Registration Dossier

Administrative data

Description of key information

Based on key study results, Montanol 800 is considered to be irritating to skin and slightly irritating to eyes.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1985
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Nottingham University, School of Agriculture, Sutton Bonington, Leicestershire, U.K.
- Age at study initiation: approximately 12-16 weeks old
- Weight at study initiation: 2.49-2.57 kg
- Housing: individually, in suspended metal cages
- Diet: Rabbit Diet (AW Tindall Limited, Holbeach, Lincolnshire, U.K.), ad libitum
- Water: mains drinking water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 18-21 °C
- Humidity: 50-65 %
- Air changes: approximately 10 changes/hour
- Photoperiod: 12 hours dark / 12 hours light

IN-LIFE DATES: From: 01-Oct-1985 To: 08-Oct-1985
Type of coverage:
other: occlusive or semi-occlusive
Preparation of test site:
other: clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 mL of undiluted test item
Duration of treatment / exposure:
4 hours
Observation period:
7 days
Number of animals:
3 rabbits
Details on study design:
TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm (area of gauze patch used)
- Type of wrap if used: gauze patch secured in position with adhesive strapping

REMOVAL OF TEST SUBSTANCE
- Washing: gentle swabbing with cotton wool soaked in ether
- Time after start of exposure: 4 hours

SCORING SYSTEM:
Approximately 1, 24, 48 and 72 hour(s) after patch removal, the test sites were examined and scored acording to the scale of Draize. The scores for erythema and oedema at the 24 and 72 hour readings were totalled for the 3 test rabbits (12 values). This total was divided by 6 to give the Primary Irritation Index of the test item. This index was used to classify the skin irritation according to the scheme shown under "Any other information on materials and methods incl. tables".
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 24 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: desquamation
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 48 hours
Score:
1
Max. score:
4
Remarks on result:
other: desquamation
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 72 hours
Score:
1
Max. score:
4
Remarks on result:
other: desquamation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 24 hours
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 48 hours
Score:
2
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 72 hours
Score:
2
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 24 hours
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Remarks on result:
other: desquamation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 48 hours
Score:
2
Max. score:
4
Remarks on result:
other: desquamation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 72 hours
Score:
2
Max. score:
4
Remarks on result:
other: desquamation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 24 hours
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 48 hours
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 72 hours
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 24 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 48 hours
Score:
1
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 72 hours
Score:
1
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 24 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 48 hours
Score:
1
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 72 hours
Score:
0
Max. score:
4
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
other: sum of 24 and 72 hour reading / 6
Score:
2.2
Remarks on result:
other: moderate irritant

Well defined erythema accompanied by minimal oedema, with the reactions extending beyond the site of application was noted in 3/3 rabbits at the 1 -hour reading and in 2/3 rabbits at subsequent 24, 48 and 72 -hour observations. The skin irritation had become less marked in one rabbit by the 24 -hour reading when barely perceptible erythema was seen in this animal. In addition, desquamation was noted in 2/3 rabbits at this stage. Similar levels of reaction persisted at subsequent 48 and 72 -hour readings. A reduction in the level of reaction was seen at day 7 when barely perceptible erythema accompanied by desquamation, with the reactions extending beyond the site of application was apparent in the remaining animal at this stage.

Interpretation of results:
moderately irritating
Remarks:
Migrated information
Executive summary:

In a primary dermal irritation study (Jones & Collier, 1985), 3 young adult New Zealand White rabbits were dermally exposed to 0.5 mL of ZD 8 Gewaschen for 4 hours. Animals then were observed for 7 days. Irritation was scored by the method of Draize (1959). The primary irritation index was used for classification of irritancy.

In this study, ZD 8 gewaschen was a moderate irritant based on well defined erythema accompanied by minimal oedema noted and scored in all rabbits.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1985
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Nottingham University, School of Agriculture, Sutton Bonington, Leicestershire, U.K.
- Age at study initiation: approximately 12-16 weeks old
- Weight at study initiation: 2.51-2.80 kg
- Housing: individually, in suspended metal cages
- Diet: Rabbit Diet (AW Tindall Limited, Holbeach, Lincolnshire, U.K.), ad libitum
- Water: mains drinking water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 17-20 °C
- Humidity: 60-68 %
- Air changes: approximately 10 changes/hour
- Photoperiod: 12 hours dark / 12 hours light

IN-LIFE DATES: From: 08-Oct-1985 To: 11-Oct-1985
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.1 mL
- Concentration: undiluted
Duration of treatment / exposure:
Single intraocular application
Observation period (in vivo):
72 hours (terminated as no reactions were apparent)
Number of animals or in vitro replicates:
3 rabbits
Details on study design:
SCORING SYSTEM: Draize (1959) scale for scoring ocular irritation. Using the numerical data obtained a modified version of the system described by Kay & Calandra (1962) was used to classify the ocular irritation potential of the test material.
Irritation parameter:
overall irritation score
Basis:
animal #1
Time point:
other: 1 hour
Score:
13
Max. score:
110
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: total score for conjunctivae, iris and cornea
Irritation parameter:
overall irritation score
Basis:
animal #2
Time point:
other: 1 hour
Score:
6
Max. score:
110
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: total score for conjunctivae, iris and cornea
Irritation parameter:
overall irritation score
Basis:
animal #3
Time point:
other: 1 hour
Score:
11
Max. score:
110
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: total score for conjunctivae, iris and cornea
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 1 hour
Score:
10
Max. score:
110
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: group mean score
Irritation parameter:
overall irritation score
Basis:
animal #1
Time point:
other: 24 hours
Score:
4
Max. score:
110
Remarks on result:
other: total score for conjunctivae, iris and cornea
Irritation parameter:
overall irritation score
Basis:
animal #2
Time point:
other: 24 hours
Score:
0
Max. score:
110
Remarks on result:
other: total score for conjunctivae, iris and cornea
Irritation parameter:
overall irritation score
Basis:
animal #3
Time point:
other: 24 hours
Score:
2
Max. score:
110
Remarks on result:
other: total score for conjunctivae, iris and cornea
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24 hours
Score:
2
Max. score:
110
Remarks on result:
other: group mean score
Irritation parameter:
overall irritation score
Basis:
animal #1
Time point:
other: 48 hours
Score:
0
Max. score:
110
Remarks on result:
other: total score for conjunctivae, iris and cornea
Irritation parameter:
overall irritation score
Basis:
animal #2
Time point:
other: 48 hours
Score:
0
Max. score:
110
Remarks on result:
other: total score for conjunctivae, iris and cornea
Irritation parameter:
overall irritation score
Basis:
animal #3
Time point:
other: 48 hours
Score:
0
Max. score:
110
Remarks on result:
other: total score for conjunctivae, iris and cornea
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 48 hours
Score:
0
Max. score:
110
Remarks on result:
other: group mean score
Irritation parameter:
overall irritation score
Basis:
animal #1
Time point:
other: 72 hours
Score:
0
Max. score:
110
Remarks on result:
other: total score for conjunctivae, iris and cornea
Irritation parameter:
overall irritation score
Basis:
animal #2
Time point:
other: 72 hours
Score:
0
Max. score:
110
Remarks on result:
other: total score for conjunctivae, iris and cornea
Irritation parameter:
overall irritation score
Basis:
animal #3
Time point:
other: 72 hours
Score:
0
Max. score:
110
Remarks on result:
other: total score for conjunctivae, iris and cornea
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 72 hours
Score:
0
Max. score:
110
Remarks on result:
other: group mean score

No evidence of corneal damage was noted throughout the 72-hour study period. Iridial inflammation was apparent in 2/3 rabbits at the 1-hour reading only. Slight conjunctivitis identified by redness (grade 2) and swelling (grades 1-2) was noted in 3/3 rabbits at the 1-hour reading. The reactions had resolved completely by the 24-hour (1/3 rabbits) or the 48-hour observation (2/3 rabbits). In addition, 0/3 rabbits showed evidence of positive ocular irritation.

Executive summary:

In a primary eye irritation study (Jones & Collier, 1985), 0.1 mL of undiluted ZD 8 Gewaschen was instilled into the conjunctival sac of the right eye of young adult New Zealand White rabbits. Animals then were observed for 72 hours following treatment. Irritation was scored by the method of Draize (1959) and the test item was classified for its ocular irritation potential according to Kay & Calandra (1962, modified). The treatment resulted in a maximum mean score of 10 and the test item was classified as a minimal irritant (class 3 on a scale of 1 to 8).

In this study, ZD 8 Gewaschen was a minimal irritant to the rabbit eye.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In a primary skin irritation study (Jones & Collier, 1985), 3 young adult New Zealand White rabbits were dermally exposed to 0.5 mL of ZD 8 Gewaschen (identical to 1-Hexanol, 2-ethyl-, manuf. of, by-products from, distn. Residues) for 4 hours. Animals then were observed for 7 days. Irritation was scored by the method of Draize (1959). The primary irritation index was used for classification of irritancy. ZD 8 gewaschen was a moderate irritant based on well defined erythema accompanied by minimal oedema noted and scored in all rabbits. The mean erythema score (24, 28 and 72 hour reading) was 1 for animal #1, and 2 for animal #2 and #3. The mean oedema score (24, 48 and 72 hour reading) was 0, 1 and 0.67 for animal #1, #2 and #3, respectively. Mild signs of irritation were still present at the end of the observation period.

In a primary eye irritation study (Jones & Collier, 1985), 0.1 mL of undiluted ZD 8 Gewaschen was instilled into the conjunctival sac of the right eye of young adult New Zealand White rabbits. Animals then were observed for 72 hours following treatment. Irritation was scored by the method of Draize (1959) and the test item was classified for its ocular irritation potential according to Kay & Calandra (1962, modified). In this study, ZD 8 Gewaschen was a minimal irritant to the rabbit eye.


Effects on skin irritation/corrosion: irritating

Effects on eye irritation: slightly irritating

Justification for classification or non-classification

Based on the results of the skin and eye irritation key toxicity studies. 1-Hexanol, 2-ethyl-, manuf. of, by-products from, distn. Residues is classified and labelled for skin irritation / corrosion according to Directive 67/548/EEC as R38, irritating to skin and according to Regulation 1272/2008/EC as Cat. 2, H315, causes skin irritation.