Registration Dossier

Administrative data

Description of key information

SKIN:

The study was carried out in accordance with the OECD guideline No. 404, 'Acute Dermal Irritation/Corrosion. The dermal route was selected because HEOX-CN may accidentally come into contact with the skin during manufacture, handling and/or use.

Three rabbits were exposed to 0.5 ml of HEOX-CN, applied onto shaved skin for 4 hours using a semi-occlusive dressing. Observations were made 1, 24, 48 and 72 hours and 7, 14 and 21 days after exposure. Different effects were observed between the edges and the remaining part of the treated skin after exposure to HEOX-CN. Signs of necrosis were apparent at the edges of the treated area in all animals, from day 1 onwards. Scabs had developed during the course of the study 7 days after exposure. Healing resulted in the presence of scar tissue in all animals. In the remaining part of the treated area, moderate to severe erythema and moderate or severe oedema were observed, which had completely resolved within 21 days after exposure. Superficial fissuring of the skin was observed in one animal and scaliness in all animals after 7 days. Bald skin and areas with increased density of hair growth in the treated area was noted in one animal at termination.

The development of scar tissue in all three animals indicate that corrosion had occurred after dermal application of HEOX-CN to the rabbit skin. Based on these results and according to the EEC criteria for classification and labelling requirements for dangerous substances and preparations (Guidelines in Commission Directive 93/21/EEC, 27th April 1993), HEOX-CN causes burns (R 34).

EU classification: Category !C (Corrosive)

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:
key study
Study period:
29th August 1995 to 19th September 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
IN-LIFE DATES: From: 29 August 1995 To 19 September, 1995:

Species: Albino Rabbit, New Zealand White, (SPF-Quality)
Source: Broekman Institute, Someren, The Netherlands.
Number: 3 male rabbits
Age at start of treatment: Approx. 8 weeks
Body weight at start: 1381 - 1439 grams
Identification: Ear tag.

ANIMAL HUSBANDRY

Condit ions
Air-conditioned room with approximately 15 air changes per hour and the environment controlled with optimal conditions considered as being a temperature of 21°C and a relative humidity of 50%. Fluctuations from these optimal conditions were noted, but were considered not to have affected study integrity. Lighting was 12 hours artificial fluorescent light and 12 hours dark per day.

Accommodation
Individually in labelled cages with perforated floors (Scanbur Denmark) and equipped with an automatic drinking system (ITL, Bergen, The Netherlands). Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.

Diet
Standard laboratory rabbit diet (LKK-20, pellet diameter 4mm, Hope Farms, Woerden, The Netherlands) approx. 100 gram per day. Certificates of analysis were examined and retained in the NOTOX archives.
In addition, hay (BMI, Helmond; The Netherlands) was provided once a week.

Water
Free access to tap-water diluted with decalcified water. Certificates of analysis were examined and retained in the NOTOX archives.
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5 ml
Duration of treatment / exposure:
See details of study design
Observation period:
See details of study design
Number of animals:
3 male rabbits
Details on study design:
Approximately 24 hours before treatment, the dorsal fur was shaved with electric clippers, exposing an area of approximately 150 square centimeters (10x15 cm').The animals were examined, and the skin to be treated in particular, prior to test substance administration and no abnormalities were detected. On test day 1, 0.5 ml of the test sUbstance was applied to the intact skin of the shaved area on one flank, using a surgical gauze patch of 2x3 cm. A similar patch (but without test substance) was applied to the contralateral flank, to act as a procedural control. Both patches were mounted on Micropore tape* , which as wrapped around the abdomen and secured with Coban elastic bandage*. Four hours after the application, the dressing was removed and the remaining test substance removed using a tissue moistened with tap-water and subsequently a dry tissue.

Whenever considered necessary the skin areas concerned of the animals were reshaved at least 3 hours before observations, to facilitate the scoring .

(•. Supplier, 3M, st. Paul, U.S.A.) .
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
(1257)
Time point:
other: 1 hour
Score:
2
Max. score:
4
Remarks on result:
other: excludes the edges, which were scored separately
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
(1258)
Time point:
other: 1 HOUR
Score:
2
Max. score:
4
Remarks on result:
other: excludes the edges, which were scored separately
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
(1260)
Time point:
other: 1 HOUR
Score:
2
Max. score:
4
Remarks on result:
other: excludes the edges, which were scored separately
Irritation parameter:
erythema score
Basis:
animal: Animals 1, 2 , and 3 had scores 2, 2 and 2 respectively
Time point:
other: 24 hours
Score:
2
Max. score:
4
Remarks on result:
other: excludes the edges, which were scored separately
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 48 hours
Score:
2
Max. score:
4
Remarks on result:
other: excludes the edges, which were scored separately
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 48 hours
Score:
2
Max. score:
4
Remarks on result:
other: excludes the edges, which were scored separately
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 48 hours
Score:
2
Max. score:
4
Remarks on result:
other: excludes the edges, which were scored separately
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 72 hours
Score:
3
Max. score:
4
Remarks on result:
other: excludes the edges, which were scored separately
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 72 hours
Score:
3
Max. score:
4
Remarks on result:
other: excludes the edges, which were scored separately
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 72 hours
Max. score:
4
Remarks on result:
other: excludes the edges, which were scored separately
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 7 days
Score:
2
Max. score:
4
Remarks on result:
other: comment: superficial fissuring of the skin and scaliness. Excludes the edges, which were scored separately.
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 7 days
Score:
3
Max. score:
4
Remarks on result:
other: Comment: Scaliness. excludes the edges, which were scored separately
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 7 days
Score:
2
Max. score:
4
Remarks on result:
other: Comments: Scaliness. excludes the edges, which were scored separately
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 14 days
Score:
2
Max. score:
4
Remarks on result:
other: excludes the edges, which were scored separately
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 14 days
Score:
0
Max. score:
4
Remarks on result:
other: excludes the edges, which were scored separately
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 14 days
Score:
0
Max. score:
4
Remarks on result:
other: excludes the edges, which were scored separately
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 21 days
Score:
0
Max. score:
4
Remarks on result:
other: Comments: Areqas with bald skin and areas with increased density of hair growth compared to adjacent skin and control area. Excludes the edges, which were scored separately
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 21 days
Score:
0
Max. score:
4
Remarks on result:
other: excludes the edges, which were scored separately
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 21 days
Score:
0
Max. score:
4
Remarks on result:
other: excludes the edges, which were scored separately
Irritant / corrosive response data:
IRRITATION AND CORROSION
Different effects were observed between the edges and the remaining part of the treated skin after 4 hours exposure to 0.5 ml of HEOX-CN.
Signs of necrosis (grey/black discolouration of the skin) were apparent at the edges of the treated area (SlO% of the total treated area) in all animals, from day 1 onwards. Scabs had developed within 7 days after exposure. Healing resulted in the presence of scar tissue (bald skin with a prominent white appearance) in all animals, apparent 14 or 21 days after exposure.
In the remaining part of the treated area, erythema and oedema were observed, which had completely resolved within 21 days after exposure. The maximum degree of oedema (moderate or severe) was observed on day 1, whereas the maximum degree of erythema (moderate to severe) was seen 72 hours after exposure. Superficial fissuring of the skin was observed in one animal and scaliness in all animals after 7 days. Bald skin and areas with increased density of hair growth, compared to the adjacent skin and control area, was noted in one animal at termination.

COLOURATION
No staining of the treated skin by the test substance was observed.

TOXICITY SYMPTOMS 1 MORTALITY
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.
Other effects:
Signs of injuries in depth were observed at the edges of the treated skin-area in all three animals. During the study, a distinction was made for the
description of the effects between the edges (See illustration; Table 1A) and the remaining part (Table provided above, under Results & Discussion) of the treated skin-area.
Interpretation of results:
Category 1C (corrosive)
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The development of scar tissue in all three animals indicate that corrosion had occurred after dermal application of HEOX-CN to the rabbit skin.
Based on these results and according to the EEC criteria for classification and labelling requirements for dangerous sUbstances and preparations (Guidelines in Commission Directive 93/21/EEC, 27th April 1993), HEOX-CN causes burns (R 34).
Executive summary:

Primary skin irritation/corrosion study with HEOX-CN (CAS 2359 -11 -7) in the rabbit (4-hour semiocclusive application).

The study was carried out in accordance with the OECD guideline No. 404, 'Acute Dermal Irritation/Corrosion' and the EEC Directive 92/69/EEC, B.4, 'Acute Toxicity - Skin irritation. This study should provide part of a rational basis for risk assessment in man. The absence of skin pigmentation in the albino rabbit facilitates the evaluation of induced skin reactions. The dermal route was selected because HEOX-CN may accidentally come into contact with the skin during manufacture, handling and/or use.

Three rabbits were exposed to 0.5 ml of HEOX-CN, applied onto shaved skin for 4 hours using a semi-occlusive dressing. Observations were made 1, 24, 48 and 72 hours and 7, 14 and 21 days after exposure. Different effects were observed between the edges and the remaining part of the treated skin after exposure to HEOX-CN. Signs of necrosis were apparent at the edges of the treated area in all animals, from day 1 onwards. Scabs had developed during the course of the study 7 days after exposure. Healing resulted in the presence of scar tissue in all animals. In the remaining part of the treated area, moderate to severe erythema and moderate or severe oedema were observed, which had completely resolved within 21 days after exposure. Superficial fissuring of the skin was observed in one animal and scaliness in all animals after 7 days. Bald skin and areas with increased density of hair growth in the treated area was noted in one animal at termination. The development of scar tissue in all three animals indicate that corrosion had occurred after dermal application of HEOX-CN to the rabbit skin.

Based on these results and according to the EEC criteria for classification and labelling requirements for dangerous substances and preparations (Guidelines in Commission Directive 93/21/EEC, 27th April 1993), HEOX-CN causes burns (R 34).

According to the Guidance to Regulation (EC) No. 1272/2008 on classification, labelling and packaging (CLP) of substances and mixtures, November 2012, the test substance is classified as Category 1C (corrosive).

Endpoint:
skin corrosion: 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 conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because the substance is classified as skin corrosion, leading to classification as serious eye damage (Category 1)
Endpoint conclusion
Endpoint conclusion:
no study available

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for selection of eye irritation endpoint:

endpoint is waived, substance is being registered solely as an intermediate under Strictly Controlled Conditions so no new testing is required

Effects on skin irritation/corrosion: corrosive

Justification for classification or non-classification

Skin: The development of scar tissue in all three animals indicate that corrosion had occurred after dermal application of HEOX-CN to the rabbit skin. Based on these results and according to the EEC criteria for classification and labelling requirements for dangerous substances and preparations (Guidelines in Commission Directive 93/21/EEC, 27th April 1993), HEOX-CN causes burns (R 34).

According to the Guidance to Regulation (EC) No. 1272/2008 on classification, labelling and packaging (CLP) of substances and mixtures, November 2012, the test substance is classified in Category 1C (Corrosive).