Registration Dossier

Administrative data

Description of key information

Skin and eye irritation are discussed.

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:
September 29 1982 to January 25 1983
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non GLP, carried out according to recognised (older) guideline, results fully documented. Considered appropriate for use based on data available and animal welfare concerns.
Reason / purpose:
reference to same study
Qualifier:
according to
Guideline:
other: Consistent with Environmental Protection Agency's Guidelines for registering pesticides in the U.S.: Hazard evaluation: Humans and Domestic Animals, Fed. Reg. 43:163 37336-37402 (1978); test exceeds the protocol recommended in the OECD Guidelines (1981)
Deviations:
no
Principles of method if other than guideline:
The primary irritation of the skin was measured by a patch-test technique on the abraded and intact skin of six Stauffland albino rabbits. Half a milliliter of the test substance was introduced under a one inch square gauze patch. The patches were secured in place by adhesive tape and wrapped with rubberized damming for a period of four hours. After 4 hours of exposure, the patches and test material were removed, and the resulting reactions were given a score. Readings were also made after 24 and 72 hours and the final score represents an avaerage of all the readings. The scoring and evaluation criteria are those described by Draize (1965).
GLP compliance:
no
Species:
rabbit
Strain:
other: Stauffland albino
Details on test animals and environmental conditions:
Animals used for this study were purchased from Phillips Rabbitry, Soquel, California.
No details on environmental conditions are provided.
Type of coverage:
occlusive
Preparation of test site:
other: abraded and intact
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5 mL
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
6
Details on study design:
The primary irritation of the skin was measured by a patch-test technique on the abraded and intact skin of six Stauffland albino rabbits. Half a milliliter of the test substance was introduced under a one inch square gauze patch. The patches were secured in place by adhesive tape and wrapped with rubberized damming for a period of four hours. After 4 hours of exposure, the patches and test material were removed, and the resulting reactions were given a score. Readings were also made after 24 and 72 hours and the final score represents an avaerage of all the readings. The scoring and evaluation criteria are those described by Draize (1965).
Irritation parameter:
overall irritation score
Basis:
animal #1
Time point:
72 h
Score:
0.5
Max. score:
1
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
overall irritation score
Basis:
animal #2
Time point:
72 h
Score:
0.67
Max. score:
1
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
overall irritation score
Basis:
animal #3
Time point:
72 h
Score:
0.33
Max. score:
1
Reversibility:
fully reversible within: 24 hours
Irritation parameter:
overall irritation score
Basis:
animal #4
Time point:
72 h
Score:
0.67
Max. score:
1
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
overall irritation score
Basis:
animal #5
Time point:
72 h
Score:
1
Max. score:
1
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: score attributed to erythema / eschar presence
Irritation parameter:
overall irritation score
Basis:
animal #6
Time point:
72 h
Score:
1
Max. score:
1
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: score attributed to erythema / eschar presence
Irritant / corrosive response data:
Fyrquel EHC Trixylenyl phosphate produced mild erythema in intact and abraded skin of 6 rabbits following 4 hour exposure. By the 24 hour observation irritation decreased in 2 rabbits. At 72 hours irritation had cleared in 4 rabbits and 2 rabbits had mild erythema.
Other effects:
None noted

Results

 

Skin type

Erythema-eschar

Observation

Edema

Observation

Sum

Total

Score*

Rabbit No

 

 

4 hr.

24 hr.

72 hr.

4 hr.

24 hr.

72 hr.

83-F-l

Intact

1

0

0

0

0

0

3.0

0.50

 

 

 

 

 

 

 

Abraded

1

1

0

0

0

0

 

 

 

 

 

 

 

 

 

 

83-F-2

Intact

1

1

0

0

0

0

4.0

0.67

 

 

 

 

 

 

 

Abraded

1

1

0

0

0

0

 

 

 

 

 

 

 

 

 

 

83-F-3

Intact

1

0

0

0

0

0

2.0

0.33

 

 

 

 

 

 

 

Abraded

1

0

0

0

0

0

 

 

 

 

 

 

 

 

 

 

83-F-4

Intact

1

1

0

0

0

0

4.0

0.67

 

 

 

 

 

 

 

Abraded

1

1

0

0

0

0

 

 

 

 

 

 

 

 

 

 

83-F-5

Intact

1

1

1

0

0

0

6.0

1.0

 

 

 

 

 

 

 

Abraded

1

1

1

0

0

0

 

 

 

 

 

 

 

 

 

 

83-F-6

Intact

1

1

1

0

0

0

6.0

1.0

 

 

 

 

 

 

 

Abraded

1

1

1

0

0

0

Primary Irritant Score

 

0.70

*Score = Sum of individual values for each rabbit divided by six.

Interpretation of results:
GHS criteria not met
Conclusions:
Fyrquel EHC (Trixylenyl phosphate) was a mild irritant to intact and abraded skin of albino rabbits after a 4 hour exposure. This formulation produced mild erythema in intact and abraded skin of 6 rabbits following 4 hour exposure. By the 24 hour observation irritation decreased in 2 rabbits. At 72 hours irritation had cleared in 4 rabbits and 2 rabbits had mild erythema.
Executive summary:

Fyrquel EHC (Trixylenyl phosphate) was a mild irritant to intact and abraded skin of albino rabbits after a 4 hour exposure. This formulation produced mild erythema in intact and abraded skin of 6 rabbits following 4 hour exposure. By the 24 hour observation irritation decreased in 2 rabbits. At 72 hours irritation had cleared in 4 rabbits and 2 rabbits had mild erythema.

On the basis of EU Criteria, the substance is not classified as a skin irritant.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not 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:
September 29 1982 to January 25 1983
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non GLP, carried out according to recognised (older) guideline, results fully documented. Considered appropriate for use based on data available and animal welfare concerns.
Reason / purpose:
reference to same study
Qualifier:
according to
Guideline:
other: Test consistent with Environmental Protection Agency's proposed guidelines, OECD guidelines and PR notice 81-3
Deviations:
no
Principles of method if other than guideline:
Stauffland albino rabbits were used for this eye irritation toxicity study. The eyes of the rabbits were examined at least 24 hours before application of the test substance for ocular and periocular abnormalities. Rabbits with preexisting ocular or periocular lesions or abnormalities were excluded from further ocular testing. One tenth of a milliliter of the test material was placed in the conjuctival sac of the left eye of each of nine rabbits. The treated eye was washed with water 20-30 seconds after exposure in 3 rabbits and the eyes were left unwashed in the remaining 6 rabbits. The untreated eye of each animal served as a negative control. The cornea, the iris and the bulbar and palpebral conjunctivae were observed at 1, 24, 48 and 72 hours and at 4 and 7 days after treatment. Observations with fluorescein staining were made 24 hours after the application of the test substance and until there was no staining for three consecutive observations. If irritation was present after 7 days, an additional observation was made every 3-4 days until the injury subsided or was found to be irreversible.
GLP compliance:
no
Species:
rabbit
Strain:
other: Stauffland albino
Details on test animals or tissues and environmental conditions:
Animals used for this study were purchased from Phillips Rabbitry, Soquel, California. No details on environmental conditions are provided.
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated left eye served as control.
Amount / concentration applied:
0.1 mL
Duration of treatment / exposure:
The treated eye was washed with water 20-30 seconds after exposure in 3 rabbits and the eyes were left unwashed in the remaining 6 rabbits.
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
9 - 6 unwashed, 3 washed eyes.
Details on study design:
Stauffland albino rabbits were used for this eye irritation toxicity study. The eyes of the rabbits were examined at least 24 hours before application of the test substance for ocular and periocular abnormalities. Rabbits with preexisting ocular or periocular lesions or abnormalities were excluded from further ocular testing.

One tenth of a milliliter of the test material was placed in the conjuctival sac of the left eye of each of nine rabbits. The treated eye was washed with water 20-30 seconds after exposure in 3 rabbits and the eyes were left unwashed in the remaining 6 rabbits. The untreated eye of each animal served as a negative control. The cornea, the iris and the bulbar and palpebral conjunctivae were observed at 1, 24, 48 and 72 hours and at 4 and 7 days after treatment. Observations with fluorescein staining were made 24 hours after the application of the test substance and until there was no staining for three consecutive observations. If irritation was present after 7 days, an additional observation was made every 3-4 days until the injury subsided or was found to be irreversible.
Irritation parameter:
overall irritation score
Basis:
animal #1
Remarks:
unwashed eye
Time point:
other: 1 hour
Score:
4
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: No effects noted at 24 hours.
Irritation parameter:
overall irritation score
Basis:
animal #2
Remarks:
unwashed eye
Time point:
other: 1 hour
Score:
4
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: No effects noted at 24 hours.
Irritation parameter:
overall irritation score
Basis:
animal #3
Remarks:
unwashed eye
Time point:
other: 1 hour
Score:
6
Max. score:
6
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: No effects noted at 24 hours.
Irritation parameter:
overall irritation score
Basis:
animal #4
Remarks:
unwashed eye
Time point:
other: 1 hour
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: No effects noted at 24 hours.
Irritation parameter:
overall irritation score
Basis:
animal #5
Remarks:
unwashed eye
Time point:
other: 1 hour
Score:
6
Max. score:
6
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: No effects noted at 24 hours.
Irritation parameter:
overall irritation score
Basis:
animal #6
Remarks:
unwashed eye
Time point:
other: 1 hour
Score:
6
Max. score:
6
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: No effects noted at 24 hours.
Irritation parameter:
overall irritation score
Basis:
animal: #7 - washed eye
Time point:
other: 1 hour
Score:
4
Max. score:
4
Reversibility:
fully reversible within: 24
Remarks on result:
other: No effects noted at 24 hours.
Irritation parameter:
overall irritation score
Basis:
animal: #8 - washed eye
Time point:
other: 1 hour
Score:
4
Max. score:
4
Reversibility:
fully reversible within: 24
Remarks on result:
other: No effects noted at 24 hours.
Irritation parameter:
overall irritation score
Basis:
animal: #9-washed eye
Time point:
other: 1 hour
Score:
6
Max. score:
6
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: No effects noted at 24 hours.
Irritant / corrosive response data:
In all rabbits, whether the eye was washed or unwashed after application, Fyrquel EHC (Trixylenyl phosphate) produced mild to moderate conjuctival irriatation. All irritation cleared within 24 hours.
Other effects:
None

Tabulated data is attached below; cannot be included within this section.

Interpretation of results:
GHS criteria not met
Conclusions:
Fyrquel EHC (Trixylenyl phosphate) was a mild irritant in the eyes of albino rabbits. in all 9 rabbits tested, whether the eye was washed (3 rabbits) or unwashed after application (6 rabbits), Fyrquel EHC (Trixylenyl phosphate) produced mild to moderate conjuctival irriatation. All irritation cleared within 24 hours.
Executive summary:

Fyrquel EHC (Trixylenyl phosphate) was a mild irritant in the eyes of albino rabbits. in all 9 rabbits tested, whether the eye was washed (3 rabbits) or unwashed after application (6 rabbits), Fyrquel EHC (Trixylenyl phosphate) produced mild to moderate conjuctival irritation. All irritation cleared within 24 hours.

The substance is not classified as an eye irritant on the basis of the results. Initial irritation is rapidly overcome both by washing and by natural biological action.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation / Corrosion.

Trixylenyl phosphate was determined to be a mild irritant to intact and abraded skin of albino rabbits after a 4 hour exposure. This formulation produced mild erythema in intact and abraded skin of 6 rabbits following 4 hour exposure. By the 24 hour observation irritation decreased in 2 rabbits. At 72 hours irritation had cleared in 4 rabbits and 2 rabbits had mild erythema. The effects observed were not enough to trigger EU classification criteria.

Eye irritation.

Trixylenyl phosphate was determined to be a mild irritant in the eyes of albino rabbits. in all 9 rabbits tested, whether the eye was washed (3 rabbits) or unwashed after application (6 rabbits). The substance produced mild to moderate conjunctival irritation. All irritation cleared within 24 hours.

Respiratory irritation was not assessed; however no effects on the animals were noted in any associated studies.

Justification for selection of skin irritation / corrosion endpoint:

Non GLP, carried out according to recognised (older) guideline, results fully documented.  Considered appropriate for use based on data available and animal welfare concerns.

Justification for selection of eye irritation endpoint:

Non GLP, carried out according to recognised (older) guideline, results fully documented.  Considered appropriate for use based on data available and animal welfare concerns.

Effect level: empty Endpoint conclusion: Adverse effect observed

Justification for classification or non-classification

The above studies have all been ranked reliability 2 according to the Klimish et al system. This ranking was deemed appropriate because the studies were not conducted to GLP or in compliance with agreed protocols. Some of the reports do not detail a specific method; however it documents dose levels and responses in detail, so is deemed appropriate for use in the support of a formal registration. Sufficient dose ranges and numbers are detailed; hence it is appropriate for use based on reliability and animal welfare grounds.

Justification for classification or non classification

The above results triggered no classification under the Dangerous Substance Directive (67/548/EEC) or the CLP Regulation (EC No 1272/2008).