Bis(O,O-diisopropyl dithiophosphate)bis(cyclohexylamine) zinc

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

(Basic data given. Limited data on animal husbandry, test substance purity not specified.)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1977

Report date:

1977

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Draize Testing method (Draize JH et al., J. Pharm. Exp. Ther. 82: 377-390, 1944) as prescribed by the FDA (in The Federal Register 38 No.187 §15000.42, USA).

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

O,O-bis(propan-2-yl) [({[bis(propan-2-yloxy)(sulfanylidene)-λ⁵-phosphanyl]sulfanyl}bis(cyclohexylazaniumyl)zinciodiuide)sulfanyl]phosphonothioate

EC Number:

809-986-4

Cas Number:

52585-16-7

Molecular formula:

C24H54N2O4P2S4Zn

IUPAC Name:

O,O-bis(propan-2-yl) [({[bis(propan-2-yloxy)(sulfanylidene)-λ⁵-phosphanyl]sulfanyl}bis(cyclohexylazaniumyl)zinciodiuide)sulfanyl]phosphonothioate

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Housing: individually
- Diet: 2 oz/day (equivalent to 56.7 g/day) Purina Rabbit Chow
- Water: ad libitum

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eye served for control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.1 g

Duration of treatment / exposure:

single application without washing

Observation period (in vivo):

7 days
Reading time points: 24, 48, 72 and 96 h and 7 days

Number of animals or in vitro replicates:

6

Details on study design:

SCORING SYSTEM: Draize scoring system

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

of 6 animals

Time point:

24/48/72 h

Score:

1.61

Max. score:

4

Reversibility:

not fully reversible within: 7 days in 6 animals

Remarks on result:

other: The chemosis effect was so severe that only 25% of the cornea was observable. The cornea scores are a minimum of the approximated score, however, maximum scores of up to 4 were included in the study report between bracket.

Results 2

Irritation parameter:

iris score

Basis:

mean

Remarks:

of 5 animals

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

not fully reversible within: 7 days in 3 animals. For 2 of these animals no score could be given on day 7.

Remarks on result:

other: The chemosis effect was so severe that only 25% of the iris was observable. For 1/6 animals no iris scores could be assigned at any reading time point; for 1/6 animals no score was assigned at the 7-day reading time point.

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

of all 6 animals

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

not fully reversible within: 7 days in 6 animals

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

of 6 animals

Time point:

24/48/72 h

Score:

3.39

Max. score:

4

Reversibility:

not fully reversible within: 7 days in 2 animals

Remarks on result:

other: Fully reversible within: 7 days in 4 animals

Irritant / corrosive response data:

The chemosis was so severe that only 25% of the cornea and iris were observable. The cornea scores are the minimum score given, however, a maximum score of up to 4 was included in the study report between brackets, indicating that scoring was difficult (see Table 1 and Table 2 under 'Any other information on results incl. tables'). Some corneal effects (score 1 - 2) were observed in 6/6 animals at the 24-, 48-, 72- and 96-hour reading time points. 7 days after instillation, the effects remained the same in 4/6 animals, and had become more severe (score 3) in 2/6 animals. In general, a worsening of the severity was observed in 4/6 animals during the observation period, while it remained the same for 2/6 animals. The highest conjunctivae score of 3 was assigned 6/6 animals at the 24-, 48- and 72-hour reading time points. The severity was reduced in 4/6 animals (score 1 - 2) 7 days after instillation and remained unchanged (score 3) in 2/6 animals. The conjunctivae was irreversible in 6/6 animals. The chemosis was severe (score 3 - 4) in all animals at the 24-, 48- and 72-hour reading time points. 96 hours after instillation, the effect had reduced in severity in 4/6 animals (score 1 - 2) while the severity was unchanged in 2/6 animals (score 3 - 4). At the 7-day reading time point, the chemosis had reversed completely in 4/6 animals, while in 2/6 the effect was still present (score 2 and 4, respectively). In 5/6 animals the iris effects were marked (score 1) from the 24-hour reading time point until the 96-hour reading time point. For 1/6 animals it was not possible to assign an iris score at any reading time point. 7 days after application, the effects has cleared in 3/6 animals, the effects remained marked (score 1) in 1/6, and for 2/6 animals it was not possible to assign an iris score.

Any other information on results incl. tables

Table 1: Individual eye irritation scores

 

Rabbit #	Time	conjunctivae		iris**	cornea***
		redness	swelling
1	24 h	3	4	?	2
	48 h	3	4	?	2
	72 h	3	4	?	2
	96 h 7 d	3 3	4 4	? ?	2 3
	Average*	3.0	4.0	-	2.0
2	24 h	2.5	3	1	1
	48 h	3	3	1	1
	72 h	3	3	1	2
	96 h 7 d	2 1	1 0	1 0	2 2
	Average*	3.0	3.0	1.0	1.33
3	24 h	3	4	1	1
	48 h	3	3	1	1
	72 h	3	3	1	2
	96 h 7 d	3 2	3 0	1 0	2 2
	Average*	3.0	3.33	1.0	1.33
4	24 h	3	4	1	2
	48 h	3	4	1	2
	72 h	3	3	1	2
	96 h 7 d	3 1	2 0	1 0	2 2
	Average*	3.0	3.67	1.0	2.0
5	24 h	3	4	1	1
	48 h	3	3	1	2
	72 h	3	3	1	2
	96 h 7 d	3 1	1 0	1 1	2 2
	Average*	3.0	3.33	1.0	1.67
6	24 h	3	3	1	1
	48 h	3	3	1	1
	72 h	3	3	1	2
	96 h 7 d	3 3	2 2	1 ?	2 3
	Average*	3.0	3.0	1.0	1.33

*(24h+48h+72h)/3.

** Only 25% of the iris was observable due to severe chemosis; the eye of animal 1

could not be scored at all and the eye of animal 6 could not be socred on day 7.

*** Only 25% of the cornea was observable due to severe chemosis.

The cornea scores are the minimum score given, however, a maximum score

(up to 4) was included in the study report between brackets indicating that scoring was difficult.

Table 2: Individual minimum and maximum cornea scores

Observation time	Rabbit No.
	1		2		3		4		5		6
Cornea score	Minimum	Maximum	Minimum	Maximum	Minimum	Maximum	Minimum	Maximum	Minimum	Maximum	Minimum	Maximum
24 h	2	4	1	4	1	3	2	2	1	4	1	4
48 h	2	4	1	3	1	2	2	2	2	3	1	4
72 h	2	4	2	3	2	2	2	3	2	4	2	4
7 days	3	4	2	2	2	2	2	2	2	1	3	4

 

Applicant's summary and conclusion

Interpretation of results:

other: Cat. 1, H318 according to Regulation (EC) No 1272/2008

Conclusions:

CLP: Cat. 1, H318