Reaction mass of Octyl-3-[3-tert-butyl-4-hydroxy-5-(5-chloro-2H-benzotriazole-2-yl)phenyl]propionate and 2-Ethylhexyl-3-[3-tert-butyl-4-hydroxy-5-(5-chloro-2H-benzotriazole-2-yl)phenyl]propionate

Endpoint summary

Description of key information

Skin irritation

The Primary Irritation Index (PII) of TK 12871 was 1.9 and TK 12871 was found to cause a slight irritation when applied to intact and abraded rabbit skin (U.S. EPA § 163.81-5, Federal Register, Vol. 43, No. 163).

 

Eye irritation

TK 12871 was found to cause a minimal irritation when applied to the rabbit eye mucosa (U.S. EPA § 163.81-4, Federal Register, Vol. 43, No. 163).

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:

From April 6, 1981 to April 15, 1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

other: the Proposed Guidelines of the United States Environmental Agency (EPA) § 163.81-5 "Primary dermal irritation study", Federal Register, Vol. 43, No. 163, August 22, 1978.

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

- Weight at study initiation: 2 to 3 kg
- Housing: individually in metal cages
- Water: ad libitum
- Acclimation period: a minimum 4 days
- Temperature (°C): 22 ± 2 °C
- Humidity (%): 55 ± 10%
- Photoperiod: 12hrs light cycle day

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

- Amount(s) applied (volume or weight with unit): 0.5 mL of the test material

Duration of treatment / exposure:

24 hour

Observation period:

24 hours, 48 hours, 72 hours, 4 days and 7 days after the patches removal

Number of animals:

For male: three
For female: three

Details on study design:

- Area of exposure: the prepared abraded and intact skin

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

1.6

Max. score:

2

Remarks on result:

probability of weak irritation

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0.3

Max. score:

2

Remarks on result:

positive indication of irritation

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 24/72 h

Score:

1.9

Max. score:

3.3

Remarks on result:

probability of weak irritation

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

24/48/72 h

Score:

1.8

Max. score:

4

Remarks on result:

probability of weak irritation

Table 1. Calculation of the primary skin irritation index

Time after exposure hours	Mean reaction score
	Erythema		Edema
	Intact skin	Abraded skin	Intact skin	Abraded skin
24	1.5	1.8	0.3	0.5
72	1.5	1.5	0.3	0.3
Primary Irritation Index (PII)* = 1.9

* The scores read after 24 and 72 hours for erythema and edema for the intact as well as for the abraded skin were summed up and divided by 4. (FHSLA § 191.11)

 

Assessment of irritation

0

0.1-1.0 = minimal

1.1-2.0 = slight

2.1-4.0 = moderate

4.1-6.0 = marked

6.1-8.0 = extreme

Interpretation of results:

GHS criteria not met

Conclusions:

According to U.S. EPA § 163.81-5, Federal Register, Vol. 43, No. 163 (1978) and assessment of irritation, the PII for TK 12871 was 1.9 and TK 12871 was found to cause a slight irritation when applied to intact and abraded rabbit skin. Therefore, TK 12871 was not met a category based on GHS criteria.

Executive summary:

This test using the procedures outlined in the CIBA-GEIGY Study Plan for 810283 and U.S. EPA § 163.81-5, Federal Register, Vol. 43, No. 163 (1978). The sites were grades for erythema and edema at 24 hours, 48 hours, 72 hours, 4 days and 7 days after the patches removal. The Primary Irritation Index for TK 12871 was calculated to be 1.9. On the basis of the test results given above and according toassessment of irritation, TK 12871 was found to cause a slight irritation when applied to intact and abraded rabbit skin.

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:

From April 6, 1981 to April 14, 1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

other: The United States Environmental Protection Agency (EPA) § 163.81-4 "Primary eye irritation study", Federal Register, Vol. 43, No. 163, August 22, 1978

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

- Weight at study initiation: 2-3 kg
- Housing: individually in metal cages
- Water: ad libitum
- Acclimation period: minimum of 4 days
- Temperature (°C): 22 ± 2 °C
- Humidity (%): 55 ± 10%
- Photoperiod: 12-hrs light cycle day

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

- Amount(s) applied (volume or weight with unit): 0.1 mL

Observation period (in vivo):

day 1, 2, 3, 4 and 7

Number of animals or in vitro replicates:

For male: three
For female: three

Irritation parameter:

cornea opacity score

Basis:

animal: #103, 104, 105, 106 107, 108

Remarks:

Not rinsed: #103, 104 and 105; rinsed: #106, 107 and 108

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal: #103, 104, 105, 106 107, 108

Remarks:

Not rinsed: #103, 104 and 105; rinsed: #106, 107 and 108

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal: #105

Remarks:

Not rinsed

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal: #103, 104, 106, 107, 108

Remarks:

Not rinsed: #103 and 104; rinsed: #106, 107 and 108

Time point:

24/48/72 h

Score:

0.66

Remarks on result:

probability of weak irritation

Irritation parameter:

chemosis score

Basis:

animal: #103, 104, 105, 107, 108

Remarks:

Not rinsed: #103, 104 and 105; rinsed: #107 and 108

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal: #106

Remarks:

Rinsed

Time point:

24/48/72 h

Score:

0.33

Remarks on result:

probability of weak irritation

Table 1. Calculation of the primary eye irritation index

Time after exposure days	Mean reaction score
	Unrinsed eyes (A)			Rinsed eyes (B)
	cornea	iris	conjunctive	cornea	iris	conjunctive
1	0	0	2.7	0	0	3.3
2	0	0	0	0	0	1.3
3	0	0	0	0	0	0
4	0	0	0	0	0	0
7	0	0	0.7	0	0	0
Subtotal	0	0	3.4	0	0	4.6
Ttotal	3.4			4.6
Primary irritation index*	0.7			0.9

*The mean reaction scores for cornea, iris and conjunctiva observed after 1, 2, 3, 4 and 7 days were summed up and the sum divided by 5.

 

Index         0            =   none

                 0.1 - 10.9     =   minimal

                 11.0 - 25.9   =   slight

                 26.0 - 55.9   =   moderate

                 56.0 - 84.0   =   marked

                 above 84.0   =   extreme

Interpretation of results:

GHS criteria not met

Conclusions:

According to U.S. EPA § 163.81-4, Federal Register, Vol. 43, No. 163 (1978), TK 12871 was found to cause a minimal irritation when applied to the rabbit eye mucosa. Therefore, TK 12871 was not met a category based on GHS criteria.

Executive summary:

This test using the procedures outlined in the CIBA-GEIGY Study Plan for 810282 and U.S. EPA § 163.81-4, Federal Register, Vol. 43, No. 163 (1978). The test material in an amount of 0.1 ml was inserted into the conjunctival sac of the left eye of the rabbits and the lids were gently closed for a few seconds. The right eye was not treated and served as an untreated control. In 3 of the 6 rabbits approximately 30 seconds after treatment the treated eye was flushed with 10 ml of physiological saline. The eye irritation was appraised with a slit-lamp on day 1, 2, 3, 4 and 7 and was scored for each individual rabbit. TK 12871 was found to cause a minimal irritation (primary irritation index 0.7) when applied to the rabbit eye mucosa. When the application site was rinsed, the irritation was found to be minimal (primary irritation index 0.9).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

The sites were grades for erythema and edema at 24 hours, 48 hours, 72 hours, 4 days and 7 days after the patches removal. The Primary Irritation Index for TK 12871 was calculated to be 1.9. On the basis of the test results given above and according to assessment of irritation, TK 12871 was found to cause a slight irritation when applied to intact and abraded rabbit skin.

 

Eye irritation

The test material in an amount of 0.1 ml was inserted into the conjunctival sac of the left eye of the rabbits and the lids were gently closed for a few seconds. The right eye was not treated and served as an untreated control. In 3 of the 6 rabbits approximately 30 seconds after treatment the treated eye was flushed with 10 ml of physiological saline. The eye irritation was appraised with a slit-lamp on day 1, 2, 3, 4 and 7 and was scored for each individual rabbit. TK 12871 was found to cause a minimal irritation (primary irritation index 0.7) when applied to the rabbit eye mucosa. When the application site was rinsed, the irritation was found to be minimal (primary irritation index 0.9).