acrylonitrile on a cotton pad for either 15 minutes or 20 hours.
Observation period:
Vernon et al: 72 hours after administration
Zeller et al: no information available
Number of animals:
Vernon et al: 6 rabbits
Zeller et al: no information available
Details on study design:
Two studies are reported in the EU RAR: Vernon et al (1969) and Zeller et al (1969). Vernon et al applied 0.5 ml acrylonitrile occlusively to shaved rabbit skin for a period of 24 hours. Skin irritancy was evaluated at 24 and 72 hours. Zeller et al (1969) applied liquid acrylonitrile on a cotton pad to shaved rabbit skin for 15 minutes or 20 hours. The skin exposed for 15 minutes was washed concentrated polyethylene glycol and water. Skin exposed for 20 hours remained unwashed.
Irritation parameter:
overall irritation score
Remarks:
erythema and oedema
Basis:
mean
Time point:
other: 0-72 h mean
Score:
3.6
Remarks on result:
other: Vernon et al (1969)
Irritant / corrosive response data:
Vernon et al (1990) report a mean irritation score of 3.6, with slightly higher scores being obtained for abraded skin.
Zeller et al (1969) report that the skin exposed for 15 minutes then washed showed oedema only, whereas skin exposed for 20 hours showed clear necrosis of the tissue.
Other effects:
No further informaton

No further information.

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
The EU RAR states the acrylonitrile is strongly irritating to the skin based on the Vernon et al (1969) data, and requires classification as an irritant, but is not corrosive.
Executive summary:

The EU RAR reports two acrylonitrile skin irritant studies in rabbits. Vernon et al (1990) report a mean irritation score of 3.6, with slightly higher scores being obtained for abraded skin. Zeller et al (1969) report that the skin exposed for 15 minutes then washed showed oedema only, whereas skin exposed for 20 hours showed clear necrosis of the tissue. The EU RAR recommends that acrylonitrile be classified as a skin irritant.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
Only two rabbits were used; the eye of one rabbit was washed, the eye of the other rabbit remained unwashed.
GLP compliance:
no
Remarks:
: older study, pre-dates GLP
Species:
rabbit
Strain:
not specified
Remarks:
albino
Details on test animals or tissues and environmental conditions:
Two albino rabbits.
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.1mL undiluted acrylonitrile
Duration of treatment / exposure:
One rabbit's treated eye was washed after 20 seconds, the second rabbit's eye was not washed.
Observation period (in vivo):
21 days
Number of animals or in vitro replicates:
2 rabbits
Details on study design:
Observations of the eye were made at 1 and 4 hours and subsequently after 1, 2, 7, 14 and 21 days.
Irritation parameter:
cornea opacity score
Basis:
other:
Time point:
21 d
Score:
ca. 1
Max. score:
3
Reversibility:
not fully reversible within: 21 days
Remarks on result:
probability of severe irritation
Irritant / corrosive response data:
Acrylonitrile produced moderate corneal opacity, moderate iritis and severe conjunctival irritation in the unwashed treated eye. The treated eye that was washed after 20 seconds exposure showed slight temporary corneal opacity, transient moderate iritic congestion and moderate conjunctival irritation.
Other effects:
No other effects reported.

Acrylonitrile produced moderate corneal opacity, moderate iritis and severe conjunctival irritation in the unwashed treated eye. The treated eye that was washed after exposure for 20 seconds showed slight temporary corneal opacity, transient moderate iridic congestion and moderate conjunctival irritation. The washed eye was normal within 3 days. The unwashed eye showed signs of healing by Day 3, with some evidence of corneal vascularisation. By Days 14 and 21, mild opacity remained with traces of vascularisation. The effects were seen in both rabbits and were not completely reversible in the unwashed eye, while by washing the eye the effects were considerably lessened, as was the duration of the effects.

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
The results of this study indicate that acrylonitrile causes eye irritation. The lack of complete reversibility of corneal effects within the 21-day study period supports the harmonised classification of the substance for serious eye damage (Cat 1) according to CLP.
Executive summary:

In a guideline-comparable study, 0.1 mL acrylonitrile was instilled into in the conjunctival sac of the right eye of two rabbits. After 20 seconds the treated eye of one of the rabbits was washed with tap water for 1 minute, the other rabbit remained unwashed. Corneal opacity/conjunctive irritation occurred up to 3 days in the washed eye and up to 21 days in the unwashed treated eye. Acrylonitrile was therefore found to be an eye irritant under the conditions of this study. The lack of complete reversibility of corneal effects within the 21-day study period supports the harmonised classification of the substance for serious eye damage (Cat 1).

Endpoint:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Qualifier:
no guideline followed
Principles of method if other than guideline:
Summaries of various eye irritation studies conducted in rabbits. Some studies are guideline-comparable, others are not.
GLP compliance:
not specified
Species:
rabbit
Strain:
not specified
Details on test animals or tissues and environmental conditions:
No further information available
Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
Volumes of 0.05 ml and 0.1 ml were applied directly into the eyes.
Duration of treatment / exposure:
The test substance was instilled into the eyes without washing.
Observation period (in vivo):
Up to 7 days post-administration
Number of animals or in vitro replicates:
1-2
Details on study design:
Acrylonitrile was administered into the eyes of rabbits and irritation scores were recorded at various time periods up to 7 days following administration. One study reports treating the control eye with NaCl solution, the remaining studies either provide no information or leave one eye untreated to serve as the control.
Irritation parameter:
conjunctivae score
Max. score:
2
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: BASF study
Irritation parameter:
chemosis score
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: BASF study
Irritation parameter:
other: Draize score
Basis:
mean
Time point:
other: 24 hours
Score:
35
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: Vernon et al
Irritation parameter:
other: Draize score
Basis:
mean
Time point:
other: 48 hours
Score:
31
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: Vernon et al
Irritation parameter:
other: Draize score
Basis:
mean
Time point:
other: 72 hours
Score:
22
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: Vernon et al
Other effects:
Some investgators report additional effects (eg.g petechiae. corneal burns, conjunctival necrosis) consistent with severe irritation.

A number of studies are summarised.

In a BASF study (1963) 0.05 ml acrylonitrile applied undiluted to the left eye of two rabbits resulted in findings at 1 hour of slight conjunctival erythema, diffuse corneal opacity, severe conjunctival oedema, miosis and discharge. At 24 hours erythema was more marked; corneal opacity remained with oedema in one animal and ciliary injection. At 48 hours erythema had reduced with corneal opacity one animal. At 72 hours all reactions had resolved in one rabbit; erythema, petechiae and diffuse corneal opacity were apparent in the other animal. Findings in the second rabbit had resolved by Day 7.

Vernon et al (1969) instilled 0.1 ml acrylonitrile was instilled in one eye of six rabbits. Ocular reactions were scored at 24, 48 and 72 hours using the original system proposed by Draize. The results from this study were presented in accordance with the Draize scoring system, taking into account both the intensity and the area of involvement. Acrylonitrile gave a maximum Draize score of 35 out of 110 at 24 hours, falling to 31 at 48 hours and 22 at 72 hours. The EU RAR reports that it is not possible to deduce the scores for intensity alone (as required for EU classification), however the reported scores and lack of reversibility within the study period indicate that the substance should be classified as an eye irritant.

In a study by Zeller et al (1969) oedema and slight necrosis of the conjunctiva after 8 days were observed in rabbits. No further details of this study are available.

In another study, following application of 0.05 ml of undiluted acrylonitrile, mild irritation was observed in the eye of a rabbit, and after one hour mild conjunctivitis had developed. Reactions resolved within 24 hours (McOmie, 1949). Other investigators report a severe burn of the cornea after application of 0.02 ml of undiluted acrylonitrile to the rabbit eye (VROM, 1984).

The DuPont study is also reported in the EU RAR.

The EU RAR used these studies to consider the classification for eye irritation. This information was considered sufficient to classify Acrylonitrile as an eye irritant with risks of serious eye damage

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
The available animal data from various sources indicate that acrylonitrile is an eye irritant.
Executive summary:

Several rabbit studies are reported in the EU RAR document; the study designs vary, however the results are consistent in demonstrating that acrylonitrile is an eye irritant..

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Skin irritation

In a guideline-comparable study (Vernon et al., 1990), 0.5 mL acrylonitrile was applied for 24 hours under occlusive conditions to the shorn (intact and abraded) dorsal skin of six New Zealand White rabbits. Dermal reactions were assessed at 24 and 72 hours following application and mean scores (24 and 72 hour) scores (on a scale of 0 to 4) for both erythema and oedema are reported. The mean score both erythema and oedema was 3.6, with slightly higher scores reported for abraded skin. This study that acrylonitrile is a skin irritant and should be classified as such. The EU RAR also reviews the available animal data on the skin irritation of acrylonitrile. The dataset consists of two studies, the most reliable of which is that of Vernon et al (1990). Both studies are consistent in indicating that acrylonitrile is a skin irritant. The animal data are consistent with experience of skin irritation in workers following accidental exposure. No further testing is proposed.

Eye irritation

In a guideline-comparable study (DuPont, 1975), 0.1 mL acrylonitrile was instilled into in the conjunctival sac of the right eye of two rabbits. After 20 seconds the treated eye of one of the rabbits was washed with tap water for 1 minute, the other rabbit remained unwashed. Corneal opacity/conjunctive irritation occurred up to 3 days in the washed eye and up to 21 days in the unwashed treated eye. Acrylonitrile was therefore found to be an eye irritant under the conditions of this study; the lack of complete reversibility of corneal effects within the 21-day study period supports the harmonised classification of the substance for serious eye damage (Cat 1). Several additional rabbit studies are reported in the EU RAR document; the indidividual study designs and quality vary, however the results are consistent in demonstrating that acrylonitrile is an eye irritant. The EU RAR concludes that classification of acrylonitrile for serious eye damage is appropriate. This classification is also consistent with human experience.

Respiratory irritation

No specific animal studies of respiratory irritancy such as the Alarie test have been carried out. The EU RAR states that both long-term and short-term toxicity studies in a range of species indicate that acrylonitrile has irritant effects on the upper respiratory tract. Occupational exposure has also been reported to result in respiratory irritation.

Justification for classification or non-classification

Acrylonitrile is listed on Annex VI of the CLP Regulation (1272/2008/EC) with classification in Skin Irritation Class 2 (H315: causes skin irritation), Eye Damage Class 1 (H318: causes serious eye damage) and STOT H335 Category 3 (May cause respiratory irritation). This classification is consistent with the available data and no changes to the harmonised classification are proposed. The EU RAR also notes isolated reports of corrosive effects of acrylonitrile following accidental human exposure. It concludes, however, that animal data and more recent human experience indicate that while acrylonitrile is irritant to skin, eye and respiratory tract it should not be considered as corrosive and that classification of acrylonitrile as a skin corrosive is not appropriate.